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Sample records for progredierende muskelsvind hos

  1. What Fuzzy HOS May Mean

    DTIC Science & Technology

    1978-11-01

    HIGHER ORDER SOFTWAHE, INC, S!806 Massacysetts Avenue Cambridge, Massachusetts 02139 i ’ ~ii ý4 TECHNICAL REPORT #18 • Bi 1 WHAT FUZZY HOS MAY MEAN 4...by H. Prade and L. Vatna i Nov~ 1978 OA.04i•. 81 3 0e 044 ;!. i81 ’- ----- - HIGHER ORDER SOFTWARE, INC. 806 Massachusetts Avenue Cambridge...reliability is then dealt with I. INTRODUCTION Higher Order Software (HOS) has been developed by Magaret Hamilton and Saydean Zeldin [43 as a

  2. The Application of HOS to PLRS

    DTIC Science & Technology

    1977-11-01

    HIGHER ORDER SOFTWARE, INC, ( - 0843 Massachusetts Avenue 0Cambridge, MA 02139 LEVE& TECHNICAL REPORT #12 THE APPLICATION OF ( HOS TO PLRS November...Technical Report #12 7. AUTHOR(s) 8. CONTRACT OR GRANT NUMBER(si Higher Order Software, Inc. DAAB07- 77-C-3349,,. 9. PERFORMING ORGANIZATION NAME AND...ADDO ESS 10. PROGRAM ELEMENT. PROJECT. TASK Higher Order Software, Inc /(as of 12/9/77, AREA&WORKUNITNUMBERS 843 Massachusetts Avenue 806

  3. Data Base Query within HOS Systems Methodology

    DTIC Science & Technology

    1982-07-01

    C?’, HIGHER ORDER SOFTWARE, INC.3 FINAL REPORT CONTRACT NO. N00014-U2-C.@I37 JULY 1962 DATA BASE QUERY HOS SYSTEMS METHODOLOGY PREPARED FOR OFFICE Of...NAVAL RESEARCH j ~ DEPARTMENT oF THE NAVY Ca 600 NORTH QUINCY STREET ARLINGTON, VIRGINIA 22217 0802 NOTICES Copyright 0 1982 by Higher Order Software...permission from Higher Order Software, Inc. DISCLAIMERS The findings in this report are not to be construed as an official Department of the Navy position

  4. Functional characterization of Candida albicans Hos2 histone deacetylase

    PubMed Central

    Karthikeyan, G; Paul-Satyaseela, Maneesh; Dhatchana Moorthy, Nachiappan; Gopalaswamy, Radha; Narayanan, Shridhar

    2014-01-01

    Candida albicans is a mucosal commensal organism capable of causing superficial (oral and vaginal thrush) infections in immune normal hosts, but is a major pathogen causing systemic and mucosal infections in immunocompromised individuals. Azoles have been very effective anti-fungal agents and the mainstay in treating opportunistic mold and yeast infections. Azole resistant strains have emerged compromising the utility of this class of drugs. It has been shown that azole resistance can be reversed by the co-administration of a histone deacetylase (HDAC) inhibitor, suggesting that resistance is mediated by epigenetic mechanisms possibly involving Hos2, a fungal deacetylase. We report here the cloning and functional characterization of  HOS2 (High Osmolarity  Sensitive) , a gene coding for fungal histone deacetylase from  C. albicans. Inhibition studies showed that Hos2 is susceptible to pan inhibitors such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), but is not inhibited by class I inhibitors such as MS-275. This  in  vitro enzymatic assay, which is amenable to high throughput could be used for screening potent fungal Hos2 inhibitors that could be a potential anti-fungal adjuvant. Purified Hos2 protein consistently deacetylated tubulins, rather than histones from TSA-treated cells. Hos2 has been reported to be a putative NAD+ dependent histone deacetylase, a feature of sirtuins. We assayed for sirtuin activation with resveratrol and purified Hos2 protein and did not find any sirtuin activity. PMID:25110576

  5. The Human Operator Simulator. Volume IX. HOS Study Guide.

    DTIC Science & Technology

    1978-09-01

    SPECIFYING A GRASP LOCATION O UNEXECUTABLE ACTIONS CAUSE SUSPENSION OF PROCEDURE 69 CONTROL MANIPULATION - DISCRETE CONTROLS -TIME TO MANIPULATE IS A...between the current location and the desired location, whether or not the crewstation geometry would actually permit such a movement. All movements are...Goldbeck and Charlet (1974), and MacPherson and Siegel (1967). 251 An explicit formula for the operation of continuous rotary con- trols is included in HOS

  6. Genetic heterogeneity in the cysA-fus region of the Bacillus subtilis chromosome: identification of the hos gene.

    PubMed Central

    Matsuzaki, S; Kobayashi, Y

    1985-01-01

    We identified a new gene, hos, which exerts different sporulation phenotypes in Bacillus subtilis strains with different genetic backgrounds. The hos+ gene showed normal sporulation in the genetic background of JH642 but showed temperature-sensitive sporulation in that of the Tano-oka W. The hos gene was mapped between cysA and rpoB. PMID:3922952

  7. A lysine deacetylase Hos3 is targeted to the bud neck and involved in the spindle position checkpoint.

    PubMed

    Wang, Mengqiao; Collins, Ruth N

    2014-09-15

    An increasing number of cellular activities can be regulated by reversible lysine acetylation. Targeting the enzymes responsible for such posttranslational modifications is instrumental in defining their substrates and functions in vivo. Here we show that a Saccharomyces cerevisiae lysine deacetylase, Hos3, is asymmetrically targeted to the daughter side of the bud neck and to the daughter spindle pole body (SPB). The morphogenesis checkpoint member Hsl7 recruits Hos3 to the neck region. Cells with a defect in spindle orientation trigger Hos3 to load onto both SPBs. When associated symmetrically with both SPBs, Hos3 functions as a spindle position checkpoint (SPOC) component to inhibit mitotic exit. Neck localization of Hos3 is essential for its symmetric association with SPBs in cells with misaligned spindles. Our data suggest that Hos3 facilitates cross-talk between the morphogenesis checkpoint and the SPOC as a component of the intricate monitoring of spindle orientation after mitotic entry and before commitment to mitotic exit.

  8. The E3 ubiquitin ligase HOS1 regulates low ambient temperature-responsive flowering in Arabidopsis thaliana.

    PubMed

    Lee, Jeong Hwan; Kim, Jae Joon; Kim, Soo Hyun; Cho, Hyun Jung; Kim, Joonki; Ahn, Ji Hoon

    2012-10-01

    Ubiquitin-dependent proteolysis regulates multiple aspects of plant growth and development, but little is known about its role in ambient temperature-responsive flowering. In addition to being regulated by daylength, the onset of flowering in many plants can also be delayed by low ambient temperatures. Here, we show that HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1), which encodes an E3 ubiquitin ligase, controls flowering time in response to ambient temperatures (16 and 23°C) and intermittent cold. hos1 mutants flowered early, and were insensitive to ambient temperature, but responded normally to vernalization and gibberellic acid. Genetic analyses suggested that this ambient temperature-insensitive flowering was independent of FLOWERING LOCUS C (FLC). Also, FLOWERING LOCUS T (FT) and TWIN SISTER OF FT (TSF) expression was up-regulated in hos1 mutants at both temperatures. The ft tsf mutation almost completely suppressed the early flowering of hos1 mutants at different temperatures, suggesting that FT and TSF are downstream of HOS1 in the ambient temperature response. A lesion in CONSTANS (CO) did not affect the ambient temperature-insensitive flowering phenotype of hos1-3 mutants. In silico analysis showed that FVE was spatiotemporally co-expressed with HOS1. A HOS1-green fluorescent protein (GFP) fusion co-localized with FVE-GFP in the nucleus at both 16 and 23°C. HOS1 physically interacted with FVE and FLK in yeast two-hybrid and co-immunoprecipitation assays. Moreover, hos1 mutants were insensitive to intermittent cold. Collectively, our results suggest that HOS1 acts as a common regulator in the signaling pathways that control flowering time in response to low ambient temperature.

  9. The Arabidopsis E3 Ubiquitin Ligase HOS1 Negatively Regulates CONSTANS Abundance in the Photoperiodic Control of Flowering[W

    PubMed Central

    Lazaro, Ana; Valverde, Federico; Piñeiro, Manuel; Jarillo, Jose A.

    2012-01-01

    The Arabidopsis thaliana early in short days6 (esd6) mutant was isolated in a screen for mutations that accelerate flowering time. Among other developmental alterations, esd6 displays early flowering in both long- and short-day conditions. Fine mapping of the mutation showed that the esd6 phenotype is caused by a lesion in the HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 (HOS1) locus, which encodes a RING finger–containing E3 ubiquitin ligase. The esd6/hos1 mutation causes decreased FLOWERING LOCUS C expression and requires CONSTANS (CO) protein for its early flowering phenotype under long days. Moreover, CO and HOS1 physically interact in vitro and in planta, and HOS1 regulates CO abundance, particularly during the daylight period. Accordingly, hos1 causes a shift in the regular long-day pattern of expression of FLOWERING LOCUS T (FT) transcript, starting to rise 4 h after dawn in the mutant. In addition, HOS1 interacts synergistically with CONSTITUTIVE PHOTOMORPHOGENIC1, another regulator of CO protein stability, in the regulation of flowering time. Taken together, these results indicate that HOS1 is involved in the control of CO abundance, ensuring that CO activation of FT occurs only when the light period reaches a certain length and preventing precocious flowering in Arabidopsis. PMID:22408073

  10. 76 FR 37876 - Hours of Service (HOS) of Drivers; Renewal of American Pyrotechnics Association (APA) Exemption...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... hours. These drivers will continue to be subject to the 14-hour cumulative on-duty limit, the 11-hour driving time limit, and the 60- and 70-hour weekly on-duty limits. The FMCSA believes that with the terms... of the HOS rules. Therefore, in the event of a crash or unintentional release or detonation...

  11. The E3 ubiquitin ligase HOS1 is involved in ethylene regulation of leaf expansion in Arabidopsis.

    PubMed

    Lee, Kyounghee; Seo, Pil Joon

    2015-01-01

    Ethylene regulates a variety of physiological processes, such as flowering, senescence, abscission, and fruit ripening. In particular, leaf expansion is also controlled by ethylene in Arabidopsis. Exogenous treatment with ethylene inhibits leaf expansion, and consistently, ethylene insensitive mutants show increased leaf area. Here, we report that the RING finger-containing E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) regulates leaf expansion in an ethylene signaling pathway. The HOS1-deficient mutant showed reduced leaf area and was insensitive to ethylene perception inhibitor, silver thiosulfate (STS). Accordingly, genes encoding ethylene signaling components were significantly up-regulated in hos1-3. This study demonstrates that the HOS1 protein is involved in ethylene signal transduction for the proper regulation of leaf expansion possibly under environmentally stressful conditions.

  12. Reversal of the relative stability of the isomeric radicals HSO and HOS upon hydration and their reactions with ozone.

    PubMed

    Steudel, Ralf; Steudel, Yana

    2010-04-01

    The radical HSO is an oxidation product of pollutants such as H(2)S and CH(3)SH in Earth's atmosphere. For the first time, the interaction of HSO and its tautomer HOS with single water molecules to yield the hydrates HSO.nH(2)O and HOS.nH(2)O was studied for n = 1-3, applying the high-level G3X(MP2) theory. A large number of structures corresponding to local minima on the potential energy surfaces has been identified. While gaseous HSO is more stable than HOS, the enthalpy diffference between HSO.nH(2)O and HOS.nH(2)O decreases with increasing degree of hydration and becomes practically zero for n = 3. Thus, in aqueous solution as well as in fog and rain droplets, HOS is expected to compete with HSO. The barrier for the tautomerization of HSO to HOS is dramatically lowered by the presence of water molecules since a cyclic transition state allows a concerted proton shift within the system of neighboring hydrogen bonds. The corresponding activation enthalpy of only 73.5 kJ mol(-1) predicted for the transformation of HSO.2H(2)O into HOS.2H(2)O may be compared to the 202 kJ mol(-1) reported for the tautomerization of the unhydrated gaseous HSO/HOS molecules. The impact of water of hydration on the fundamental vibrational modes of HSO and HOS has also been studied. Furthermore, HOS is predicted to dimerize at low temperatures to give two van der Waals molecules with singlet (symmetry C(2)) or triplet configuration (symmetry C(2h)), the latter being more stable than the singlet isomer. The disproportionation of 2HSO to H(2)S and SO(2) is predicted to be exothermic by -263.5 kJ mol(-1). The reaction of HSO with ozone to HSO(2) and O(2) is also strongly exothermic by -274.0 kJ mol(-1) and seems to proceed without any barrier. HOS forms a 1:1 van der Waals complex with O(3); the redox reaction of its two components is calculated as exothermic by -410.9 kJ mol(-1) and results in a rather stable adduct between HOSO and O(2) with the structure of a peroxo isomer of HOSO(3

  13. A lysine deacetylase Hos3 is targeted to the bud neck and involved in the spindle position checkpoint

    PubMed Central

    Wang, Mengqiao; Collins, Ruth N.

    2014-01-01

    An increasing number of cellular activities can be regulated by reversible lysine acetylation. Targeting the enzymes responsible for such posttranslational modifications is instrumental in defining their substrates and functions in vivo. Here we show that a Saccharomyces cerevisiae lysine deacetylase, Hos3, is asymmetrically targeted to the daughter side of the bud neck and to the daughter spindle pole body (SPB). The morphogenesis checkpoint member Hsl7 recruits Hos3 to the neck region. Cells with a defect in spindle orientation trigger Hos3 to load onto both SPBs. When associated symmetrically with both SPBs, Hos3 functions as a spindle position checkpoint (SPOC) component to inhibit mitotic exit. Neck localization of Hos3 is essential for its symmetric association with SPBs in cells with misaligned spindles. Our data suggest that Hos3 facilitates cross-talk between the morphogenesis checkpoint and the SPOC as a component of the intricate monitoring of spindle orientation after mitotic entry and before commitment to mitotic exit. PMID:25057019

  14. HOS cell adhesion on Ti6Al4V surfaces texturized by laser engraving

    NASA Astrophysics Data System (ADS)

    Sandoval Amador, A.; Carreño Garcia, H.; Escobar Rivero, P.; Peña Ballesteros, D. Y.; Estupiñán Duran, H. A.

    2016-02-01

    The cell adhesion of the implant is determinate by the chemical composition, topography, wettability, surface energy and biocompatibility of the biomaterial. In this work the interaction between human osteosarcoma HOS cells and textured Ti6Al4V surfaces were evaluated. Ti6Al4V surfaces were textured using a CO2 laser in order to obtain circular spots on the surfaces. Test surfaces were uncoated (C1) used as a control surface, and surfaces with points obtained by laser engraving, with 1mm spacing (C2) and 0.5mm (C3). The HOS cells were cultured in RPMI-1640 medium with 10% fetal bovine serum and 1% antibiotics. No cells toxicity after one month incubation time occurred. The increased cell adhesion and cell spreading was observed after 1, 3 and 5 days without significant differences between the sample surfaces (C2 and C3) and control (uncoated) at the end of the experiment.

  15. A theoretical investigation of HSO/HOS and their positive ions

    SciTech Connect

    Plummer, P.L.M. Department of Physics, University of Missouri-Columbia, Columbia, MO )

    1990-06-01

    The formation and eventual fate of sulfur-containing aerosols play a central role in global pollution. An understanding of the oxidation paths for sulfur species and of the formation and stability of radical and ionic intermediates is required for optimum control of acid deposition. To gain insight into these processes {ital ab} {ital initio} calculations were performed for ground and first excited electronic states of the isomers HSO/HOS and for the ground and first two excited states for their positive ions, HSO{sup +}/HOS{sup +}. A variety of basis sets were used for calculations at the self-consistent field (SCF) level. (Full details available in supplementary material for this article.) These calculations included full optimization of the geometry and examination of the potential surface for transition states. Post Hartree--Fock calculations were performed and included Moller--Plesset calculations through fourth order with quadruple excitations as well as configuration interaction including all double excitations. The effect of geometry optimization at the MP4 level and the effect of freezing the core orbitals in the calculations were examined. Five transition states for the isomerization of HSO to HOS were located for the ground and excited electronic states of the neutral and ion systems. For all transition states in both systems, the geometry resembles an isosceles triangle. The barriers to rearrangement are quite high, ranging from {similar to}20 to {similar to}60 kcal/mol depending on the state. Two of the barriers were approximately symmetric while three were asymmetric with a lower barrier for HSO to HOS isomerization.

  16. The Hos2 Histone Deacetylase Controls Ustilago maydis Virulence through Direct Regulation of Mating-Type Genes

    PubMed Central

    Elías-Villalobos, Alberto; Fernández-Álvarez, Alfonso; Moreno-Sánchez, Ismael; Helmlinger, Dominique; Ibeas, José I.

    2015-01-01

    Morphological changes are critical for host colonisation in plant pathogenic fungi. These changes occur at specific stages of their pathogenic cycle in response to environmental signals and are mediated by transcription factors, which act as master regulators. Histone deacetylases (HDACs) play crucial roles in regulating gene expression, for example by locally modulating the accessibility of chromatin to transcriptional regulators. It has been reported that HDACs play important roles in the virulence of plant fungi. However, the specific environment-sensing pathways that control fungal virulence via HDACs remain poorly characterised. Here we address this question using the maize pathogen Ustilago maydis. We find that the HDAC Hos2 is required for the dimorphic switch and pathogenic development in U. maydis. The deletion of hos2 abolishes the cAMP-dependent expression of mating type genes. Moreover, ChIP experiments detect Hos2 binding to the gene bodies of mating-type genes, which increases in proportion to their expression level following cAMP addition. These observations suggest that Hos2 acts as a downstream component of the cAMP-PKA pathway to control the expression of mating-type genes. Interestingly, we found that Clr3, another HDAC present in U. maydis, also contributes to the cAMP-dependent regulation of mating-type gene expression, demonstrating that Hos2 is not the only HDAC involved in this control system. Overall, our results provide new insights into the role of HDACs in fungal phytopathogenesis. PMID:26317403

  17. Butyl benzyl phthalate suppresses the ATP-induced cell proliferation in human osteosarcoma HOS cells

    SciTech Connect

    Liu, P.-S.; Chen, C.-Y.

    2010-05-01

    Butyl benzyl phthalate (BBP), an endocrine disruptor present in the environment, exerts its genomic effects via intracellular steroid receptors and elicits non-genomic effects by interfering with membrane ion-channel receptors. We previously found that BBP blocks the calcium signaling coupled with P2X receptors in PC12 cells (Liu and Chen, 2006). Osteoblast P2X receptors were recently reported to play a role in cell proliferation and bone remodeling. In this present study, the effects of BBP on ATP-induced responses were investigated in human osteosarcoma HOS cells. These receptors mRNA had been detected, named P2X4, P2X7, P2Y2, P2Y4, P2Y5, P2Y9, and P2Y11, in human osteosarcoma HOS cells by RT-PCR. The enhancement of cell proliferation and the decrease of cytoviability had both been shown to be coupled to stimulation via different concentrations of ATP. BBP suppressed the ATP-induced calcium influx (mainly coupled with P2X) and cell proliferation but not the ATP-induced intracellular calcium release (mainly coupled with P2Y) and cytotoxicity in human osteosarcoma HOS cells. Suramin, a common P2 receptor's antagonist, blocked the ATP-induced calcium signaling, cell proliferation, and cytotoxicity. We suggest that P2X is mainly responsible for cell proliferation, and P2Y might be partially responsible for the observed cytotoxicity. BBP suppressed the calcium signaling coupled with P2X, suppressing cell proliferation. Since the importance of P2X receptors during bone metastasis has recently become apparent, the possible toxic risk of environmental BBP during bone remodeling is a public problem of concern.

  18. The negative regulator of plant cold responses, HOS1, is a RING E3 ligase that mediates the ubiquitination and degradation of ICE1

    PubMed Central

    Dong, Chun-Hai; Agarwal, Manu; Zhang, Yiyue; Xie, Qi; Zhu, Jian-Kang

    2006-01-01

    Plant responses to cold stress are mediated by a transcriptional cascade, in which the transcription factor ICE1 and possibly related proteins activate the expression of C-repeat (CRT)-binding factors (CBFs), leading to the transcription of downstream effector genes. The variant RING finger protein high expression of osmotically responsive gene (HOS)1 was identified genetically as a negative regulator of cold responses. We present evidence here that HOS1 is an E3 ligase required for the ubiquitination of ICE1. HOS1 physically interacts with ICE1 and mediates the ubiquitination of ICE1 both in vitro and in vivo. We found that cold induces the degradation of ICE1 in plants, and this degradation requires HOS1. Consistent with enhanced cold-responsive gene expression in loss-of-function hos1 mutant plants, overexpression of HOS1 represses the expression of CBFs and their downstream genes and confers increased sensitivity to freezing stress. Our results indicate that cold stress responses in Arabidopsis are attenuated by a ubiquitination/proteasome pathway in which HOS1 mediates the degradation of the ICE1 protein. PMID:16702557

  19. HosA, a MarR Family Transcriptional Regulator, Represses Nonoxidative Hydroxyarylic Acid Decarboxylase Operon and Is Modulated by 4-Hydroxybenzoic Acid.

    PubMed

    Roy, Ajit; Ranjan, Akash

    2016-02-23

    Members of the Multiple antibiotic resistance Regulator (MarR) family of DNA binding proteins regulate transcription of a wide array of genes required for virulence and pathogenicity of bacteria. The present study reports the molecular characterization of HosA (Homologue of SlyA), a MarR protein, with respect to its target gene, DNA recognition motif, and nature of its ligand. Through a comparative genomics approach, we demonstrate that hosA is in synteny with nonoxidative hydroxyarylic acid decarboxylase (HAD) operon and is present exclusively within the mutS-rpoS polymorphic region in nine different genera of Enterobacteriaceae family. Using molecular biology and biochemical approach, we demonstrate that HosA binds to a palindromic sequence downstream to the transcription start site of divergently transcribed nonoxidative HAD operon and represses its expression. Furthermore, in silico analysis showed that the recognition motif for HosA is highly conserved in the upstream region of divergently transcribed operon in different genera of Enterobacteriaceae family. A systematic chemical search for the physiological ligand revealed that 4-hydroxybenzoic acid (4-HBA) interacts with HosA and derepresses HosA mediated repression of the nonoxidative HAD operon. Based on our study, we propose a model for molecular mechanism underlying the regulation of nonoxidative HAD operon by HosA in Enterobacteriaceae family.

  20. 78 FR 26690 - Hours of Service (HOS) of Drivers; Application for Renewal and Expansion of American Pyrotechnics...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-07

    ... Expansion of American Pyrotechnics Association (APA) Exemption From the 14-Hour Rule During Independence Day... the 2013 and 2014 Independence Day periods because compliance with the current 14- hour rule in 49 CFR... Association Exemption From the 14-Hour HOS Rule During 2013 and 2014 Independence Day Celebrations for...

  1. 76 FR 16852 - Hours of Service (HOS) of Drivers; Assessing the Safety Impact of the Exemption From the 14-Hour...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ... Pyrotechnics Association (APA) an exemption from the current HOS prohibition against driving a commercial motor... 381.300(b)). APA's Independence Day Operations and the Exemption from 49 CFR 395.3(a)(2) APA is a... fireworks-related services for many years. The CMV drivers employed by APA members transport fireworks over...

  2. Red Light-Mediated Degradation of CONSTANS by the E3 Ubiquitin Ligase HOS1 Regulates Photoperiodic Flowering in Arabidopsis

    PubMed Central

    Lazaro, Ana; Mouriz, Alfonso; Piñeiro, Manuel; Jarillo, José A.

    2015-01-01

    The regulation of CONSTANS (CO) gene expression is crucial to accurately measure changes in daylength, which influences flowering time in Arabidopsis thaliana. CO expression is under both transcriptional and posttranslational control mechanisms. We previously showed that the E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 (HOS1) physically interacts with CO in Arabidopsis. This interaction is required to precisely modulate the timing of CO accumulation and, consequently, to maintain low levels of FLOWERING LOCUS T expression during the first part of the day. The data presented here demonstrate that HOS1 is involved in the red light-mediated degradation of CO that takes place in the early stages of the daylight period. Our results show that phytochrome B (phyB) is able to regulate flowering time, acting in the phloem companion cells, as previously described for CO and HOS1. Moreover, we reveal that phyB physically interacts with HOS1 and CO, indicating that the three proteins may be present in a complex in planta that is required to coordinate a correct photoperiodic response in Arabidopsis. PMID:26373454

  3. Red Light-Mediated Degradation of CONSTANS by the E3 Ubiquitin Ligase HOS1 Regulates Photoperiodic Flowering in Arabidopsis.

    PubMed

    Lazaro, Ana; Mouriz, Alfonso; Piñeiro, Manuel; Jarillo, José A

    2015-09-01

    The regulation of CONSTANS (CO) gene expression is crucial to accurately measure changes in daylength, which influences flowering time in Arabidopsis thaliana. CO expression is under both transcriptional and posttranslational control mechanisms. We previously showed that the E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 (HOS1) physically interacts with CO in Arabidopsis. This interaction is required to precisely modulate the timing of CO accumulation and, consequently, to maintain low levels of FLOWERING LOCUS T expression during the first part of the day. The data presented here demonstrate that HOS1 is involved in the red light-mediated degradation of CO that takes place in the early stages of the daylight period. Our results show that phytochrome B (phyB) is able to regulate flowering time, acting in the phloem companion cells, as previously described for CO and HOS1. Moreover, we reveal that phyB physically interacts with HOS1 and CO, indicating that the three proteins may be present in a complex in planta that is required to coordinate a correct photoperiodic response in Arabidopsis. © 2015 American Society of Plant Biologists. All rights reserved.

  4. Expression, Functional Characterization and X-ray Analysis of HosA, A Member of MarR Family of Transcription Regulator from Uropathogenic Escherichia coli.

    PubMed

    Roy, Ajit; Reddi, Ravikumar; Sawhney, Bhavik; Ghosh, Debasish Kumar; Addlagatta, Anthony; Ranjan, Akash

    2016-08-01

    Regulators belonging to multiple antibiotic resistance regulator (MarR) family are widespread in prokaryotes and are involved in regulation of genes that are responsible for virulence and pathogenicity in most of the clinically important pathogens. Here we report the transcriptional, biophysical, and X-ray analyses of homologue of SlyA (HosA), a member of MarR family that is predominantly present in the pathogenic strains of Enterobacteriaceae family. The initiation of hosA transcription was observed to occur at two independent start sites and subsequent binding study has revealed that the purified HosA interacts with its upstream region suggesting a probable autoregulation. The secondary structure analysis through circular dichroism spectroscopy demonstrated that HosA is predominantly composed of the alpha helix with higher thermal stability. To further understand the three-dimensional structure, HosA was crystallized and the crystals were diffracted to maximum of 2.9 Ǻ on exposure to X-rays. Analysis of the X-ray crystallographic data suggested a primitive space group (P 6 ? 2 2), with unit cell parameters a = b = 64.19 Å and c = 244.25 Å. The solvent content and Matthews coefficient were 41 % and 2.11 Å(3) Da(-1), respectively, which indicated the existence of two molecules of HosA in the asymmetric unit of crystal.

  5. Development and Validation of Written Exam Items for the Agricultural Hazardous Occupations Orders (AgHOs) Certification Training Program.

    PubMed

    Mann, A J; Field, W E; Tormoehlen, R; French, B F

    2016-04-01

    Research was conducted to develop and validate a pool of exam items that can be used to test the readiness of youth, ages 14-15 years, to be certified under the current federally mandated Agricultural Hazardous Occupations Orders (AgHOs). The AgHOs require training prior to employment in agricultural workplaces that the Secretary of Labor has determined are especially hazardous for youth within the prescribed age range. Under the current provisions of the AgHOs certification process, non-exempt youth seeking employment in agriculture are required to pass a written exam concentrating on safe work practices as partial satisfaction to receive certification of eligibility for employment to perform certain tasks. However, the regulations provide little guidance concerning the format of the exam, subject matter to be covered, degree of difficulty, or minimum passing score. As part of the USDA-sponsored Hazardous Occupations Safety Training in Agriculture (HOSTA) initiative, efforts have been made to develop consistent and evidence-based testing methods for disseminating the test protocols to instructors. The goal was to expand, enhance, and maintain the reliability of the exam item pool for the AgHOs certification process. Item development was based on the HOSTA-supported Gearing Up for Safety: Production Agriculture Safety Training for Youth curriculum. To ensure adequate item availability, the current item pool was expanded to include a minimum of two test items for each of the 157 cognitive-based core competencies developed as part of the Gearing Up curriculum design process. Administering 70-item exams that were generated from the item pool to 568 youth, ages 13-18 years, provided evidence of item validity. The result was a pool of 367 validated exam items.

  6. On the Detectability of the X 2A" HSS, HSO, and HOS Radicals in the Interstellar Medium

    NASA Astrophysics Data System (ADS)

    Fortenberry, Ryan C.; Francisco, Joseph S.

    2017-02-01

    {\\tilde{X}}2A\\prime\\prime HSS has yet to be observed in the gas phase in the interstellar medium (ISM). HSS has been observed in cometary material and in high abundance. However, its agglomeration to such bodies or dispersal from them has not been observed. Similarly, HSO and HOS have not been observed in the ISM, either, even though models support their formation from reactions of known sulfur monoxide and hydrogen molecules, among other pathways. Consequently, this work provides high-level, quantum chemical rovibrational spectroscopic constants and vibrational frequencies in order to assist in interstellar searches for these radical molecules. Furthermore, the HSO‑HOS isomerization energy is determined to be 3.63 kcal mol‑1, in line with previous work, and the dipole moment of HOS is 36% larger at 3.87 D than HSO, making the less stable isomer more rotationally intense. Finally, the S‑S bond strength in HSS is shown to be relatively weak at 30% of the typical disulfide bond energy. Consequently, HSS may degrade into SH and sulfur atoms, making any ISM abundance of HSS likely fairly low, as recent interstellar surveys have observed.

  7. The E3 Ubiquitin Ligase HOS1 Regulates Arabidopsis Flowering by Mediating CONSTANS Degradation Under Cold Stress*

    PubMed Central

    Jung, Jae-Hoon; Seo, Pil Joon; Park, Chung-Mo

    2012-01-01

    The timing of flowering is coordinated by a web of gene regulatory networks that integrates developmental and environmental cues in plants. Light and temperature are two major environmental determinants that regulate flowering time. Although prolonged treatment with low nonfreezing temperatures accelerates flowering by stable repression of FLOWERING LOCUS C (FLC), repeated brief cold treatments delay flowering. Here, we report that intermittent cold treatments trigger the degradation of CONSTANS (CO), a central activator of photoperiodic flowering; daily treatments caused suppression of the floral integrator FLOWERING LOCUS T (FT) and delayed flowering. Cold-induced CO degradation is mediated via a ubiquitin/proteasome pathway that involves the E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 1 (HOS1). HOS1-mediated CO degradation occurs independently of the well established cold response pathways. It is also independent of the light signaling repressor CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase and light wavelengths. CO has been shown to play a key role in photoperiodic flowering. Here, we demonstrated that CO served as a molecular hub, integrating photoperiodic and cold stress signals into the flowering genetic pathways. We propose that the HOS1-CO module contributes to the fine-tuning of photoperiodic flowering under short term temperature fluctuations, which often occur during local weather disturbances. PMID:23135282

  8. Isolation and characterization of rice (Oryza sativa L.) E3-ubiquitin ligase OsHOS1 gene in the modulation of cold stress response.

    PubMed

    Lourenço, Tiago; Sapeta, Helena; Figueiredo, Duarte D; Rodrigues, Mafalda; Cordeiro, André; Abreu, Isabel A; Saibo, Nelson J M; Oliveira, M Margarida

    2013-11-01

    Plants can cope with adverse environmental conditions through the activation of stress response signalling pathways, in which the proteasome seems to play an important role. However, the mechanisms underlying the proteasome-mediated stress response in rice are still not fully understood. To address this issue, we have identified a rice E3-ubiquitin ligase, OsHOS1, and characterized its role in the modulation of the cold stress response. Using a RNA interference (RNAi) transgenic approach we found that, under cold conditions, the RNAi::OsHOS1 plants showed a higher expression level of OsDREB1A. This was correlated with an increased amount of OsICE1, a master transcription factor of the cold stress signalling. However, the up-regulation of OsDREB1A was transient and the transgenic plants did not show increased cold tolerance. Nevertheless, we could confirm the interaction of OsHOS1 with OsICE1 by Yeast-Two hybrid and bi-molecular fluorescence complementation in Arabidopsis protoplasts. Moreover, we could also determine through an in vitro degradation assay that the higher amount of OsICE1 in the transgenic plants was correlated with a lower amount of OsHOS1. Hence, we could confirm the involvement of the proteasome in this response mechanism. Taken together our results confirm the importance of OsHOS1, and thus of the proteasome, in the modulation of the cold stress signalling in rice.

  9. HOS cell adhesion on TiO2 nanotubes texturized by laser engraving

    NASA Astrophysics Data System (ADS)

    Sandoval Amador, A.; Montañez Supelano, N. D.; Arias, A. M. Vera; Escobar Rivero, P.; Peña Ballesteros, D. Y.

    2017-01-01

    Due to its outstanding properties, the titanium and its alloys have been widely used in the dental and orthopaedic fields as biomaterials. The TiO2 nanotubes surface and the texturized process by laser engraving enables significantly accelerated osteoblast adhesion on the biomaterial. For this reason in this paper, the HOS cell responses on TiO2 nanotubes fabricated on Ti6Al4V alloy and texturized by laser engraving were evaluated. The test surfaces were carried out on smooth Ti6Al4V as control, TiO2 nanotubes (NT) and surfaces with micropoints obtained by laser engraving, with 1mm spacing (NTP1) and 0.5mm (NTP2). The results show that the texturized process enables decreases the contact angle thus improving wettability of the TiO2 nanotubes surface. The NTP1 and NTP2 surfaces show excellent cell adhesion and spreading on the surface, which is evident in epifluorescence microscopy images. Furthermore, the NTP1 and NTP2 surfaces improved the cell proliferation at 18% and 16% respectively in relation with NT surface, showing that the laser texturing improves cell response of TiO2 nanotubes.

  10. fau and its ubiquitin-like domain (FUBI) transforms human osteogenic sarcoma (HOS) cells to anchorage-independence.

    PubMed

    Rossman, Toby G; Visalli, Melissa A; Komissarova, Elena V

    2003-03-27

    Arsenite is the most likely carcinogenic form of arsenic in the environment. Previously, expression cloning for cDNAs whose overexpression confers arsenite-resistance in Chinese hamster V79 cells identified two genes: fau and a novel gene, asr2. The fau gene encodes a ubiquitin-like protein (here called FUBI) fused to the ribosomal S30 protein. Since the expression of the fox sequence (antisense to fau) increased the tumorigenicity of a mouse sarcoma virus, it was proposed that fau might be a tumor suppressor gene. We intended to test its ability to block arsenite-induced transformation of human osteogenic sarcoma (HOS) cells to anchorage-independence. Instead, we found that overexpressing fau itself was able to transform HOS cells. When the two domains were expressed separately, only FUBI was transforming and only the S30 domain conferred arsenite resistance. An incidental finding was the transforming activity of the selectable marker, hyg. FUBI belongs to the ubiquitin-like protein group that is capable of forming conjugates to other proteins, although none have so far been identified. Alternatively, FUBI may act as a substitute or inhibitor of ubiquitin, to which it is most closely related, or to close ubiquitin-like relatives UCRP, FAT10, and/or Nedd8.

  11. Computer-aided diagnosis of Myocardial Infarction using ultrasound images with DWT, GLCM and HOS methods: A comparative study.

    PubMed

    Vidya, K Sudarshan; Ng, E Y K; Acharya, U Rajendra; Chou, Siaw Meng; Tan, Ru San; Ghista, Dhanjoo N

    2015-07-01

    Myocardial Infarction (MI) or acute MI (AMI) is one of the leading causes of death worldwide. Precise and timely identification of MI and extent of muscle damage helps in early treatment and reduction in the time taken for further tests. MI diagnosis using 2D echocardiography is prone to inter-/intra-observer variability in the assessment. Therefore, a computerised scheme based on image processing and artificial intelligent techniques can reduce the workload of clinicians and improve the diagnosis accuracy. A Computer-Aided Diagnosis (CAD) of infarcted and normal ultrasound images will be useful for clinicians. In this study, the performance of CAD approach using Discrete Wavelet Transform (DWT), second order statistics calculated from Gray-Level Co-Occurrence Matrix (GLCM) and Higher-Order Spectra (HOS) texture descriptors are compared. The proposed system is validated using 400 MI and 400 normal ultrasound images, obtained from 80 patients with MI and 80 normal subjects. The extracted features are ranked based on t-value and fed to the Support Vector Machine (SVM) classifier to obtain the best performance using minimum number of features. The features extracted from DWT coefficients obtained an accuracy of 99.5%, sensitivity of 99.75% and specificity of 99.25%; GLCM have achieved an accuracy of 85.75%, sensitivity of 90.25% and specificity of 81.25%; and HOS obtained an accuracy of 93.0%, sensitivity of 94.75% and specificity of 91.25%. Among the three techniques presented DWT yielded the highest classification accuracy. Thus, the proposed CAD approach may be used as a complementary tool to assist cardiologists in making a more accurate diagnosis for the presence of MI.

  12. Recycling of Volatiles in Subduction Zones: Evidence from H-O-S Isotopic Signatures of Indonesian Arc Basalts

    NASA Astrophysics Data System (ADS)

    de Hoog, J. C.; Taylor, B. E.; van Bergen, M. J.

    2001-05-01

    Subaerial lavas from eight volcanoes, situated in different sectors of the Indonesian arc system, have been analyzed for hydrogen, oxygen and sulfur isotopic compositions. The lavas are mostly basaltic and cover a range from low-K tholeiitic to high-K calc-alkaline affinities. The following whole-rock compositions were observed: δ D = -109 to -57‰ V-SMOW (avg = -89‰ ), δ 18O = +5.3 to +6.7‰ V-SMOW (avg = +5.9‰ ), δ 34S = +2.0 to +7.8‰ V-CDT (avg = +4.7‰ ). All samples are strongly degassed, as average water contents are ~0.15 wt.% and average sulfur concentrations are ~14 ppm. Because degassing-induced shifts in sulfur isotopes are limited at magmatic temperatures and oxidation states typical of basalts, the data suggest that, in all cases, the magma source in the sub-arc mantle is significantly enriched in 34S compared to MORB-source mantle. Hydrogen isotopes fractionate strongly, and our data are most consistent with multi-stage degassing of magmatic water. Based on primary H-O-S isotopic signatures inferred for the Indonesian arc basalts and on assumed compositions of the pre-subduction mantle, we performed mass-balance calculations to estimate volatile concentrations in the slab component. The results indicate that addition of about 1-1.5 wt.% aqueous fluid containing 1.5% sulfur will produce the H-O-S isotopic compositions of primary basaltic melts of the volcanoes studied. Alternatively, the slab-derived material may consist of a mix of melts and fluids, in which melts can be more voluminous, but fluids dominate the budgets of sulfur, hydrogen, and other hydrophile elements. Irrespective of the preferred model, S and H2O contents must have increased considerably in the sub-arc mantle (to ~350 ppm and ~1.3 wt.%, respectively). The S value is consistent with estimates based on primary sulfur contents in arc basalts ( ~2000 ppm), but the H2O concentration is higher than the mantle can accommodate, as it will induce melting. We argue, however, that

  13. Computer-aided diagnosis of psoriasis skin images with HOS, texture and color features: A first comparative study of its kind.

    PubMed

    Shrivastava, Vimal K; Londhe, Narendra D; Sonawane, Rajendra S; Suri, Jasjit S

    2016-04-01

    Psoriasis is an autoimmune skin disease with red and scaly plaques on skin and affecting about 125 million people worldwide. Currently, dermatologist use visual and haptic methods for diagnosis the disease severity. This does not help them in stratification and risk assessment of the lesion stage and grade. Further, current methods add complexity during monitoring and follow-up phase. The current diagnostic tools lead to subjectivity in decision making and are unreliable and laborious. This paper presents a first comparative performance study of its kind using principal component analysis (PCA) based CADx system for psoriasis risk stratification and image classification utilizing: (i) 11 higher order spectra (HOS) features, (ii) 60 texture features, and (iii) 86 color feature sets and their seven combinations. Aggregate 540 image samples (270 healthy and 270 diseased) from 30 psoriasis patients of Indian ethnic origin are used in our database. Machine learning using PCA is used for dominant feature selection which is then fed to support vector machine classifier (SVM) to obtain optimized performance. Three different protocols are implemented using three kinds of feature sets. Reliability index of the CADx is computed. Among all feature combinations, the CADx system shows optimal performance of 100% accuracy, 100% sensitivity and specificity, when all three sets of feature are combined. Further, our experimental result with increasing data size shows that all feature combinations yield high reliability index throughout the PCA-cutoffs except color feature set and combination of color and texture feature sets. HOS features are powerful in psoriasis disease classification and stratification. Even though, independently, all three set of features HOS, texture, and color perform competitively, but when combined, the machine learning system performs the best. The system is fully automated, reliable and accurate.

  14. Overexpression of an Orchid (Dendrobium nobile) SOC1/TM3-Like Ortholog, DnAGL19, in Arabidopsis Regulates HOS1-FT Expression.

    PubMed

    Liu, Xiao-Ru; Pan, Ting; Liang, Wei-Qi; Gao, Lan; Wang, Xiao-Jing; Li, Hong-Qing; Liang, Shan

    2016-01-01

    Flowering in the appropriate season is critical for successful reproduction in angiosperms. The orchid species, Dendrobium nobile, requires vernalization to achieve flowering in the spring, but the underlying regulatory network has not been identified to date. The MADS-box transcription factor DnAGL19 was previously identified in a study of low-temperature treated D. nobile buds and was suggested to regulate vernalization-induced flowering. In this study, phylogenetic analysis of DnAGL9 and the MADS-box containing proteins showed that DnAGL19 is phylogenetically closely related to the SOC1-like protein from orchid Dendrobium Chao Parya Smile, DOSOC1. The orchid clade closed to but is not included into the SOC1-1/TM3 clades associated with either eudicots or monocots, suggesting that DnAGL19 is an SOC1-1/TM3-like ortholog. DnAGL19 was found to be highly expressed in pseudobulbs, leaves, roots, and axillary buds but rarely in flowers, and to be substantially upregulated in axillary buds by prolonged low-temperature treatments. Overexpression of DnAGL19 in Arabidopsis thaliana resulted in a small but significantly reduced time to bolting, suggesting that flowering time was slightly accelerated under normal growth conditions. Consistent with this, the A. thaliana APETELA1 (AP1) gene was expressed at an earlier stage in transgenic lines than in wild type plants, while the FLOWERING LOCUS T (FT) gene was suppressed, suggesting that altered regulations on these transcription factors caused the weak promotion of flowering. HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 1 (HOS1) was slightly activated under the same conditions, suggesting that the HOS1-FT module may be involved in the DnAGL19-related network. Under vernalization conditions, FT expression was significantly upregulated, whereas HOS1 expression in the transgenic A. thaliana has a level similar to that in wild type. Taken together, these results suggest that DnAGL19 controls the action of the HOS1-FT module

  15. CO Substitution in HOs3(CO)10(l-SC6H4Me-4) by the Diphosphine 4,5-Bis(diphenylphosphino)-4-cyclopentadiene-1,3-dione (bpcd): Structural and DFT Evaluation of the Isomeric Clusters HOs3(CO)8(bpcd)(mu-SC6H4Me-4)

    SciTech Connect

    Yang, Li; Nesterov, Vladimir; Wang, Xiaoping; Richmond, Michael G.

    2012-01-01

    The reaction of the cluster HOs{sub 3}(CO){sub 10}({mu}-SC{sub 6}H{sub 4}Me-4) (1) with the diphosphine 4,5-bis(diphenylphosphino)-4-cyclopentadiene-1,3-dione (bpcd) has been investigated. 1 reacts with bpcd at room temperature in the presence of Me{sub 3}NO to give the isomeric clusters 1,2-HOs{sub 3}(CO)8(bpcd)({mu}-SC{sub 6}H{sub 4}Me-4) (2a) and 1,1-HOs{sub 3}(CO)8(bpcd)({mu}-SC{sub 6}H{sub 4}Me-4) (2b). Clusters 2a and 2b have been isolated, and the molecular structure of each compound has been established by X-ray crystallography. The X-ray structure of 2a confirms the coordination of one of the non-hydride-bridged Os-Os vectors by the bpcd ligand, while the structure of 2b exhibits a chelating bpcd ligand that is bound to one of the osmium centers ligated by the thiolate and hydrido ligands. 2a and 2b are stable in refluxing toluene and show no evidence for bridge-to-chelate isomerization of the ancillary bpcd ligand. DFT calculations on 2a and 2b indicate that the former cluster is the thermodynamically more stable isomer. Near-UV irradiation of 2b leads to CO loss and ortho metalation of the thiolate moiety, yielding the dihydride cluster H{sub 2}Os{sub 3}(CO)7(bpcd)({mu},{sigma}-SC{sub 6}H{sub 3}Me-4) (3). The conversion of 2b to 3 and free CO is computed to be endothermic by 14.1 kcal/mol and the reaction is driven by the entropic release of CO. The photochemically promoted ortho-metalation reaction is isomer dependent since cluster 2a is inert under identical conditions.

  16. Extensive Functional Redundancy in the Regulation of Candida albicans Drug Resistance and Morphogenesis by Lysine Deacetylases Hos2, Hda1, Rpd3, and Rpd31

    PubMed Central

    Li, Xinliu; Robbins, Nicole; O’Meara, Teresa R.; Cowen, Leah E.

    2016-01-01

    Summary Current treatment efforts for fungal infections are hampered by the limited availability of antifungal drugs and by the emergence of drug resistance. A powerful strategy to enhance the efficacy of antifungal drugs is to inhibit the molecular chaperone Hsp90. Hsp90 governs drug resistance, morphogenesis, and virulence in a leading fungal pathogen of humans, Candida albicans. Our previous work with Saccharomyces cerevisiae established acetylation as a novel mechanism of posttranslational control of Hsp90 function in fungi. We implicated lysine deacetylases (KDACs) as key regulators of resistance to the most widely deployed class of antifungals, the azoles, in both S. cerevisiae and C. albicans. Here, we demonstrate high levels of functional redundancy among the KDACs that are important for regulating Hsp90 function. We identify Hos2, Hda1, Rpd3, and Rpd31 as the KDACs mediating azole resistance and morphogenesis in C. albicans. Furthermore, we identify lysine 30 and 271 as critical acetylation sites on C. albicans Hsp90, and substitutions at these residues compromised Hsp90 function. Finally, we show that pharmacological inhibition of KDACs phenocopies pharmacological inhibition of Hsp90 and abrogates Hsp90-dependent azole resistance in numerous Candida species. This work illuminates new facets to the impact of KDACs on fungal drug resistance and morphogenesis, provides important insights into the divergence of the C. albicans Hsp90 regulatory network, and reveals new targets for development of antifungal drugs. PMID:27868254

  17. TNF-alpha-dependent activation of NF-kappa B in human osteoblastic HOS-TE85 cells is repressed in vector-averaged gravity using clinostat rotation.

    PubMed

    Kobayashi, K; Kambe, F; Kurokouchi, K; Sakai, T; Ishiguro, N; Iwata, H; Koga, K; Gruener, R; Seo, H

    2000-12-09

    Effects of vector-averaged gravity on tumor necrosis factor (TNF)-alpha-dependent activation of nuclear factor kappa B (NF-kappa B) in human osteoblastic HOS-TE85 cells were investigated by culturing the cells using clinostat rotation (clinorotation). Cell cultures were rotated for 72 h at 40 rpm in a clinostat. At the end of clinorotation, the cells were treated with TNF-alpha for 30 min under stationary conditions. Electrophoretic mobility shift assays revealed that TNF-alpha-dependent activation of NF-kappa B was markedly reduced in the clinorotated cells when compared with the cells in control stationary cultures or after horizontal rotation (motional controls). The NF-kappa B-dependent transactivation was also impaired in the clinorotated cells, as evidenced by a transient transfection assay with a reporter plasmid containing multimerized NF-kappa B sites. Consistent with these findings, the TNF-alpha-dependent induction of endogenous NF-kappa B-responsive genes p105, I kappa B-alpha, and IL-8, was significantly attenuate in clinorotated cells. These results demonstrate that vector-averaged gravity inhibits the responsiveness of osteoblasts to TNF-alpha by repressing NF-kappa B activation. Copyright 2000 Academic Press.

  18. The effect of Me2SO overexposure during cryopreservation on HOS TE85 and hMSC viability, growth and quality.

    PubMed

    Morris, Timothy J; Picken, Andrew; Sharp, Duncan M C; Slater, Nigel K H; Hewitt, Christopher J; Coopman, Karen

    2016-12-01

    With the cell therapy industry continuing to grow, the ability to preserve clinical grade cells, including mesenchymal stem cells (MSCs), whilst retaining cell viability and function remains critical for the generation of off-the-shelf therapies. Cryopreservation of MSCs, using slow freezing, is an established process at lab scale. However, the cytotoxicity of cryoprotectants, like Me2SO, raises questions about the impact of prolonged cell exposure to cryoprotectant at temperatures >0 °C during processing of large cell batches for allogenic therapies prior to rapid cooling in a controlled rate freezer or in the clinic prior to administration. Here we show that exposure of human bone marrow derived MSCs to Me2SO for ≥1 h before freezing, or after thawing, degrades membrane integrity, short-term cell attachment efficiency and alters cell immunophenotype. After 2 h's exposure to Me2SO at 37 °C post-thaw, membrane integrity dropped to ∼70% and only ∼50% of cells retained the ability to adhere to tissue culture plastic. Furthermore, only 70% of the recovered MSCs retained an immunophenotype consistent with the ISCT minimal criteria after exposure. We also saw a similar loss of membrane integrity and attachment efficiency after exposing osteoblast (HOS TE85) cells to Me2SO before, and after, cryopreservation. Overall, these results show that freezing medium exposure is a critical determinant of product quality as process scale increases. Defining and reporting cell sensitivity to freezing medium exposure, both before and after cryopreservation, enables a fair judgement of how scalable a particular cryopreservation process can be, and consequently whether the therapy has commercial feasibility.

  19. Expression and function of the ACE2/angiotensin(1-7)/Mas axis in osteosarcoma cell lines U-2 OS and MNNG-HOS.

    PubMed

    Ender, Stephan Albrecht; Dallmer, Andrea; Lässig, Florian; Lendeckel, Uwe; Wolke, Carmen

    2014-08-01

    The renin-angiotensin-system (RAS), via its classical angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin II type 1 receptor (AT1R)-axis, is associated with proliferation and metastasis of numerous types of solid tumor. AT1R blockers reduce tumor volume and decrease liver and lung metastasis in murine models of osteosarcoma. Expression and function of the alternative ACE2/Ang(1-7)/Mas axis in osteosarcoma is yet to be studied. In the present study, the basic and interleukin (IL)-1β-stimulated expression of components of this alternative RAS axis were analyzed and the impact of Mas on proliferation and/or migration of U-2 OS and MNNG-HOS osteosarcoma cells was studied. Quantitative polymerase chain reaction revealed that the two cell lines expressed the Ang(1‑7)-generating peptidases ACE2, neutral endopeptidase 24.11 and prolyl-endopeptidase together with the putative receptor for Ang(1-7), Mas. IL-1β provoked an induction of Mas mRNA and protein expression which was associated with a reduction of proliferation and migration. By contrast, small interfering RNA-mediated knockdown of Mas expression led to increased cell proliferation. In conclusion, osteosarcoma cells express a functional active alternative ACE2/Ang(1-7)/Mas axis. The induction and reinforcement of this axis may be beneficial for the treatment of osteosarcoma by reducing growth and preventing cancer metastasis. These effects may be achieved directly by the administration of Mas agonists or, indirectly, via blocking the classical AngII RAS axis via ACE inhibitors or AT1R antagonists.

  20. Etude structurale des sulfotellurures de terres rares ( LS) 2Te 1+ x ( L = Tb, Dy, Ho, Er, Tm et Y). I. Sous-structure de la phase ordonnée de (HoS) 2Te 1,34. Structure de la phase desordonnée de (TbS) 2Te

    NASA Astrophysics Data System (ADS)

    Ghémard, G.; Etienne, J.; Flahaut, J.

    1982-11-01

    The lanthanide sulfotellurides ( LS) 2Te 1+ x (0 ≤ x < 0.50) show order-disorder phenomena. Above 450°C, they crystallize in a partially disordered structure, orthorhombic with cell parameters a, b, and c close to 4.1, 5.2, and 13.6 Å, respectively. This structure is determined from diffractometer data on a (HoS) 2Te 1.34 crystal ( R = 0.061). It is built up along the c axis from ( L4S) tetrahedra layers, separated by Te planes. Disorder and nonstoichiometry are related to the two vacant Te sites.

  1. Isomerization of the diphosphine ligand 3,4-bis(diphenylphosphino)-5-methoxy-2(5H)-furanone (bmf) at a triosmium cluster and P C bond cleavage in the unsaturated cluster 1,1-Os3(CO)9(bmf): Synthesis and X-ray diffraction structures of the isomeric Os3(CO)10(bmf) clusters and HOs3(CO)8( -C6H4)[ -PhPCC(Ph2P)CH(OMe)OC(O)

    SciTech Connect

    Kandala, Srikanth; Yang, Li; Campana, Charles F.; Nesterov, Vladimir; Richmond, Michael G.

    2010-07-01

    The labile cluster 1,2-Os3(CO)10(MeCN)2 (1) reacts with the chiral diphosphine ligand 3,4-bis(diphenylphosphino)-5-methoxy-2(5H)-furanone (bmf) to furnish 1,2-Os3(CO)10(bmf) (2a) in high yield. Heating cluster 2a over the temperature range 358 383 K under CO leads to isomerization of the bmf ligand and formation of the diphosphine-chelated cluster 1,1-Os3(CO)10(bmf) (2b) and an equilibrium mixture consisting of 2a and 2b in a 15:85 ratio. Extended thermolysis of an equilibrium mixture of Os3(CO)10(bmf) is accompanied by CO loss and ortho-metalation of an aryl ring to afford an inseparable mixture of three diastereomeric hydride clusters HOs3(CO)9(C29H23O3P2) (3a c). Thermolysis of HOs3(CO)9(C29H23O3P2) (3a c) in refluxing toluene leads to P C bond cleavage and formation of the benzyne-substituted clusters HOs3(CO)8( -C6H4)( -C23H19O3P2) (4a,b) as a 4:1 mixture of diastereomers. The unequivocal identity of the major benzyne-substituted cluster has been determined by X-ray diffraction analysis, where the activation of one of the phenyl groups situated to the furanone carbonyl group in the bmf ligand has been established. The isomerization and activation of the bmf ligand are contrasted with other Os3(CO)10(diphosphine) derivatives prepared by our groups.

  2. New osmium cluster compounds containing the heterocyclic ligand 2,3-bis-(diphenylphosphino)quinoxaline (dppq): Ligand isomerization and crystal structures of dppq, the isomeric clusters Os3(CO)10(dppq), and HOs3(CO)9[ -2,3-PhP(h1-C6H4)(Ph2P)quinoxaline

    SciTech Connect

    Hunt, Sean W; Yang, Li; Wang, Xiaoping; Richmond, Michael G.

    2011-01-01

    Treatment of the labile cluster 1,2-Os{sub 3}(CO){sub 10}(MeCN){sub 2} (1) with the diphosphine ligand 2,3-bis(diphenylphosphino)quinoxaline (dppq) at room temperature affords 1,2-Os{sub 3}(CO){sub 10}(dppq) (2b) as the kinetic product of ligand substitution in 84% yield. 2b isomerizes to the thermodynamically more stable dppq-chelated cluster 1,1-Os{sub 3}(CO){sub 10}(dppq) (2c) as the sole observable product under CO at temperatures below 358 K. The kinetics for the conversion of 2b {yields} 2c have been investigated by NMR spectroscopy in CDCl{sub 3} over the temperature range 323-353 K, and the reaction was found to exhibit a rate law that is first order in 2b. The calculated activation parameters [{Delta}H{sup {ne}} = 25.4(4) kcal/mol; {Delta}S{sup {ne}} = -3(1) eu] support an intramolecular isomerization scenario, one that involves the migration of phosphine and CO groups about the cluster polyhedron. The disposition of the dppq ligand in the isomeric Os{sub 3}(CO){sub 10}(dppq) clusters has been established by X-ray crystallography and {sup 31}P NMR spectroscopy. Photolysis of 2c at 366 nm leads to CO loss and ortho metalation of one of the aryl groups on the Ph{sub 2}P moiety to furnish the hydride cluster HOs{sub 3}(CO){sub 9}[{mu}-PhP({eta}{sup 1}-C{sub 6}H{sub 4})(Ph{sub 2}P)quinoxaline] (3). The isomerization behavior exhibited by 2b follows that of related diphosphine-substituted Os{sub 3} clusters prepared by us.

  3. The U.S. Navy’s Military Sealift Command 2008 in Review

    DTIC Science & Technology

    2008-01-01

    HOS Bluewater, MV HOS Silverstar and MV HOS Gemstone provided deep submergence rescue and submarine escort support services for the Navy’s submarine...Submarine and Special Warfare Support Ships - 7 MV C-Champion MV C-Commando MV Dolores Chouest MV HOS Bluewater MV HOS Gemstone MV HOS Greystone MV

  4. An algorithm for space-time block code classification using higher-order statistics (HOS).

    PubMed

    Yan, Wenjun; Zhang, Limin; Ling, Qing

    2016-01-01

    This paper proposes a novel algorithm for space-time block code classification, when a single antenna is employed at the receiver. The algorithm exploits the discriminating features provided by the higher-order cumulants of the received signal. It does not require estimation of channel and information of the noise. Computer simulations are conducted to evaluate the performance of the proposed algorithm. The results show the performance of the algorithm is good.

  5. 76 FR 30232 - Hours of Service (HOS) of Drivers; Application of American Pyrotechnics Association (APA) for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-24

    ... exemption from FMCSA's regulation that drivers of commercial motor vehicles (CMVs) may not drive after the.... These drivers would not be allowed to drive after accumulating a total of 14 hours of on- duty time, following 10 consecutive hours off duty, and would continue to be subject to the 11-hour driving time limit...

  6. HOS network-based classification of power quality events via regression algorithms

    NASA Astrophysics Data System (ADS)

    Palomares Salas, José Carlos; González de la Rosa, Juan José; Sierra Fernández, José María; Pérez, Agustín Agüera

    2015-12-01

    This work compares seven regression algorithms implemented in artificial neural networks (ANNs) supported by 14 power-quality features, which are based in higher-order statistics. Combining time and frequency domain estimators to deal with non-stationary measurement sequences, the final goal of the system is the implementation in the future smart grid to guarantee compatibility between all equipment connected. The principal results are based in spectral kurtosis measurements, which easily adapt to the impulsive nature of the power quality events. These results verify that the proposed technique is capable of offering interesting results for power quality (PQ) disturbance classification. The best results are obtained using radial basis networks, generalized regression, and multilayer perceptron, mainly due to the non-linear nature of data.

  7. Materials Data on HoS2 (SG:227) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  8. 77 FR 38378 - Hours of Service (HOS) of Drivers; Revision of Exemption; American Pyrotechnics Association (APA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ... 029329 34. Pyro Spectaculars North, Inc.... 5301 Lang Avenue McClellan, CA 95652......... 1671438 35... Mile Azle Rd...... Fort Worth, TX 76135........ 0116910 6. B.J. Alan Company 555 Martin Luther King, Jr...... 4300 Logan Lancaster Rd..... Lancaster, OH 395079 22. Hi-Tech FX, LLC 1135 Ave. I Fort Madison,...

  9. 76 FR 37880 - Hours of Service (HOS) of Drivers; Granting of Exemption; American Pyrotechnics Association (APA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    .... Pyro Spectaculars North, Inc.. 5301 Lang Avenue, 1671438 McClellan, CA 95652. 8. Pyrotechnic Display... Extravaganza........ 58 Maple Lane, 2064141 Otisville, NY 10963. 5. Hi-Tech FX, LLC 1135 Ave. I, Fort...

  10. Materials Data on HOs6C18S2O19 (SG:2) by Materials Project

    SciTech Connect

    Kristin Persson

    2016-06-01

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  11. Materials Data on HOs3C10ClO10 (SG:2) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-07-09

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  12. The U.S. Navy’s Military Sealift Command 2009 in Review

    DTIC Science & Technology

    2009-01-01

    MV HOS Gemstone provided submarine escort support services for the Navy’s submarine forces. MV HOS Black Powder and MV HOSWestwind were substituted...Chouest MV HOS Gemstone MV HOS Silverstar MV HOS Westwind Oceanographic Survey Ships - 7 USNS Bowditch (T-AGS 62) USNS Bruce C. Heezen (T-AGS 64) USNS

  13. 77 FR 40142 - Applications for Exemption: Commercial Driver's License (CDL) and Hours-of-Service (HOS) of Drivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ... carrier operations without the exemption [49 CFR 381.305(b)]. The application must include a written assessment of the safety impacts the exemption may have. It must also describe how the applicant would ensure... application, the safety assessment, and all other information relevant to the application. The Agency...

  14. Stabilitet i uppfostringsattityder hos daghemspersonal (Stability of Attitudes of Child-Rearing by Personnel at Day-Care Centers).

    ERIC Educational Resources Information Center

    Ekholm, Bodil; And Others

    All day care personnel (about 900) in a Swedish commune answered a questionnaire concerning attitudes toward child rearing. The questionnaire consisted of 10 short descriptions of daily day care situations representing a child rearing dilemma which could be solved in different ways. Respondents indicated their views of typical and preferred ways…

  15. Daghemsklimat: Uppfostringsattityder, engagemang och kanslor infor arbetet hos daghemspersonal. (Attitudes of Child-Rearing, Engagements and Feelings towards Work by Personnel at Day-Care Centers).

    ERIC Educational Resources Information Center

    Jonsson, Arne

    Approximately 900 employees in the day care centers in one Swedish commune answered a questionnaire measuring child rearing attitudes and personnel's engagement and feelings concerning their work with the children. The child rearing attitudes were described as either "present-focused" or "future-focused." Of particular interest…

  16. Daghemsklimat: Uppfostringsattityder, engagemang och kanslor infor arbetet hos daghemspersonal. (Attitudes of Child-Rearing, Engagements and Feelings towards Work by Personnel at Day-Care Centers).

    ERIC Educational Resources Information Center

    Jonsson, Arne

    Approximately 900 employees in the day care centers in one Swedish commune answered a questionnaire measuring child rearing attitudes and personnel's engagement and feelings concerning their work with the children. The child rearing attitudes were described as either "present-focused" or "future-focused." Of particular interest…

  17. Signal analysis applications of nonlinear dynamics and higher-order statistics

    NASA Astrophysics Data System (ADS)

    Solinsky, James C.; Feeney, John J.

    1994-03-01

    The use of higher-order statistics (HOS) in acoustic, and financial signal analysis applications is outlined in theory and followed with specific data examples. HOS analysis is used to identify data regions of interest, and nonlinear dynamics (ND) analysis is used in a 4D embedded space to show structural density changes resulting from the HOS regions. A second-order statistical comparison is made with the same data processed to have random Fourier phase, since the HOS information is contained in this nonrandom phase. These empirical results indicate that HOS data regions are structural distortions to a second-order planar disk in the 4D ND analysis space.

  18. Higher order software - A methodology for defining software

    NASA Technical Reports Server (NTRS)

    Hamilton, M.; Zeldin, S.

    1976-01-01

    Higher order software (HOS) is concerned only with computable functions and relationships. The HOS methodology can be used for the definition of software for multiprogrammed, multiprocessor, or multicomputer systems. A description of HOS methodology is presented, giving attention to questions of formulation, interface correctness, specification language principles, and HOS analyzers. Aspects of system design are considered, and details of software management are discussed. Attention is given to modularity as defined by HOS, frozen module management, the assembly control supervisor, and aspects of reliability and efficiency.

  19. The cold signaling attenuator HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 activates FLOWERING LOCUS C transcription via chromatin remodeling under short-term cold stress in Arabidopsis.

    PubMed

    Jung, Jae-Hoon; Park, Ju-Hyung; Lee, Sangmin; To, Taiko Kim; Kim, Jong-Myong; Seki, Motoaki; Park, Chung-Mo

    2013-11-01

    Exposure to short-term cold stress delays flowering by activating the floral repressor FLOWERING LOCUS C (FLC) in Arabidopsis thaliana. The cold signaling attenuator HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 (HOS1) negatively regulates cold responses. Notably, HOS1-deficient mutants exhibit early flowering, and FLC expression is suppressed in the mutants. However, it remains unknown how HOS1 regulates FLC expression. Here, we show that HOS1 induces FLC expression by antagonizing the actions of FVE and its interacting partner histone deacetylase 6 (HDA6) under short-term cold stress. HOS1 binds to FLC chromatin in an FVE-dependent manner, and FVE is essential for the HOS1-mediated activation of FLC transcription. HOS1 also interacts with HDA6 and inhibits the binding of HDA6 to FLC chromatin. Intermittent cold treatments induce FLC expression by activating HOS1, which attenuates the activity of HDA6 in silencing FLC chromatin, and the effects of intermittent cold are diminished in hos1 and fve mutants. These observations indicate that HOS1 acts as a chromatin remodeling factor for FLC regulation under short-term cold stress.

  20. Visual performance modeling in the human operator simulator

    NASA Technical Reports Server (NTRS)

    Strieb, M. I.

    1979-01-01

    A brief description of the history of the development of the human operator simulator (HOS) model is presented. Features of the HOS micromodels that impact on the obtainment of visual performance data are discussed along with preliminary details on a HOS pilot model designed to predict the results of visual performance workload data obtained through oculometer studies on pilots in real and simulated approaches and landings.

  1. HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 Is Required for Circadian Periodicity through the Promotion of Nucleo-Cytoplasmic mRNA Export in Arabidopsis[W][OPEN

    PubMed Central

    MacGregor, Dana R.; Gould, Peter; Foreman, Julia; Griffiths, Jayne; Bird, Susannah; Page, Rhiannon; Stewart, Kelly; Steel, Gavin; Young, Jack; Paszkiewicz, Konrad; Millar, Andrew J.; Halliday, Karen J.; Hall, Anthony J.; Penfield, Steven

    2013-01-01

    Cold acclimation has been shown to be attenuated by the degradation of the INDUCER OF CBF EXPRESSION1 protein by the E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 (HOS1). However, recent work has suggested that HOS1 may have a wider range of roles in plants than previously appreciated. Here, we show that hos1 mutants are affected in circadian clock function, exhibiting a long-period phenotype in a wide range of temperature and light environments. We demonstrate that hos1 mutants accumulate polyadenylated mRNA in the nucleus and that the circadian defect in hos1 is shared by multiple mutants with aberrant mRNA export, but not in a mutant attenuated in nucleo-cytoplasmic transport of microRNAs. As revealed by RNA sequencing, hos1 exhibits gross changes to the transcriptome with genes in multiple functional categories being affected. In addition, we show that hos1 and other previously described mutants with altered mRNA export affect cold signaling in a similar manner. Our data support a model in which altered mRNA export is important for the manifestation of hos1 circadian clock defects and suggest that HOS1 may indirectly affect cold signaling through disruption of the circadian clock. PMID:24254125

  2. HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 is required for circadian periodicity through the promotion of nucleo-cytoplasmic mRNA export in Arabidopsis.

    PubMed

    MacGregor, Dana R; Gould, Peter; Foreman, Julia; Griffiths, Jayne; Bird, Susannah; Page, Rhiannon; Stewart, Kelly; Steel, Gavin; Young, Jack; Paszkiewicz, Konrad; Millar, Andrew J; Halliday, Karen J; Hall, Anthony J; Penfield, Steven

    2013-11-01

    Cold acclimation has been shown to be attenuated by the degradation of the INDUCER OF CBF EXPRESSION1 protein by the E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 (HOS1). However, recent work has suggested that HOS1 may have a wider range of roles in plants than previously appreciated. Here, we show that hos1 mutants are affected in circadian clock function, exhibiting a long-period phenotype in a wide range of temperature and light environments. We demonstrate that hos1 mutants accumulate polyadenylated mRNA in the nucleus and that the circadian defect in hos1 is shared by multiple mutants with aberrant mRNA export, but not in a mutant attenuated in nucleo-cytoplasmic transport of microRNAs. As revealed by RNA sequencing, hos1 exhibits gross changes to the transcriptome with genes in multiple functional categories being affected. In addition, we show that hos1 and other previously described mutants with altered mRNA export affect cold signaling in a similar manner. Our data support a model in which altered mRNA export is important for the manifestation of hos1 circadian clock defects and suggest that HOS1 may indirectly affect cold signaling through disruption of the circadian clock.

  3. Evaluating outcomes of care and targeting quality improvement using Medicare health outcomes survey data.

    PubMed

    Bowen, Sonya E

    2012-01-01

    The Medicare Health Outcomes Survey (HOS) provides a rich source of outcomes data on the Medicare Advantage (MA) program for the US Department of Health and Human Services, managed care organizations participating in Medicare, quality improvement organizations, and health services researchers working to improve quality of care for Medicare enrollees. Since 1998, the Centers for Medicare and Medicaid Services has collected longitudinal functional status information to assess the performance of Medicare managed care organizations. This introduction reviews the goals of the HOS program, how the HOS supports health care reform, and outlines recent HOS studies exploring data applications for monitoring outcomes and implementing quality improvement activities.

  4. Urokinase-Type Plasminogen Activator in a Human Sarcoma Cellular Model for Metastasis in Athymic Mice

    DTIC Science & Technology

    1990-05-01

    cell line ( Sao - 2 ) with osteoblastic properties. Cancer...conditions The TE - 85 human osteosarcoma cell line , designated HOS, and its v-Ki-ras transformant line , KHOS/NP (R-970-5), were obtained from ATCC...hours, as opposed to ə% in HOS. On the other hand, these two cell lines showed no differences in their chemotactic response to conditioned

  5. Coexisting urogenital anomaly and duodenal atresia in two atypical Holt–Oram syndrome

    PubMed Central

    Ali, Tuncer Ahmet; Afra, Karavelioğlu; Didem, Baskin Embleton; Muhsin, Elmas

    2016-01-01

    Holt–Oram syndrome (HOS) is a rare autosomal dominant disorder, characterized by upper limb dysplasia and congenital cardiac defect. We report two cases with HOS, first associated with renal agenesis, coronal hypospadias, urethral duplication and second associated with duodenal atresia and horseshoe kidney that have not been reported in English literature. PMID:27695215

  6. How In-Service Science Teachers Integrate History and Nature of Science in Elementary Science Courses

    ERIC Educational Resources Information Center

    Hacieminoglu, Esme

    2014-01-01

    The purpose of this study is to investigate how the in-service science teachers' (IST) perceptions and practices about curriculum and integration of the history of science (HOS) and the nature of science (NOS) affect their science courses. For this aim, how ISTs integrated the NOS and HOS in their elementary science courses for understanding of…

  7. Using a Professional Development Program for Enhancing Chilean Biology Teachers' Understanding of Nature of Science (NOS) and Their Perceptions about Using History of Science to Teach NOS

    ERIC Educational Resources Information Center

    Pavez, José M.; Vergara, Claudia A.; Santibañez, David; Cofré, Hernán

    2016-01-01

    A number of authors have recognized the importance of understanding the nature of science (NOS) for scientific literacy. Different instructional strategies such as decontextualized, hands-on inquiry, and history of science (HOS) activities have been proposed for teaching NOS. This article seeks to understand the contribution of HOS in enhancing…

  8. The Use of Help Options in Multimedia Listening Environments to Aid Language Learning: A Review

    ERIC Educational Resources Information Center

    Mohsen, Mohammed Ali

    2016-01-01

    This paper provides a comprehensive review on the use of help options (HOs) in the multimedia listening context to aid listening comprehension (LC) and improve incidental vocabulary learning. The paper also aims to synthesize the research findings obtained from the use of HOs in Computer-Assisted Language Learning (CALL) literature and reveals the…

  9. Holt–Oram Syndrome: Anesthetic Challenges and Safe Outcome

    PubMed Central

    Rana, Meenal; Solanki, Sohan Lal; Agarwal, Vandana; Divatia, Jigeeshu V

    2017-01-01

    Holt–Oram syndrome (HOS) is an autosomal dominant disease with skeletal and cardiac manifestations. We here are presenting a 31-year-old man and a diagnosed case of HOS, with an ulceroproliferative lesion on lateral border of the tongue, was posted for wide excision of lesion with primary closure and left side radical neck dissection. PMID:28074809

  10. Using a Professional Development Program for Enhancing Chilean Biology Teachers' Understanding of Nature of Science (NOS) and Their Perceptions about Using History of Science to Teach NOS

    ERIC Educational Resources Information Center

    Pavez, José M.; Vergara, Claudia A.; Santibañez, David; Cofré, Hernán

    2016-01-01

    A number of authors have recognized the importance of understanding the nature of science (NOS) for scientific literacy. Different instructional strategies such as decontextualized, hands-on inquiry, and history of science (HOS) activities have been proposed for teaching NOS. This article seeks to understand the contribution of HOS in enhancing…

  11. The Use of Help Options in Multimedia Listening Environments to Aid Language Learning: A Review

    ERIC Educational Resources Information Center

    Mohsen, Mohammed Ali

    2016-01-01

    This paper provides a comprehensive review on the use of help options (HOs) in the multimedia listening context to aid listening comprehension (LC) and improve incidental vocabulary learning. The paper also aims to synthesize the research findings obtained from the use of HOs in Computer-Assisted Language Learning (CALL) literature and reveals the…

  12. History of science content analysis of Chinese science textbooks from the perspective of acculturation

    NASA Astrophysics Data System (ADS)

    Ma, Yongjun; Wan, Yanlan

    2017-08-01

    Based on previous international studies, a content analysis scheme has been designed and used from the perspective of culture to study the history of science (HOS) in science textbooks. Nineteen sets of Chinese science textbooks have been analyzed. It has been found that there are noticeable changes in the quantity, content, layout, presentation, and writing intention of the HOS sections in textbooks from different time periods. What's more, the textbooks aim at presenting the scientific culture and aim to help students understand it better. However, the cultural associations of the HOS in textbooks is insufficient and significant differences exist among textbooks of different subjects. In order to explore the reasons why the presentation of HOS in various subjects is different, we made a specific comparison of curriculum standards of two subjects with great differences and interviewed the editors-in-chief of two textbooks. Results show that one of the most important reasons for the different writings of the HOS in textbooks is that different subject curriculum standards attach greater importance to the HOS. In addition, the attention to the HOS by editors-in-chief, the tradition of studying the HOS within the history of the discipline, and the reference textbooks in compiling textbooks are all important influence factors. Some suggestions for future textbooks compilation are given at the end.

  13. Technical decision-making with higher order structure data: starting a new dialogue.

    PubMed

    Gabrielson, John P; Weiss, William F

    2015-04-01

    Characterization of the higher order structure (HOS) of biological products has been growing in importance in recent years. Scientists in the biopharmaceutical industry, academic researchers, and regulators are all increasingly aware of the critical role that HOS plays in maintaining the stability and intended biological function of biopharmaceutical products. We organized a consortium of scientists and researchers from industry and academic institutions to address how HOS data can be used most effectively to drive decisions during product development. In this commentary, we introduce the purpose, objectives, and scope of the consortium and then provide some brief points to consider in the context of characterizing HOS of biopharmaceutical products. Scientific advances in HOS analysis, as well as continued dialogue among academia, industry, and regulatory agencies will ensure that appropriate methodologies are used to inform technical decision-making during biopharmaceutical development. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. Bilateral Scapulohumeral Ankylosis after Prolonged Mechanical Ventilation

    PubMed Central

    Schreinemakers, J. Rieneke; van Noort, Arthur; Rademakers, Maarten V.

    2016-01-01

    This case demonstrates a rarely reported bilateral scapulohumeral bony ankylosis. A young woman developed extensive heterotopic ossifications (HOs) in both shoulder joints after being mechanically ventilated for several months at the intensive care unit in a comatose status. She presented with a severe movement restriction of both shoulder joints. Surgical resection of the bony bridges was performed in 2 separate sessions with a significant improvement of shoulder function afterwards. No postoperative complications, pain, or recurrence of HOs were noted at 1-year follow-up. Mechanical ventilation, immobilization, neuromuscular blockage, and prolonged sedation are known risk factors for the development of HOs in the shoulder joints. Relatively early surgical resection of the HOs can be performed safely in contrary to earlier belief. Afterwards, nonsteroidal anti-inflammatory drugs and/or radiation therapy can be possible treatment modalities to prevent recurrence of HOs. PMID:27583120

  15. Perceptions About the Present and Future of Surgical Simulation: A National Study of Mixed Qualitative and Quantitative Methodology.

    PubMed

    Yiasemidou, Marina; Glassman, Daniel; Tomlinson, James; Song, David; Gough, Michael J

    Assess expert opinion on the current and future role of simulation in surgical education. Expert opinion was sought through an externally validated questionnaire that was disseminated electronically. Heads of Schools of Surgery (HoS) (and deputies) and Training Program Directors (TPD) (and deputies). Simulation was considered a good training tool (HoS: 15/15, TPD: 21/21). The concept that simulation is useful mostly to novices and for basic skills acquisition was rejected (HoS: 15/15, TPDs: 21/21; HoS: 13/15, TPDs: 18/21). Further, simulation is considered suitable for teaching nontechnical skills (HoS: 13/15, TPDs: 20/21) and re-enacting stressful situations (HoS: 14/15, TPDs: 15/21). Most respondents also felt that education centers should be formally accredited (HoS: 12/15, TPDs: 16/21) and that consultant mentors should be appointed by every trust (HoS: 12/15, TPDs: 19/21). In contrast, there were mixed views on its use for trainee assessment (HoS: 6/15, TPDs: 14/21) and whether it should be compulsory (HoS: 8/15, TPDs: 11/21). The use of simulation for the acquirement of both technical and nontechnical skills is strongly supported while views on other applications (e.g., assessment) are conflicting. Further, the need for center accreditation and supervised, consultant-led teaching is highlighted. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  16. Small interfering RNA of alkaline phosphatase inhibits matrix mineralization.

    PubMed

    Kotobuki, Noriko; Matsushima, Asako; Kato, Youichi; Kubo, Yoko; Hirose, Motohiro; Ohgushi, Hajime

    2008-05-01

    To investigate the cascade of matrix mineralization, cells expressing high and low alkaline phosphatase (ALP) were separated from human osteoblast-like (HOS) cells by fluorescence-activated cell sorting with an ALP antibody. After these cells had been recloned from single cells and then cultured under osteogenic conditions, high-ALP-expressing HOS (H-HOS) cells showed matrix mineralization, but low-ALP-expressing HOS (L-HOS) cells did not. The interaction among osteogenic-related genes, such as runt-related transcription factor 2 (RUNX2), collagen type I alpha1 chain (COL1A1), tissue non-specific ALP, and osteocalcin (OCN), is well known as being related to matrix mineralization. Quantitative real-time polymerase chain reaction revealed that the gene expression of ALP was higher in H-HOS cells than in L-HOS, whereas the gene expression of RUNX2, COL1A1, and OCN was lower in H-HOS cells than in L-HOS cells. When small interfering RNAs (siRNAs) of these osteogenic-related genes were introduced into H-HOS cells by transfection, only ALP siRNA inhibited matrix mineralization. Furthermore, the expression of not only the ALP gene, but also the COL1A1 and RUNX2 genes was influenced by the inhibition of ALP, although the expression of OCN was not affected by the inhibition of ALP. We have been able to confirm that the ALP gene is a strong candidate as the trigger of matrix mineralization. These results indicate the usefulness of cloned osteogenic cells in investigating the molecular mechanisms of matrix mineralization, the function of which can be modulated by using a variety of siRNAs.

  17. Prognostic value of a pre-freeze hypo-osmotic swelling test on the post-thaw quality of dog semen.

    PubMed

    Karger, S; Geiser, B; Grau, M; Burfeind, O; Heuwieser, W; Arlt, S P

    2016-03-01

    Throughout cryopreservation, sperm are exposed to major osmotic challenges. Only intact membranes of sperm cells are able to regulate these volumetric changes, which can be determined by the hypo-osmotic swelling test (HOS test). Correlations between the HOS test and conventional semen variables are inconsistent. Therefore, the objectives of this study were (1) to examine relationships between HOS test results and standard semen variables before freezing and after thawing and (2) to evaluate the prognostic value of the HOS assessments on post-thaw quality of dog semen. Semen of 35 dogs was collected and analyzed before freezing and after thawing following a 7-day freeze-thaw interval. Conventional semen variables such as sperm cell motility, membrane integrity morphology were evaluated and the HOS test was conducted with results from this test being recorded. In fresh semen the HOS test was positively correlated with progressive motility of sperm cells: r=0.52, sperm cell membrane integrity: r=0.50 and normal sperm cell morphology: r=0.46 (P<0.05). In frozen-thawed semen, the data obtained with the HOS test were positively correlated with progressive sperm cell motility: r=0.67 and membrane integrity: r=0.86 (P<0.05). The data obtained with the HOS test in fresh semen were positively correlated with sperm cell membrane integrity: r=0.50 normal sperm cell morphology: r=0.55 and data from the HOS test (r=0.43; P<0.05) with frozen-thawed semen. For the prediction of individual cryopreservation capacity, results from assessment of the fresh semen variables of good and poor semen quality were statistically compared. Based on these results, it is not possible to predict the quality of frozen-thawed dog semen using the HOS test. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Surgical learning activities for house officers: do they improve the surgical experience?

    PubMed

    Maweni, R M; Foley, R W; Lupi, M; Shier, D; Ronan O'Connell, P; Vig, S

    2016-11-01

    To ascertain whether house officers (HOs) attain a more satisfactory surgical rotation experience when they perform basic surgical learning activities. We also sought to establish how many and which learning activities HOs achieve and the effect on their surgical experience. A questionnaire listing 20 learning activities and questions regarding satisfaction with an overall experience was disseminated to HOs in the UK and Ireland who had completed ≥3 months of surgical rotations. Satisfaction with surgical experience was dichotomised in order to perform logistic regression using R Studio software v0.98. The survey was completed by 150 respondents, with 26 % completing at least 10 basic surgical learning activities during their surgical rotation. On multivariate analysis, the completion of these learning activities was significantly associated with a satisfactory rotation experience (p < 0.001). Furthermore, the use of a checklist of surgical activities provided to HOs was associated with a significant increase in the performance of learning activities (p = 0.003). Surgical HOs who were informed about potential basic surgical learning activities that can be performed during their rotations performed significantly more of these activities. And these activities were associated with a significantly greater satisfaction with surgical rotations. Therefore, we recommend facilitating HOs completion of these activities as this will ensure that basic surgical competencies are achieved and that HOs will be more satisfied with their surgical experience.

  19. Atypical Carpal Tunnel Syndrome in a Holt Oram Patient: A Case Report and Literature Review

    PubMed Central

    Mace, James; Reddy, Srikanth; Mohil, Randeep

    2014-01-01

    We present a case report of a patient diagnosed with Holt-Oram syndrome (HOS) presenting with clinical and electrophysiologically confirmed carpal tunnel syndrome. Pre-operative Magnetic resonance imaging revealed an abnormal course of the median nerve; as such an atypical incision and approach were carried out to decompress the nerve to excellent post operative clinical effect. To our knowledge this is the first description of abnormal nervous course in a patient with HOS leading to peripheral entrapment. A literature surrounding the important aspects of HOS to the orthopaedic surgeon is presented concomitantly. PMID:25621081

  20. 75 FR 31790 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-04

    ... outcomes measures, the HOS is used to collect the Management of Urinary Incontinence in Older Adults... : 0938-0701; Frequency: Yearly; Affected Public: Individuals and households; Number of Respondents: 1,099...

  1. 77 FR 47850 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ... outcomes measures, the HOS is used to collect the Management of Urinary Incontinence in ] Older Adults... not changed. Form Number: CMS-10203 (OCN: 0938-0701); Frequency: Yearly; Affected Public: Individuals...

  2. Baicalin induces apoptosis in human osteosarcoma cell through ROS-mediated mitochondrial pathway.

    PubMed

    Wan, Daqian; Ouyang, Huoniu

    2017-09-05

    Baicalin is extracted from a traditional Chinese herb, Scutellaria baicalensis. In this study, the anticancer activity and underlying mechanisms of baicalin towards human osteosarcoma cell (HOS) were investigated. Baicalin could inhibit HOS cell proliferation in a concentration-dependent manner. Mitochondrial membrane potential decreased obviously after treated with different concentration of baicalin by flow cytometry assay and revealed that baicalin triggered a significant generation of reactive oxygen species (ROS). Western blotting assay further revealed that baicalin-induced cell apoptosis by suppressing Bcl-2 level, then activating caspase-9 and caspase-3. In vivo experiment, baicalin significantly suppressed tumour growth in female BALB/C nude mice bearing HOS tumours. In addition, baicalin did show toxicity to treated animal by comparing the body weight increase and mortality. In general, the present results demonstrated that baicalin-induced apoptosis in human osteosarcoma cell via a ROS-mediated mitochondrial pathway. The paper indicated that baicalin is a promising candidate for the treatment of HOS.

  3. Interaction of Salmonella enterica Serovar Typhimurium with Intestinal Organoids Derived from Human Induced Pluripotent Stem Cells.

    PubMed

    Forbester, Jessica L; Goulding, David; Vallier, Ludovic; Hannan, Nicholas; Hale, Christine; Pickard, Derek; Mukhopadhyay, Subhankar; Dougan, Gordon

    2015-07-01

    The intestinal mucosa forms the first line of defense against infections mediated by enteric pathogens such as salmonellae. Here we exploited intestinal "organoids" (iHOs) generated from human induced pluripotent stem cells (hIPSCs) to explore the interaction of Salmonella enterica serovar Typhimurium with iHOs. Imaging and RNA sequencing were used to analyze these interactions, and clear changes in transcriptional signatures were detected, including altered patterns of cytokine expression after the exposure of iHOs to bacteria. S. Typhimurium microinjected into the lumen of iHOs was able to invade the epithelial barrier, with many bacteria residing within Salmonella-containing vacuoles. An S. Typhimurium invA mutant defective in the Salmonella pathogenicity island 1 invasion apparatus was less capable of invading the iHO epithelium. Hence, we provide evidence that hIPSC-derived organoids are a promising model of the intestinal epithelium for assessing interactions with enteric pathogens.

  4. First report of Pandora neoaphidis resting spore formation in vivo in aphid hosts under field conditions

    USDA-ARS?s Scientific Manuscript database

    The entomopathogenic fungus PANDORA NEOAPHIDIS is a recognized pathogen of aphids, causing natural epizootics in aphid populations, and interacts favorably with aphid predators and parasitoids. Survival of entomophthoralean fungi in periods of unsuitable weather conditions or lack of appropriate hos...

  5. Intravenous administration of hyperoxygenated solution attenuates pulmonary edema formation in phosgene-induced acute lung injury in rabbits.

    PubMed

    Wang, Ling; Liu, Chunran; Zhang, Hui; Gao, Changjun; Chai, Wei; Xu, Ruifen; Wang, Hui-xia; Xu, Lixian

    2010-11-01

    The aim of this study was to investigate the post-treatment effect of intravenous hyperoxygenated solution (HOS) on pulmonary parameters in rabbits whole-body-exposed to the toxic gas phosgene. Twenty-four New Zealand rabbits were divided into four groups randomly: rabbits were exposed whole-body to either filtered room air or 539 ppm phosgene for 5 minutes followed by room air washout for 5 minutes. Phosgene-exposed group (exposed to phosgene without treatment, PH group); Control group (exposed to air, Control group); Lactate Ringer's solution (LRS)-treated group (intravenous infusion of LRS by 30 ml·kg-1 after phosgene exposure, LRS group); Hyperoxygenated solution (HOS)-treated group (intravenous infusion of HOS after phosgene exposure by 30 mL·kg-1, HOS group). Arterial blood was collected for blood gas analysis at 1, 3, 8, and 12 hours after phosgene or air exposure. Rabbits were put to death 12 hours after exposure. Lung edema was assessed gravimetrically by measuring tissue wet/dry weight ratio (W/D) and lung coefficient (LC). Bronchoalveolar lavage (BAL) was performed and fluid was analyzed for total maloaldehyde (MDA), glutathione peroxidase (GSH-Px), and protein concentration. Lungs were perfused with saline to remove blood, snap-frozen in liquid nitrogen (N2), analyzed for tissue reduced glutathione (GSH) and oxidized glutathione (GSSG). Parts of lung tissues were reserved for histopathology examination. In the PH, LRS, and HOS groups, phosgene inhalation caused serious lung edema, W/D and LC, lung tissue GSSG, BALF MDA, and protein content increased significantly. Meanwhile, PaO2, lung tissue GSH, and BALF GSH-Px decreased markedly. However, after HOS treatment in the HOS group, PaO2 was clearly higher than that in the PH group and LRS group at 3, 8, 12 hours (P < 0.01). W/D and LC, lung tissue GSSG, BALF MDA, and protein content in the HOS group were apparently lower than that in the PH group and LRS group (P < 0.01). In the HOS group, lung tissue

  6. An observational study of the safety benefits of electronic logging devices using carrier-collected data.

    PubMed

    Hickman, Jeffrey S; Guo, Feng; Camden, Matthew C; Dunn, Naomi J; Hanowski, Richard J

    2017-04-03

    Fatigue has been shown to be a contributing factor in many large truck crashes. Long duty periods, irregular work schedules, and poor sleeping environments make fatigue a noteworthy concern in trucking operations. One way to limit fatigued driving is through prescriptive hours-of-service (HOS) regulations. This duty status information is typically recorded in written logs; however, more trucking companies are moving toward electronic HOS recorders. These devices were first marketed as productivity tools; however, more recently they have been touted for their safety benefits in reducing fatigued truck drivers (because falsifying electronic logs is difficult). The purpose of the current study was to assess the benefits of electronic logging devices (ELDs) on safety and HOS violations in trucks as they operated during normal revenue service. Data on crashes, HOS violations, mileage, and onboard safety systems were obtained from participating motor carriers. Although the final data sets included data from 11 carriers representing medium and large carriers (including a total of 82,943 crashes, 970 HOS violations, and 224,034 truck-years that drove a total of 15.6 billion miles), the data set in the study was skewed toward larger, for-hire carriers and may not represent the overall U.S. trucking population. After controlling for calendar year, carriers in the data set, onboard safety system status, and long-haul/regional indicator, ELD-equipped trucks had a significantly lower total crash rate (11.7% reduction), preventable crash rate (5.1% reduction), driving-related HOS violation rate (53% reduction), and non-driving-related HOS violation rate (49% reduction) than trucks not equipped with ELDs. The results show a clear safety benefit, in terms of crash and HOS violation reductions, for trucks equipped with ELDs.

  7. A Review of Depleted Uranium Biological Effects: In Vitro Studies (Briefing charts)

    DTIC Science & Technology

    2010-11-01

    Specific Effects in Vitro: Heavy Metal Mutagenicity, Genotoxicity Neoplastic Transformation: Comparison of DU and 238U at Equal Concentrations (HPRT...change change Heavy Metal Genotoxicity Miller et al, Carcinogenesis, Vol 22, 2001. Miller et al., Metal Ions in Biology and Medicine...of Bystander HOS Cells Co-cultured with HOS Cells Exposed to Heavy Metal So yes, beware thy neighbor Bystander Effects Adaptive response - No

  8. Holt-Oram syndrome and diaphragmatic hernia associate with paracentric inversion of chromosome 8

    SciTech Connect

    Eswara, M.S.; Batanian, J.R.

    1994-09-01

    Holt-Oram syndrome (HOS) consists of congenital heart disease, usually atrial septal defect, along with thumb anomalies and occasionally more extensive limb defects. Inheritance is autosomal dominant. Previous reports have associated HOS with cytogenetic abnormalities on chromosomes 4, 14 and 20. Recently a linkage study has suggested a HOS locus on chromosome 12. We describe another case of HOS with a de novo cytogenetic abnormality. On prenatal ultrasound, IUGR, oligohydramnios and left diaphragmatic hernia were noted. Following delivery, patient was placed on extra-corporeal membrane oxygenation because of severe lung hypoplasia; diaphragmatic hernia was repaired with mesh graft. He expired on day 17 of life. On exam, he had subtle dysmorphic features with hypotelorism and abnormal folding of the ear lobes. He had bilateral radial aplasia, aplasia of thumbs, index and middle fingers, along with the metacarpals. On autopsy he was found to have atrial septal defect of the ostium secundum type, right side aortic arch with vascular ring formation, bicuspid pulmonic valve and severe lung hypoplasia worse on the left. Cytogenetic analysis on blood and skin showed 48,XX,inv(8)(q24.2q13). Chromosome fragility study was negative. Parental chromosomes were normal. Our observation of inv(8)q with HOS and diaphragmatic hernia may indicate genetic heterogeneity with this condition. Regulation of morphogenesis is likely under the control of a hierarchy of genes; multiple loci for conditions such as HOS would not be surprising.

  9. A gene for Holt-Oram syndrome maps to chromosome 12q24.1

    SciTech Connect

    Bonnet, D.; Pelet, A.; Sidi, D.

    1994-09-01

    Originally described in 1960, Holt-Oram syndrome (HOS, MIM:142900) is a rare autosomal dominant disorder of unknown origin (1/100,000 live births) characterized by congenital septal heart defects with associated malformations of upper limbs. We have reported on the mapping of a gene causing HOS to the distal long arm of chromosome 12 (12q21-qter) by linkage analysis in 9 multiplex families (Zmax=8.19 at the D12S354 locus). In addition, multipoint linkage analysis provided evidence for mapping of the disease locus to the genetic interval (7cM) defined by loci D12S105 and D12S79. In situ hybridization of YACs containing the flanking loci D12S105 and D12S79 demonstrates that the HOS locus maps to 12q24.1 thus exluding the candidate genes KOX20 and KOX1. We tested three HOS multiplex families with polydactily or without heart defect and showed that they do not map to chromosome 12q (homog-test: {chi}{sup 2}=13.28, p=0.0001). This observation supports the view that genetic heterogeneity holds true for typical HOS only. The mapping of a gene for HOS is, to our knowledge, the first chromosomal localization of a gene responsible for congenital septal defect in human. The characterization of the disease causing gene will hopefully shed light on the molecular mechanisms that govern heart septation and limb development in the early stages of embryogenesis.

  10. Using a Professional Development Program for Enhancing Chilean Biology Teachers' Understanding of Nature of Science (NOS) and Their Perceptions About Using History of Science to Teach NOS

    NASA Astrophysics Data System (ADS)

    Pavez, José M.; Vergara, Claudia A.; Santibañez, David; Cofré, Hernán

    2016-05-01

    A number of authors have recognized the importance of understanding the nature of science (NOS) for scientific literacy. Different instructional strategies such as decontextualized, hands-on inquiry, and history of science (HOS) activities have been proposed for teaching NOS. This article seeks to understand the contribution of HOS in enhancing biology teachers' understanding of NOS, and their perceptions about using HOS to teach NOS. These teachers ( N = 8), enrolled in a professional development program in Chile are, according to the national curriculum, expected to teach NOS, but have no specific NOS and HOS training. Teachers' views of NOS were assessed using the VNOS-D+ questionnaire at the beginning and at the end of two modules about science instruction and NOS. Both the pre- and the post-test were accompanied by interviews, and in the second session we collected information about teachers' perceptions of which interventions had been more significant in changing their views on NOS. Finally, the teachers also had to prepare a lesson plan for teaching NOS that included HOS. Some of the most important study results were: significant improvements were observed in teachers' understanding of NOS, although they assigned different levels of importance to HOS in these improvements; and although the teachers improved their understanding of NOS, most had difficulties in planning lessons about NOS and articulating historical episodes that incorporated NOS. The relationship between teachers' improved understanding of NOS and their instructional NOS skills is also discussed.

  11. Bedomning Av Kommunikativ Formaga Hos Personer Med Utvecklingsstorning. Teknik, Kommunikation, Handikapp Forskningsrapport nr 12 (Assessment of the Communicative Ability in Persons with Mental Retardation. Technology, Communication, Disability Research Report No. 12). TeleCommunity, RACE 2033 (Research in Advanced Communications Technologies in Europe).

    ERIC Educational Resources Information Center

    Brodin, Jane; Thurfjell, Fredrik

    This report was developed as part of a Swedish study to examine whether videotelephones can be used to develop the communicative ability of individuals with mental retardation and whether access to telecommunications increased the possibilities of social integration. Communication was viewed as sharing a feeling, action, or experience with another…

  12. Altered iron homeostasis involvement in arsenite-mediated cell transformation

    PubMed Central

    Wu, Jing; Eckard, Jonathan; Chen, Haobin; Costa, Max; Frenkel, Krystyna; Huang, Xi

    2010-01-01

    Chronic exposure to low doses of arsenite causes transformation of human osteogenic sarcoma (HOS) cells. Although oxidative stress is considered important in arsenite-induced cell transformation, the molecular and cellular mechanisms by which arsenite transforms human cells are still unknown. In the present study, we investigated whether altered iron homeostasis, known to affect cellular oxidative stress, can contribute to the arsenite-mediated cell transformation. Using arsenite-induced HOS cell transformation as a model, it was found that total iron levels are significantly higher in transformed HOS cells in comparison to parental control HOS cells. Under normal iron metabolism conditions, iron homeostasis is tightly controlled by inverse regulation of ferritin and transferrin receptor (TfR) through iron regulatory proteins (IRP). Increased iron levels in arsenite transformed cells should theoretically lead to higher ferritin and lower TfR in these cells than in controls. However, the results showed that both ferritin and TfR are decreased, apparently through two different mechanisms. A lower ferritin level in cytoplasm was due to the decreased mRNA in the arsenite-transformed HOS cells, while the decline in TfR was due to a lowered IRP-binding activity. By challenging cells with iron, it was further established that arsenite-transformed HOS cells are less responsive to iron treatment than control HOS cells, which allows accumulation of iron in the transformed cells, as exemplified by significantly lower ferritin induction. On the other hand, caffeic acid phenethyl ester (CAPE), an antioxidant previously shown to suppress As-mediated cell transformation, prevents As-mediated ferritin depletion. In conclusion, our results suggest that altered iron homeostasis contributes to arsenite-induced oxidative stress and, thus, may be involved in arsenite-mediated cell transformation. PMID:16443159

  13. Evaluation of sperm functional attributes in relation to in vitro sperm-zona pellucida binding ability and cleavage rate in assessing frozen thawed buffalo (Bubalus bubalis) semen quality.

    PubMed

    Selvaraju, S; Ravindra, J P; Ghosh, J; Gupta, P S P; Suresh, K P

    2008-07-01

    The objective of this study was to evaluate sperm functional attributes in relation to in vitro sperm-zona binding ability and cleavage rate in assessing frozen thawed buffalo (Bubalus bubalis) semen quality. Frozen-thawed forty-eight ejaculates from eight Surti buffalo bulls (six ejaculates/bull) obtained by artificial vagina were used. Frozen semen from each bull was thawed, pooled, and subjected for sperm functional (six replicates) and in vitro fertilization (four replicates) tests. The progressive forward motility, plasmalemma functional integrity assessed by fluorogenic [6-carboxyfluorescein diacetate (CFDA), and propidium iodide (PI)], hypoosmotic swelling (HOS), and hypoosmotic swelling-Giemsa (HOS-G) test, mitochondrial membrane potential, sperm nuclear morphology, the number of sperm bound to zona and cleavage rate differed significantly (P<0.05) between bulls. When the animals were grouped based on cleavage rate (group I, >40% cleavage rate, n=5, and group II, <40% cleavage rate, n=3), in vitro fertility parameters and all the sperm functional attributes except sperm nuclear morphology differed significantly (P<0.05). The proportions of sperm with functional plasmalemma in the tail and intact acrosome assessed by HOS-G test (25.33, range: 17.48-40.27) were significantly (P<0.001) lower than the functional plasmalemma in the tail assessed by HOS test (39.80, range: 27.85-54.67). The number of sperm bound to zona had significant correlations with the mitochondrial membrane potential (r=0.90, P<0.01) and plasmalemma integrity (fluorogenic, r=0.74 and HOS, r=0.79, P<0.05) and HOS-G, r=0.87, P<0.01). The cleavage rate had significant (P<0.05) correlations with the mitochondrial membrane potential (r=0.70) and plasmalemma integrity measured by HOS-G test (r=0.68). The present study indicates that these attributes could represent important determinants of buffalo sperm quality influencing cleavage rate.

  14. Psychometric Evaluation of the Lower Extremity Computerized Adaptive Test, the Modified Harris Hip Score, and the Hip Outcome Score

    PubMed Central

    Hung, Man; Hon, Shirley D.; Cheng, Christine; Franklin, Jeremy D.; Aoki, Stephen K.; Anderson, Mike B.; Kapron, Ashley L.; Peters, Christopher L.; Pelt, Christopher E.

    2014-01-01

    Background: The applicability and validity of many patient-reported outcome measures in the high-functioning population are not well understood. Purpose: To compare the psychometric properties of the modified Harris Hip Score (mHHS), the Hip Outcome Score activities of daily living subscale (HOS-ADL) and sports (HOS-sports), and the Lower Extremity Computerized Adaptive Test (LE CAT). The hypotheses was that all instruments would perform well but that the LE CAT would show superiority psychometrically because a combination of CAT and a large item bank allows for a high degree of measurement precision. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Data were collected from 472 advanced-age, active participants from the Huntsman World Senior Games in 2012. Validity evidences were examined through item fit, dimensionality, monotonicity, local independence, differential item functioning, person raw score to measure correlation, and instrument coverage (ie, ceiling and floor effects), and reliability evidences were examined through Cronbach alpha and person separation index. Results: All instruments demonstrated good item fit, unidimensionality, monotonicity, local independence, and person raw score to measure correlations. The HOS-ADL had high ceiling effects of 36.02%, and the mHHS had ceiling effects of 27.54%. The LE CAT had ceiling effects of 8.47%, and the HOS-sports had no ceiling effects. None of the instruments had any floor effects. The mHHS had a very low Cronbach alpha of 0.41 and an extremely low person separation index of 0.08. Reliabilities for the LE CAT were excellent and for the HOS-ADL and HOS-sports were good. Conclusion: The LE CAT showed better psychometric properties overall than the HOS-ADL, HOS-sports, and mHHS for the senior population. The mHHS demonstrated pronounced ceiling effects and poor reliabilities that should be of concern. The high ceiling effects for the HOS-ADL were also of concern. The LE CAT was superior

  15. Genetic profiling of two phenotypically distinct outbred rats derived from a colony of the Zucker fatty rats maintained at Tokyo Medical University.

    PubMed

    Nakanishi, Satoshi; Kuramoto, Takashi; Kashiwazaki, Naomi; Yokoi, Norihide

    2017-05-03

    The Zucker fatty (ZF) rat is an outbred rat and a well-known model of obesity without diabetes, harboring a missense mutation (fatty, abbreviated as fa) in the leptin receptor gene (Lepr). Slc:Zucker (Slc:ZF) outbred rats exhibit obesity while Hos:ZFDM-Lepr(fa) (Hos:ZFDM) outbred rats exhibit obesity and type 2 diabetes. Both outbred rats have been derived from an outbred ZF rat colony maintained at Tokyo Medical University. So far, genetic profiles of these outbred rats remain unknown. Here, we applied a simple genotyping method using Ampdirect reagents and FTA cards (Amp-FTA) in combination with simple sequence length polymorphisms (SSLP) markers to determine genetic profiles of Slc:ZF and Hos:ZFDM rats. Among 27 SSLP marker loci, 24 loci (89%) were fixed for specific allele at each locus in Slc:ZF rats and 26 loci (96%) were fixed in Hos:ZFDM rats, respectively. This indicates the low genetic heterogeneity in both colonies of outbred rats. Nine loci (33%) showed different alleles between the two outbred rats, suggesting considerably different genetic profiles between the two outbred rats in spite of the same origin. Additional analysis using 72 SSLP markers further supported these results and clarified the profiles in detail. This study revealed that genetic profiles of the Slc:ZF and Hos:ZFDM outbred rats are different for about 30% of the SSLP marker loci, which is the underlying basis for the phenotypic difference between the two outbred rats.

  16. A polysaccharide from Agaricus blazei inhibits proliferation and promotes apoptosis of osteosarcoma cells.

    PubMed

    Wu, Bei; Cui, Juncheng; Zhang, Chaogui; Li, Zhihong

    2012-05-01

    Many reports have proved that traditional Chinese herbal medicines (TCM) have become popular used in disease prevention and as alternatives to cancer chemotherapy. In this study, we purified a polysaccharide (ABP-Ia) from the fruiting bodies of Agaricus blazei and identified its molecular weight to be 4.2×10(5)Da. ABP-Ia was a heteropolysaccharide fraction consisting of glucose, mannose, and galactose in a molar ratio of 1:1:1, along with trace of rhamnose. The effect of ABP-Ia at three concentrations of 100, 200 and 400 μg/mL on the cell growth and apoptosis was evaluated in osteosarcoma cell lines HOS and a normal human osteoblast cell line NHOst. ABP-Ia had a significant inhibitory effect against the growth of HOS cells, whereas a mild cytotoxicity to the HOS cells mediated by ABP-Ia was observed, which was in accordance with the results that ABP-Ia substantially induced apoptosis in a dose-dependent fashion in the HOS cells. However ABP-Ia had no or minor inhibitory and cytotoxic effects on the viability of NHOst cells even at the high concentration of 400 μg/mL. Base on all the observations, we could conclude that ABP-Ia had an evident inhibitory effect on the growth of HOS cells mainly through induction of apoptosis, with a minor toxicity to normal human osteoblast cell.

  17. Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells.

    PubMed

    Husmann, Knut; Ducommun, Pascal; Sabile, Adam A; Pedersen, Else-Marie; Born, Walter; Fuchs, Bruno

    2015-09-04

    The poor outcome of osteosarcoma (OS), particularly in patients with metastatic disease and a five-year survival rate of only 20%, asks for more effective therapeutic strategies targeting malignancy-promoting mechanisms. Dysregulation of C-MET, its ligand hepatocyte growth factor (HGF) and the fusion oncogene product TPR-MET, first identified in human MNNG-HOS OS cells, have been described as cancer-causing factors in human cancers. Here, the expression of these molecules at the mRNA and the protein level and of HGF-stimulated signaling and downregulation of C-MET was compared in the parental low metastatic HOS and MG63 cell lines and the respective highly metastatic MNNG-HOS and 143B and the MG63-M6 and MG63-M8 sublines. Interestingly, expression of TPR-MET was only observed in MNNG-HOS cells. HGF stimulated the phosphorylation of Akt and Erk1/2 in all cell lines investigated, but phospho-Stat3 remained at basal levels. Downregulation of HGF-stimulated Akt and Erk1/2 phosphorylation was much faster in the HGF expressing MG63-M8 cells than in HOS cells. Degradation of HGF-activated C-MET occurred predominantly through the proteasomal and to a lesser extent the lysosomal pathway in the cell lines investigated. Thus, HGF-stimulated Akt and Erk1/2 signaling as well as proteasomal degradation of HGF activated C-MET are potential therapeutic targets in OS.

  18. Investigating the mechanical properties of zona pellucida of whole human oocytes by atomic force spectroscopy.

    PubMed

    Andolfi, Laura; Masiero, Elena; Giolo, Elena; Martinelli, Monica; Luppi, Stefania; Dal Zilio, Simone; Delfino, Ines; Bortul, Roberta; Zweyer, Marina; Ricci, Giuseppe; Lazzarino, Marco

    2016-08-08

    The role of mechanics in numerous biological processes is nowadays recognized, while in others, such as the fertilization process, it is still neglected. In the case of oocytes the description of their mechanical properties could improve the comprehension of the oocyte-spermatozoon interaction and be helpful for application in in vitro fertilization (IVF) clinics. Herein the mechanical properties of whole human oocytes (HOs) immediately after retrieval are investigated by indentation measurements with atomic force spectroscopy under physiological conditions. Measurements are performed on immature (metaphase I - MI) and mature (metaphase II - MII) HOs. According to their morphological characteristics MII-HOs are classified as "suitable" and "rejected"; these latter would be usually rejected for intracytoplasmic sperm injection (ICSI). For all maturation stages we observe that the elastic response of the zona pellucida (ZP) outer layer was different and distinguishable from the rest of the ZP-HO. The elasticity of this ZP outer layer varies with maturation and quality: stiffness decreases from immature MI to good quality MII, up to poor-quality rejected MII. An indirect analysis with IVF outcome indicates that the ZP outer layer of analysed HOs donated by women who achieved pregnancy is stiffer than that of HOs from women with negative outcome. Our findings suggest that mechanical properties can represent important oocyte quality indicators that may be exploited for the design of innovative ICSI dedicated cell sorters.

  19. Patient-Reported Outcome questionnaires for hip arthroscopy: a systematic review of the psychometric evidence

    PubMed Central

    2011-01-01

    Background Hip arthroscopies are often used in the treatment of intra-articular hip injuries. Patient-reported outcomes (PRO) are an important parameter in evaluating treatment. It is unclear which PRO questionnaires are specifically available for hip arthroscopy patients. The aim of this systematic review was to investigate which PRO questionnaires are valid and reliable in the evaluation of patients undergoing hip arthroscopy. Methods A search was conducted in Pubmed, Medline, CINAHL, the Cochrane Library, Pedro, EMBASE and Web of Science from 1931 to October 2010. Studies assessing the quality of PRO questionnaires in the evaluation of patients undergoing hip arthroscopy were included. The quality of the questionnaires was evaluated by the psychometric properties of the outcome measures. The quality of the articles investigating the questionnaires was assessed by the COSMIN list. Results Five articles identified three questionnaires; the Modified Harris Hip Score (MHHS), the Nonarthritic Hip Score (NAHS) and the Hip Outcome Score (HOS). The NAHS scored best on the content validity, whereas the HOS scored best on agreement, internal consistency, reliability and responsiveness. The quality of the articles describing the HOS scored highest. The NAHS is the best quality questionnaire. The articles describing the HOS are the best quality articles. Conclusions This systematic review shows that there is no conclusive evidence for the use of a single patient-reported outcome questionnaire in the evaluation of patients undergoing hip arthroscopy. Based on available psychometric evidence we recommend using a combination of the NAHS and the HOS for patients undergoing hip arthroscopy. PMID:21619610

  20. The hypo-osmotic swelling test for evaluation of sperm membrane integrity.

    PubMed

    Ramu, Sivakumar; Jeyendran, Rajasingam S

    2013-01-01

    A functional membrane is requisite for the fertilizing ability of spermatozoa, as it plays an integral role in sperm capacitation, acrosome reaction, and binding of the spermatozoon to the egg surface. The hypo-osmotic swelling (HOS) test evaluates the functional integrity of the sperm's plasma membrane and also serves as a useful indicator of fertility potential of sperm. The HOS test predicts membrane integrity by determining the ability of the sperm membrane to maintain equilibrium between the sperm cell and its environment. Influx of the fluid due to hypo-osmotic stress causes the sperm tail to coil and balloon or "swell." A higher percentage of swollen sperm indicates the presence of sperm having a functional and intact plasma membrane. Here, we present the detailed protocol for performing the HOS test and explain the results for interpretation.

  1. Technical Decision Making With Higher Order Structure Data: Perspectives on Higher Order Structure Characterization From the Biopharmaceutical Industry.

    PubMed

    Weiss, William F; Gabrielson, John P; Al-Azzam, Wasfi; Chen, Guodong; Davis, Darryl L; Das, Tapan K; Hayes, David B; Houde, Damian; Singh, Satish K

    2016-12-01

    Characterization of the higher order structure (HOS) of protein-based biopharmaceutical products is an important aspect of their development. Opinions vary about how best to apply biophysical methods, in which contexts to use these methods, and how to use the resulting data to make technical decisions as drug candidates are commercialized [Gabrielson JP, Weiss WF IV. J Pharm Sci. 2015;104(4):1240-1245]. The aim of this commentary is to provide guidance for the development and implementation of a robust and comprehensive HOS characterization strategy. We first consider important concepts involved in developing a strategy that is appropriately suited to a particular biologic, and then discuss ways industry can partner with academia, technology companies, government laboratories, and regulatory agencies to improve the consistency with which HOS characterization is applied across the biopharmaceutical industry. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  2. Users guide: The LaRC human-operator-simulator-based pilot model

    NASA Technical Reports Server (NTRS)

    Bogart, E. H.; Waller, M. C.

    1985-01-01

    A Human Operator Simulator (HOS) based pilot model has been developed for use at NASA LaRC for analysis of flight management problems. The model is currently configured to simulate piloted flight of an advanced transport airplane. The generic HOS operator and machine model was originally developed under U.S. Navy sponsorship by Analytics, Inc. and through a contract with LaRC was configured to represent a pilot flying a transport airplane. A version of the HOS program runs in batch mode on LaRC's (60-bit-word) central computer system. This document provides a guide for using the program and describes in some detail the assortment of files used during its operation.

  3. Recent Applications of Higher-Order Spectral Analysis to Nonlinear Aeroelastic Phenomena

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.; Hajj, Muhammad R.; Dunn, Shane; Strganac, Thomas W.; Powers, Edward J.; Stearman, Ronald

    2005-01-01

    Recent applications of higher-order spectral (HOS) methods to nonlinear aeroelastic phenomena are presented. Applications include the analysis of data from a simulated nonlinear pitch and plunge apparatus and from F-18 flight flutter tests. A MATLAB model of the Texas A&MUniversity s Nonlinear Aeroelastic Testbed Apparatus (NATA) is used to generate aeroelastic transients at various conditions including limit cycle oscillations (LCO). The Gaussian or non-Gaussian nature of the transients is investigated, related to HOS methods, and used to identify levels of increasing nonlinear aeroelastic response. Royal Australian Air Force (RAAF) F/A-18 flight flutter test data is presented and analyzed. The data includes high-quality measurements of forced responses and LCO phenomena. Standard power spectral density (PSD) techniques and HOS methods are applied to the data and presented. The goal of this research is to develop methods that can identify the onset of nonlinear aeroelastic phenomena, such as LCO, during flutter testing.

  4. Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells

    SciTech Connect

    Husmann, Knut; Ducommun, Pascal; Sabile, Adam A.; Pedersen, Else-Marie; Born, Walter; Fuchs, Bruno

    2015-09-04

    The poor outcome of osteosarcoma (OS), particularly in patients with metastatic disease and a five-year survival rate of only 20%, asks for more effective therapeutic strategies targeting malignancy-promoting mechanisms. Dysregulation of C-MET, its ligand hepatocyte growth factor (HGF) and the fusion oncogene product TPR-MET, first identified in human MNNG-HOS OS cells, have been described as cancer-causing factors in human cancers. Here, the expression of these molecules at the mRNA and the protein level and of HGF-stimulated signaling and downregulation of C-MET was compared in the parental low metastatic HOS and MG63 cell lines and the respective highly metastatic MNNG-HOS and 143B and the MG63-M6 and MG63-M8 sublines. Interestingly, expression of TPR-MET was only observed in MNNG-HOS cells. HGF stimulated the phosphorylation of Akt and Erk1/2 in all cell lines investigated, but phospho-Stat3 remained at basal levels. Downregulation of HGF-stimulated Akt and Erk1/2 phosphorylation was much faster in the HGF expressing MG63-M8 cells than in HOS cells. Degradation of HGF-activated C-MET occurred predominantly through the proteasomal and to a lesser extent the lysosomal pathway in the cell lines investigated. Thus, HGF-stimulated Akt and Erk1/2 signaling as well as proteasomal degradation of HGF activated C-MET are potential therapeutic targets in OS. - Highlights: • Expression of TPR-MET was only observed in MNNG-HOS cells. • HGF stimulated the phosphorylation of Akt and Erk1/2 but not of Stat3 in osteosarcoma cell lines. • Degradation of HGF-activated C-MET occurred predominantly through the proteasomal pathway.

  5. The Rice E3-Ubiquitin Ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 Modulates the Expression of ROOT MEANDER CURLING, a Gene Involved in Root Mechanosensing, through the Interaction with Two ETHYLENE-RESPONSE FACTOR Transcription Factors1

    PubMed Central

    Lourenço, Tiago F.; Serra, Tânia S.; Cordeiro, André M.; Swanson, Sarah J.; Gilroy, Simon; Saibo, Nelson J.M.; Oliveira, M. Margarida

    2015-01-01

    Plant roots can sense and respond to a wide diversity of mechanical stimuli, including touch and gravity. However, little is known about the signal transduction pathways involved in mechanical stimuli responses in rice (Oryza sativa). This work shows that rice root responses to mechanical stimuli involve the E3-ubiquitin ligase rice HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 (OsHOS1), which mediates protein degradation through the proteasome complex. The morphological analysis of the roots in transgenic RNA interference::OsHOS1 and wild-type plants, exposed to a mechanical barrier, revealed that the OsHOS1 silencing plants keep a straight root in contrast to wild-type plants that exhibit root curling. Moreover, it was observed that the absence of root curling in response to touch can be reverted by jasmonic acid. The straight root phenotype of the RNA interference::OsHOS1 plants was correlated with a higher expression rice ROOT MEANDER CURLING (OsRMC), which encodes a receptor-like kinase characterized as a negative regulator of rice root curling mediated by jasmonic acid. Using the yeast two-hybrid system and bimolecular fluorescence complementation assays, we showed that OsHOS1 interacts with two ETHYLENE-RESPONSE FACTOR transcription factors, rice ETHYLENE-RESPONSIVE ELEMENT BINDING PROTEIN1 (OsEREBP1) and rice OsEREBP2, known to regulate OsRMC gene expression. In addition, we showed that OsHOS1 affects the stability of both transcription factors in a proteasome-dependent way, suggesting that this E3-ubiquitin ligase targets OsEREBP1 and OsEREBP2 for degradation. Our results highlight the function of the proteasome in rice response to mechanical stimuli and in the integration of these signals, through hormonal regulation, into plant growth and developmental programs. PMID:26381316

  6. Validation of the Spanish version of the Hip Outcome Score: a multicenter study.

    PubMed

    Seijas, Roberto; Sallent, Andrea; Ruiz-Ibán, Miguel Angel; Ares, Oscar; Marín-Peña, Oliver; Cuéllar, Ricardo; Muriel, Alfonso

    2014-05-13

    The Hip Outcome Score (HOS) is a self-reported questionnaire evaluating the outcomes of treatment interventions for hip pathologies, divided in 19 items of activities of daily life (ADL) and 9 sports' items. The aim of the present study is to translate and validate HOS into Spanish. A prospective and multicenter study with 100 patients undergoing hip arthroscopy was performed between June 2012 and January 2013. Crosscultural adaptation was used to translate HOS into Spanish. Patients completed the questionnaire before and after surgery. Feasibility, reliability, internal consistency, construct validity (correlation with Western Ontario and McMaster Universities Osteoarthritis Index), ceiling and floor effects and sensitivity to change were assessed for the present study. Mean age was 45.05 years old. 36 women and 64 men were included. Feasibility: 13% had at least one missing item within the ADL subscale and 17% within the sport subscale. Reliability: the translated version of HOS was highly reproducible with intraclass correlation coefficient of 0.95 for ADL and 0.94 for the sports subscale. Internal consistency was confirmed with Cronbach's alpha >0.90 in both subscales. Construct validity showed statistically significant correlation with WOMAC. Ceiling effect was observed in 6% and 12% for ADL and sports subscale, respectively. Floor effect was found in 3% and 37% ADL and sports subscale, respectively. Large sensitivity to change was shown in both subscales. The translated version of HOS into Spanish has shown to be feasible, reliable and sensible to changes for patients undergoing hip arthroscopy. This validated translation of HOS allows for comparisons between studies involving either Spanish- or English-speaking patients. Prognostic study, Level I.

  7. Patient reported outcomes for patients who returned to sport compared with those who did not after hip arthroscopy: minimum 2-year follow-up

    PubMed Central

    Domb, Benjamin G.; Dunne, Kevin F.; Martin, Timothy J.; Gui, Chengcheng; Finch, Nathan A.; Vemula, S. Pavan; Redmond, John M.

    2016-01-01

    Previous studies assessed elite athletes’ return to sport (RTS) after hip arthroscopy, but few investigated a cohort including athletes from all levels of sport. This study compared athletes who returned to sport to those who did not, based on four patient-reported outcome (PRO) scores, including the Hip Outcome Score—Sports Specific Subscale (HOS-SSS). Between September 2008 and April 2012, hip arthroscopies were performed on 157 patients (168 hips) who reported playing a sport preoperatively and indicated their level of sports activity post-operatively. Two-year follow-up was available for 148 (94%) amateur and professional athletes with a total of 158 hips. Of these 60 cases (65 hips) did not return to sports (NRTS) and were in the NRTS group. The remaining 88 cases (93 hips) constituted the RTS group. The modified Harris Hip Score, Non-Arthric Hip Score, Hip Outcome-Activities of Daily Living (HOS-ADL), and HOS-SSS were used to assess outcomes. The HOS-SSS was used to assess specific sport-related movement. Both groups demonstrated significant improvement at 2 years post-operatively in visual analog score and four PRO scores (P < 0.001). There was no significant preoperative differences in HOS-SSS scores between groups; however, the RTS group had significantly higher HOS-SSS scores at 1 and 2 years post-surgery. Post-operatively, the RTS group had significantly better ability to jump, land from a jump, stop quickly and perform cutting/lateral movements (P < 0.05). In summary, patients who indicated RTSs demonstrated significantly higher PRO scores and abilities to perform several sport-related movements, compared with patients who did not. PMID:27583148

  8. Molecular genetic analysis of cold-regulated gene transcription.

    PubMed

    Viswanathan, C; Zhu, Jian-Kang

    2002-07-29

    Chilling and freezing temperatures adversely affect the productivity and quality of crops. Hence improving the cold hardiness of crop plants is an important goal in agriculture, which demands a clear understanding of cold stress signal perception and transduction. Pharmacological and biochemical evidence shows that membrane rigidification followed by cytoskeleton rearrangement, Ca(2+) influx and Ca(2+)-dependent phosphorylation are involved in cold stress signal transduction. Cold-responsive genes are regulated through C-repeat/dehydration-responsive elements (CRT/DRE) and abscisic acid (ABA)-responsive element cis elements by transacting factors C-repeat binding factors/dehydration-responsive element binding proteins (CBFs/DREBs) and basic leucine zippers (bZIPs) (SGBF1), respectively. We have carried out a forward genetic analysis using chemically mutagenized Arabidopsis plants expressing cold-responsive RD29A promoter-driven luciferase to dissect cold signal transduction. We have isolated the fiery1 (fry1) mutant and cloned the FRY1 gene, which encodes an inositol polyphosphate 1-phosphatase. The fry1 plants showed enhanced induction of stress genes in response to cold, ABA, salt and dehydration due to higher accumulation of the second messenger, inositol (1,4,5)- triphosphate (IP(3)). Thus our study provides genetic evidence suggesting that cold signal is transduced through changes in IP(3) levels. We have also identified the hos1 mutation, which showed super induction of cold-responsive genes and their transcriptional activators. Molecular cloning and characterization revealed that HOS1 encodes a ring finger protein, which has been implicated as an E3 ubiquitin conjugating enzyme. HOS1 is present in the cytoplasm at normal growth temperatures but accumulates in the nucleus upon cold stress. HOS1 appears to regulate temperature sensing by the cell as cold-responsive gene expression occurs in the hos1 mutant at relatively warm temperatures. Thus HOS1 is a

  9. Validation of the Spanish version of the hip outcome score: a multicenter study

    PubMed Central

    2014-01-01

    Background The Hip Outcome Score (HOS) is a self-reported questionnaire evaluating the outcomes of treatment interventions for hip pathologies, divided in 19 items of activities of daily life (ADL) and 9 sports’ items. The aim of the present study is to translate and validate HOS into Spanish. Methods A prospective and multicenter study with 100 patients undergoing hip arthroscopy was performed between June 2012 and January 2013. Crosscultural adaptation was used to translate HOS into Spanish. Patients completed the questionnaire before and after surgery. Feasibility, reliability, internal consistency, construct validity (correlation with Western Ontario and McMaster Universities Osteoarthritis Index), ceiling and floor effects and sensitivity to change were assessed for the present study. Results Mean age was 45.05 years old. 36 women and 64 men were included. Feasibility: 13% had at least one missing item within the ADL subscale and 17% within the sport subscale. Reliability: the translated version of HOS was highly reproducible with intraclass correlation coefficient of 0.95 for ADL and 0.94 for the sports subscale. Internal consistency was confirmed with Cronbach’s alpha >0.90 in both subscales. Construct validity showed statistically significant correlation with WOMAC. Ceiling effect was observed in 6% and 12% for ADL and sports subscale, respectively. Floor effect was found in 3% and 37% ADL and sports subscale, respectively. Large sensitivity to change was shown in both subscales. Conclusion The translated version of HOS into Spanish has shown to be feasible, reliable and sensible to changes for patients undergoing hip arthroscopy. This validated translation of HOS allows for comparisons between studies involving either Spanish- or English-speaking patients. Level of evidence Prognostic study, Level I PMID:24884511

  10. The Johnson-Neyman procedure as an alternative to ANCOVA.

    PubMed

    D'Alonzo, Karen T

    2004-11-01

    ANCOVA is a widely used statistical procedure that is particularly useful in analyzing data from experimental designs. There are, however, a number of assumptions that must be tested before proceeding with the ANCOVA. Of particular concern is the assumption of homogeneity of regression slopes (HOS). When the HOS assumption has been violated, the researcher needs to look for an alternative approach to the ANCOVA. The Johnson-Neyman procedure (J-N) is presented as such an alternative. Although the calculations for the procedure are somewhat tedious and are not currently a standard feature of statistical software packages, an alternative approach using SAS syntax codes is presented.

  11. Prognostic value of various spermatological attributes as predictors of zona binding and zona penetration of buffalo (Bubalus bubalis) semen.

    PubMed

    Selvaraju, S; Ghosh, J; Ravindra, J P

    2009-02-01

    Twenty-four ejaculates from six (four ejaculates each) Surti buffalo bulls aged 4-8 years were used to assess various attributes of spermatozoa influencing the zona-binding and zona-penetration tests. Ejaculates from each bulls were subjected to in vitro sperm--zona binding and sperm--zona penetration tests (four replicates per bull) using immature buffalo oocytes. The average number of spermatozoa bound per oocyte was 27.79 +/- 5.90. The average number of spermatozoa penetrated per oocyte was 3.35 +/- 0.64. The average number of zona-bound and -penetrated spermatozoa differed significantly between animals. Significant difference (p < 0.05) was observed between the plasmalemma integrity as assessed by eosin--nigrosin stain and hypo-osmotic swelling (HOS) test. Furthermore, the percentage of cells positive for the HOS test, i.e. functional membrane integrity (51.25 +/- 2.32) was significantly (p < 0.05) higher than hypo-osmotic swelling-Giemsa (HOS-G) test, i.e. the subpopulation of spermatozoa positive for functional membrane and acrosomal integrities (42.87 +/- 4.56). The HOS test had significant correlations with plasmalemma integrity as measured by the vital stain, eosin--nigrosin (r = 0.85, p < 0.05). The HOS-G test also had significant correlation with plasmalemma integrity measured by vital stains such as eosin--nigrosin (r = 0.90, p < 0.05) and fluorogenic stains [carboxyfluorescein diacetate (CFDA) and propidium iodide (PI); r = 0.92, p < 0.01] and HOS test (r = 0.93), acrosomal integrity (r = 0.86, p < 0.05) and mitochondrial membrane potential (r = 0.99, p < 0.01). The plasmalemma integrity (fluorogenic stain), functional membrane integrity (HOS test), subpopulation of spermatozoa positive for functional membrane and acrosomal integrities (HOS-G test) and mitochondrial membrane potential had significant (p < 0.05) correlation with sperm zona binding and penetration. The present study indicates that these parameters could represent important determinants

  12. Functional health outcomes as a measure of health care quality for Medicare beneficiaries.

    PubMed Central

    Bierman, A S; Lawrence, W F; Haffer, S C; Clancy, C M

    2001-01-01

    OBJECTIVE: the Medicare Health Outcomes Survey (HOS), a new quality measure in the Health Plan Employer Data and Information Set, is designed to assess physical and mental functional health outcomes of Medicare beneficiaries enrolled in Medicare+Choice organizations. We discuss the rationale for the HOS measure together with methodologic challenges in its use and interpretation, using descriptive data from the baseline Medicare HOS to illustrate some of these challenges. DATA SOURCES/STUDY DESIGN: The 1999 Cohort 2 Medicare HOS baseline data were used for a cross-sectional descriptive analysis. A random sample of 1,000 beneficiaries from each health plan with a Medicare+Choice contract was surveyed (N = 156,842; 282 organizations included in these analyses) . PRINCIPAL FINDINGS: The HOS measure is designed to assess a previously unmeasured dimension of quality. Plan-level variation was seen across all baseline measures of sociodemographic characteristics and illness burden. At the individual level socioeconomic position as measured by educational attainment was strongly associated with functional status. The least educated beneficiaries had the highest burden of illness on all measures examined, and there was a consistent and significant gradient in health and functional status across all levels of education. In analyses stratified by race and ethnicity, socioeconomic gradients in f un ct ion persist ed. CONCLUSIONS Despite limitations, by focusing at t en t ion on the need to improve functional health out comes among elderly Medicare beneficiaries enrolled in Medicare+Choice, the HOS can serve as an important new tool to support efforts to improve health care quality. The HOS provides valuable information at the federal, state, and health plan levels that can be used to identify, prioritize, and evaluate quality improvement interventions and monitor progress for the program overall as well as for vulnerable subgroups. To interpret the HOS as a quality measure

  13. Quantifying wave-breaking dissipation using nonlinear phase-resolved wave-field simulations

    NASA Astrophysics Data System (ADS)

    Qi, Y.; Xiao, W.; Yue, D. K. P.

    2014-12-01

    We propose to understand and quantify wave-breaking dissipation in the evolution of general irregular short-crested wave-fields using direct nonlinear phase-resolved simulations based on a High-Order Spectral (HOS) method (Dommermuth & Yue 1987). We implement a robust phenomenological-based energy dissipation model in HOS to capture the effect of wave-breaking dissipation on the overall wave-field evolution (Xiao et al 2013). The efficacy of this model is confirmed by direct comparisons against measurements for the energy loss in 2D and 3D breaking events. By comparing simulated wave-fields with and without the dissipation model in HOS, we obtain the dissipation field δ(x,y,t), which provides the times, locations and intensity of wave breaking events (δ>δc). This is validated by comparison of HOS simulations with Airborne Terrain Mapper (ATM) measurements in the recent ONR Hi-Res field experiment. Figure (a) shows one frame of simulated wave-field (with dissipation model). Figure (b) is the corresponding measurement from ATM, where a large wave breaking event was captured. Figure (c) is the 3D view of the simulated wave-field with the colored region representing dissipation with δ>δc. The HOS predicted high-dissipation area is found to agree well with the measured breaking area. Based on HOS predicted high-dissipation area (δ>δc), we calculate Λ(c) (Phillips 1985), the distribution of total length of breaking wave front per unit surface area per unit increment of breaking velocity c. Figure (d) shows the distribution Λ(c) calculated from HOS. For breaking speeds c greater than 5m/s, the simulated Λ(c) is in qualitative agreement with Phillips theoretical power-law of Λ(c)~c-6. From δ(x,y,t), we further quantify wave breaking by calculating the whitecap coverage rate Wr(t) and energy dissipation rate ΔE'(t), and study the evolution of Wr and ΔE' to understand the role of wave breaking in nonlinear wave-field evolution. We obtain HOS simulations

  14. Derivation of Intestinal Organoids from Human Induced Pluripotent Stem Cells for Use as an Infection System.

    PubMed

    Forbester, Jessica L; Hannan, Nicholas; Vallier, Ludovic; Dougan, Gordon

    2016-08-31

    Intestinal human organoids (iHOs) provide an effective system for studying the intestinal epithelium and its interaction with various stimuli. By using combinations of different signaling factors, human induced pluripotent stem cells (hIPSCs) can be driven to differentiate down the intestinal lineage. Here, we describe the process for this differentiation, including the derivation of hindgut from hIPSCs, embedding hindgut into a pro-intestinal culture system and passaging the resulting iHOs. We then describe how to carry out microinjections to introduce bacteria to the apical side of the intestinal epithelial cells (IECs).

  15. Health observatories in iran.

    PubMed

    Rashidian, A; Damari, B; Larijani, B; Vosoogh Moghadda, A; Alikhani, S; Shadpour, K; Khosravi, A

    2013-01-01

    The Islamic Republic of Iran, in her 20 year vision by the year 2025, is a developed country with the first economic, scientific and technological status in the region, with revolutionary and Islamic identity, inspiring Islamic world, as well as effective and constructive interaction in international relations. Enjoying health, welfare, food security, social security, equal opportunities, fair income distribution, strong family structure; to be away from poverty, corruption, and discrimination; and benefiting desirable living environment are also considered out of characteristics of Iranian society in that year. Strategic leadership towards perceived vision in each setting requires restrictive, complete and timely information. According to constitution of National Institute for Health Researches, law of the Fifth Development Plan of the country and characteristics of health policy making, necessity of designing a Health Observatory System (HOS) was felt. Some Principles for designing such system were formulated by taking following steps: reviewing experience in other countries, having local history of the HOS in mind, superior documents, analysis of current production and management of health information, taking the possibilities to run a HOS into account. Based on these principles, the protocol of HOS was outlined in 3 different stages of opinion poll of informed experts responsible for production on management of information, by using questionnaires and Focus Group Discussions. The protocol includes executive regulations, the list of health indicators, vocabulary and a calendar for periodic studies of the community health situation.

  16. 78 FR 39057 - Hours of Service of Drivers; Renewal and Expansion of American Pyrotechnics Association Exemption...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-28

    ... Pyrotechnics Association Exemption From the 14-Hour Rule During Independence Day Celebrations AGENCY: Federal... Independence Day periods because compliance with the current 14- hour rule in 49 CFR 395.3(a)(2) by its members... Carriers From the 14-Hour HOS Rule During 2013 and 2014 Independence Day Celebrations Motor Carrier......

  17. Effects of blockade of endogenous Gi signaling in Tie2-expressing cells on bone formation in a mouse model of heterotopic ossification.

    PubMed

    Wang, Liping; Carroll, Dylan O'; Liu, Xuhui; Roth, Theresa; Kim, Hubert; Halloran, Bernard; Nissenson, Robert A

    2015-08-01

    Available evidence indicates that some Tie2-expressing (Tie2(+) ) cells serve as multipotent progenitors that have robust BMP-dependent osteogenic activity and mediate heterotopic ossification (HO). Since signaling through the G protein Gi is required for cell motility, we hypothesized that blockade of endogenous Gi signaling in Tie2(+) cell populations would prevent HO formation. Blockade of Gi signaling in Tie2(+) cells was accomplished in transgenic mice with expression of pertussis toxin (PTX) under the control of the Tie2 promoter (Tie2(+) /PTX(+) ). Bone formation within HOs was evaluated 2 weeks after BMP injection. Expression of PTX in Tie2(+) cells significantly reduced the bone volume (BV) of HOs in male and female mice. Orthotopic bones were assessed at the distal femur and expression of PTX significantly increased trabecular bone fractional volume and bone formation rate in females only. In adult Tie2(+) /GFP(+) mice, GFP(+) cells appeared both inside and at the surfaces of bone tissue within HOs and in orthotopic bones. In summary, blockade of Gi signaling in Tie2(+) cells reduced the accrual of HOs and stimulated osteogenesis in orthotopic bones. Targeting of Gi protein coupled receptors in Tie2(+) cells may be a novel therapeutic strategy in states of abnormal bone formation such as osteoporosis and HO. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. Unraveling the Slut Narrative: Gender Constraints on Adolescent Girls' Sexual Decision-Making

    ERIC Educational Resources Information Center

    Summit, Aleza K.; Kalmuss, Debra; DeAtley, Jenifer; Levack, Andrew

    2016-01-01

    Limited research exists on the slut labeling process, a key means of enforcing rules around appropriate female sexuality. This study explores that process through qualitative interviews with 44 adolescent girls in Travis County, Texas. Labeling girls as sluts or hos was pervasive and was based on a number of factors beyond sexual behavior,…

  19. Bile Acid Responses in Methane and Non-Methane Producers to Standard Breakfast Meals

    USDA-ARS?s Scientific Manuscript database

    Bile acids and their conjugates are important regulators of glucose homeostasis. Previous research has revealed the ratio of cholic acid to deoxycholic acid to affect insulin resistance in humans. Bile acid de-conjugation and intestinal metabolism depend on gut microbes which may be affected by hos...

  20. Increased risk of nonalcoholic fatty liver disease with occupational stress in Chinese policemen: A 4-year cohort study.

    PubMed

    Li, Chen; Xing, Jing-Jing; Shan, An-Qi; Leng, Ling; Liu, Jin-Chuan; Yue, Song; Yu, Hao; Chen, Xi; Tian, Feng-Shi; Tang, Nai-Jun

    2016-11-01

    Nonalcoholic fatty liver disease (NAFLD) and occupational stress have been recognized as major public health concerns. We aimed to explore whether occupational stress was associated with NAFLD in a police population.A total of 6559 male police officers were recruited for this prospective study in April 2007. Among them, 2367 eligible subjects participated in follow-up from 2008 to 2011. NAFLD was diagnosed based on standard criteria. Occupational stress was evaluated by Occupational Stress Inventory-Revised scores.The incidence of NAFLD was 31.2% in the entire police. After adjusting for traditional risk factors, moderate occupational stress (MOS), high occupational stress (HOS), and high personal strain (HPS) were risk factors (MOS: hazard ratio [HR] = 1.237, 95% confidence interval [CI] = 1.049-1.460; HOS: HR = 1.727, 95% CI = 1.405-2.124; HPS: HR = 3.602, 95% CI = 1.912-6.787); and low occupational stress (LOS) and low personal strain (LPS) were protective factors (LOS: HR = 0.366, 95% CI = 0.173-0.776; LPS: HR = 0.490, 95% CI = 0.262-0.919) for NAFLD in the entire police cohort. HOS and HPS remained robust among traffic police.HOS and HPS were independent predictors for the development of NAFLD in a Chinese police population. Additional future prospective investigations are warranted to validate our findings.

  1. A Review of Signal Detection Using the Bispectrum with Applications in Underwater Acoustics

    DTIC Science & Technology

    1994-01-01

    or polyspectra) technique. Examples comparing power spectral and bpspectral analysis include the following topics: the identification of signals...HOS) or polyspectra) technique. Examples comparing power Spectral and b-spectral analysis include the following topics: the identification of signals...that no pocessing gain is derived from bispectral analysis . It is shown that the resolution for direct methods using no formal cumulant construction

  2. 76 FR 5324 - Hours of Service of Drivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-31

    ... public listening session and on-line comment and question session. SUMMARY: FMCSA announces that it will... rulemaking (NPRM) on hours-of-service (HOS) requirements, which it published in the Federal Register on December 29, 2010. Specifically, the Agency wants to know what factors, issues, and data it should consider...

  3. Fuzzy Logic Based Resource Manager for a Team of UAVs

    DTIC Science & Technology

    2006-06-01

    ntabooBuildings, Trees, Smoke Plumes, Suspended not present, i.e., IT E riskVI,Fr) is zero, then Sand, Birds/Insects, Other UA Vs, Air Polution , (4) i=1 Civilian...sent then the travel time is increased. The time increase will Snow, Hail, Air Pocket, Wind, Wind Shear, Hos- be significant ifthe risk is high. tile

  4. Percutaneous Absorption of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) From Soil (Journal Article)

    EPA Science Inventory

    Eight dermal absorption (two in vivo; six in vitro) and one intravenous experiment were conducted using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) either neat (high dose at ~250 µg/cm2 and low dose at 10 ng/cm2) or sorbed on a low organic (LOS) or high organic (HOS) soil at 1 ppm...

  5. Effect of centre-edge angle on clinical and quality of life outcomes after arthroscopic acetabular labral debridement.

    PubMed

    Wu, Ziying; Chen, Shiyi; Li, Yunxia; Li, Hong; Chen, Jiwu

    2016-07-01

    The aim of this study was to compare clinical and quality of life outcomes following arthroscopic acetabular labral debridement between patients with different centre-edge (CE) angle. A total of 79 patients who underwent hip labral debridement were enrolled in this study. Radiographic measurements of CE angle were collected, and patients were assigned into a normal group (25° < CE angle <40°, n = 68) and dysplasia group (CE angle <20°, n = 11). Clinical outcomes were evaluated by modified Harris Hip Score (mHHS), Hip Outcome Score (HOS) for activities of daily living (ADL) and sports and Short Form 12 (SF-12). At the final follow-up, the normal group showed significant improvements in mHHS, HOS (ADL and sports) and SF-12 (P < 0.05). However, the dysplasia group revealed significant improvements in mHHS, HOS (ADL) and SF-12 physical component summary (PCS) (P < 0.05) and no significant changes in HOS sports and SF-12 mental component summary (MCS) (P > 0.05). Additionally, there was a greater improvement in clinical scores post-operatively in the normal group compared with the dysplasia group (P < 0.05). Arthroscopic acetabular labral debridement resulted in significantly greater clinical and quality of life outcomes in patients with CE angle >25° compared with patients with CE angle < 20°.

  6. Addressing Nature of Science Core Tenets with the History of Science: An Example with Sickle-Cell Anemia & Malaria

    ERIC Educational Resources Information Center

    Howe, Erica M.

    2007-01-01

    The history of science (HOS) has proven to be a useful pedagogical tool to help students learn about what has come to be regarded as an agreed upon set of core nature of science (NOS) tenets. The following article illustrates an example of how teachers can instrumentally use the history of research on heterozygote protection in sickle-cell anemia…

  7. Equivalent System Verification and Evaluation of Augmentation Effects on Fighter Approach and Landing Flying Qualities. Volume 2. Program Plan, Test Data and Analysis.

    DTIC Science & Technology

    1981-09-01

    PITCH ATTITUDE INITIAL RESPONSE, RESPONSE TO INPUTS PREDICTABILITY OF FINAL RESPONSE- orbe. REqgIRED TO PEFR K: ANY SPECIAL PILOT INPUTS? - ANY...Low Order System (Los) FREDUENCY C RN/ ICC ) Control System P1 (HOs) E. EY PW,3 01.1 Tie I Vtsuwe D-12 Anlytical dwircterstleu - Fitah late k.spiss ad

  8. Smoking influence on sperm vitality, DNA fragmentation, reactive oxygen species and zinc in oligoasthenoteratozoospermic men with varicocele.

    PubMed

    Taha, E A; Ezz-Aldin, A M; Sayed, S K; Ghandour, N M; Mostafa, T

    2014-08-01

    This study aimed to assess the influence of smoking duration and intensity on sperm vitality, sperm DNA fragmentation, reactive oxygen species (ROS) and zinc (Zn) levels in oligoasthenoteratozoospermic (OAT) men with varicocele (Vx). A total of 246 men were investigated who were divided into OAT nonsmokers, OAT smokers, OAT nonsmokers and OAT smokers with Vx. They were subjected to history taking, clinical examination and semen analysis. In their semen, sperm hypo-osmotic swelling (HOS) test, sperm DNA fragmentation test, seminal ROS and seminal Zn were assessed. The results demonstrated significantly decreased HOS test, seminal Zn level and significantly increased sperm DNA fragmentation, seminal ROS levels in OAT smokers with Vx more than OAT smokers compared with OAT nonsmokers. Smoking intensity, smoking duration and Vx grade demonstrated significant negative correlations with sperm motility, HOS test percentage and significant positive correlations with sperm DNA fragmentation, seminal ROS level. It is concluded that smoking has a negative impact on sperm progressive motility, HOS test, seminal Zn and positive impact on sperm DNA fragmentation, semen ROS level that are exaggerated if Vx is associated being correlated with smoking intensity, smoking duration and Vx grade. © 2013 Blackwell Verlag GmbH.

  9. Comprehensive Characterization of Relationship Between Higher-Order Structure and FcRn Binding Affinity of Stress-Exposed Monoclonal Antibodies.

    PubMed

    Tsuchida, Daisuke; Yamazaki, Katsuyoshi; Akashi, Satoko

    2016-04-01

    In biopharmaceutical development, information regarding higher-order structure (HOS) is important to verify quality and characterize protein derivatives. In this study, we aimed to characterize the association between HOS and pharmacokinetic property of a stress-exposed monoclonal antibody (mAb). Purity, primary structure, thermal stability, and HOS were evaluated for mAbs exposed to heat, photo-irradiation, and chemical oxidation. To investigate conformation of stress-exposed mAbs, hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) was utilized. No distinct difference in secondary or tertiary structure between stress-exposed and non-stressed samples was found by conventional spectroscopic techniques. In binding activity with the neonatal Fc receptor (FcRn), however, a marked decline was observed for force-oxidized mAb and a slight decline was observed for heat- and photodegraded mAbs. Using differential scanning calorimetry, a change in thermal stability was observed in the CH2 domain for all the stress-exposed samples. Using HDX-MS analyses, individual regions with altered conformation could be identified for heat-degraded and force-oxidized samples. These findings indicate that comprehensive study is important for detecting conformational changes and helpful for predicting biophysical property, and that the evaluation of HOS using several analytical techniques is indispensable for confirming biopharmaceutical quality.

  10. Genomic and biological characterization of Tomato necrotic streak virus, a novel subgroup 2 ilarvirus infecting tomato in Florida

    USDA-ARS?s Scientific Manuscript database

    Tomato necrotic streak virus (TomNSV) is a recently described ilarvirus that was detected in tomato in Florida. The full TomNSV genome sequence revealed it to be a novel subgroup 2 ilarvirus with little nucleotide identity to other previously reported tomato-infecting ilarviruses. Experimental hos...

  11. Bobcat (Lynx rufus) as a new natural intermediate host for Sarcocystis neurona

    USDA-ARS?s Scientific Manuscript database

    The protozoan Sarcocystis neurona is an important cause of severe clinical disease of horses (called equine protozoal myeloencephalitis, EPM), marine mammals, companion animals, and several species of wildlife animals in the Americas. The Virginia opossum (Didelphis virginiana) is its definitive hos...

  12. The U.S. Air Service in World War I. Volume 1

    DTIC Science & Technology

    1978-01-01

    Thaw ................................................... 57 Spad VII ................................................................. 60 Repair...before the close of hos- tilities. Cinema Training Films. Through the lnterallied Photographic Conference ar- rangements had been made for the...Capts. Virginius E. Clark and Edgar S. Gorrell. 8. Maj. William Thaw , 3d Pursuit Group; Maj. Charles Biddle, 4th Group; Capt. Dudley L. Hill, 5th Group

  13. Microarray Comparison of Endophyte-Infected and Endophyte-Free Tall Fescue

    USDA-ARS?s Scientific Manuscript database

    Many grasses have mutualistic symbioses with fungi of the family Clavicipitaceae: Tall fescue (Festuca arudinacea = Lolium arundinaceum) can harbor the obligate endophyte, Neotyphodium coenophialum that are asexually propagated and transmitted via host seeds. In an effort to begin to dissect the hos...

  14. Unraveling the Slut Narrative: Gender Constraints on Adolescent Girls' Sexual Decision-Making

    ERIC Educational Resources Information Center

    Summit, Aleza K.; Kalmuss, Debra; DeAtley, Jenifer; Levack, Andrew

    2016-01-01

    Limited research exists on the slut labeling process, a key means of enforcing rules around appropriate female sexuality. This study explores that process through qualitative interviews with 44 adolescent girls in Travis County, Texas. Labeling girls as sluts or hos was pervasive and was based on a number of factors beyond sexual behavior,…

  15. Technical decision-making with higher order structure data: specific binding of a nonionic detergent perturbs higher order structure of a therapeutic monoclonal antibody.

    PubMed

    Budyak, Ivan L; Doyle, Brandon L; Weiss, William F

    2015-04-01

    Robust higher order structure (HOS) characterization capability and strategy are critical throughout biopharmaceutical development from initial candidate selection and formulation screening to process optimization and manufacturing. This case study describes the utility of several orthogonal HOS methods as investigational tools during purification process development. An atypically high level of residual detergent in a development drug substance batch of a therapeutic monoclonal antibody triggered a root cause investigation. Several orthogonal biophysical techniques were used to uncover and characterize a specific interaction between the detergent and the antibody. Isothermal titration calorimetry (ITC) was used to quantify the molar ratio and affinity of the binding event, and circular dichroism (CD) spectroscopy and differential scanning calorimetry (DSC) were used to evaluate corresponding impacts on secondary/tertiary structure and thermal stability, respectively. As detergents are used routinely in biopharmaceutical processing, this case study highlights the value and power of HOS data in informing technical investigations and underlines the importance of HOS characterization as a component of overall biopharmaceutical analytical control strategy. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Signal Processing Design of Low Probability of Intercept Waveforms via Intersymbol Dither

    DTIC Science & Technology

    2008-03-01

    Blind Least Mean Square Shalvi- Weinstein Spectrum Fitting Block Subspace SOS Based HOS Based Bussgang Algorithms Cumulants Godard Algorithms Sato...Transactions on, 6(5):1743– 1763, May 2007. 2. Ding, Z., R. A. Kennedy, B. D. O. Anderson, and C. R. Johnson Jr. “Ill- convergence of Godard blind

  17. The Psychometric Properties of the Agricultural Hazardous Occupations Order Certification Training Program Written Examinations

    ERIC Educational Resources Information Center

    French, Brian F.; Breidenbach, Daniel H.; Field, William E.; Tormoehlen, Roger

    2007-01-01

    The written certification exam that accompanies the Gearing Up for Safety-Agricultural Production Safety Training for Youth curriculum was designed to partially meet the testing requirements of the Agricultural Hazardous Occupations Order (AgHOs) Certification Training Program. This curriculum and accompanying assessment tools are available for…

  18. 77 FR 64093 - Hours of Service of Drivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-18

    ...: FMCSA announces that it will hold a public listening session to solicit information, concepts, ideas, and information on hours-of- service (HOS) requirements for drivers of passenger-carrying commercial... number is 1-805-884-8511. Internet Address for Live Webcast. FMCSA will post specific information on how...

  19. 78 FR 76392 - Hours of Service of Drivers: Application for Exemption; David Muresan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

    ... employ), including ``rest'' and ``sleep.'' Mr. Muresan believes that the Agency's HOS rules do not... 11 hours followed by 2 to 10 hours of rest/sleep'' and would be required to ``. . . sleep at least 8... at rest/sleep has full authority to accept or not to drive again and has authority to decide if he is...

  20. 75 FR 13441 - Hours of Service; Limited 90-Day Waiver for the Distribution of Anhydrous Ammonia in Agricultural...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-22

    ... Federal Motor Carrier Safety Administration 49 CFR Part 395 Hours of Service; Limited 90-Day Waiver for... Federal hours- of-service (HOS) regulations for the transportation of anhydrous ammonia from any distribution point to a local farm retailer or to the ultimate consumer, and from a local farm retailer to the...

  1. Peach is an occasional host for Rhagoletis pomonella (Walsh, 1867) (Diptera: Tephritidae) larvae in Western Washington State, USA

    USDA-ARS?s Scientific Manuscript database

    Peach, Prunus persica (L.) Batsch (Rosaceae), has been reported to be a host of the apple maggot fly, Rhagoletis pomonella (Walsh), 1867 (Diptera: Tephritidae), an important quarantine pest of apple (Malus domestica Borkhausen) (Rosaceae) in the western U.S.A. However, all reports of peach as a hos...

  2. Thermal Coupling and Damage Mechanisms of 1.06 Micron Laser Radiation and Laser-Produced Plasma on Selected Materials

    DTIC Science & Technology

    1982-12-01

    CinffejdIn Office) 15. SECURITY CLASS. ( hos rpa rfp ISO . OECLASSIVICATION/lDOWNGRAONG SCIOULE I$. 0e5?RI5SjfION ST,%rtME0 T (of this Repot) Approved -.or...Polished 2024 Aluminum before Irradiation, SEM 50001 . II Figure 19. 1 Micron Silicon Coating over Polished 2024 Aluminum after Irradiation with 9.8 MW/cm

  3. Holt-Oram syndrome with intermediate atrioventricular canal defect, and aortic coarctation: functional characterization of a de novo TBX5 mutation.

    PubMed

    Baban, Anwar; Pitto, Letizia; Pulignani, Silvia; Cresci, Monica; Mariani, Laura; Gambacciani, Carolina; Digilio, Maria Cristina; Pongiglione, Giacomo; Albanese, Sonia

    2014-06-01

    Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder characterized by upper limb defects and congenital heart defects (CHD), which are often simple septal and conduction defects, less frequently complex CHDs. We report on a 9 year-old boy with clinical and radiologic features of HOS consisting of bilateral asymmetric hypoplastic thumbs, generalized brachydactyly, limited supination due to radioulnar synostosis, and sloping shoulders, and intermediate atrioventricular canal defect (AVCD) with aortic coarctation. A de novo, previously described mutation, (Arg279ter) was identified in the TBX5 gene. Molecular characterization of this mutation was carried out due to the atypical CHD. In order to investigate whether the mutated transcript of TBX5 was able to escape the post-transcriptional surveillance mechanism and to produce a truncated TBX5 protein, we analyzed the TBX5 transcript, and protein pattern in HOS, and WT cardiac tissues. Our results demonstrate that the mutant TBX5 transcript is cleared by the cellular mechanism of surveillance. This data provides some support for the hypothesis that a dominant negative mutation, which strongly impairs the WT allele, might be too hazardous to be maintained. The literature suggests that HOS is relatively common among syndromes associated with AVCD.

  4. Truck drivers hours-of-service regulations and occupational health.

    PubMed

    Jensen, Anker; Dahl, Søren

    2009-01-01

    Major industrialised countries, like the United States, Canada, Australia and countries of the European Union (EU) have Hours-of-Service (HoS) regulations for truck drivers that stipulate duration of continuous driving and rest periods. The purported aim is the improvement of road safety by reducing fatigue and drowsiness, but the regulations can also have a strong impact on the working conditions for drivers. Better working conditions for truck drivers is one of the aims of the EU HoS regulations, but they do not seem to fully produce the desired benefits. Truck drivers continue to have a high prevalence of back disorders, which have been linked with the time spent driving. They also have a high incidence of heart disease, which might be due to stress factors at work. Stress levels can be affected by HoS regulations, that leave the driver little job control and lead to social isolation. HoS regulations could contribute more to the improvement of working conditions of truck drivers through counteracting irregular work schedules, night driving and social isolation. Moving the focus from simple control of time spent driving or not driving to fatigue management could improve job control and working conditions for truck drivers without loss of traffic safety.

  5. Proposed performance standards for the Agricultural Hazardous Occupations Order certification training program.

    PubMed

    French, B F; Field, W E; Tormoehlen, R

    2007-07-01

    The performance standards that accompany Gearing Up for Safety, the agricultural production safety training curriculum for youth, were designed to meet the certification testing requirements of the Agricultural Hazardous Occupations Order (AgHOs) certification training program. The AgHOs requires that certain youth who are older than 13 and younger than 16 years of age complete a prescribed training program before being eligible for employment on farms to perform certain tasks considered hazardous. These training resources will be available for implementation and can be accessed by contacting the second author. To our knowledge, up until this time, few, if any, standardized testing procedures or instruments have had the necessary psychometric evidence to support use of the resulting scores to assess the readiness of youth to meet the basic certification requirements contained in the AgHOs. This article describes the rationale, methods, and key findings from a standard-setting session held to establish minimum passing scores for a proposed testing process. The test will be used as a component of the Gearing Up for Safety certification process for youth workers seeking employment to perform job functions as specified under the AgHOs. Readers may be able to apply this standardized testing process, or similarly accepted processes, to other or future testing and certification projects involving agricultural safety and health.

  6. 77 FR 31684 - Hours of Service of Drivers: RockTenn, Exemption Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-29

    ... Federal Motor Carrier Safety Administration Hours of Service of Drivers: RockTenn, Exemption Application AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of final disposition... from the driver hours-of-service (HOS) provisions of the Federal Motor Carrier Safety...

  7. Application of higher order statistics/spectra in biomedical signals--a review.

    PubMed

    Chua, Kuang Chua; Chandran, Vinod; Acharya, U Rajendra; Lim, Choo Min

    2010-09-01

    For many decades correlation and power spectrum have been primary tools for digital signal processing applications in the biomedical area. The information contained in the power spectrum is essentially that of the autocorrelation sequence; which is sufficient for complete statistical descriptions of Gaussian signals of known means. However, there are practical situations where one needs to look beyond autocorrelation of a signal to extract information regarding deviation from Gaussianity and the presence of phase relations. Higher order spectra, also known as polyspectra, are spectral representations of higher order statistics, i.e. moments and cumulants of third order and beyond. HOS (higher order statistics or higher order spectra) can detect deviations from linearity, stationarity or Gaussianity in the signal. Most of the biomedical signals are non-linear, non-stationary and non-Gaussian in nature and therefore it can be more advantageous to analyze them with HOS compared to the use of second-order correlations and power spectra. In this paper we have discussed the application of HOS for different bio-signals. HOS methods of analysis are explained using a typical heart rate variability (HRV) signal and applications to other signals are reviewed.

  8. Epigenetic mechanisms at work: Exploiting nutrient-specific modulation of genetic networks

    USDA-ARS?s Scientific Manuscript database

    “Epigenetics” was used to describe actions of genes with their environment that bring the phenotype into being”. The modern version of epigenetics includes the molecular mechanisms that influence the phenotypic outcome of a gene or genome, in absence of changes to the underlying DNA sequence. A hos...

  9. Burn Care in Iraq

    DTIC Science & Technology

    2007-01-01

    tent configuration and later occupied Ibn Sina Hospital, in the international zone in Baghdad, Iraq. In the tent configura- tion, the 28th CSH provided...at Ibn Sina Hos- pital continuously. In a relatively austere general hospital environment, burn care has been provided with a focus on the

  10. Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi

    PubMed Central

    Elías-Villalobos, Alberto; Helmlinger, Dominique; Ibeas, José I.

    2015-01-01

    Fungi, as every living organism, interact with the external world and have to adapt to its fluctuations. For pathogenic fungi, such interaction involves adapting to the hostile environment of their host. Survival depends on the capacity of fungi to detect and respond to external stimuli, which is achieved through a tight and efficient genetic control. Chromatin modifications represent a well-known layer of regulation that controls gene expression in response to environmental signals. However, less is known about the chromatin modifications that are involved in fungal virulence and the specific cues and signalling pathways that target chromatin modifications to specific genes. In a recently published study, our research group identified one such regulatory pathway. We demonstrated that the histone deacetylase (HDAC) Hos2 is involved in yeast-to-hyphal transition (dimorphism) and it is associated with the virulence of the maize pathogen Ustilago maydis, the causative agent of smut disease in corn. Hos2 activates mating-type genes by directly binding to their gene bodies. Furthermore, Hos2 acts downstream of the nutrient-sensing cyclic AMP-Protein Kinase A pathway. We also found that another HDAC, Clr3, contributes to this regulation, possibly in cooperation with Hos2. As a whole, our data suggest that there is a direct link between changes in the environment and acetylation of nucleosomes within certain genes. We propose that histone acetylation is critical to the proper timing and induction of transcription of the genes encoding factors that coordinate changes in morphology with pathogenesis.

  11. "The Use of History of Mechanics in Teaching Motion and Force Units"

    ERIC Educational Resources Information Center

    Seker, Hayati; Welsh, Laura C.

    2006-01-01

    This paper reports a 4-month study that investigated the effectiveness of curriculum materials incorporating the history of science (HOS) on learning science, understanding the nature of science (NOS), and students' interest in science. With regards to these objectives, three different class contexts were developed with three main types of…

  12. North- and South-Bicyclo[3.1.0]Hexene Nucleosides: The Effect of Ring Planarity on Anti-HIV Activity | Center for Cancer Research

    Cancer.gov

    The picture shows the locked north (blue) and south (red) bicyclo[3.1.0]hexane nucleosides in the normal pseudorotational cycle, and the corresponding shift to a smaller cycle (nmax=7°) caused by the insertion of a double bond. The former nucleosides are inactive, while the flattening of the embedded cyclopentene ring provides active compounds against HOS cells infected with HIV.

  13. 75 FR 17207 - Electronic On-Board Recorders for Hours-of-Service Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-05

    ... Regulations (FMCSRs) to incorporate new performance standards for electronic on-board recorders (EOBRs... installation of EOBRs meeting the new performance standards. If FMCSA determines, based on HOS records reviewed... existing performance standards for on-board recording devices. The Motor Carrier Safety Act of 1984 (Pub. L...

  14. Addressing Nature of Science Core Tenets with the History of Science: An Example with Sickle-Cell Anemia & Malaria

    ERIC Educational Resources Information Center

    Howe, Erica M.

    2007-01-01

    The history of science (HOS) has proven to be a useful pedagogical tool to help students learn about what has come to be regarded as an agreed upon set of core nature of science (NOS) tenets. The following article illustrates an example of how teachers can instrumentally use the history of research on heterozygote protection in sickle-cell anemia…

  15. Effects of Cu-doped 45S5 bioactive glass on the lipid peroxidation-associated growth of human osteoblast-like cells in vitro.

    PubMed

    Milkovic, Lidija; Hoppe, Alexander; Detsch, Rainer; Boccaccini, Aldo R; Zarkovic, Neven

    2014-10-01

    Bioactive glass (BG) is a highly attractive material, exhibiting both osteoinductive and osteoconductive properties, which is known to provide a growth enhancing surface for bone cells. Previous studies have shown that lipid peroxidation and in particular generation of 4-hydroxynonenal (HNE) is involved in the growth of human osteoblast-like cells, HOS, on BG. Copper (Cu), which is an essential cofactor of several enzymes as well as a proangiogenic and an antimicrobial agent, is known to induce lipid peroxidation. Therefore, the enrichment of BG with Cu could potentially have beneficial effects on the growth of the bone cells. In this study, we investigated the effects of copper-doped 45S5 BG on the growth of HOS cells and the generation of HNE. Our results confirmed the association of HNE with the growth of HOS cells. The effects of added Cu were dose-dependent. Specifically, low concentrations (i.e., 0.1% w/w) of Cu improved viability and enhanced HOS cell growth, whereas higher Cu concentrations [i.e., 2.5% and 1% (w/w)] were cytotoxic. The observed effects of Cu concentration on cell growth correlated with the level of HNE production. Therefore, Cu containing BG may represent a useful biomaterial for research and development studies of bone regeneration.

  16. Cyclopiazonic acid is a pathogenicity factor for Aspergillus flavus and a promising target for screening germplasm for ear rot resistance

    USDA-ARS?s Scientific Manuscript database

    Aspergillus flavus, an opportunistic pathogen, contaminates maize and other key crops with carcinogenic aflatoxins (AF). Besides AF, A. flavus makes many more secondary metabolites (SMs), whose toxicity in insects or vertebrates has been studied. However, the role of SMs in the invasion of plant hos...

  17. The Patient Acceptable Symptomatic State for the Modified Harris Hip Score and Hip Outcome Score Among Patients Undergoing Surgical Treatment for Femoroacetabular Impingement.

    PubMed

    Chahal, Jaskarndip; Van Thiel, Geoffrey S; Mather, Richard C; Lee, Simon; Song, Sang Hoon; Davis, Aileen M; Salata, Michael; Nho, Shane J

    2015-08-01

    There is minimal information available on the threshold at which patients consider themselves to be well for patient-reported outcome measures used in patients treated with hip arthroscopy for femoroacetabular impingement (FAI). To determine the patient acceptable symptomatic state (PASS) for the modified Harris Hip Score (mHHS) and the Hip Outcome Score (HOS) in patients with FAI treated with arthroscopic hip surgery. Cohort study (diagnosis); Level of evidence, 2. A consecutive series of patients at a single institution with FAI who were treated with arthroscopic labral surgery, acetabular rim trimming, and femoral osteochondroplasty were eligible. The mHHS (score range, 0-100) and the HOS (score range, 0-100) were administered at baseline and at 12 months postoperatively. An external anchor question at 1 year postoperatively was utilized to determine PASS values: "Taking into account all the activities you have during your daily life, your level of pain, and also your functional impairment, do you consider that your current state is satisfactory?" There were 130 patients (mean ± SD age, 35.6 ± 11.7 years), and 42.3% were male. Based on a receiver operator curve analysis, the PASS values-at which patients considered their status to be satisfactory-at 1 year after surgery were 74 (mHHS), 87 (HOS-activities of daily living subscale), and 75 (HOS-sports subscale). The PASS threshold was not affected by baseline scores across different instruments. However, patients with higher baseline scores were more likely to achieve the PASS (odds ratios: 3.36 [mHHS], 3.83 [HOS-activities of daily living], 3.38 [HOS-sports]). Age and sex were not significantly related to the odds of achieving the PASS for the mHHS or the HOS. This is the first study to determine the PASS for 2 commonly used hip joint patient-reported outcome measures in patients undergoing surgery for FAI. The study findings can allow researchers to determine if interventions related to FAI are meaningful to

  18. Polarity, selectivity and performance of hydrophilic organic/salt-containing aqueous two-phase system on counter-current chromatography for polar compounds.

    PubMed

    Liu, Dan; Hong, Zhilai; Gao, Mingzhe; Wang, Zhixin; Gu, Ming; Zhang, Xiaozhe; Xiao, Hongbin

    2016-05-27

    The essential attributes of a solvent system for separation polar compounds on CCC are polarity, selectively and performance. Here, hydrophilic organic/salt-containing aqueous two-phase system (HO/S TPS) was evaluated as an alternative solvent system for CCC separation of polar compounds. Polarity measurements based on Rohrschneider-Snyder parameter was developed as quantitative assessing the polarity of HO/S TPS and comparing with an organic/aqueous system. All investigated 1-butanol/ethanol/saturated ammonium sulfate solution/water (BEAsWat) and 1-butanol/ethanol/saturated dipotassium hydrogen phosphate solution/water (BEDhpWat) systems with polarity values of organic phase from 4.5 to 6.8, were more polar than chloroform/methanol/water (1/1/1). The considerable water content of BEAsWat and BEDhpWat (0/1/1/1/) was 45.4 and 42.6% (w%) of hydrophilic organic phase, and 66.4 and 51.2% (w%) of salt-containing aqueous phase, respectively, closed to conventional aqueous two-phase system. Therefore, the polarity of HO/S TPS is in the middle of organic/aqueous and aqueous two-phase system. The LogKC values of twenty four polar compounds as model mixture confirmed that the polarities of HO/S TPSs were matched to that of the polar compounds and shown to be a very selective technique capable of separating positional isomers. Moreover, BEAsWat and BEDhpWat systems can be easily retained in CCC column with suitable elution mode. The hydrodynamic behavior reversion of HO/S TPS on hydrodynamic CCC was observed and was tentatively explained based on the density difference. Finally, caffeoylquinic acid isomers and dihydroxybenzoic acid isomers were successfully separated with HO/S TPS on CCC, respectively. Those results demonstrate that HO/S TPS on CCC is a performant and stable way to separate polar compounds from natural products.

  19. Rules to fly by: pigeons navigating horizontal obstacles limit steering by selecting gaps most aligned to their flight direction.

    PubMed

    Ros, Ivo G; Bhagavatula, Partha S; Lin, Huai-Ti; Biewener, Andrew A

    2017-02-06

    Flying animals must successfully contend with obstacles in their natural environments. Inspired by the robust manoeuvring abilities of flying animals, unmanned aerial systems are being developed and tested to improve flight control through cluttered environments. We previously examined steering strategies that pigeons adopt to fly through an array of vertical obstacles (VOs). Modelling VO flight guidance revealed that pigeons steer towards larger visual gaps when making fast steering decisions. In the present experiments, we recorded three-dimensional flight kinematics of pigeons as they flew through randomized arrays of horizontal obstacles (HOs). We found that pigeons still decelerated upon approach but flew faster through a denser array of HOs compared with the VO array previously tested. Pigeons exhibited limited steering and chose gaps between obstacles most aligned to their immediate flight direction, in contrast to VO navigation that favoured widest gap steering. In addition, pigeons navigated past the HOs with more variable and decreased wing stroke span and adjusted their wing stroke plane to reduce contact with the obstacles. Variability in wing extension, stroke plane and wing stroke path was greater during HO flight. Pigeons also exhibited pronounced head movements when negotiating HOs, which potentially serve a visual function. These head-bobbing-like movements were most pronounced in the horizontal (flight direction) and vertical directions, consistent with engaging motion vision mechanisms for obstacle detection. These results show that pigeons exhibit a keen kinesthetic sense of their body and wings in relation to obstacles. Together with aerodynamic flapping flight mechanics that favours vertical manoeuvring, pigeons are able to navigate HOs using simple rules, with remarkable success.

  20. Anti-inflammatory effects of sucrose-derived oligosaccharides produced by a constitutive mutant L. mesenteroides B-512FMCM dextransucrase in high fat diet-fed mice.

    PubMed

    Kang, Min-Gyung; Lee, Hee Jae; Cho, Jae-Young; Kim, Kanghwa; Yang, Soo Jin; Kim, Doman

    2016-08-26

    Oligosaccharide (OS) is used as a sugar replacement as well as an ingredient in functional foods because of its beneficial effects, mainly on reducing calorie content and promoting intestinal health. By contrast, the effects of OS on inflammation are less well investigated. The purpose of this study was to investigate the effects of sucrose-derived OS on glucose control and inflammation in high fat (HF) diet-fed mice. Male C57BL6 mice were randomly assigned to six treatment groups (n = 10-14 mice per group): 1) lean control (CON), 2) HF control, 3) HF-low sucrose (LS, 100 mg/kg/day), 4) HF-high sucrose (HS, 1000 mg/kg/day), 5) HF-low OS (LOS, 100 mg/kg/day), and 6) HF-high OS (HOS, 1000 mg/kg/day). PBS (vehicle), sucrose, and OS were administered by stomach gavage. Body weight, food intake, and markers of liver function (activities of aspartate aminotransferase and alanine aminotransferase) were not affected by the treatments. HOS treatment decreased levels of serum glucose, insulin, and homeostasis model assessment-insulin resistance compared with sucrose treatment. However, serum adiponectin levels of the HOS group were higher than those of the sucrose groups. Serum levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and fetuin-A were lower in the HOS group than in the sucrose groups. Hepatic gene expression levels of pro-inflammatory cytokines and related factors (fetuin-A, NF-κB, TLR4, TNF-alpha, and IL-6) were decreased and the levels of insulin signaling-related molecules (sirtuin 1, insulin receptor, and Akt) were increased in HOS-treated mice as compared with sucrose-treated mice. These results demonstrate that OS treatment is effective in improving glucose control and inflammation in high fat diet-fed mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Molecular cloning and expression analysis of KIN10 and cold-acclimation related genes in wild banana 'Huanxi' (Musa itinerans).

    PubMed

    Liu, Weihua; Cheng, Chunzhen; Lai, Gongti; Lin, Yuling; Lai, Zhongxiong

    2015-01-01

    Banana cultivars may experience chilling or freezing injury in some of their cultivated regions, where wild banana can still grow very well. The clarification of the cold-resistant mechanism of wild banana is vital for cold-resistant banana breeding. In this study, the central stress integrator gene KIN10 and some cold-acclimation related genes (HOS1 and ICE1s) from the cold-resistant wild banana 'Huanxi' (Musa itinerans) were cloned and their expression patterns under different temperature treatments were analyzed. Thirteen full-length cDNA transcripts including 6 KIN10s, 1 HOS1 and 6 ICE1s were successfully cloned. Quantitative real-time PCR (qRT-PCR) results showed that all these genes had the highest expression levels at the critical temperature of banana (13 °C). Under chilling temperature (4 °C), the expression level of KIN10 reduced significantly but the expression of HOS1 was still higher than that at the optimal temperature (28 °C, control). Both KIN10 and HOS1 showed the lowest expression levels at 0 °C, the expression level of ICE1, however, was higher than control. As sucrose plays role in plant cold-acclimation and in regulation of KIN10 and HOS1 bioactivities, the sucrose contents of wild banana under different temperatures were detected. Results showed that the sucrose content increased as temperature lowered. Our result suggested that KIN10 may participate in cold stress response via regulating sucrose biosynthesis, which is helpful in regulating cold acclimation pathway in wild banana.

  2. Palmitic acid in the sn-2 position of dietary triacylglycerols does not affect insulin secretion or glucose homeostasis in healthy men and women

    PubMed Central

    Filippou, A; Teng, K-T; Berry, S E; Sanders, T A B

    2014-01-01

    Background/objectives: Dietary triacylglycerols containing palmitic acid in the sn-2 position might impair insulin release and increase plasma glucose. Subjects/Methods: We used a cross-over designed feeding trial in 53 healthy Asian men and women (20–50 years) to test this hypothesis by exchanging 20% energy of palm olein (PO; control) with randomly interesterified PO (IPO) or high oleic acid sunflower oil (HOS). After a 2-week run-in period on PO, participants were fed PO, IPO and HOS for 6 week consecutively in randomly allocated sequences. Fasting (midpoint and endpoint) and postprandial blood at the endpoint following a test meal (3.54 MJ, 14 g protein, 85 g carbohydrate and 50 g fat as PO) were collected for the measurement of C-peptide, insulin, glucose, plasma glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, lipids and apolipoproteins; pre-specified primary and secondary outcomes were postprandial changes in C-peptide and plasma glucose. Results: Low density lipoprotein cholesterol was 0.3 mmol/l (95% confidence interval (95% CI)) 0.1, 0.5; P<0.001) lower on HOS than on PO or IPO as predicted, indicating good compliance to the dietary intervention. There were no significant differences (P=0.58) between diets among the 10 male and 31 female completers in the incremental area under the curve (0–2 h) for C-peptide in nmol.120 min/l: GM (95% CI) were PO 220 (196, 245), IPO 212 (190, 235) and HOS 224 (204, 244). Plasma glucose was 8% lower at 2 h on IPO vs PO and HOS (both P<0.05). Conclusion: Palmitic acid in the sn-2 position does not adversely impair insulin secretion and glucose homeostasis. PMID:25052227

  3. Validation of the sperm quality analyzer and the hypo-osmotic swelling test for frozen-thawed ram and minke whale (Balaenoptera bonarensis) spermatozoa.

    PubMed

    Fukui, Yutaka; Togawa, Morihiko; Abe, Norihito; Takano, Yuuki; Asada, Masatsugu; Okada, Aki; Iida, Kenji; Ishikawa, Hajime; Ohsumi, Seiji

    2004-02-01

    The object of the present study was to investigate the validation of the sperm quality analyzer (SQA) and the hypo-osmotic swelling (HOS) test with standard sperm analysis methods in frozen-thawed ram and minke whale spermatozoa. In rams, highly significant correlations were observed in the percentage of motile spermatozoa (P<0.01) and sperm concentration (P<0.01) between the standard and SQA methods. But, the percentage of morphologically normal spermatozoa did not significantly correlate between the standard and SQA methods. The percentages of swollen spermatozoa at 15 minutes by the HOS test were significantly correlated with the motility by the standard (P<0.05) and by the SQA (P<0.05) methods. For minke whale spermatozoa, the SVI (sperm viability index) values by the standard method were significantly (P<0.001) correlated with the sperm motility index (SMI) values by SQA. The percentage of motile spermatozoa was also significantly correlated (P<0.01) with the motility measured by SQA. Using different hypo-osmotic solutions and incubation times, the HOS test with 25, 100 and 150 mOsM did not show significant variations. Motility observed by the standard method and the percentage of swollen spermatozoa were significantly correlated (P<0.05). These results indicate that the SQA and HOS test can be utilized to assess the post-thawing motility of ram and minke whale spermatozoa, and that the SQA and HOS test values are significantly correlated in ram spermatozoa. However, sperm concentration and morphologically normal spermatozoa are not assessed accurately by SQA in minke whales.

  4. A correlation between selenium and carnitine levels with hypo-osmotic swelling test for sperm membrane in low-grade varicocele patients

    PubMed Central

    PAJOVIC, B.; DIMITROVSKI, A.; RADOJEVIC, N.; VUKOVIC, M.

    2017-01-01

    OBJECTIVE The hypo-osmotic swelling (HOS) test predicts membrane integrity by determining the ability of the sperm membrane to maintain equilibrium between the sperm cell and its environment. The aim of our study was to determine the correlation between selenium and carnitine levels in the seminal fluid with HOS test for sperm membrane in low-grade varicocele patients. PATIENTS AND METHODS Study numbered 64 examinees who suffered from low-grade varicocele and were divided into two groups, according to fertility potential and HOS test outcome. The study also included a control group of 64 healthy subjects, with no varicocele. RESULTS From the Shapiro-Wilk’s test, it is clear that carnitine distribution differs significantly from normal (0.938, p = 0.03). In distribution of selenium, Kolmogorov-Smirnov test clearly shows statistically significant deviation from the normal curve (z = 0.225, p < 0.000), likewise Shapiro-Wilk’s statistic (0.787, p < 0.000). According to the results, the second group had significantly higher levels of carnitine and selenium than the first group of examinees (p < 0.05); therefore, when we compared epididymal markers with HOS tests outcomes, we found significant differences between the two groups. There were no significant differences between second group and healthy subjects (p > 0.05). CONCLUSIONS HOS test outcome in varicocele patients is directly proportional to the carnitine and selenium levels, which could play a major role in both determining fertility parameters and in the treatment of its impairment. This result is important for sub-clinical varicocele in infertile patients with normal semen analysis, since there is no evidence of benefit from any treatment so far. PMID:26957259

  5. IMPROVEMENTS IN KNEE EXTENSION STRENGTH ARE ASSOCIATED WITH IMPROVEMENTS IN SELF-REPORTED HIP FUNCTION FOLLOWING ARTHROSCOPY FOR FEMOROACETABULAR IMPINGEMENT SYNDROME

    PubMed Central

    Ellis, Thomas J.; Amesur, Ajit K.; Hewett, Timothy E.; Di Stasi, Stephanie

    2016-01-01

    Background Recovery of strength is critical for return to sport, and is a known predictor of functional outcomes in post-surgical orthopedic populations. Muscle weakness is a known impairment in patients with femoroacetabular impingement syndrome (FAIS) but whether improvements in muscle strength after arthroscopy are associated with improved hip function is unknown. Hypothesis/Purpose To examine the relationships between changes in hip and thigh muscle strength and self-reported function in athletes undergoing arthroscopy for FAIS. Study Design Single cohort descriptive and correlational study Methods Twenty-eight athletes underwent strength testing and completed the Hip Outcome Score Activities of Daily Living (HOS-ADL) and Sports (HOS-S) subscales prior to and six months after surgery. Isokinetic knee extension and flexion strength were measured using a Biodex dynamometer at 60 °/s and 300 °/s. Isometric hip abduction strength was measured using a custom dynamometer. Changes in strength, limb symmetry, and HOS scores were assessed using paired t-tests. Spearman's rank correlations were used to examine relationships between change in involved limb strength and change in HOS scores. Results Subjects were tested an average of 32 days before and 178 days after surgery. HOS-ADL and HOS-S subscales improved by a mean of 19.0 ± 21.1 and 23.8 ± 31.9, respectively, over time (p < 0.001). Hip abduction strength did not increase over time in either limb (p ≥ 0.27). Involved limb knee flexion and extension strength did not increase significantly over time (p-values: 0.10-0.48) with the exception of knee extension at 300 °/s (p = 0.04). Uninvolved limb knee extension strength at both velocities and knee flexion strength at 60 °/s improved significantly over time (p < 0.012). Increases in knee extension strength (60 °/s) of the involved limb were significantly correlated with improvements on the HOS-ADL (r = 0.431; 0 = 0

  6. Platelet-Rich Plasma Injections With Needle Tenotomy for Gluteus Medius Tendinopathy

    PubMed Central

    Lee, James J.; Harrison, Julian R.; Boachie-Adjei, Kwadwo; Vargas, Elizabeth; Moley, Peter J.

    2016-01-01

    Background: Gluteal tendinopathy is a prevalent condition that can be associated with significant pain and disability. To date, no studies have prospectively assessed the efficacy of intratendinous platelet-rich plasma (PRP) injections as a minimally invasive treatment for gluteus medius tendinopathy. Purpose: To prospectively assess the efficacy of intratendinous PRP injections as treatment for chronic recalcitrant gluteus medius tendinopathy. Study Design: Case series; Level of evidence, 4. Methods: During the study period between July 2011 and November 2015, data were collected from the Hospital for Special Surgery Center for Hip Preservation Outcomes Registry on participants who underwent ultrasound-guided intratendinous PRP injections for recalcitrant gluteus medius tendinosis and/or partial tears of the tendon associated with moderate to severe lateral hip pain for longer than 3 months. All participants were assessed pre- and postinjection with 4 outcome measures: modified Harris Hip Score (mHHS), Hip Outcome Score–Activities of Daily Living subscale (HOS-ADL), Hip Outcome Score–Sport-Specific subscale (HOS-Sport), and the International Hip Outcome Tool–33 (iHOT-33). Demographic data, including age, sex, height, weight, body mass index, and smoking status, were also collected. Results: A total of 21 patients were included in the study, with a mean follow-up of 19.7 months (range, 12.1-32.3 months). The mean improvements from preinjection to postinjection follow-up were 56.73 to 74.17 for mHHS, 68.93 to 84.14 for HOS-ADL, 45.54 to 66.72 for HOS-Sport, and 34.06 to 66.33 for iHOT-33. All mean outcome measure improvements were clinically and statistically significant (P < .001). Length of follow-up was positively correlated with improvements in HOS-ADL (P = .021) and HOS-Sport (P = .004) scores. No adverse events were observed during or after the procedure. Conclusion: In this registry study with prospective follow-up, we found ultrasound

  7. alpha-Diimine Ligand Coordination and C H Bond Activation in the Reaction of Os3(CO)10(MeCN)2 with 6-R-2,2'-Bipyridine (where R = Et, Ph): X-ray Diffraction Structures of the Ortho-Metalated

    SciTech Connect

    Carrano, Carl J.; Wang, Xiaoping; Poola, Bhaskar; Powell, Cynthia B.; Richmond, Michael G.

    2009-01-01

    The reactivity of the labile cluster Os3(CO)10(MeCN)2 (1) with the monofunctionalized heterocyclic ligands 6-R-2,2 -bipyridine (where R = Et, Ph) has been investigated. The alkyl-substituted heterocycle 6-Et-2,2 -bipyridine reacts with 1 in refluxing CH2Cl2 to give an isomeric mixture of HOs3(CO)9(N2C12H11) due to cyclometalation of the side-chain ethyl group (2) and ortho metalation of the unsubstituted bipyridine ring (3). The solid-state structure of the latter cluster, HOs3(CO)9(N2C10H6-6-Et) (3), has unequivocally established the site of the C-H bond activation in the product. Treatment of 1 with the aryl-substituted ligand 6-Ph-2,2 -bipyridine proceeds similarly with ortho metalation at the ancillary phenyl group and the C-6 ortho site of the unsubstituted bipyridine ring, as verified by 1H NMR spectroscopy. The X-ray diffraction structure of the thermodynamically more stable bipyridine-metalated cluster HOs3(CO)9(N2C10H6-6-Ph) (5) has been determined. The course of these reactions is discussed with respect to our recent study involving the reaction of cluster 1 with the ligand 6-Me-2,2 -bipyridine. Graphical Abstract The reaction between the labile cluster Os3(CO)10(MeCN)2 (1) and the monofunctionalized heterocyclic ligand 6-Et-2,2 -bipyridine proceeds readily at room temperature to furnish an isomeric mixture of the cyclometalated and ortho-metalated hydride-bridged clusters HOs3(CO)9(N2C12H11) (2 and 3). Treatment of 1 with 6-Ph-2,2 -bipyridine also yields two distinct hydride-containing clusters that result from independent ortho-metalation paths involving the 6-phenyl substituent and unsubstituted bipyridine group. The bipyridine-derived ortho metalation attendant in the new clusters HOs3(CO)9(N2C10H6-6-Et) (3) and HOs3(CO)9(N2C10H6-6-Ph) (5) has been established by X-ray crystallography.

  8. Correlation Between Changes in Visual Analog Scale and Patient-Reported Outcome Scores and Patient Satisfaction After Hip Arthroscopic Surgery.

    PubMed

    Chandrasekaran, Sivashankar; Gui, Chengcheng; Walsh, John P; Lodhia, Parth; Suarez-Ahedo, Carlos; Domb, Benjamin G

    2017-09-01

    Improvements in pain, function, and patient satisfaction are used to evaluate the outcomes of hip arthroscopic surgery. To identify correlations between the visual analog scale (VAS) score for pain and patient satisfaction with 4 commonly used patient-reported outcome (PRO) scores to determine to what extent changes in these 2 parameters are reflected in each of the PRO scores. Cohort study (diagnosis); Level of evidence, 3. Patients undergoing hip arthroscopic surgery between February 2008 and February 2013 were assessed prospectively before surgery, at 3 months, and annually thereafter with the modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), Hip Outcome Score-sports-specific subscale (HOS-SSS), and Hip Outcome Score-activities of daily living (HOS-ADL). Patients were also assessed using a 10-point VAS for pain and queried for satisfaction at the same time points ("0" indicated no pain, and "10" indicated complete satisfaction with surgery). The VAS score and patient satisfaction were correlated with changes in the 4 PRO scores. During the study period, 1417 patients underwent hip arthroscopic surgery, of whom 1137 patients had 2-year postoperative PRO scores after primary surgery. There was a significant improvement in all PRO scores at 2-year follow-up. The mean improvements in mHHS, NAHS, HOS-ADL, and HOS-SSS scores were 16.7, 21.6, 19.7, and 22.7 points, respectively. The mean improvement in the VAS score was 2.9 points. Mean patient satisfaction at 2-year follow-up was 7.74 (of 10). There was a statistically significant correlation between the VAS and patient satisfaction scores and changes in each of the 4 PRO scores. The strength of the correlation was moderate. This study demonstrated a moderate correlation between the VAS and patient satisfaction outcomes and changes in 4 commonly used PRO scores in hip arthroscopic surgery (mHHS, HOS-ADL, HOS-SSS, and NAHS). In addition to several PRO instruments, a VAS for pain and patient satisfaction

  9. Radiolysis of rutin in aerated ethanolic solution

    NASA Astrophysics Data System (ADS)

    Deng, Wuguo; He, Yongke; Fang, Xingwang; Wu, Jilan

    1998-12-01

    Radiolysis of rutin was performed in aerated ethanolic solution. Two major radiolytic products (RP1, RP2) were isolated by HPLC, and their possible structures were deduced from their UV, IR and MS spectra, and elementary analysis as well. The G-values of RP1 and RP2 increase with increasing rutin concentration, and in all cases both of them equal the G-value of rutin consumption. The addition of rutin leads to the decrease of G(H 2O 2) but has little effect on G(CH 3CHO). Therefore the formation of RP1 and RP2 was proposed to be from further addition of HO%s rad 2 to the phenolic radical (generated from H-abstraction by HO%s rad 2) followed by fragmentation.

  10. A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome.

    PubMed

    Morine, Mikio; Kohmoto, Tomohiro; Masuda, Kiyoshi; Inagaki, Hidehito; Watanabe, Miki; Naruto, Takuya; Kurahashi, Hiroki; Maeda, Kazuhisa; Imoto, Issei

    2015-12-01

    Holt-Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and congenital heart defects and caused by numerous germline mutations of TBX5 producing preterminal stop codons. Here, we report on a novel and unusual heterozygous TBX5 microdeletion with microinsertion (microindel) mutation (c.627delinsGTGACTCAGGAAACGCTTTCCTGA), which is predicted to synthesize a truncated TBX5 protein, detected in a sporadic patient with clinical features of HOS prenatally diagnosed by ultrasonography. This uncommon and relatively large inserted sequence contains sequences derived from nearby but not adjacent templates on both sense and antisense strands, suggesting two possible models, which require no repeat sequences, causing this complex microindel through the bypass of large DNA adducts via an error-prone DNA polymerase-mediated translesion synthesis.

  11. Characterization of tissue plasminogen activator binding proteins isolated from endothelial cells and other cell types

    SciTech Connect

    Beebe, D.P.; Wood, L.L.; Moos, M. )

    1990-07-15

    Human tissue plasminogen activator (t-PA) was shown to bind specifically to human osteosarcoma cells (HOS), and human epidermoid carcinoma cells (A-431 cells). Crosslinking studies with DTSSP demonstrated high molecular weight complexes (130,000) between {sup 125}I-t-PA and cell membrane protein on human umbilical vein endothelial cells (HUVEC), HOS, and A-431 cells. A 48-65,000 molecular weight complex was demonstrated after crosslinking t-PA peptide (res. 7-20) to cells. Ligand blotting of cell lysates which had been passed over a t-PA affinity column revealed binding of t-PA to 54,000 and 95,000 molecular weight proteins. Several t-PA binding proteins were identified in immunopurified cell lysates, including tubulin beta chain, plasminogen activator inhibitor type 1 and single chain urokinase.

  12. Fluoride-Induced Oxidative and Inflammatory Stress in Osteosarcoma Cells: Does It Affect Bone Development Pathway?

    PubMed

    Gandhi, Deepa; Naoghare, Pravin K; Bafana, Amit; Kannan, Krishnamurthi; Sivanesan, Saravanadevi

    2017-01-01

    Oxidative stress is reported to negatively affect osteoblast cells. Present study reports oxidative and inflammatory signatures in fluoride-exposed human osteosarcoma (HOS) cells, and their possible association with the genes involved in osteoblastic differentiation and bone development pathways. HOS cells were challenged with sublethal concentration (8 mg/L) of sodium fluoride for 30 days and analyzed for transcriptomic expression. In total, 2632 transcripts associated with several biological processes were found to be differentially expressed. Specifically, genes involved in oxidative stress, inflammation, osteoblastic differentiation, and bone development pathways were found to be significantly altered. Variation in expression of key genes involved in the abovementioned pathways was validated through qPCR. Expression of serum amyloid A1 protein, a key regulator of stress and inflammatory pathways, was validated through western blot analysis. This study provides evidence that chronic oxidative and inflammatory stress may be associated with the fluoride-induced impediment in osteoblast differentiation and bone development.

  13. Tbx5 Buffers Inherent Left/Right Asymmetry Ensuring Symmetric Forelimb Formation

    PubMed Central

    Nishimoto, Satoko; Kucharska, Anna; Newbury-Ecob, Ruth; Logan, Malcolm P. O.

    2016-01-01

    The forelimbs and hindlimbs of vertebrates are bilaterally symmetric. The mechanisms that ensure symmetric limb formation are unknown but they can be disrupted in disease. In Holt-Oram Syndrome (HOS), caused by mutations in TBX5, affected individuals have left-biased upper/forelimb defects. We demonstrate a role for the transcription factor Tbx5 in ensuring the symmetric formation of the left and right forelimb. In our mouse model, bilateral hypomorphic levels of Tbx5 produces asymmetric forelimb defects that are consistently more severe in the left limb than the right, phenocopying the left-biased limb defects seen in HOS patients. In Tbx hypomorphic mutants maintained on an INV mutant background, with situs inversus, the laterality of defects is reversed. Our data demonstrate an early, inherent asymmetry in the left and right limb-forming regions and that threshold levels of Tbx5 are required to overcome this asymmetry to ensure symmetric forelimb formation. PMID:27992425

  14. FAME, a microprocessor based front-end analysis and modeling environment

    NASA Technical Reports Server (NTRS)

    Rosenbaum, J. D.; Kutin, E. B.

    1980-01-01

    Higher order software (HOS) is a methodology for the specification and verification of large scale, complex, real time systems. The HOS methodology was implemented as FAME (front end analysis and modeling environment), a microprocessor based system for interactively developing, analyzing, and displaying system models in a low cost user-friendly environment. The nature of the model is such that when completed it can be the basis for projection to a variety of forms such as structured design diagrams, Petri-nets, data flow diagrams, and PSL/PSA source code. The user's interface with the analyzer is easily recognized by any current user of a structured modeling approach; therefore extensive training is unnecessary. Furthermore, when all the system capabilities are used one can check on proper usage of data types, functions, and control structures thereby adding a new dimension to the design process that will lead to better and more easily verified software designs.

  15. The Software Security Problem and How to Solve It. Revision 1

    DTIC Science & Technology

    1977-07-01

    Steven Cushing DAAG29-76-C-0061 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT, PROJECT. TASK Higher Order Software, Inc. AREA & WORK UNIT...Continue on-faww, side if necemary and Identify by block number) security, protection, specification, Higher Order Software, hierarchical modelinq...of reliability. The Higher Order Software (HOS) methodology was developed as a means of guaranteeing system reliability and as such is an inherently

  16. Increased risk of nonalcoholic fatty liver disease with occupational stress in Chinese policemen

    PubMed Central

    Li, Chen; Xing, Jing-Jing; Shan, An-Qi; Leng, Ling; Liu, Jin-Chuan; Yue, Song; Yu, Hao; Chen, Xi; Tian, Feng-Shi; Tang, Nai-Jun

    2016-01-01

    Abstract Nonalcoholic fatty liver disease (NAFLD) and occupational stress have been recognized as major public health concerns. We aimed to explore whether occupational stress was associated with NAFLD in a police population. A total of 6559 male police officers were recruited for this prospective study in April 2007. Among them, 2367 eligible subjects participated in follow-up from 2008 to 2011. NAFLD was diagnosed based on standard criteria. Occupational stress was evaluated by Occupational Stress Inventory-Revised scores. The incidence of NAFLD was 31.2% in the entire police. After adjusting for traditional risk factors, moderate occupational stress (MOS), high occupational stress (HOS), and high personal strain (HPS) were risk factors (MOS: hazard ratio [HR] = 1.237, 95% confidence interval [CI] = 1.049–1.460; HOS: HR = 1.727, 95% CI = 1.405–2.124; HPS: HR = 3.602, 95% CI = 1.912–6.787); and low occupational stress (LOS) and low personal strain (LPS) were protective factors (LOS: HR = 0.366, 95% CI = 0.173–0.776; LPS: HR = 0.490, 95% CI = 0.262–0.919) for NAFLD in the entire police cohort. HOS and HPS remained robust among traffic police. HOS and HPS were independent predictors for the development of NAFLD in a Chinese police population. Additional future prospective investigations are warranted to validate our findings. PMID:27861366

  17. Matrix Metalloproteinase 1 promotes tumor formation and lung metastasis in an intratibial injection osteosarcoma mouse model.

    PubMed

    Husmann, Knut; Arlt, Matthias J E; Muff, Roman; Langsam, Bettina; Bertz, Josefine; Born, Walter; Fuchs, Bruno

    2013-02-01

    Proteolytic degradation of the extracellular matrix (ECM) is an important process during tumor invasion. Matrix Metalloproteinase 1 (MMP-1) is one of the proteases that degrade collagen type I, a major component of bone ECM. In the present study, the biological relevance of MMP-1 in osteosarcoma (OS) tumor growth and metastasis was investigated in vitro and in vivo. Human OS cells in primary culture expressed MMP-1 encoding mRNA at considerably higher levels than normal human bone cells. In addition, MMP-1 mRNA and protein expression in the highly metastatic human osteosarcoma 143-B cell line was remarkably higher than in the non-metastatic parental HOS cell line. Stable shRNA-mediated downregulation of MMP-1 in 143-B cells impaired adhesion to collagen I and anchorage-independent growth, reflected by a reduced ability to grow in soft agar. Upon intratibial injection into SCID mice, 143-B cells with shRNA-downregulated MMP-1 expression formed smaller primary tumors and significantly lower numbers of lung micro- and macrometastases than control cells. Conversely, HOS cells stably overexpressing MMP-1 showed an enhanced adhesion capability to collagen I and accelerated anchorage-independent growth compared to empty vector-transduced control cells. Furthermore, and most importantly, individual MMP-1 overexpression in HOS cells enabled the formation of osteolytic primary tumors and lung metastasis while the HOS control cells did not develop any tumors or metastases after intratibial injection. The findings of the present study reveal an important role of MMP-1 in OS primary tumor and metastasis formation to the lung, the major organ of OS metastasis. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Reactions of 2,4-hexadiyne-1,6-diol with [H2Os3(CO)9(PR3)] clusters. Cyclization of the diyne and reversible exchange of the phosphine ligands between different positions of the "Os3C3" framework.

    PubMed

    Tunik, Sergey P; Khripun, Vassily D; Haukka, Matti; Pakkanen, Tapani A

    2004-06-07

    Reactions between unsaturated [H(2)Os(3)(CO)(9)(PR(3))] clusters (PR(3)= PPh(3), P(4-CF(3)-C(6)H(4))(3), PEt(3)) and 2,4-hexadiyne-1,6-diol have been studied. It was found that the diyne ligand easily reacts with all these complexes to give [HOs(3)(CO)8(PR3)-[mu3, eta1:eta3:eta1)-(CH(3)-C-C=CH-CH=C-O)

  19. MANPRINT Methods Monograph: Aiding the Development of Manpower-Based System Evaluation

    DTIC Science & Technology

    1989-06-01

    available to time required for each task of each job. The third method links a cognitive workload model to the time required model to provide a more...comparability analysis, motion-time estimation techniques, subject matter expert estimates, or HOS modeling , compute performance times for each operator...3.3.3 The Files. . . . . . EI-134 3.3.4 The Models . ... ............... El-135 3.4 Estimated Analysis Time . ............ E1-135 El-4 MANPOWER

  20. Neoplastic transformation of human cells in vitro.

    PubMed

    Rhim, J S

    1993-01-01

    Efforts to investigate the progression of events that lead normal human cells in culture to become neoplastic in response to carcinogenic agents have been aided by the development of the suitable in vitro model systems. For initial human cell transformation studies, a flat, nontumorigenic clonal line, originally derived from a human osteosarcoma (HOS), was used. When treated with chemical carcinogens such as N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and 3-methyl-cholanthrene (3MC), the HOS cells underwent morphological alterations and acquired tumorigenic properties. These cell lines were very useful inasmuch as a non-ras cellular transforming gene, met, and an activated H-ras oncogene have been isolated from MNNG-transformed and 3MC-transformed HOS lines, respectively, by DNA transfection procedure. Alteration of p53 gene in chemically transformed HOS cell lines has recently been shown. Although carcinogens cause human cancer, normal human cells in culture have proven difficult to achieve. Neoplastic transformation of human cells in culture has recently been achieved by a stepwise fashion-immortalization and conversion of the immortalized cells to tumorigenic cells. One of the critical initial events in the progression of normal human cells to tumor cells is the escape from cellular senescence. With few exceptions, normal human cells require immortalization to provide a practical system for transformation studies. Thus, the role of carcinogenic agents in the development of human cancers is now being defined using a variety of human cells. The neoplastic transformation in human cell cultures is reviewed. In doing so, this author attempts to put into perspective the history of human cell transformation by carcinogenic agents, and to discuss the current state of the art in transformation of human cells in culture; thus providing insight into the molecular and cellular mechanisms involved in the conversion of normal cells to a neoplastic state of growth.

  1. The Vital Presence: The Generalship of Field Marshal Viscount William Slim General Officer Commanding XIV Army in the Burma Theater 1943-1945

    DTIC Science & Technology

    2013-03-25

    in theatre. Additionally, Mountbatten proposed Operation DRACULA developed by hos own staff, intended as an 23 ambitious combined airborne...amphibious assault to seize Rangoon by coup de main, then push north to link up with XIV Army fixing Japanese in Central Burma.75 DRACULA required...north of the city. It would matter little, Operation DRACULA had been revitalized as Slim’s success in Central Burma became apparent and the XXVI

  2. Quercetin Inhibits Cell Migration and Invasion in Human Osteosarcoma Cells.

    PubMed

    Lan, Haifeng; Hong, Wei; Fan, Pan; Qian, Dongyang; Zhu, Jianwei; Bai, Bo

    2017-09-21

    Osteosarcoma is a malignant tumor associated with high mortality; however, no effective therapies for the disease have been developed. Several studies have focused on elucidating the pathogenesis of osteosarcoma and have aimed to develop novel therapies for the disease. Quercetin is a vital dietary flavonoid that has been shown to have a variety of anticancer effects, as it induces cell cycle arrest, apoptosis, and differentiation and is involved in cell adhesion, metastasis and angiogenesis. Herein, we aimed to investigate the effects of quercetin on osteosarcoma migration and invasion in vitro and in vivo and to explore the molecular mechanisms underlying its effects on osteosarcoma migration and invasion. Cell viability, cell cycle activity and cell apoptosis were measured using CCK-8 assay and flow cytometry, and cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The mRNA and protein expression levels of several proteins of interest were assessed by real-time quantitative PCR and western blotting, respectively. Moreover, a nude mouse model of human osteosarcoma lung metastasis was established to assess the anti-metastatic effects of quercetin in vivo. We noted no significant differences in cell cycle activity and apoptosis between HOS and MG63 cells and control cells. Treatment with quercetin significantly attenuated cell migration and invasion in HOS and MG63 cells compared with treatment with control medium. Moreover HIF-1α, VEGF, MMP2, and MMP9 mRNA and protein expression levels were significantly downregulated in HOS cells treated with quercetin compared with HOS cells treated with controls. Additionally, treatment with quercetin attenuated metastatic lung tumor formation and growth in the nude mouse model of osteosarcoma compared with treatment with controls. Our findings regarding the inhibitory effects of quercetin on cell migration and invasion suggest that quercetin may have potential as a therapy for human

  3. An Analysis of Perturbed Quantization Steganography in the Spatial Domain

    DTIC Science & Technology

    2005-03-01

    331-336, 1996. [Bis95] C. Bishop. “ Neural Networks for Pattern Recognition ,” Oxford University Press, 1995. [Bro96] A. Brown. S-Tools...from a set of both clean and stego-images, and the data is then trained and classified using such tools as neural networks [HoS04], a fisher linear 26...IN THE SPATIAL DOMAIN Matthew D. Spisak, BS Approved: / signed

  4. Designing a Machinery Control System (MCS) Security Testbed

    DTIC Science & Technology

    2014-09-01

    other aspect of this collection of information, including suggestions for reducing this burden, to Washington headquarters Services , Directorate for...level simulator dial FLT fault GUI graphical user interface HMI human machine interface HOS human machine interface override station ISCS...encouragement, structure and basic core values you gave me have always guided me to success. I would like to thank Prof. Mark Gondree and Prof. Thuy Nguyen as

  5. HO1 mRNA and Protein do not Change in Parallel in Bronchial Biopsies of Patients After Long Term Exposure to Sulfur Mustard

    PubMed Central

    Nourani, Mohammad Reza; Yazdani, Samaneh; Roudkenar, Mehryar Habibi; Ebrahimi, Majid; Halabian, Raheleh; Mirbagheri, Leila; Ghanei, Mostafa; Fooladi, Abbas Ali Imani

    2010-01-01

    Sulfur mustard (SM), is an alkylating agent and has been emerged as a chemical weapon in various battlefields. More recently, SM was employed in the Iraq conflict against Iranian military forces and civilians. Nowadays there are more than 40,000 people suffering from pulmonary lesions special chronic obstructive pulmonary disease (COPD) due to mustard gas in Iran. SM causes the endogenous production of reactive oxygen species (ROS). Heme oxygenases (HOs) are the rate-limiting enzyme for heme metabolism. Numerous studies have confirmed that HOs are concerned in diverse biological processes such as anti-oxidation. The present study was undertaken to consider the regulation of HO-1 and HO-2 n the human airway wall, and to suggest a probable role that HOs may play in cellular defense against oxidative stress due to SM. In this research ten unexposed SM individuals and twenty SM exposed patients were included. Evaluation of HO-1& HO -2 expressions in unexposed and SM exposed patients samples was performed by semiquantitative RT-PCR, real-time RT-PCR and Immunohistochemistry analysis. While unexposed SM samples expressed same levels of HOs, expression level of HO-1 was upregulated about 3.58 ± 1.93 folds in SM exposed patients in comparison with unexposed ones, we could not find any difference in expression of HO-2 n two groups. In contrast, Immunohistochemistry results showed negative HO-1 protein expression in SM injured patients. Our results revealed that HO1 may plays an important role in cellular protection against oxidative stress due to mustard gas toxicity in airway wall of SM exposed patients at mRNA level, but translational modifications might cause decrease in the amount of HO1 protein. PMID:20981135

  6. Recent Applications of the Volterra Theory to Aeroelastic Phenomena

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.; Haji, Muhammad R; Prazenica, Richard J.

    2005-01-01

    The identification of nonlinear aeroelastic systems based on the Volterra theory of nonlinear systems is presented. Recent applications of the theory to problems in experimental aeroelasticity are reviewed. These results include the identification of aerodynamic impulse responses, the application of higher-order spectra (HOS) to wind-tunnel flutter data, and the identification of nonlinear aeroelastic phenomena from flight flutter test data of the Active Aeroelastic Wing (AAW) aircraft.

  7. Guidance for Medical Screening of Commercial Aerospace Passengers

    DTIC Science & Technology

    2006-01-01

    significant trauma • History of decompression syndrome (DCS) • Anemia or other blood disorders • Heart or circulatory disorders, including implanted ...pacemaker or defibrillator • Mental disorders • Claustrophobia • Attempted suicide • Use of medications • Alcohol or drug dependence or abuse...other admission to hos- pital • Recent significant trauma • Anemia or other blood disorders • Heart or circulatory disorders, including implanted

  8. Alpha-CaMKII plays a critical role in determining the aggressive behavior of human osteosarcoma

    PubMed Central

    Daft, Paul G.; Yuan, Kaiyu; Warram, Jason M.; Klein, Michael J.; Siegal, Gene P.; Zayzafoon, Majd

    2013-01-01

    Osteosarcoma is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in osteosarcoma treatment, more specific molecular targets are needed as potential therapeutic options. One target of interest is alpha-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation and differentiation. Here, we investigate the role of α-CaMKII in the growth and tumorigenicity of human osteosarcoma. We show that α-CaMKII is highly expressed in primary osteosarcoma tissue derived from 114 patients and is expressed in varying levels in different human osteosarcoma cell lines (HOS, MG-63, MNNG/HOS and 143B). To examine whether α-CaMKII regulates osteosarcoma tumorigenic properties, we genetically inhibited α-CaMKII in two osteosarcoma cell lines using two different α-CaMKII shRNAs delivered by lentiviral vectors and overexpressed α-CaMKII by retrovirus. The genetic deletion of α-CaMKII by shRNA in MG-63 and 143B cells resulted in decreased proliferation (50 and 41%), migration (22 and 25%) and invasion (95 and 90%), respectively. The overexpression of α-CaMKII in HOS cells resulted in increased proliferation (240%), migration (640%) and invasion (10,000%). Furthermore, α-CaMKII deletion in MG-63 cells significantly reduced tumor burden in vivo (65%), while α-CaMKII overexpression resulted in tumor formation in a previously non-tumor forming osteosarcoma cell line (HOS). Our results suggest that α-CaMKII plays a critical role in determining the aggressive phenotype of osteosarcoma, and its inhibition could be an attractive therapeutic target to combat this devastating adolescent disease. PMID:23364534

  9. PEO Soldier Simulation Roadmap: Initial Steps in Implementation

    DTIC Science & Technology

    2005-07-01

    Data Manger (EDM), AW Block 2 Helicopter Oxygen System (HOS) Laser Eye Protection (AW-LEP) Retinal Scanning Display (AW-RSD) SRU-37/P One Man Life Raft...AN/PVS-10 & Long Range SNS) Soldier Night Vision Devices (AN/PVS-7 NVG & AN/PVS-14 MNVD) STORM Micro-Laser Ranger Finder (MLRF) Target Acquisition...choice of weapon, engagement choice of optic, choice decisions of posture Engagement decision, actual target location, range, weather and terrain

  10. Management of Complex Abdominal Wall Defects Associated with Penetrating Abdominal Trauma

    DTIC Science & Technology

    2014-05-09

    management of the abdominal wall was determined by a multidisciplinary team of general and plastic surgeons, intensivists and specialist nurses . The...otomy is performed when the patient’s physiology has normalised, usually at 12–72 h after the damage control procedure. Closure of the midline... nurse specialist, microbiology, intensive care, the hos- pital medical director and the orthopaedic surgeons if there was concomitant bony or extremity

  11. Surgery in World War II. Activities of Surgical Consultants. Volume 2

    DTIC Science & Technology

    1964-01-01

    civilian hospitals, with the exception that, in military hos- l)itals, provision was not made for the use of cyclopropane and carbon dioxide absorption...provided for use of carbon dioxide absorption and cyclopropane. Personnel in anesthesia were found to 1e well trained and adequately able to make an...British sources. It was pointed out that British machines in American hospitals permitted attachment of cylinders containing pure carbon dioxide , a

  12. Radiation- and Depleted Uranium-Induced Carcinogenesis Studies: Characterization of the Carcinogenic Process and Development of Medical Countermeasures

    DTIC Science & Technology

    2005-01-01

    osteoblast cells, HOS) to evaluate the carcinogenic potential of DU in vitro by assessing morphological transformation, genotoxicity ( chromosomal aberrations...hypoxanthine reductase transferase (HPRT) assay, and chromosomal ab- erration assays, i.e., micronuclei, we have examined the carcinogenic, mutagenic, and...or chromosomal aberrations (i.e., micronuclei) [Miller 1998a, Miller 2001]. These in vitro results continue to suggest that DU has carcinogenic

  13. Visfatin triggers the in vitro migration of osteosarcoma cells via activation of NF-κB/IL-6 signals.

    PubMed

    Wang, Guang-Ji; Shen, Ning-Jiang; Cheng, Liang; Yehan Fang; Huang, Hui; Li, Kang-Hua

    2016-11-15

    Pulmonary metastasis is the major challenge for clinical treatment of osteosarcoma patients. Recent studies indicated that visfatin, a 52kDa adipocytokine, can trigger the cell motility of various cancers, while its role in the progression of osteosarcoma remains not clear. Our present study revealed that visfatin can significantly promote the in vitro migration and invasion of osteosarcoma MG-63 and HOS cells and up regulate the expression of matrix metalloproteinase-2 (MMP-2) and fibronectin (FN). Furthermore, visfatin treatment also increased the expression of IL-6 in both MG-63 and HOS cells via a time dependent manner, while anti-IL-6 antibody can significantly attenuate visfatin induced cell invasion and up regulation of MMP-2 and FN. It suggested that up regulation of IL-6 mediated visfatin induced in vitro motility of osteosarcoma cells. Visfatin treatment can increase the phosphorylation of both p65 and ERK1/2 in MG-63 and HOS cells, while only the inhibitor of NF-κB, BAY 11-7082, can abolish visfatin induced up regulation of IL-6. BAY 11-7082 also attenuated visfatin induced upregulation of MMP-2 and FN in MG-63 cells. Western blot analysis revealed that visfatin treatment can significantly increase the phosphorylation of IκBα and IKKβ in MG-63 cells. ACHP, the inhibitor of IKK-β, blocked visfatin induced expression of IL-6 mRNA in both MG-63 and HOS cells. Collectively, our data suggested that visfatin can increase the motility of osteosarcoma cells via up regulation of NF-κB/IL-6 signals. It indicated that visfatin might be a potential therapeutic target of osteosarcoma treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Morphologic characterization of osteosarcoma growth on the chick chorioallantoic membrane

    PubMed Central

    2010-01-01

    Background The chick chorio-allantoic membrane (CAM) assay is a commonly used method for studying angiogenic or anti-angiogenic activities in vivo. The ease of access allows direct monitoring of tumour growth by biomicroscopy and the possibility to screen many samples in an inexpensive way. The CAM model provides a powerful tool to study effects of molecules, which interfere with physiological angiogenesis, or experimental tumours derived from cancer cell lines. We therefore screened eight osteosarcoma cell lines for their ability to form vascularized tumours on the CAM. Findings We implanted 3-5 million cells of human osteosarcoma lines (HOS, MG63, MNNG-HOS, OST, SAOS, SJSA1, U2OS, ZK58) on the CAM at day 10 of embryonic development. Tumour growth was monitored by in vivo biomicroscopy at different time points and tumours were fixed in paraformaldehyde seven days after cell grafting. The tissue was observed, photographed and selected cases were further analyzed using standard histology. From the eight cell lines the MNNG-HOS, U2OS and SAOS were able to form solid tumours when grafted on the CAM. The MNNG-HOS tumours showed the most reliable and consistent growth and were able to penetrate the chorionic epithelium, grow in the CAM stroma and induce a strong angiogenic response. Conclusions Our results show that the CAM assay is a useful tool for studying osteosarcoma growth. The model provides an excellent alternative to current rodent models and could serve as a preclinical screening assay for anticancer molecules. It might increase the speed and efficacy of the development of new drugs for the treatment of osteosarcoma. PMID:20202196

  15. Technical decision making with higher order structure data: impact of a formulation change on the higher order structure and stability of a mAb.

    PubMed

    Gruia, Flaviu; Du, Jiali; Santacroce, Paul V; Remmele, Richard L; Bee, Jared S

    2015-04-01

    Changes in formulation may be required during the development of protein therapeutics. Some of the changes may alter the protein higher order structure (HOS). In this note, we show how the change from a trehalose-based formulation to an arginine-based formulation concomitantly impacted the tertiary structure and the thermal stability of a mAb (mAb1). The secondary structure was not disrupted by the formulation change. The destabilization of the tertiary structure did not affect the long-term stability or the bioactivity of mAb1. This indicates that loss of conformational stability was likely compensated by improvements in the colloidal stability of mAb1 in the arginine-based formulation. The formulation-induced changes in HOS were reversible as proven by measurements after dilution in a common buffer (phosphate-buffered saline). For aggregation driven by assembly of aggregates (colloidally limited), small changes in conformational structure and stability as measured by HOS methods may not necessarily be predictive of long-term stability. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Nobiletin inhibits human osteosarcoma cells metastasis by blocking ERK and JNK-mediated MMPs expression.

    PubMed

    Cheng, Hsin-Lin; Hsieh, Ming-Ju; Yang, Jia-Sin; Lin, Chiao-Wen; Lue, Ko-Haung; Lu, Ko-Hsiu; Yang, Shun-Fa

    2016-06-07

    Nobiletin, a polymethoxyflavone, has a few pharmacological activities, including anti-inflammation and anti-cancer effects. However, its effect on human osteosarcoma progression remains uninvestigated. Therefore, we examined the effectiveness of nobiletin against cellular metastasis of human osteosarcoma and the underlying mechanisms. Nobiletin, up to 100 μM without cytotoxicity, significantly decreased motility, migration and invasion as well as enzymatic activities, protein levels and mRNA expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in U2OS and HOS cells. In addition to inhibition of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), the inhibitory effect of nobiletin on the DNA-binding activity of the transcription factor nuclear factor-kappa B (NF-κB), cAMP response element-binding protein (CREB), and specificity protein 1 (SP-1) in U2OS and HOS cells. Co-treatment with ERK and JNK inhibitors and nobiletin further reduced U2OS cells migration and invasion. These results indicated that nobiletin inhibits human osteosarcoma U2OS and HOS cells motility, migration and invasion by down-regulating MMP-2 and MMP-9 expressions via ERK and JNK pathways and through the inactivation of downstream NF-κB, CREB, and SP-1. Nobiletin has the potential to serve as an anti-metastatic agent for treating osteosarcoma.

  17. Nobiletin inhibits human osteosarcoma cells metastasis by blocking ERK and JNK-mediated MMPs expression

    PubMed Central

    Cheng, Hsin-Lin; Hsieh, Ming-Ju; Yang, Jia-Sin; Lin, Chiao-Wen; Lue, Ko-Haung; Lu, Ko-Hsiu; Yang, Shun-Fa

    2016-01-01

    Nobiletin, a polymethoxyflavone, has a few pharmacological activities, including anti-inflammation and anti-cancer effects. However, its effect on human osteosarcoma progression remains uninvestigated. Therefore, we examined the effectiveness of nobiletin against cellular metastasis of human osteosarcoma and the underlying mechanisms. Nobiletin, up to 100 μM without cytotoxicity, significantly decreased motility, migration and invasion as well as enzymatic activities, protein levels and mRNA expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in U2OS and HOS cells. In addition to inhibition of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), the inhibitory effect of nobiletin on the DNA-binding activity of the transcription factor nuclear factor-kappa B (NF-κB), cAMP response element-binding protein (CREB), and specificity protein 1 (SP-1) in U2OS and HOS cells. Co-treatment with ERK and JNK inhibitors and nobiletin further reduced U2OS cells migration and invasion. These results indicated that nobiletin inhibits human osteosarcoma U2OS and HOS cells motility, migration and invasion by down-regulating MMP-2 and MMP-9 expressions via ERK and JNK pathways and through the inactivation of downstream NF-κB, CREB, and SP-1. Nobiletin has the potential to serve as an anti-metastatic agent for treating osteosarcoma. PMID:27144433

  18. Improvement of liquid and frozen-thawed semen quality of Nili-Ravi buffalo bulls (Bubalus bubalis) through supplementation of fat.

    PubMed

    Adeel, M; Ijaz, A; Aleem, M; Rehman, H; Yousaf, M S; Jabbar, M A

    2009-05-01

    The aim of the study was to investigate the effects of dietary fat on quality of liquid and frozen-thawed semen of Nili-Ravi buffalo bulls. Adult bulls (n=21) were fed a balanced ration (Con; n=7) or the same ration either containing sunflower oil (SF-O; n=7) or whole sunflower seeds (SF-S; n=7) for 63 days. Body weight and body condition score of each bull was recorded on days 0, 30 and 60 of the experiment. Semen was collected on days 39, 46, 53 and 60, frozen by a fast method and stored at -196 degrees C for 24h. Sperm motility was assessed using a bright field microscope. Plasma membrane integrity of fresh and frozen-thawed spermatozoa was assessed using a hypo-osmotic swelling (HOS) assay. The concentration of spermatozoa and volume of semen was not different among groups on various days of collection. Sunflower-enriched diets did not affect the motility and number of HOS-positive spermatozoa in the fresh semen. Motility and HOS of post-thawed spermatozoa were higher (p<0.05) in bulls fed the sunflower-enriched diets. Similarly, diets did not affect the body condition score and body weight of bulls. In conclusion, feeding of sunflower oil or sunflower seed as fat sources can improve the quality of buffalo bull spermatozoa.

  19. Osteoprotegerin regulates cancer cell migration through SDF-1/CXCR4 axis and promotes tumour development by increasing neovascularization.

    PubMed

    Benslimane-Ahmim, Zahia; Pereira, Jessica; Lokajczyk, Anna; Dizier, Blandine; Galy-Fauroux, Isabelle; Fischer, Anne-Marie; Heymann, Dominique; Boisson-Vidal, Catherine

    2017-06-01

    We previously reported that OPG is involved in ischemic tissue neovascularization through the secretion of SDF-1 by pretreated-OPG endothelial colony-forming cells (ECFCs). As the vascularization is one of the key factor influencing the tumour growth and cancer cell dissemination, we investigated whether OPG was able to modulate the invasion of human MNNG-HOS osteosarcoma and DU145 prostate cancer cell lines in vitro and in vivo. Cell motility was analysed in vitro by using Boyden chambers. Human GFP-labelled MMNG-HOS cells were inoculated in immunodeficient mice and the tumour nodules formed were then injected with OPG and/or FGF-2, AMD3100 or 0.9% NaCl (control group). Tumour growth was manually followed and angiogenesis was assessed by immunohistochemistry. In vitro, SDF-1 released by OPG-pretreated ECFCs markedly attracted both MNNG-HOS and DU145 cells and induced spontaneous migration of cancer cells. In vivo, tumour volumes were significantly increased in OPG-treated group compared to the control group and OPG potentiated the effect of FGF-2. Concomitantly, OPG alone or combined with FGF-2 increased the number of new vasculature compared to the control group. Interestingly AMD3100, an inhibitor of SDF-1, prevented the in vivo effects of OPG induced by SDF-1 This study provides experimental evidence that OPG promotes tumour development trough SDF-1/CXCR4 axis.

  20. Updated U.S. population standard for the Veterans RAND 12-item Health Survey (VR-12).

    PubMed

    Selim, Alfredo J; Rogers, William; Fleishman, John A; Qian, Shirley X; Fincke, Benjamin G; Rothendler, James A; Kazis, Lewis E

    2009-02-01

    The purpose of this project was to develop an updated U.S. population standard for the Veterans RAND 12-item Health Survey (VR-12). We used a well-defined and nationally representative sample of the U.S. population from 52,425 responses to the Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002. We applied modified regression estimates to update the non-proprietary 1990 scoring algorithms. We applied the updated standard to the Medicare Health Outcomes Survey (HOS) to compute the VR-12 physical (PCS((MEPS standard))) and mental (MCS((MEPS standard))) component summaries based on the MEPS. We compared these scores to PCS and MCS based on the 1990 U.S. population standard. Using the updated U.S. population standard, the average VR-12 PCS((MEPS standard)) and MCS((MEPS standard)) scores in the Medicare HOS were 39.82 (standard deviation [SD] = 12.2) and 50.08 (SD = 11.4), respectively. For the same Medicare HOS, the average PCS and MCS scores based on the 1990 standard were 1.40 points higher and 0.99 points lower in comparison to VR-12 PCS and MCS, respectively. Changes in the U.S. population between 1990 and today make the old standard obsolete for the VR-12, so the updated standard developed here is widely available to serve as such a contemporary standard for future applications for health-related quality of life (HRQoL) assessments.

  1. Exponential integrators for a Markov chain model of the fast sodium channel of cardiomyocytes.

    PubMed

    Starý, Tomás; Biktashev, Vadim N

    2015-04-01

    The modern Markov chain models of ionic channels in excitable membranes are numerically stiff. The popular numerical methods for these models require very small time steps to ensure stability. Our objective is to formulate and test two methods addressing this issue, so that the timestep can be chosen based on accuracy rather than stability. Both proposed methods extend Rush-Larsen technique, which was originally developed to Hogdkin-Huxley type gate models. One method, "matrix Rush-Larsen" (MRL) uses a matrix reformulation of the Rush-Larsen scheme, where the matrix exponentials are calculated using precomputed tables of eigenvalues and eigenvectors. The other, "hybrid operator splitting" (HOS) method exploits asymptotic properties of a particular Markov chain model, allowing explicit analytical expressions for the substeps. We test both methods on the Clancy and Rudy (2002) I(Na)Markov chain model. With precomputed tables for functions of the transmembrane voltage, both methods are comparable to the forward Euler method in accuracy and computational cost, but allow longer time steps without numerical instability. We conclude that both methods are of practical interest. MRL requires more computations than HOS, but is formulated in general terms which can be readily extended to other Markov chain channel models, whereas the utility of HOS depends on the asymptotic properties of a particular model. The significance of the methods is that they allow a considerable speed-up of large-scale computations of cardiac excitation models by increasing the time step, while maintaining acceptable accuracy and preserving numerical stability.

  2. A pilot study to determine whether health care professionals perceive stigma in heterozygote carrier identification and disclosure decisions.

    PubMed

    Moffett, Alexander; Ross, Lainie Friedman

    2011-08-01

    We conducted an empirical pilot study to assess the attitudes of health care professionals (HCPs) to the personal identification of heterozygote carrier status for two autosomal recessive conditions (cystic fibrosis and a hemoglobinopathy) and for an X-linked disorder (Duchenne muscular dystrophy) using the Health Orientation Scale (HOS) and a modified HIV Stigma Scale. Attitudes towards carrier identification of children were also assessed. Three hundred and ten of 742 (42%) eligible HCPs fully or partly completed the survey. As measured with the HOS and the modified HIV scale, respondents had a more negative reaction to the hypothetical discovery of being a carrier for an autosomal recessive genetic condition that was less likely given their self-identified ancestry. Female respondents had a more negative reaction on both scales to being a carrier for an X-linked disorder than men thought their partners would feel. However, the differences found on the HOS and modified HIV scale are small and their clinical relevance unknown. Fifty-seven percent of respondents agreed that parents should tell their children to keep their carrier status private with many (44%) agreeing that children who learn that they are carriers may suffer from a decrease in self-esteem. The vast majority of respondents would inform immediate family members and HCPs of their carrier status, but would be unlikely to share this information with neighbors or employers. Further study is needed to develop a heterozygote genetic carrier stigma scale.

  3. Hematopoiesis toxicity induced by 4-methylumbelliferon determined in an invertebrate model organism.

    PubMed

    Fang, Yan; He, Yue; Wang, Hua; Yan, Siqi; Xing, Rui; Yin, Weimin; Sima, Yanghu; Xu, Shiqing

    2016-01-01

    Umbelliferone has potential value as it has an inhibitory effect on tumor cells; however, its impact on an animal's circulatory system and hematopoietic function has not been reported. In this study, 4-methylumbelliferon (4-MU), an umbelliferone derivative, was used as a model drug, and its potential toxicity on hemocytes and hematopoietic organs (HOs) was investigated using an invertebrate animal model, the silkworm, Bombyx mori. The results showed that the level of reactive oxygen species in HOs increased when larvae (third day of the fifth instar) were orally exposed to 4 mM 4-MU for 8 min, followed by the induction of improved antioxidative metabolism of coenzymes in hemolymph. Exposure to 4-MU also significantly upregulated the expression levels of several genes in the hemolymph and fat body (a detoxification tissue similar to the liver in mammals) including antimicrobial peptide gene cecropinA and moricin, and a phagocytosis-related gene, tetraspanin E, suggesting an increased antioxidant level and antimicrobial ability of the circulatory system. However, the percentage of dead hemocytes increased and hematopoiesis significantly decreased in HOs, indicating the toxic effect of 4-MU on hemocytes and hematopoiesis, despite it inducing enhanced antioxidant and antimicrobial activity in the circulatory system.

  4. Object representation for multi-beam sonar image using local higher-order statistics

    NASA Astrophysics Data System (ADS)

    Li, Haisen; Gao, Jue; Du, Weidong; Zhou, Tian; Xu, Chao; Chen, Baowei

    2017-01-01

    Multi-beam sonar imaging has been widely used in various underwater tasks such as object recognition and object tracking. Problems remain, however, when the sonar images are characterized by low signal-to-noise ratio, low resolution, and amplitude alterations due to viewpoint changes. This paper investigates the capacity of local higher-order statistics (HOS) to represent objects in multi-beam sonar images. The Weibull distribution has been used for modeling the background of the image. Local HOS involving skewness is estimated using a sliding computational window, thus generating the local skewness image of which a square structure is associated with a potential object. The ability of object representation with different signal-to-noise ratio (SNR) between object and background is analyzed, and the choice of the computational window size is discussed. In the case of the object with high SNR, a novel algorithm based on background estimation is proposed to reduce side lobe and retain object regions. The performance of object representation has been evaluated using real data that provided encouraging results in the case of the object with low amplitude, high side lobes, or large fluctuant amplitude. In conclusion, local HOS provides more reliable and stable information relating to the potential object and improves the object representation in multi-beam sonar image.

  5. Pericellular matrix formation alters the efficiency of intracellular uptake of oligonucleotides in osteosarcoma cells.

    PubMed

    Suzuki, Yoshitaka; Nishida, Yoshihiro; Naruse, Takahiro; Gemba, Takefumi; Ishiguro, Naoki

    2009-03-01

    One of the crucial roles of tumor extracellular matrix is to act as a barrier to drug delivery. In this study, we analyzed the relationship between the formation of tumor extracellular matrix and the efficiency of intracellular uptake of oligonucleotides in human osteosarcoma cell lines, HOS, and MG-63. Oligonucleotides used in this study were nuclear factor-kappa B (NF-kappaB) decoy, which might be a therapeutic tool for neoplasms. Pericellular matrix formation was examined by particle exclusion assay. Cellular uptake of fluorescein isothiocyanate-labeled NF-kappaB decoy was evaluated by fluorescent microscopy and flow cytometry. Effects of NF-kappaB decoy on cell viability and cell cycle arrest in MG-63 cells were determined by MTT assay and flow cytometry, respectively. MG-63 cells exhibited abundant pericellular matrix with time compared with HOS cells. Uptake of fluorescein isothiocyanate-labeled NF-kappaB decoy decreased in MG-63 cells with time but not in HOS cells in both monolayer and three-dimensional culture using matrigel. However, after enzymatic removal of pericellular matrix, the uptake markedly recovered in MG-63 cells. NF-kappaB decoy inhibited cell proliferation and induced G0/G1 cell cycle arrest in MG-63 cells. These results suggest that abundant pericellular matrix might disturb the uptake of NF-kappaB decoy, and modification of pericellular matrix composition would increase the efficacy of exogenous oligonucleotides treatment for neoplasms.

  6. Percutaneous absorption of 3,3',4,4'-tetrachlorobiphenyl (PCB 77) from soil.

    PubMed

    Roy, Timothy A; Hammerstrom, Karen; Schaum, John

    2009-01-01

    Six dermal absorption experiments (one in vivo, five in vitro) were conducted using 3,3',4,4'-tetrachlorobiphenyl (TCB) either neat at 141 microg/cm2 or sorbed on a low organic (LOS) or high organic (HOS) soil at 6-10 microg/cm2. All soil experiments were conducted at 1000 ppm and soil loads of 6-10 mg soil/cm(2). After 96 h the percentage of applied dose absorbed (PADA) for TCB sorbed on LOS was 49.7 (rat, in vivo), 31.9 (rat, in vitro), and 7.4 (human, in vitro). The 96-h PADA for TCB sorbed on HOS was 9.6% (rat, in vitro). Generally, rat skin was observed to be four- to ninefold more permeable to TCB than human skin (in vitro). At steady state, the dermal flux of TCB on LOS at 1000 ppm and on HOS at 1000 ppm (both in vitro, rat) was 33 and 10 ng/cm2/h, respectively (ratio = 3.3).

  7. Can today's house officers teach effectively? An assessment in undergraduate emergency training.

    PubMed

    Iblher, Peter; Zupanic, Michaela; Karsten, Jan; Brauer, Kirk

    2015-06-01

    Previous publications describe house officers (HOs) as unaware of their ineffective teaching skills. The aim of this study was to evaluate the role of teaching seniority in the comparison of teaching skills between HOs and faculty. Ten HOs (F: n=4, M: n=6, age: 35.1±6.8 years) and nine faculty (F: n=3, M: n=6, age: 41.4±4.9 years) who actively teach undergraduate emergency medicine were immediately evaluated at the end of the course by their students using the questionnaire SFDP26. The questionnaire consists of one item on 'overall teaching effectiveness' (OTE) (1=very poor to 5=excellent) and 25 items measured on a five-point Likert scale (1-5=strongly disagree to strongly agree) divided into seven subscales: 1, 'establishing the learning climate' (LC); 2, 'control of session' (CS); 3, 'communication of goals' (CG); 4, 'facilitating understanding and retention' (UR); 5, 'evaluation' (E); 6, 'feedback' (FB) and 7, 'promoting self-directed learning' (SL). The sample included 173 medical students in their third year of training who were randomly assigned to the instructors. A Mann-Whitney U-test was used to calculate group-related differences (resident vs. teaching faculty). For significant differences, effect size was calculated (r=Z/√N). No sex-related differences were found. Significantly better ratings for HOs were found in subscales: 1, 'LC' (P=0.001; r=0.20); 2, 'CS' (P=0.037; r=0.15); 5, 'E' (P=0.007; r=0.20); 6, 'FB' (P=0.001; r=0.23); 7, 'SL' (P=0.004; r=0.24) and 'OTE' (P=0.027; r=0.26). From a learner's perspective, the quality of teaching provided by HOs was rated at least similar and mostly better overall than that provided by faculty. These findings contradict results from previous studies on the quality of HO teaching and therefore warrant further assessment.

  8. Emotion classification in Parkinson's disease by higher-order spectra and power spectrum features using EEG signals: a comparative study.

    PubMed

    Yuvaraj, R; Murugappan, M; Ibrahim, Norlinah Mohamed; Omar, Mohd Iqbal; Sundaraj, Kenneth; Mohamad, Khairiyah; Palaniappan, R; Satiyan, M

    2014-03-01

    Deficits in the ability to process emotions characterize several neuropsychiatric disorders and are traits of Parkinson's disease (PD), and there is need for a method of quantifying emotion, which is currently performed by clinical diagnosis. Electroencephalogram (EEG) signals, being an activity of central nervous system (CNS), can reflect the underlying true emotional state of a person. This study applied machine-learning algorithms to categorize EEG emotional states in PD patients that would classify six basic emotions (happiness and sadness, fear, anger, surprise and disgust) in comparison with healthy controls (HC). Emotional EEG data were recorded from 20 PD patients and 20 healthy age-, education level- and sex-matched controls using multimodal (audio-visual) stimuli. The use of nonlinear features motivated by the higher-order spectra (HOS) has been reported to be a promising approach to classify the emotional states. In this work, we made the comparative study of the performance of k-nearest neighbor (kNN) and support vector machine (SVM) classifiers using the features derived from HOS and from the power spectrum. Analysis of variance (ANOVA) showed that power spectrum and HOS based features were statistically significant among the six emotional states (p < 0.0001). Classification results shows that using the selected HOS based features instead of power spectrum based features provided comparatively better accuracy for all the six classes with an overall accuracy of 70.10% ± 2.83% and 77.29% ± 1.73% for PD patients and HC in beta (13-30 Hz) band using SVM classifier. Besides, PD patients achieved less accuracy in the processing of negative emotions (sadness, fear, anger and disgust) than in processing of positive emotions (happiness, surprise) compared with HC. These results demonstrate the effectiveness of applying machine learning techniques to the classification of emotional states in PD patients in a user independent manner using EEG signals. The

  9. Clinical Outcomes Comparing Capsular Repair vs. No Repair Following Hip Arthroscopy: A Prospective, Randomized, Control Study

    PubMed Central

    Sugarman, Etan P.; Birns, Michael E.; Fishman, Matthew; Patel, Deepan N.; Goldsmith, Laura; Greene, Renee Shirley; Banffy, Michael B.

    2017-01-01

    Objectives: As hip arthroscopy procedures become more common there is increasing concern of iatrogenic instability from excessive capsulotomy during surgery. As a result, greater attention is being focused preserving hip capsule integrity following surgery. To date, there are no large scale prospective blinded studies that address whether capsular closure has any detrimental effect on outcomes. Our goal is to evaluate outcomes in patients undergoing interportal capsulotomy repair compared to outcomes when not repairing the capsule. The purpose of this study is to demonstrate a clinical/functional difference at 1 & 2 year follow up between patients who undergo capsular repair vs no repair following hip arthroscopy. Our hypothesis is that restoration of normal capsular anatomy with interportal repair will achieve similar clinical outcomes as the “no repair” group without functional deficits from over-constraint. Methods: Adult patients were recruited from November 2013 to July 2015 who were scheduled to undergo hip arthroscopy for femoral acetabular. Subjects were randomized into either the capsular repair (CR) or no repair (NR) groups. Standard AP/Dunn view radiographs were evaluated and alpha angle (AA) /center-edge (CEA) angle measurements were performed for all patients preoperatively. All patients underwent standard hip arthroscopy with labral repair +/- CAM/pincer lesion resection. Primary clinical outcomes were measured via the Hip Outcome Score Activities of Daily Living (HOS-ADL) and Sport-Specific (HOS-SS) subscales at 3 months, 6 months and 1 year. Secondary outcome measures included the modified Harris Hip Score (mHHS), visual analog scale (VAS), the international hip outcome tool (iHOT-12), and the Veterans RAND 12 Item Health Survey (VR-12) scores. Results: A total of 56 patients were included in this study (30 male, 26 females) with a mean age of 33 years. Follow up was available for 49 patients at 6 months, 41 patients at 1 year and 26 patients at

  10. TRPV4 partially participates in proliferation of human brain capillary endothelial cells.

    PubMed

    Hatano, Noriyuki; Suzuki, Hiroka; Itoh, Yuka; Muraki, Katsuhiko

    2013-03-12

    The vanilloid type 4 transient receptor potential channel (TRPV4) is a potential environmental sensor to multiple stimuli in many types of cells. In this study, we show that TRPV4 activated by 4α-phorbol 12,13-didecanoate (4αPDD) and hypo-osmotic stimulation (HOS) is a regulator of intracellular calcium ([Ca(2+)](i)) in human brain capillary endothelial cells (HBCEs), and its activation can partially regulate cell proliferation of HBCEs. The expression of TRPV4 in HBCEs was analyzed at the mRNA and protein levels. The function of TRPV4 in HBCEs was evaluated using a TRPV4 agonist, 4αPDD, and HOS while measuring [Ca(2+)](i) and membrane currents. Analysis of the mRNA transcripts of the TRPV subfamily revealed that TRPV2 and TRPV4 were expressed in HBCEs. Immunoreactivity to the TRPV4 protein was also detected in HBCEs, which were positively stained by von Willebrand factor and CD31. When 4αPDD was applied, [Ca(2+)](i) in HBCEs was elevated in a concentration-dependent manner. In addition, exposure of HBCEs to HOS at 228mOsm induced an elevation of [Ca(2+)](i). Application of 4αPDD also activated non-selective cation currents (NSCCs). Pretreatment of HBCEs with short interference RNA targeting TRPV4 (siRNA) significantly reduced the 4αPDD-induced elevation of [Ca(2+)](i). When HBCEs were treated for 24h with concentrations of 4αPDD between 0.3 and 3 μM, the cell proliferation was potentiated in a concentration-dependent manner. The potentiation was partially inhibited in HBCEs treated with siRNA. These data suggest that endogenous TRPV4, which functions as a regulator of [Ca(2+)](i) in HBCEs, partially controls cell proliferation. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Nondisease genetic testing: reporting of muscle SNPs shows effects on self-concept and health orientation scales.

    PubMed

    Gordon, Erynn S; Gordish-Dressman, Heather A; Devaney, Joseph; Clarkson, Priscilla; Thompson, Paul; Gordon, Paul; Pescatello, Linda S; Hubal, Monica J; Pistilli, Emidio E; Gianetti, Gary; Kelsey, Bethany; Hoffman, Eric P

    2005-09-01

    The purpose of this study was to assess the impact of genetic self-knowledge (nondisease genotype information) on individual self-concept and Health Orientation Scale (HOS). Adult volunteers (n=257) were recruited from an ongoing genetic association study identifying muscle quantitative trait loci (QTLs). Participants completed psychosocial assessments before and after 12 weeks of resistance training of the nondominant arm. At study exit, a genetic counselor informed participants of genetic test results on three to four genes that have an association with muscle-related traits, and counseled subjects on the potential significance of these findings. The second psychosocial assessment was performed immediately following this counseling session. The Tennessee Self-Concept Scale v.2 (TSCS:2) and the HOS showed female subjects to have a significantly greater positive change between first and second assessments, relative to male subjects. Most self-concept subscales improved significantly, when 'neutral' genotypes (no anticipated beneficial or deleterious impact) were reported, compared to positive genotypes. TSCS:2 subscales showing improvement included: total (P=0.013); physical (P=0.004); satisfaction (P=0.019); and behavioral (P=0.047). HOS subscales showing improvement included health image concern (P=0.006); and health expectations (P=0.047). In conclusion, these results suggest that genetic self-knowledge affects self-concept, consistent with the 'attribution' theory. Individuals who received neutral genetic information attributed positive changes from the exercise program to their own abilities, while those who received positive information were more likely to attribute positive changes to their genetics. This study is limited by the ability to determine the direction of the impact of nondisease genetic information presented to participants.

  12. Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

    PubMed

    Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

    2016-03-01

    Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

  13. Changes in soil bacterial community triggered by drought-induced gap succession preceded changes in soil C stocks and quality

    PubMed Central

    Yuste, Jorge Curiel; Barba, Josep; Fernandez-Gonzalez, Antonio José; Fernandez-Lopez, Manuel; Mattana, Stefania; Martinez-Vilalta, Jordi; Nolis, Pau; Lloret, Francisco

    2012-01-01

    The aim of this study was to understand how drought-induced tree mortality and subsequent secondary succession would affect soil bacterial taxonomic composition as well as soil organic matter (SOM) quantity and quality in a mixed Mediterranean forest where the Scots pine (Pinus sylvestris) population, affected by climatic drought-induced die-off, is being replaced by Holm-oaks (HO; Quercus ilex). We apply a high throughput DNA pyrosequencing technique and 13C solid-state Nuclear Magnetic Resonance (CP-MAS 13C NMR) to soils within areas of influence (defined as an surface with 2-m radius around the trunk) of different trees: healthy and affected (defoliated) pines, pines that died a decade ago and healthy HOs. Soil respiration was also measured in the same spots during a spring campaign using a static close-chamber method (soda lime). A decade after death, and before aerial colonization by the more competitive HOs have even taken place, we could not find changes in soil C pools (quantity and/or quality) associated with tree mortality and secondary succession. Unlike C pools, bacterial diversity and community structure were strongly determined by tree mortality. Convergence between the most abundant taxa of soil bacterial communities under dead pines and colonizer trees (HOs) further suggests that physical gap colonization was occurring below-ground before above-ground colonization was taken place. Significantly higher soil respiration rates under dead trees, together with higher bacterial diversity and anomalously high representation of bacteria commonly associated with copiotrophic environments (r-strategic bacteria) further gives indications of how drought-induced tree mortality and secondary succession were influencing the structure of microbial communities and the metabolic activity of soils. PMID:23301169

  14. Role of Naturally Occurring Basic Amino Acid Substitutions in the Human Immunodeficiency Virus Type 1 Subtype E Envelope V3 Loop on Viral Coreceptor Usage and Cell Tropism

    PubMed Central

    Kato, Kayoko; Sato, Hironori; Takebe, Yutaka

    1999-01-01

    To assess the role of naturally occurring basic amino acid substitutions in the V3 loop of human immunodeficiency virus type 1 (HIV-1) subtype E on viral coreceptor usage and cell tropism, we have constructed a panel of chimeric viruses with mutant V3 loops of HIV-1 subtype E in the genetic background of HIV-1LAI. The arginine substitutions naturally occurring at positions 8, 11, and 18 of the V3 loop in an HIV-1 subtype E X4 strain were systematically introduced into that of an R5 strain to generate a series of V3 loop mutant chimera. These chimeric viruses were employed in virus infectivity assays using HOS-CD4 cells expressing either CCR5 or CXCR4, peripheral blood mononuclear cells, T-cell lines, or macrophages. The arginine substitution at position 11 of the V3 loop uniformly caused the loss of infectivity in HOS-CD4-CCR5 cells, indicating that position 11 is critical for utilization of CCR5. CXCR4 usage was conferred by a minimum of two arginine substitutions, regardless of combination, whereas arginine substitutions at position 8 and 11 were required for T-cell line tropism. Nonetheless, macrophage tropism was not conferred by the V3 loop of subtype E R5 strain per se. We found that the specific combinations of amino acid changes in HIV-1 subtype E env V3 loop are critical for determining viral coreceptor usage and cell tropism. However, the ability to infect HOS-CD4 cells through either CXCR4 or CCR5 is not necessarily correlated with T-cell or macrophage tropism, suggesting that cellular tropism is not dictated solely by viral coreceptor utilization. PMID:10364300

  15. Observation of radiation-specific damage in human cells exposed to depleted uranium: dicentric frequency and neoplastic transformation as endpoints.

    PubMed

    Miller, A C; Xu, J; Stewart, M; Brooks, K; Hodge, S; Shi, L; Page, N; McClain, D

    2002-01-01

    Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalised human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. DU possesses both a radiological (alpha-particle) and chemical (metal) component. Since DU has a low specific activity in comparison to natural uranium, it is not considered to be a significant radiological hazard. The potential contribution of radiation to DU-induced biological effects is unknown and the involvement of radiation in DU-induced biological effects could have significant implications for current risk estimates for internalised DU exposure. Two approaches were used to address this question. The frequency of dicentrics was measured in HOS cells following DU exposure in vitro. Data demonstrated that DU exposure (50 microM, 24 h) induced a significant elevation in dicentric frequency in vitro in contrast to incubation with the heavy metals, nickel and tungsten which did not increase dicentric frequency above background levels. Using the same concentration (50 microM) of three uranyl nitrate compounds that have different uranium isotopic concentrations and therefore, different specific activities, the effect on neoplastic transformation in vitro was examined. HOS cells were exposed to one of three-uranyl nitrate compounds (238U-uranyl nitrate, specific activity 0.33 microCi.g-1; DU-uranyl nitrate, specific activity 0.44 microCi.g-1; and 235U-uranyl nitrate, specific activity 2.2 microCi.g-1) delivered at a concentration of 50 microM for 24 h. Results showed, at equal uranium concentration, there was a specific activity dependent increase in neoplastic transformation frequency. Taken together these data suggest that radiation can play a role in DU-induced biological effects in vitro.

  16. Effect of management system and season on semen freezability in Jakhrana bucks

    PubMed Central

    Kumar, Narendra; Rai, B.; Bhat, Showkat A.; Kharche, S. D.; Gangwar, Chetna; Jindal, S. K.; Chandra, Subhash

    2016-01-01

    Aim: The objective of the study was to determine the effect of the management system (intensive and semi-intensive) and season (autumn and winter) on semen freezability in Jakhrana bucks. Materials and Methods: A total of 24 Jakhrana bucks of same body weight and age (BW=30 kg, age=1 year) were randomly allotted into two groups, viz., Group I (intensive system, 12 bucks) and Group II (semi-intensive system, 12 bucks). These two groups were statistically tested for their homogeneity with respect to age and BW. Semen was collected twice weekly using an artificial vagina during two seasons: autumn (September-November) and winter (December-February). A total of 240 semen samples (120 from each group and season) were evaluated for post-thaw motility (PTM), viability, abnormality, functional membrane integrity (hypo-osmotic swelling [HOS]) response and acrosomal integrity. Results: The mean values of PTM and acrosomal integrity of spermatozoa were significantly (p<0.01) higher in Group II as compared to Group I. The mean values of viability and abnormality were also differed significant (p<0.05) between groups. However, the mean values of HOS response were found non-significant (p>0.05) between groups. The season showed a significant effect on all parameters except viability and HOS response. The PTM and acrosomal integrity of spermatozoa were significantly (p<0.01) higher in winter as compared to autumn season. Abnormality of spermatozoa was significantly (p<0.05) lower in winter season. Conclusions: This study indicates that both management system and season influence semen freezability. The semen collected from bucks reared under the semi-intensive system and winter season showed better semen freezability characteristics. PMID:27051208

  17. Classification of emotional states from electrocardiogram signals: a non-linear approach based on hurst

    PubMed Central

    2013-01-01

    Background Identifying the emotional state is helpful in applications involving patients with autism and other intellectual disabilities; computer-based training, human computer interaction etc. Electrocardiogram (ECG) signals, being an activity of the autonomous nervous system (ANS), reflect the underlying true emotional state of a person. However, the performance of various methods developed so far lacks accuracy, and more robust methods need to be developed to identify the emotional pattern associated with ECG signals. Methods Emotional ECG data was obtained from sixty participants by inducing the six basic emotional states (happiness, sadness, fear, disgust, surprise and neutral) using audio-visual stimuli. The non-linear feature ‘Hurst’ was computed using Rescaled Range Statistics (RRS) and Finite Variance Scaling (FVS) methods. New Hurst features were proposed by combining the existing RRS and FVS methods with Higher Order Statistics (HOS). The features were then classified using four classifiers – Bayesian Classifier, Regression Tree, K- nearest neighbor and Fuzzy K-nearest neighbor. Seventy percent of the features were used for training and thirty percent for testing the algorithm. Results Analysis of Variance (ANOVA) conveyed that Hurst and the proposed features were statistically significant (p < 0.001). Hurst computed using RRS and FVS methods showed similar classification accuracy. The features obtained by combining FVS and HOS performed better with a maximum accuracy of 92.87% and 76.45% for classifying the six emotional states using random and subject independent validation respectively. Conclusions The results indicate that the combination of non-linear analysis and HOS tend to capture the finer emotional changes that can be seen in healthy ECG data. This work can be further fine tuned to develop a real time system. PMID:23680041

  18. Orthopedic manifestations in patients with mucopolysaccharidosis type II (Hunter syndrome) enrolled in the Hunter Outcome Survey

    PubMed Central

    Link, Bianca; de Camargo Pinto, Louise Lapagesse; Giugliani, Roberto; Wraith, James Edmond; Guffon, Nathalie; Eich, Elke; Beck, Michael

    2010-01-01

    Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare, inherited disorder caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase. As a result of this deficiency, glycosaminoglycans accumulate in lysosomes in many tissues, leading to progressive multisystemic disease. The cardiopulmonary and neurological problems associated with MPS II have received considerable attention. Orthopedic manifestations are common but not as well characterized. This study aimed to characterize the prevalence and severity of orthopedic manifestations of MPS II and to determine the relationship of these signs and symptoms with cardiovascular, pulmonary and central nervous system involvement. Orthopedic manifestations of MPS II were studied using cross-sectional data from the Hunter Outcome Survey (HOS). The HOS is a global, physician-led, multicenter observational database that collects information on the natural history of MPS II and the long-term safety and effectiveness of enzyme replacement therapy. As of January 2009, the HOS contained baseline data on joint range of motion in 124 males with MPS II. In total, 79% of patients had skeletal manifestations (median onset, 3.5 years) and 25% had abnormal gait (median onset, 5.4 years). Joint range of motion was restricted for all joints assessed (elbow, shoulder, hip, knee and ankle). Extension was the most severely affected movement: the exception to this was the shoulder. Surgery for orthopedic problems was rare. The presence of orthopedic manifestations was associated with the presence of central nervous system and pulmonary involvement, but not so clearly with cardiovascular involvement. Orthopedic interventions should be considered on an individual-patient basis. Although some orthopedic manifestations associated with MPS II may be managed routinely, a good knowledge of other concurrent organ system involvement is essential. A multidisciplinary approach is required. PMID:21808707

  19. The sleep of commercial vehicle drivers under the 2003 hours-of-service regulations.

    PubMed

    Hanowski, Richard J; Hickman, Jeffery; Fumero, Maria C; Olson, Rebecca L; Dingus, Thomas A

    2007-11-01

    Previous research has found that commercial drivers get an average of 5.18 h of sleep per night. The revised hours-of-service (HOS) regulations (in the United States) are in place to provide drivers with more opportunities to get sleep. However, are drivers really getting more sleep under these new regulations? Also, is there a relationship between sleep quantity and involvement in critical incident (crashes, near-crashes, or crash-relevant conflicts)? Data from 73 truck drivers, collected during a naturalistic driving study after the implementation of the 2003 HOS regulations, were analyzed to determine overall sleep quantity (using actigraphy), along with sleep quantity prior to being involved in a critical incident. Sixty-two drivers had at least seven consecutive days (Monday through Sunday) of reliable actigraphy data; mean sleep quantity per 24-h period (midnight centered using the Cole-Kripke algorithm) for these drivers was 6.28 h (S.D.=1.42 h). Fifty-eight critical incidents were recorded in the 10th and 11th driving hours. Analysis results indicated that drivers received significantly less sleep in the period prior to a critical incident as compared to their mean overall sleep quantity. The results of this study indicate drivers may be getting more sleep under the revised 2003 HOS regulations as compared to the old regulations. In addition, significantly less sleep in the 24-h period prior to involvement in a critical incident suggests driver fatigue may have been a potential contributing factor in these critical incidents.

  20. Mesenchymal stem cells increase proliferation but do not change quiescent state of osteosarcoma cells: Potential implications according to the tumor resection status

    PubMed Central

    Avril, Pierre; Le Nail, Louis-Romée; Brennan, Meadhbh Á.; Rosset, Philippe; De Pinieux, Gonzague; Layrolle, Pierre; Heymann, Dominique; Perrot, Pierre; Trichet, Valérie

    2015-01-01

    Conventional therapy of primary bone tumors includes surgical excision with wide resection, which leads to physical and aesthetic defects. For reconstruction of bone and joints, allografts can be supplemented with mesenchymal stem cells (MSCs). Similarly, adipose tissue transfer (ATT) is supplemented with adipose-derived stem cells (ADSCs) to improve the efficient grafting in the correction of soft tissue defects. MSC-like cells may also be used in tumor-targeted cell therapy. However, MSC may have adverse effects on sarcoma development. In the present study, human ADSCs, MSCs and pre-osteoclasts were co-injected with human MNNG-HOS osteosarcoma cells in immunodeficient mice. ADSCs and MSCs, but not the osteoclast precursors, accelerated the local proliferation of MNNG-HOS osteosarcoma cells. However, the osteolysis and the metastasis process were not exacerbated by ADSCs, MSCs, or pre-osteoclasts. In vitro proliferation of MNNG-HOS and Saos-2 osteosarcoma cells was increased up to 2-fold in the presence of ADSC-conditioned medium. In contrast, ADSC-conditioned medium did not change the dormant, quiescent state of osteosarcoma cells cultured in oncospheres. Due to the enhancing effect of ADSCs/MSCs on in vivo/in vitro proliferation of osteosarcoma cells, MSCs may not be good candidates for osteosarcoma-targeted cell therapy. Although conditioned medium of ADSCs accelerated the cell cycle of proliferating osteosarcoma cells, it did not change the quiescent state of dormant osteosarcoma cells, indicating that ADSC-secreted factors may not be involved in the risk of local recurrence. PMID:26998421

  1. Changes in soil bacterial community triggered by drought-induced gap succession preceded changes in soil C stocks and quality.

    PubMed

    Yuste, Jorge Curiel; Barba, Josep; Fernandez-Gonzalez, Antonio José; Fernandez-Lopez, Manuel; Mattana, Stefania; Martinez-Vilalta, Jordi; Nolis, Pau; Lloret, Francisco

    2012-12-01

    The aim of this study was to understand how drought-induced tree mortality and subsequent secondary succession would affect soil bacterial taxonomic composition as well as soil organic matter (SOM) quantity and quality in a mixed Mediterranean forest where the Scots pine (Pinus sylvestris) population, affected by climatic drought-induced die-off, is being replaced by Holm-oaks (HO; Quercus ilex). We apply a high throughput DNA pyrosequencing technique and (13)C solid-state Nuclear Magnetic Resonance (CP-MAS (13)C NMR) to soils within areas of influence (defined as an surface with 2-m radius around the trunk) of different trees: healthy and affected (defoliated) pines, pines that died a decade ago and healthy HOs. Soil respiration was also measured in the same spots during a spring campaign using a static close-chamber method (soda lime). A decade after death, and before aerial colonization by the more competitive HOs have even taken place, we could not find changes in soil C pools (quantity and/or quality) associated with tree mortality and secondary succession. Unlike C pools, bacterial diversity and community structure were strongly determined by tree mortality. Convergence between the most abundant taxa of soil bacterial communities under dead pines and colonizer trees (HOs) further suggests that physical gap colonization was occurring below-ground before above-ground colonization was taken place. Significantly higher soil respiration rates under dead trees, together with higher bacterial diversity and anomalously high representation of bacteria commonly associated with copiotrophic environments (r-strategic bacteria) further gives indications of how drought-induced tree mortality and secondary succession were influencing the structure of microbial communities and the metabolic activity of soils.

  2. The influence of elementary silver versus titanium on osteoblasts behaviour in vitro using human osteosarcoma cell lines.

    PubMed

    Hardes, Jendrik; Streitburger, Arne; Ahrens, Helmut; Nusselt, Thomas; Gebert, Carsten; Winkelmann, Winfried; Battmann, Achim; Gosheger, Georg

    2007-01-01

    Purpose. The antimicrobial effect of a silver-coated tumor endoprosthesis has been proven in clinical and experimental trials. However, in the literature there are no reports concerning the effect of elementary silver on osteoblast behaviour. Therefore, the prosthetic stem was not silver-coated because of concerns regarding a possible inhibition of the osseointegration. The aim of the present study was to investigate the effect of 5-25 mg of elementary silver in comparison to Ti-6Al-4V on human osteosarcoma cell lines (HOS-58, SAOS). Methods. Cell viability was determined by measuring the MTT proliferation rate. Cell function was studied by measuring alkaline phosphatase (AP) activity and osteocalcine production. Results. In the HOS-58 cells, the AP activity was statistically significant (P < 0.05) higher at a supplement of 5-10 mg of silver than of Ti-6 Al-4V at the same doses. For both cell lines, a supplement above 10 mg of silver resulted in a reduced AP activity in comparision to the Ti-6 Al-4V group, but a statistically significant difference (P < 0.05) was observed at a dose of 25 mg for the SAOS cells only. At doses of 20-25 mg in the HOS-58 cells and 10-25 mg in the SAOS cells, the reduction of the proliferation rate by silver was statistically significant (P < 0.05) compared to the Ti-6 Al-4V supplement. Discussion. In conclusion, elementary silver exhibits no cytotoxicity at low concentrations. In contrast, it seems to be superior to Ti-6 Al-4V concerning the stimulation of osteogenic maturation at these concentrations, whereas at higher doses it causes the known cytotoxic properties.

  3. The Influence of Elementary Silver Versus Titanium on Osteoblasts Behaviour In Vitro Using Human Osteosarcoma Cell Lines

    PubMed Central

    Hardes, Jendrik; Streitburger, Arne; Ahrens, Helmut; Nusselt, Thomas; Gebert, Carsten; Winkelmann, Winfried; Battmann, Achim; Gosheger, Georg

    2007-01-01

    Purpose. The antimicrobial effect of a silver-coated tumor endoprosthesis has been proven in clinical and experimental trials. However, in the literature there are no reports concerning the effect of elementary silver on osteoblast behaviour. Therefore, the prosthetic stem was not silver-coated because of concerns regarding a possible inhibition of the osseointegration. The aim of the present study was to investigate the effect of 5–25 mg of elementary silver in comparison to Ti-6Al-4V on human osteosarcoma cell lines (HOS-58, SAOS). Methods. Cell viability was determined by measuring the MTT proliferation rate. Cell function was studied by measuring alkaline phosphatase (AP) activity and osteocalcine production. Results. In the HOS-58 cells, the AP activity was statistically significant (P < 0.05) higher at a supplement of 5–10 mg of silver than of Ti-6 Al-4V at the same doses. For both cell lines, a supplement above 10 mg of silver resulted in a reduced AP activity in comparision to the Ti-6 Al-4V group, but a statistically significant difference (P < 0.05) was observed at a dose of 25 mg for the SAOS cells only. At doses of 20–25 mg in the HOS-58 cells and 10–25 mg in the SAOS cells, the reduction of the proliferation rate by silver was statistically significant (P < 0.05) compared to the Ti-6 Al-4V supplement. Discussion. In conclusion, elementary silver exhibits no cytotoxicity at low concentrations. In contrast, it seems to be superior to Ti-6 Al-4V concerning the stimulation of osteogenic maturation at these concentrations, whereas at higher doses it causes the known cytotoxic properties. PMID:17680031

  4. Correlation between seminal lead and cadmium and seminal parameters in idiopathic oligoasthenozoospermic males

    PubMed Central

    Taha, Emad A.; Sayed, Sohair K.; Ghandour, Nagwa M; Mahran, Ali M.; Saleh, Medhat A.; Amin, Magdy M.

    2013-01-01

    Introduction The exact causes of the decline in semen quality are not yet known, environmental factors have been considered to play an important role. Lead (Pb) and Cadmium (Cd) are two of the well-known reproductive toxicants to which humans are exposed occupationally and environmentally and can lead to negative effects on the testicular functions. The aim of this study was to evaluate lead and cadmium levels in seminal plasma of men with idiopathic oligoasthenozoospermia in comparison to fertile healthy controls and to correlate these levels with conventional semen parameters, sperm hypo-osmotic swelling (HOS) percentage, sperm DNA fragmentation percentage, and semen reactive oxygen species (ROS) levels. Material and Methods Thirty infertile male patients with idiopathic oligo and/or asthenozoospermia and thirty healthy fertile men, which was the control group, were included in the study. Lead and cadmium levels in seminal plasma, semen parameters, sperm HOS, sperm DNA fragmentation percentage and semen ROS assay were measured in all subjects. Results There was a significant increase in seminal lead and cadmium levels among infertile males in comparison to controls. There were significant negative correlations between seminal lead and cadmium levels on one hand and certain semen parameters especially progressive sperm motility and vitality (HOS). Importantly, significant positive correlations were noted between seminal lead and cadmium levels on one hand and sperm DNA fragmentation percentage and semen ROS level in infertile men and controls on the other hand. Conclusions Thus, men with idiopathic male infertility had higher levels of lead and cadmium in their semen which correlated with impairment of sperm motility and vitality percentages and more importantly with higher sperm DNA fragmentation% and semen ROS level. PMID:24579002

  5. Linear and nonlinear analysis of normal and CAD-affected heart rate signals.

    PubMed

    Acharya, U Rajendra; Faust, Oliver; Sree, Vinitha; Swapna, G; Martis, Roshan Joy; Kadri, Nahrizul Adib; Suri, Jasjit S

    2014-01-01

    Coronary artery disease (CAD) is one of the dangerous cardiac disease, often may lead to sudden cardiac death. It is difficult to diagnose CAD by manual inspection of electrocardiogram (ECG) signals. To automate this detection task, in this study, we extracted the heart rate (HR) from the ECG signals and used them as base signal for further analysis. We then analyzed the HR signals of both normal and CAD subjects using (i) time domain, (ii) frequency domain and (iii) nonlinear techniques. The following are the nonlinear methods that were used in this work: Poincare plots, Recurrence Quantification Analysis (RQA) parameters, Shannon entropy, Approximate Entropy (ApEn), Sample Entropy (SampEn), Higher Order Spectra (HOS) methods, Detrended Fluctuation Analysis (DFA), Empirical Mode Decomposition (EMD), Cumulants, and Correlation Dimension. As a result of the analysis, we present unique recurrence, Poincare and HOS plots for normal and CAD subjects. We have also observed significant variations in the range of these features with respect to normal and CAD classes, and have presented the same in this paper. We found that the RQA parameters were higher for CAD subjects indicating more rhythm. Since the activity of CAD subjects is less, similar signal patterns repeat more frequently compared to the normal subjects. The entropy based parameters, ApEn and SampEn, are lower for CAD subjects indicating lower entropy (less activity due to impairment) for CAD. Almost all HOS parameters showed higher values for the CAD group, indicating the presence of higher frequency content in the CAD signals. Thus, our study provides a deep insight into how such nonlinear features could be exploited to effectively and reliably detect the presence of CAD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Higher-Order Spectral Analysis of a Nonlinear Pitch and Plunge Apparatus

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.; Strganac, Thomas W.; Hajj, Muhammad R.

    2005-01-01

    Simulated aeroelastic responses of a nonlinear pitch and plunge apparatus are analyzed using various statistical signal processing techniques including higher-order spectral methods. A MATLAB version of the Nonlinear Aeroelastic Testbed Apparatus (NATA) at the Texas A&M University is used to generate various aeroelastic response data including limit cycle oscillations (LCO). Traditional and higher-order spectral (HOS) methods are applied to the simulated aeroelastic responses. Higher-order spectral methods are used to identify critical signatures that indicate the transition from linear to nonlinear (LCO) aeroelastic behavior.

  7. Environmental Impact Statement. Proposed Closure of Los Angeles AFB, California and Relocation of Space Systems Division. Appendix F. Public Comments

    DTIC Science & Technology

    1990-11-01

    ALL OF THOSE ON TER ORIGINAL DRAFT DISTRIBUTION WCRA OCCUR AN A C11R1YT RES0LT OF EASE CLOSURE A LIST,.1 IU VIRAL RWVIROURENTAL IMPACT UTATERERT A US ...a -thre = =.hos~ ag .1 F.2-12,5o 1. ~ FO OFFC=A USE ONLY atef4har-- l t-h h FOR OFFIC`AL USE ONLY DOCUMENT 202 DOCUbIEN 2021 1.0. C0.ol 800 .0 0...DIVISION APPENDIX F PUBLIC COMMENTS United States Air Force November 1990 NO OF!sol wer FOR OFFICIAL USE ONLY! 3 I I I I I This Page Intentionally Left Blank

  8. US Army Medical Bioengineering Research and Development Laboratory Annual Progress Report FY1981.

    DTIC Science & Technology

    1981-10-01

    Medical Fquipment 11 SCIENTIFIC AND TECNOLOGICAL AREAS* 011-’?400 Bioengineer ing ; 009800 !A-cdiral and Hos )ital F uipment; III STiAT DATE...GENERATED PASSED ON TO THE COMBAT DEVELOPER. WORK HAS ALSO BEEN PERFORMED ON THE PACKAGING OF A FUNCTIONAL MOBILE AID STATION IN A LARGER ARMORED...E. NAME " , 22 CEAWDOD Picto, CA ,.t SRly C,.IICItM C. (U) MOBILE LITTER ;(U) LITTER CARRIER ;(U) WHEELED LITTER ) STANDARD ARMY ITTER . l i A ,.T]AE

  9. A Review of Models of the Fluidic Generator.

    DTIC Science & Technology

    1980-11-01

    ATTN l)ELA SAS-T INI. R ’ C’S N VANRIF ’ PORN )LC.iS C ENTER W HITE SANDS MISSILE RANGE, NIM HOS02 mMANDICE 1.PA IFD)LOS’ 1CS ARPMY "SH " STO G CPOR...8217,’IL.F F ’I 󈨋 ;11’FF-- :’v IMMIGRATION ANTI NATURALIZATION SERVICE ATN . M. H5MAN COMMANDER 425 "I" STREET NW I- BAY , N , AIR FORCE AVIONICS LABORATORY

  10. Blind deconvolution of the seismic source time function based on higher order statistics of regional coda waves

    NASA Astrophysics Data System (ADS)

    Sèbe, Olivier; Guilbert, Jocelyn; Bard, Pierre-Yves

    2010-05-01

    Recovering the source time function (STF) of a seismic event provides essential information on the nature and physical mechanisms of the source. Nevertheless, the broad-band estimation of STF is often a difficult task particularly at regional distance where the unknown high heterogeneity of the crustal limits wave inversion to the low frequency content of the source. On the other hand, the widely used empirical Green's function (EGF) suffers from certain limitations towards the selection of valuable empirical green function, especially for small events. Several studies have proved the usefulness of the S coda wave for source parameter estimation such as its moment or its power spectrum. Unfortunately, as these methods are based on second order statistics (power spectrum), the phase of the source spectrum is lost as well as the event STF. In this study, we have developed an original method to recover STF based on the higher order statistic (HOS) blind deconvolution of the S wave coda excitation. Under the assumption that the coda excitation time series is a non-Gaussian independent and identically distributed random signal, this higher order spectral approach provides the amplitude and especially the phase of source spectrum, allowing thus the complete estimation of the seismic STF. We propose a two step algorithm to recover the seismic STF: first, the diffuse coda wave field is whitened to remove the non-stationary attenuation effect; second the STF of the event is estimated from the HOS of the whitened coda excitation such as its bicorrelation and tricorrelation. This algorithm has been tested on regional records of the Rambervillers, 22/02/2003, Ml=5.4 earthquake, located in North-east of France. As the convergence rate of the higher order statistic is slower than second order one, their estimation requires rather long time series and high signal to noise ratio. In order to improve the signal to noise ratio for HOS estimation, a multi-stations stacking procedure

  11. The Costs and Benefits of the Soviet Empire, 1981-1983.

    DTIC Science & Technology

    1986-08-01

    CA qO4OA 2118 ,Ts it hos h’-c-n cipp -aad fol ptT.,ii: r.!-,ise end .il.-: it:: distribution n lunhlmi.td. L -- . . . .i m m mm Ill J PREFACE This...technology. In principle, the cost model should include all of these offset ele- ments. However, our estimates are limited by the data available, as were...each year of the 1971-1980 and 1981-1983 periods, according to the model : CSE, - ae", where a is the rate of growth (or decline) for the t years of

  12. Return-to-play rates following arthroscopic treatment of femoroacetabular impingement in competitive baseball players.

    PubMed

    Degen, Ryan M; Fields, Kara G; Wentzel, C Sally; Bartscherer, Bethanne; Ranawat, Anil S; Coleman, Struan H; Kelly, Bryan T

    2016-11-01

    Femoroacetabular impingement (FAI) has been increasingly recognized in cutting sports including soccer, hockey and football. More recently, the prevalence among overhead athletes has also been recognized. The purpose of this study was to review impingement patterns, return-to-play rates and clinical outcome following arthroscopic treatment of FAI among high-level baseball players. Between 2010 and 2014, 70 competitive baseball players (86 hips; age 22.4 ± 4.5 years) were identified. Demographics and return-to-play rates were recorded. Patient-reported outcome scores, including the Modified Harris Hip Score (mHHS), the Hip Outcome Score-Activity of Daily Living (HOS-ADL), the Sport-specific Subscale (HOS-SSS), and the International Hip Outcome Tool (iHOT-33), were collected pre-operatively at 6 months and 1year (n = 34, 49% of cohort). The cohort included professional (27.1%), college (57.1%), high-school (8.6%) and club-team athletes (7.1%). Infielder (37.5%), pitcher (22.9%) and catcher (16.7%) were the most common positions. Average follow-up was 16.8 months (range 12.1-34.2). There was no relationship between playing position and impingement pattern (p ≥ 0.459), or between symptom laterality and handedness, batting position or playing position (p ≥ 0.179). One patient required revision surgery (infection). Return to sport rate was 88%, at a mean of 8.6 ± 4.2 months, with 97.7% returning at/above their pre-injury level of play. There was significant improvement in all outcome measures: mHHS (60.1 ± 11.9 to 93 ± 9.5), HOS-ADL (71.3 ± 16.7 to 96.3 ± 3.6), HOS-SSS (51.3 ± 24.8 to 92.3 ± 8.2) and iHOT-33 (40.7 ± 19.9 to 85.9 ± 14) (p < 0.001). Arthroscopic treatment of FAI in competitive baseball players resulted in high return-to-play rates at short-term follow-up, with significant improvements in clinical outcome scores.

  13. Assessing long-term return to play after hip arthroscopy in football players evaluating risk factors for good prognosis.

    PubMed

    Barastegui, D; Seijas, R; Alvarez-Diaz, P; Rivera, E; Alentorn-Geli, E; Steinbacher, G; Cuscó, X; Cugat, R

    2017-05-17

    Groin pain is the third most common disease in football players and has often been associated with hip pathology such as femoroacetabular impingement and labral lesions. Hip arthroscopy offers possibilities of function restoration via minimally invasive procedures. The aim of this study is to evaluate professional football player's injuries and their return to play after hip arthroscopy for FAI and labral injuries. Patients that underwent hip arthroscopy between 2009 and 2014 were selected retrospectively. From this population, only professional soccer players competing at national level were included (Tegner 10). Arthroscopic surgery was proposed in patients with persistent pain. All patients were assessed for VAS score preoperatively and at 3, 6, 12 and 24 months post-op. HOS (sport and DLA) and mHHS tests were performed at the same time periods. All patients were men with a mean age of 26.5 ± 7.1 years old. Preoperative VAS (7.4 ± 1.3), HOS ADL (67.7 ± 5.5), HOS sport (37.6 ± 18.7) and mHHS (72.5 ± 8.8) showed improved scores during long-term follow-up. Time to return to play was 10.8 months (SD ± 4.3), with range between 4 and 20 months. Mean follow-up was 45.4 ± 15.6 months (range from 26 to 72 months). No differences were observed between non-active and active patients at final follow-up with respect to chondral lesions, but significant differences were observed with reference to management of the labrum (p = 0.031), where a higher rate of labrectomies existed among inactive patients and a higher rate of suture among active patients. Hip arthroscopy is a safe procedure with very good return to play results, but for optimized return to football one should consider patient age at the time of surgery, the condition of the labrum and low scores on the Harris Hip Score (mHHS) and HOS (sport version) as predictive factors for poor prognosis. Level of evidence IV.

  14. Monitoring outcomes for the Medicare Advantage program: methods and application of the VR-12 for evaluation of plans.

    PubMed

    Kazis, Lewis E; Selim, Alfredo J; Rogers, William; Qian, Shirley X; Brazier, John

    2012-01-01

    The Veterans RAND 12-Item Health Survey (VR-12) is one of the major patient-reported outcomes for ranking the Medicare Advantage (MA) plans in the Health Outcomes Survey (HOS). Approaches for scoring physical and mental health are given using contemporary norms and regression estimators. A new metric approach for the VR-12 called the "VR-6D" is presented with case-mix adjustments for monitoring plans that combine utilities and mortality. Results show that the models for ranking health outcomes of the plans are robust and credible. Future directions include the use of utilities for evaluating and ranking of MA plans.

  15. A Survey of Concurrency Control Mechanisms for Centralized and Distributed Databases.

    DTIC Science & Technology

    1981-02-01

    request is an update. Secondly, if some sites fail (due to, e.g., either hardware or soft- ware malfunction) or if some communication links fail (making...cooperate #1 backup #2a host reusqusqu t sre coprt svrserver server hot#2b hos akphs akp host 0 by ack #2c by ack #3c b Figure 4. Message Flow in a... communication between any two nodes in different sets is not possible. Furthermore, at every site, except the one where LC resides, there is a local

  16. Amateur and Recreational Athletes Return to Sport at a High Rate Following Hip Arthroscopy for Femoroacetabular Impingement.

    PubMed

    Weber, Alexander E; Kuhns, Benjamin D; Cvetanovich, Greg L; Grzybowski, Jeffrey S; Salata, Michael J; Nho, Shane J

    2017-04-01

    To compare the return-to-play rates, patient-reported outcome (PRO) scores, and satisfaction between high-level amateur athletes and recreational athletes and to evaluate for differences in ability to return to sport in these groups based on patient-related and sport-related characteristics. Clinical data were retrieved for 66 (26 male/40 female) consecutive athletes undergoing hip arthroscopy for femoroacetabular impingement. Athletes were classified as high-level amateur or recreational. Athletes were also divided into 6 distinct sporting categories based on the physical demands on the hip. Preoperative and 2-year PROs including a sport-specific questionnaire, modified Harris Hip Score (MHHS), and Hip Outcome Scores with Activities of Daily Living (HOS-ADL) and Sports-Specific (HOS-SS) subscales were collected. Of the 66 patients, 49 were recreational and 17 were high-level amateur athletes (10 high school and 7 collegiate). High-level athletes were significantly younger than recreational athletes (18.4 ± 2.3 years vs 29.7 ± 6.8 years; P < .001). After 2 years, all PROs had improved significantly, with no differences between the 2 athletic groups. There was a high overall rate of return for both recreational and high-level amateur athletes (94% vs 88%; P = .60). Increasing preoperative withdrawal time from sport prior to surgery was associated with decreased HOS-SS (r = 0.33; P = .04) and MHHS scores (r = 0.02; P = .02). Overall, athletes who had withdrawn from sport for greater than 8 months before surgery returned to sport significantly more slowly (P = .01). Increasing body mass index (BMI) was associated with lower improvements in HOS (r = 0.26; P = .04) and MHHS scores (r = 0.38; P < .01). Recreational athletes, despite being significantly older than their high-level counterparts, return to play at a similar high rate and with comparable PROs. Increasing preoperative cessation time from sport significantly prolongs return to sport

  17. Heme Utilization by Pathogenic Bacteria: Not All Pathways Lead to Biliverdin

    PubMed Central

    2015-01-01

    Conspectus The eukaryotic heme oxygenases (HOs) (E.C. 1.14.99.3) convert heme to biliverdin, iron, and carbon monoxide (CO) in three successive oxygenation steps. Pathogenic bacteria require iron for survival and infection. Extracellular heme uptake from the host plays a critical role in iron acquisition and virulence. In the past decade, several HOs required for the release of iron from extracellular heme have been identified in pathogenic bacteria, including Corynebacterium diphtheriae, Neisseriae meningitides, and Pseudomonas aeruginosa. The bacterial enzymes were shown to be structurally and mechanistically similar to those of the canonical eukaryotic HO enzymes. However, the recent discovery of the structurally and mechanistically distinct noncanonical heme oxygenases of Staphylococcus aureus and Mycobacterium tuberculosis has expanded the reaction manifold of heme degradation. The distinct ferredoxin-like structural fold and extreme heme ruffling are proposed to give rise to the alternate heme degradation products in the S. aureus and M. tuberculosis enzymes. In addition, several “heme-degrading factors” with no structural homology to either class of HOs have recently been reported. The identification of these “heme-degrading proteins” has largely been determined on the basis of in vitro heme degradation assays. Many of these proteins were reported to produce biliverdin, although no extensive characterization of the products was performed. Prior to the characterization of the canonical HO enzymes, the nonenzymatic degradation of heme and heme proteins in the presence of a reductant such as ascorbate or hydrazine, a reaction termed “coupled oxidation”, served as a model for biological heme degradation. However, it was recognized that there were important mechanistic differences between the so-called coupled oxidation of heme proteins and enzymatic heme oxygenation. In the coupled oxidation reaction, the final product, verdoheme, can readily be

  18. Higher-order spectra for identification of nonlinear modal coupling

    NASA Astrophysics Data System (ADS)

    Hickey, Daryl; Worden, Keith; Platten, Michael F.; Wright, Jan R.; Cooper, Jonathan E.

    2009-05-01

    Over the past four decades considerable work has been done in the area of power spectrum estimation. The information contained within the power spectrum relates to a signal's autocorrelation or 'second-order statistics'. The power spectrum provides a complete statistical description of a Gaussian process; however, a problem with this information is that it is phase blind. This problem is addressed if one turns to a system's frequency response function (FRF). The FRF graphs the magnitude and phase of the frequency response of a system; in order to do this it requires information regarding the frequency content of the input and output signals. Situations arise in science and engineering whereby signal analysts are required to look beyond second-order statistics and analyse a signal's higher-order statistics (HOS). HOS or spectra give information on a signal's deviation from Gaussianity and consequently are a good indicator function for the presence of nonlinearity within a system. One of the main problems in nonlinear system identification is that of high modal density. Many modelling schemes involve making some expansion of the nonlinear restoring force in terms of polynomial or other basis terms. If more than one degree-of-freedom is involved this becomes a multivariate problem and the number of candidate terms in the expansion grows explosively with the order of nonlinearity and the number of degrees-of-freedom. This paper attempts to use HOS to detect and qualify nonlinear behaviour for a number of symmetrical and asymmetrical systems over a range of degrees-of-freedom. In doing so the paper also attempts to show that HOS are a more sensitive tool than the FRF in detecting nonlinearity. Furthermore, the object of this paper is to try and identify which modes couple in a nonlinear manner in order to reduce the number of candidate coupling terms, for a model, as much as possible. The bispectrum method has previously been applied to simple low-DOF systems with high

  19. A human operator simulator model of the NASA Terminal Configured Vehicle (TCV)

    NASA Technical Reports Server (NTRS)

    Glenn, F. A., III; Doane, S. M.

    1981-01-01

    A generic operator model called HOS was used to simulate the behavior and performance of a pilot flying a transport airplane during instrument approach and landing operations in order to demonstrate the applicability of the model to problems associated with interfacing a crew with a flight system. The model which was installed and operated on NASA Langley's central computing system is described. Preliminary results of its application to an investigation of an innovative display system under development in Langley's terminal configured vehicle program are considered.

  20. Changes in Levels of Seminal Nitric Oxide Synthase, Macrophage Migration Inhibitory Factor, Sperm DNA Integrity and Caspase-3 in Fertile Men after Scrotal Heat Stress

    PubMed Central

    Shi, Zhi-Da; Wang, Lei-Guang; Qiu, Yi

    2015-01-01

    Background This study observes changes in levels of seminal nitric oxide (NO), nitric oxide synthase (NOS), macrophage migration inhibitory factor (MIF), sperm DNA integrity, chromatin condensation and Caspase-3in adult healthy men after scrotal heat stress (SHS). Methods Exposure of the scrotum of 25 healthy male volunteers locally at 40–43°C SHS belt warming 40 min each day for successive 2 d per week. The course of SHS was continuously 3 months. Routine semen analysis, hypo-osmotic swelling (HOS) test, Aniline blue (AB) staining, HOS/AB and terminal deoxynucleotidyl transferase-mediated d UDP nick-end labeling (TUNEL) were carried out before, during and after SHS. Seminal NO and NOS contents were determined by nitrate reduction method. The activated Caspase-3 levels of spermatozoa and MIF in seminal plasma were measured by the enzyme-linked immunosorbent assay (ELISA) method. Statistical significance between mean values was determined using statistical ANOVA tests. Results The mean parameters of sperm concentration, motile and progressive motile sperm and normal morphological sperm were significantly decreased in groups during SHS 1, 2 and 3 months compared with those in groups of pre-SHS (P<0.001). Statistically significant differences of sperm DNA fragmentation, normal sperm membrane, and Caspase-3 activity as well as the level of NO, NOS and MIF in semen were observed between the groups before SHS and after SHS 3 months and the groups during SHS 1, 2 and 3 months (P<0.001). After three months of the SHS, various parameters recovered to the level before SHS. WBC in semen showed a positively significant correlation with the levels of NO, NOS, MIF and Caspase-3 activity. The percentage of abnormal sperm by using the test of HOS showed a positively significant correlation with that of HOS/AB. Conclusions The continuously constant SHS can impact the semen quality and sperm DNA and chromatin, which may be contributed to the high level of NO, NOS, MIF and Caspase

  1. ‘HeART of Stroke (HoS)’, a community-based Arts for Health group intervention to support self-confidence and psychological well-being following a stroke: protocol for a randomised controlled feasibility study

    PubMed Central

    Ellis-Hill, Caroline; Gracey, Fergus; Thomas, Sarah; Lamont-Robinson, Catherine; Thomas, Peter W; Marques, Elsa M R; Grant, Mary; Nunn, Samantha; Cant, Robin P I; Galvin, Kathleen T; Reynolds, Frances; Jenkinson, Damian F

    2015-01-01

    Introduction Over 152 000 people in the UK have strokes annually and a third experience residual disability. Low mood also affects a third of stroke survivors; yet psychological support is poor. While Arts for Health interventions have been shown to improve well-being in people with mild-to-moderate depression post-stroke, their role in helping people regain sense of self, well-being and confidence has yet to be evaluated. The main aim of this study is to explore the feasibility of conducting a pragmatic multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of an Arts for Health group intervention (‘HeART of Stroke’ (HoS)) for stroke survivors. HoS is a 10-session artist-facilitated group intervention held in the community over 14 weeks. It offers a non-judgemental, supportive environment for people to explore sense of self, potentially enhancing well-being and confidence. Methods and analysis Sixty-four people, up to 2 years post-stroke, recruited via secondary care research staff or community stroke/rehabilitation teams in two UK centres will be randomised to either HoS plus usual care or usual care only. Self-reported outcomes, measured at baseline and approximately 5 months postrandomisation, will include stroke-related, well-being, mood, self-esteem, quality of life and process measures. Analyses will focus on estimating key feasibility parameters (eg, rates of recruitment, retention, intervention attendance). We will develop outcome and resource use data collection methods to inform an effectiveness and cost-effectiveness analysis in the future trial. Interviews, with a sample of participants, will explore the acceptability of the intervention and study processes, as well as experiences of the HoS group. Ethics and dissemination National Health Service (NHS), Research and Development and University ethical approvals have been obtained. Two peer-reviewed journal publications are planned plus one service user led

  2. Hospital Admissions Related to Mental Disorders in U.S. Army Soldiers in Iraq and Afghanistan

    DTIC Science & Technology

    2009-10-01

    disorder), somatoform/ dissociative/ factitious , and other mental disorders. ICD-9-CM codes E950-E959 were used to identify attempted suicide-related/self...dissociative/ factitious Other Mental ICD-9 Codes 290-319 291, 303, 305.0, 292 (except 292.2), 304, 305.2-305.7, 305.9 309.0, 309.24, 309.28, 309.3... factitious disorders. Risk Analysis of Mental Disorders—OIF One thousand, five hundred sixty-five soldiers had 1,633 hos- pitalizations in OIF, with a

  3. Gulf Security and the Gulf Arab Contribution

    DTIC Science & Technology

    1991-06-01

    could be of use in threatening shipping, and the tactical transports could deliver up to 64 paratroopers per aircraft." 9. James Bruce, "Treading a... Tbi . document hos been -i r x v e d i| puhlice- ie cd d -ale; its SECURITY CLASSIFICATION OF THIS PAGE REPORT DOCUMENTATION PAGE , la. REPORT SECURITY...ORGANIZATION 6b OFFICE SYMBOL 7a NAME OF MONITORING ORGANIZATION (If applicable) US NAVAL WAR COLLEGE I 6c. ADDRESS (City, State, and ZIPCode) 7b ADDRESS (City

  4. Anterior Inferior Iliac Spine Morphology and Outcomes of Hip Arthroscopy in Soccer Athletes: A Comparison to Nonkicking Athletes.

    PubMed

    Nawabi, Danyal H; Degen, Ryan M; Fields, Kara G; Wentzel, Catherine S; Adeoye, Olusanjo; Kelly, Bryan T

    2017-04-01

    To describe the anterior inferior iliac spine (AIIS) morphology and clinical outcomes following arthroscopic surgical decompression in a group of high-level soccer athletes presenting with symptomatic hip impingement when compared with a control group of nonkicking athletes. From 2009 to 2012, we retrospectively reviewed our prospective hip registry for soccer athletes who underwent arthroscopic treatment for femoroacetabular impingement (FAI) with 2-year follow-up, comparing with a control group of nonkicking athletes. Demographics were collected and radiographic studies (plain radiograph and computed tomographic scan) reviewed for several parameters, including AIIS morphology. Patient-reported outcome scores, including modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL) and Sport-Specific Subscale (HOS-SSS), and International Hip Outcome Tool-33 (iHOT-33), were administered preoperatively, at 6 months, and at 1, 2, and 3 years postoperatively. Twenty-six soccer players (34 hips) and 87 nonkicking athletes (115) hips were identified. Demographics, including age (19.2 ± 4.1 vs 20.1 ± 3.8 years) and gender distribution (53.8% vs 51.7% male), were similar between the soccer and nonkicking athletes (P = .288, .849). Eighty-four percent of soccer players demonstrated some abnormality of the AIIS extending to (type II, 52%) or below the anterior acetabular rim (type III, 32%), compared with 52% nonkicking athletes (P < .001). At a mean follow-up of 35 months (range, 24-57 months) there was significant improvement in all outcome scores in both groups from pre- to postoperation (P < .001). There was no evidence of differences in outcome scores between groups (mHSS: 89 ± 14.6 vs 88.2 ± 14.4, P = .804; HOS-ADL: 94.1 ± 9.1 vs 92.2 ± 11.1, P = .431; HOS-SSS: 86 ± 17.1 vs 81.3 ± 24.3, P = .362) with the exception of iHOT-33 (81.7 ± 19 vs 70.3 ± 23.6, P = .027). High-level soccer players have a significantly higher rate

  5. Pseudoirroratin A, a new cytotoxic ent-kaurene diterpene from Isodon pseudo-irrorata.

    PubMed

    Zhang, Hongjie; Fan, Zhuting; Tan, Ghee T; Chai, Hee-Byung; Pezzuto, John M; Sun, Handong; Fong, Harry H S

    2002-02-01

    A new ent-kaurene diterpene, pseudoirroratin A (1), and a known diterpene, pseurata A, were isolated from Isodon pseudo-irrorata. Compound 1 showed significant cytotoxicity against the Lu1, SW626, LNCaP, KB, and HOS cancer cell lines with IC(50) values of 0.26 (0.75), 0.20 (0.57), 0.90 (2.59), 0.90 (2.59), and 0.50 (1.44) microg/mL (microM), respectively. The structure of 1 was elucidated by spectroscopic means including 1D and 2D NMR techniques.

  6. Probing cell traction forces in confined microenvironments†

    PubMed Central

    Raman, Phrabha S.; Paul, Colin D.; Stroka, Kimberly M.; Konstantopoulos, Konstantinos

    2017-01-01

    Cells migrate in vivo within three-dimensional (3D) extracellular matrices. Cells also migrate through 3D longitudinal channels formed between the connective tissue and the basement membrane of muscle, nerve, and epithelium. Although traction forces have been measured during 2D cell migration, no assay has been developed to probe forces during migration through confined microenvironments. We thus fabricated a novel microfluidic device consisting of deflectable PDMS microposts incorporated within microchannels of varying cross-sectional areas. Using NIH-3T3 fibroblasts and human osteosarcoma (HOS) cells as models, we found that the average traction forces per post decreased upon increasing confinement. Inhibition of myosin-II function by blebbistatin in HOS cells decreased traction forces in unconfined (wide) channels but failed to alter them in confined spaces. Myosin activation by calyculin A also failed to affect traction forces in confining channels but increased them in wide channels. These observations underlie the importance of the physical microenvironment in the regulation of cell migration and cellular traction forces. PMID:24100608

  7. Echovirus 1 replication, not only virus binding to its receptor, VLA-2, is required for the induction of cellular immediate-early genes.

    PubMed Central

    Huttunen, P; Heino, J; Hyypiä, T

    1997-01-01

    Induction of immediate-early genes c-jun, junB, and c-fos was demonstrated during echovirus 1 infection in a human osteogenic sarcoma (HOS) cell line. Tenfold induction was seen at 10 h postinfection, corresponding approximately to the end of the first replication cycle of the virus. Echovirus 1 uses VLA-2 integrin as its cellular receptor, and ligand binding by integrin is known to trigger signal transduction pathways ultimately activating immediate-early genes. In the present study, however, VLA-2 binding alone was not sufficient to induce their expression; viral replication was needed. This conclusion was based on the observations that no stimulation of the immediate-early genes occurred in the MG-63 cell line where the virus attached only to VLA-2 but was not able to replicate and that induction of these genes was observed when the HOS cells were infected with echovirus type 7, known to use a different cellular receptor. Induction was not seen in the presence of the antiviral compound WIN 54954, which evidently inhibits the uncoating but not receptor binding of echovirus 1, suggesting that viral replication triggers the activation of the immediate-early genes. The induction of these genes may have a role in viral replication and in the pathogenesis of infection. PMID:9094704

  8. Low seminal zinc bound to high molecular weight proteins in asthenozoospermic patients: evidence of increased sperm zinc content in oligoasthenozoospermic patients.

    PubMed

    Carpino, A; Siciliano, L; Petroni, M F; De Stefano, C; Aquila, S; Andó, S; Petrone, M F

    1998-01-01

    Total seminal zinc concentration, seminal zinc fraction bound to high molecular weight proteins (HMW-Zn%) and zinc content in spermatozoa were assayed in the ejaculates of 90 asthenozoospermic patients subdivided into two study groups: normoasthenozoospermics (group I: n = 50) and oligoasthenozoospermics (group II: n = 40). The zinc concentrations of patients were compared with those of a control group of donors showing normal semen parameters. All samples were also investigated for their sperm membrane functional integrity by the hypo-osmotic swelling test (HOS). The results showed normal total zinc concentrations but very low HMW-Zn% values (P < 0.001) in seminal plasma of the two groups of asthenozoospermic patients compared to the controls. Furthermore higher zinc amounts (P < 0.001) were measured in spermatozoa of oligoasthenozoospermic patients compared to group I and to the control group. Oligoasthenozoospermics also displayed a lower HOS score (P < 0.001) compared to the other two groups. These data suggest that the increased unbound seminal zinc could contribute to the decrease of sperm motility in normoasthenozoospermic and oligoasthenozoospermic patients. A further impairment in sperm motility could occur in the oligoasthenozoospermic patients where the increase of seminal free zinc was followed by a major zinc uptake by spermatozoa. The higher intrasperm zinc content in these patients could be a reflection of their low sperm membrane functionality.

  9. Do Inquiring Minds Have Positive Attitudes? The Science Education of Preservice Elementary Teachers

    PubMed Central

    Riegle-Crumb, Catherine; Morton, Karisma; Moore, Chelsea; Chimonidou, Antonia; Labrake, Cynthia; Kopp, Sacha

    2016-01-01

    Due to their potential impact on students' cognitive and non-cognitive outcomes, the negative attitudes towards science held by many elementary teachers are a critical issue that needs to be addressed. This study focuses on the science education of pre-service elementary teachers with the goal of improving their attitudes before they begin their professional lives as classroom teachers. Specifically, this study builds on a small body of research to examine whether exposure to inquiry-based science content courses that actively involve students in the collaborative process of learning and discovery can promote a positive change in attitudes towards science across several different dimensions. To examine this issue, surveys and administrative data were collected from over 200 students enrolled in the Hands on Science (HoS) program for pre-service teachers at the University of Texas at Austin, as well as more than 200 students in a comparison group enrolled in traditional lecture-style classes. Quantitative analyses reveal that after participating in HoS courses, pre-service teachers significantly increased their scores on scales measuring confidence, enjoyment, anxiety, and perceptions of relevance, while those in the comparison group experienced a decline in favorable attitudes to science. These patterns offer empirical support for the attitudinal benefits of inquiry-based instruction and have implications for the future learning opportunities available to students at all education levels. PMID:27667862

  10. Biological performance of titania containing phosphate-based glasses for bone tissue engineering applications.

    PubMed

    Abou Neel, Ensanya Ali; Chrzanowski, Wojciech; Knowles, Jonathan Campbell

    2014-02-01

    The interplay between glass chemistry, structure, degradation kinetics, and biological activity provides flexibility for the development of scaffolds with highly specific cellular response. The aim of this study was therefore to investigate the role of titania inclusion into the phosphate-based glass on its ability to stimulate osteoblast-like human osteosarcoma (HOS) cells to adhere, proliferate and differentiate. In depth morphological and biochemical characterisation was performed on HOS cells cultured on the surface of glass discs. Cell proliferation was also studied in the presence of the glass extract. Cell differentiation, through osteoblast phenotype genes, alkaline phosphatase (ALP) activity and osteocalcin production, was carried out using normal or osteogenic media. Both Thermanox® and titania free glass were used as controls. The data demonstrated that titania inclusion provides desired cytocompatible surface that supported initial cell attachment, sustained viability, and increased cell proliferation similar or significantly higher than Thermanox®. The modified glasses regulated osteoblastic cell differentiation as detected by osteoblast phenotype gene transcription and upregulated ALP and osteocalcin expression. Using osteogenic media had no significant effect on ALP activity and osteocalcin expression. Therefore, titania modified phosphate glasses may have future use as bone tissue engineering scaffolds.

  11. Evaluation of mercury cycling and hypolimnetic oxygenation in mercury-impacted seasonally stratified reservoirs in the Guadalupe River watershed, California

    NASA Astrophysics Data System (ADS)

    McCord, Stephen A.; Beutel, Marc W.; Dent, Stephen R.; Schladow, S. G.

    2016-10-01

    Surface water reservoirs trap inorganic mercury delivered from their watersheds, create conditions that convert inorganic mercury to highly toxic methylmercury (MeHg), and host sportfish in which MeHg bioaccumulates. The Santa Clara Valley Water District (District) actively manages and monitors four mercury-impaired reservoirs that help to serve communities in South San Francisco Bay, California. The Guadalupe River watershed, which contains three of those reservoirs, also includes the New Almaden mercury-mining district, the largest historic mercury producer in North America. Monthly vertical profiles of field measurements and grab samples in years 2011-2013 portray annual cycling of density stratification, dissolved oxygen (DO), and MeHg. Monitoring results highlight the role that hypolimnetic hypoxia plays in MeHg distribution in the water column, as well as the consistent, tight coupling between MeHg in ecological compartments (water, zooplankton, and bass) across the four reservoirs. Following the 2011-2013 monitoring period, the District designed and installed hypolimnetic oxygenation systems (HOS) in the four reservoirs in an effort to repress MeHg buildup in bottom waters and attain regulatory targets for MeHg in water and fish tissue. Initial HOS operation in Calero Reservoir in 2014 enhanced bottom water DO and depressed hypolimnetic buildup of MeHg, but did not substantially decrease mercury levels in zooplankton or small fish.

  12. Observations of ELM Magnetic Precursors and Harmonic Oscillations in NSTX

    NASA Astrophysics Data System (ADS)

    Kelly, F.; Frederickson, E.; Bell, R.; Tritz, K.; Takahashi, H.; Maingi, R.; NSTX Collaboration

    2011-10-01

    Recent experiments on NSTX have shown n=1 dominant and n=2 mode ELM magnetic precursors with mode frequency in the 30 to 90 kHz range. The growing magnetic oscillations measured with the NSTX high-n Mirnov diagnostic occurred simultaneous with the onset of the increase in fast D α signal. These bursts of dominantly n=1, some n=2 and fewer higher modes resemble the predictions of a model simulation of ELMs by T. Evans in which a feedback amplification mechanism causes explosive growth of the separatrix topology driven by thermoelectric currents in flux tubes connecting the divertor plates. The n=1 mode remained dominant as wall recycling was reduced with lithium conditioning and n=3 RMP was applied, suggesting the trigger mechanism remained the same. Sufficient lithium suppressed ELMs and made the occurrence of low-frequency, low-n Harmonics Oscillations (HOs) more frequent. The HOs are consistent with modes localized in the edge with the frequency of the n = 1 harmonic near the rotation frequency of the edge plasma. Work supported in part by US DOE contract no. DE-AC02-09CH11466.

  13. Heme Oxygenase Database (HemeOxDB) and QSAR Analysis of Isoform 1 Inhibitors.

    PubMed

    Amata, Emanuele; Marrazzo, Agostino; Dichiara, Maria; Modica, Maria N; Salerno, Loredana; Prezzavento, Orazio; Nastasi, Giovanni; Rescifina, Antonio; Romeo, Giuseppe; Pittalà, Valeria

    2017-07-14

    Due to increasing interest in the field of heme oxygenases (HOs), we built a ligand database called HemeOxDB that includes the entire set of known HO-1 and HO-2 inhibitors, resulting in more than 400 compounds. The HemeOxDB is available online at http://www.researchdsf.unict.it/hemeoxdb/, and having a robust search engine allows end users to build complex queries, sort tabulated results, and generate color-coded two- and three-dimensional graphs. This database will grow to be a tool for the design of potent and selective HO-1 or HO-2 inhibitors. We were also interested in virtually searching for alternative inhibitors, and, for the first time in the field of HOs, a quantitative structure-activity relationship (QSAR) model was built using half-maximal inhibitory concentration (IC50 ) values of the whole set of known HO-1 inhibitors, taken from the HemeOxDB and employing the Monte Carlo technique. The statistical quality suggested that the model is robust and possesses desirable predictive potential. The screening of US Food and Drug Administration (FDA)-approved drugs, external to our dataset, suggested new predicted inhibitors, opening the way for replacing imidazole groups. The HemeOxDB and the QSAR model reported herein may help in prospectively identifying or repurposing new drugs with optimal structural attributes for HO enzyme inhibition. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Breathing sounds spectral and higher order statistics changes from wakefulness to sleep in apneic and non-apneic people.

    PubMed

    Soltanzadeh, R; Moussavi, Z

    2014-01-01

    Breathing sounds analysis conveys valuable information in relation to obstructive sleep apnea (OSA) during both sleep and wakefulness. In this study, we investigated whether the breathings sounds spectral and higher order statistics characteristics (HOS) change from wakefulness to sleep, and more importantly whether this change is associated with severity of OSA. Tracheal breathing sounds of 6 individuals with severe OSA and 6 non-OSA individuals during wakefulness and stage 2 of sleep, both in supine position, were used in this study. The sounds were recorded simultaneously with full overnight polysomnography (PSG) assessment. First, the sounds of 5 noise-free breathing cycles were extracted and sequestered into inspiratory and expiratory phase segments manually for each study subject. After normalizing each sound segment to its energy, spectral and HOS features were calculated. Several features including the median bispectral frequency (MBF), spectral bandwidth (BW) and bispectrum Harmonic Mean (HM) were found to change statistically significantly from wakefulness to sleep mostly in severe OSA group but not as much in non-OSA group. The most prominent and consistent change between the two groups of OSA and non-OSA was observed in MBF; it changed from wakefulness to sleep in the two groups in an opposite manner; this observation is congruent with the hypothesis that the upper airway in OSA population has an increased non-homogeneity.

  15. Response of cyanobacteria to low atmosphere pressure

    NASA Astrophysics Data System (ADS)

    Qin, Lifeng; Ai, Weidang; Guo, Shuangsheng; Tang, Yongkang; Yu, Qingni; Shen, Yunze; Ren, Jin

    Maintaining a low pressure environment would reduce the technological complexity and constructed cost of future lunar base. To estimate the effect of hypobaric of controlled ecological life support system in lunar base on terrestrial life, cyanobacteria was used as the model to exam the response of growth, morphology, physiology to it. The decrease of atmosphere pressure from 100 KPa to 50 KPa reducing the growth rates of Microcystis aeruginosa, Merismopedia.sp, Anabaena sp. PCC 7120, Anabaena Hos-aquae, the chlorophyll a content in Microcystis aeruginosa, Merismopedia.sp, Anabaena Hos-aquae, the carotenoid content in Microcystis aeruginosa, Merismopedia.sp and Anabaena sp. PCC 7120, the phycocyanin content in Microcystis aeruginosa. This study explored the biological characteristics of the cyanobacteria under low pressure condition, which aimed at understanding the response of the earth's life to environment for the future moon base, the results enrich the research contents of the lunar biology and may be referred for the research of other terrestrial life, such as human, plant, microbe and animal living in life support system of lunar base.

  16. On the blind source separation of human electroencephalogram by approximate joint diagonalization of second order statistics.

    PubMed

    Congedo, Marco; Gouy-Pailler, Cédric; Jutten, Christian

    2008-12-01

    Over the last ten years blind source separation (BSS) has become a prominent processing tool in the study of human electroencephalography (EEG). Without relying on head modeling BSS aims at estimating both the waveform and the scalp spatial pattern of the intracranial dipolar current responsible of the observed EEG. In this review we begin by placing the BSS linear instantaneous model of EEG within the framework of brain volume conduction theory. We then review the concept and current practice of BSS based on second-order statistics (SOS) and on higher-order statistics (HOS), the latter better known as independent component analysis (ICA). Using neurophysiological knowledge we consider the fitness of SOS-based and HOS-based methods for the extraction of spontaneous and induced EEG and their separation from extra-cranial artifacts. We then illustrate a general BSS scheme operating in the time-frequency domain using SOS only. The scheme readily extends to further data expansions in order to capture experimental source of variations as well. A simple and efficient implementation based on the approximate joint diagonalization of Fourier cospectral matrices is described (AJDC). We conclude discussing useful aspects of BSS analysis of EEG, including its assumptions and limitations.

  17. Do Inquiring Minds Have Positive Attitudes? The Science Education of Preservice Elementary Teachers.

    PubMed

    Riegle-Crumb, Catherine; Morton, Karisma; Moore, Chelsea; Chimonidou, Antonia; Labrake, Cynthia; Kopp, Sacha

    2015-09-01

    Due to their potential impact on students' cognitive and non-cognitive outcomes, the negative attitudes towards science held by many elementary teachers are a critical issue that needs to be addressed. This study focuses on the science education of pre-service elementary teachers with the goal of improving their attitudes before they begin their professional lives as classroom teachers. Specifically, this study builds on a small body of research to examine whether exposure to inquiry-based science content courses that actively involve students in the collaborative process of learning and discovery can promote a positive change in attitudes towards science across several different dimensions. To examine this issue, surveys and administrative data were collected from over 200 students enrolled in the Hands on Science (HoS) program for pre-service teachers at the University of Texas at Austin, as well as more than 200 students in a comparison group enrolled in traditional lecture-style classes. Quantitative analyses reveal that after participating in HoS courses, pre-service teachers significantly increased their scores on scales measuring confidence, enjoyment, anxiety, and perceptions of relevance, while those in the comparison group experienced a decline in favorable attitudes to science. These patterns offer empirical support for the attitudinal benefits of inquiry-based instruction and have implications for the future learning opportunities available to students at all education levels.

  18. Sperm characteristics following freezing in extenders supplemented with whole egg yolk and different concentrations of low-density lipoproteins in the collared peccary (Pecari tajacu).

    PubMed

    Souza, Ana Liza Paz; Lima, Gabriela Liberalino; Peixoto, Gislayne Christianne Xavier; de Souza Castelo, Thibério; Oliveira, Maria Glaucia Carlos; de Paula, Valéria Veras; Silva, Alexandre Rodrigues

    2015-12-01

    The aim of the current study was to compare sperm quality characteristics of the collared peccary (Pecari tajacu) following freezing in extenders supplemented with whole egg yolk and different concentrations of low-density lipoproteins (LDL). Semen from 11 adult males was obtained by electroejaculation and evaluated for sperm motility, vigor, morphology as well as membrane integrity analyzed by the hypo-osmotic swelling (HOS) test and a fluorescent staining. Moreover, the semen was diluted in a Tris-based extender containing 20% egg yolk (control group) or 5, 10 or 20% LDL (treatment groups). The semen samples were frozen in liquid nitrogen and thawed in a water bath for 60s at 37°C. The treatments did not affect (p>0.05) sperm vigor, morphology or membrane integrity analyzed by the HOS test. However, post-thaw sperm motility was significantly higher (p<0.05) in the extender supplemented with 20% LDL (36.4 ± 5.3%) compared with the egg yolk extender and extender supplemented with 10% LDL. Furthermore, the percentage of membrane-intact frozen-thawed spermatozoa analyzed by the fluorescent staining was significantly higher (p<0.05) in the extender supplemented with 20% LDL (27.4 ± 6.5%) than in the other groups. In conclusion, 20% LDL can be used to substitute the whole egg yolk as a cryoprotective additive for freezing semen of the collared peccary.

  19. The Cancer-Related Transcription Factor Runx2 Modulates Cell Proliferation in Human Osteosarcoma Cell Lines

    PubMed Central

    Lucero, Claudia M.J.; Vega, Oscar A.; Osorio, Mariana M.; Tapia, Julio C.; Antonelli, Marcelo; Stein, Gary S.; Van Wijnen, Andre J.; Galindo, Mario A.

    2013-01-01

    Runx2 regulates osteogenic differentiation and bone formation, but also suppresses pre-osteoblast proliferation by affecting cell cycle progression in the G1 phase. The growth suppressive potential of Runx2 is normally inactivated in part by protein destabilization, which permits cell cycle progression beyond the G1/S phase transition, and Runx2 is again up-regulated after mitosis. Runx2 expression also correlates with metastasis and poor chemotherapy response in osteosarcoma. Here we show that six human osteosarcoma cell lines (SaOS, MG63, U2OS, HOS, G292, and 143B) have different growth rates, which is consistent with differences in the lengths of the cell cycle. Runx2 protein levels are cell cycle-regulated with respect to the G1/S phase transition in U2OS, HOS, G292, and 143B cells. In contrast, Runx2 protein levels are constitutively expressed during the cell cycle in SaOS and MG63 cells. Forced expression of Runx2 suppresses growth in all cell lines indicating that accumulation of Runx2 in excess of its pre-established levels in a given cell type triggers one or more anti-proliferative pathways in osteosarcoma cells. Thus, regulatory mechanisms controlling Runx2 expression in osteosarcoma cells must balance Runx2 protein levels to promote its putative oncogenic functions, while avoiding suppression of bone tumor growth. PMID:22949168

  20. The cancer-related transcription factor Runx2 modulates cell proliferation in human osteosarcoma cell lines.

    PubMed

    Lucero, Claudia M J; Vega, Oscar A; Osorio, Mariana M; Tapia, Julio C; Antonelli, Marcelo; Stein, Gary S; van Wijnen, Andre J; Galindo, Mario A

    2013-04-01

    Runx2 regulates osteogenic differentiation and bone formation, but also suppresses pre-osteoblast proliferation by affecting cell cycle progression in the G(1) phase. The growth suppressive potential of Runx2 is normally inactivated in part by protein destabilization, which permits cell cycle progression beyond the G(1)/S phase transition, and Runx2 is again up-regulated after mitosis. Runx2 expression also correlates with metastasis and poor chemotherapy response in osteosarcoma. Here we show that six human osteosarcoma cell lines (SaOS, MG63, U2OS, HOS, G292, and 143B) have different growth rates, which is consistent with differences in the lengths of the cell cycle. Runx2 protein levels are cell cycle-regulated with respect to the G(1)/S phase transition in U2OS, HOS, G292, and 143B cells. In contrast, Runx2 protein levels are constitutively expressed during the cell cycle in SaOS and MG63 cells. Forced expression of Runx2 suppresses growth in all cell lines indicating that accumulation of Runx2 in excess of its pre-established levels in a given cell type triggers one or more anti-proliferative pathways in osteosarcoma cells. Thus, regulatory mechanisms controlling Runx2 expression in osteosarcoma cells must balance Runx2 protein levels to promote its putative oncogenic functions, while avoiding suppression of bone tumor growth. Copyright © 2012 Wiley Periodicals, Inc.

  1. A preference-based measure of health: the VR-6D derived from the veterans RAND 12-Item Health Survey.

    PubMed

    Selim, Alfredo J; Rogers, William; Qian, Shirley X; Brazier, John; Kazis, Lewis E

    2011-10-01

    The Veterans RAND 12-Item Health Survey (VR-12) is currently the major endpoint used in the Medicare managed care outcomes measure in the Healthcare Effectiveness Data and Information Set (HEDIS(®)), referred to as the Health Outcomes Survey (HOS). The purpose of this study is to adapt the Brazier SF-6D utility measure to the VR-12 to generate a single utility index. We used the HOS cohorts 2 and 3 for SF-36 data and 9 for VR-12 data. We calculated SF-6D scores from the SF-36 using the algorithms developed by Brazier and colleagues. The values of the Brazier SF-6D were used to estimate utility scores from the VR-12 using a mapping approach based on a 2-stage mapping procedure, named as VR-6D. The VR-6D derived from the VR-12 has similar distributional properties as the SF-6D. The change in VR-6D showed significant variations across disease groups with different levels of morbidity and mortality. This study produced a utility measure for the VR-12 that is comparable to the SF-6D and responsive to change. The VR-6D can be used in evaluations of health care plans and cost-effectiveness analysis to compare the health gains that health care interventions can achieve.

  2. Flow cytometry application in the assessment of sperm DNA integrity of men with asthenozoospermia.

    PubMed

    Piasecka, M; Gaczarzewicz, D; Laszczyńska, M; Starczewski, A; Brodowska, A

    2007-01-01

    Sperm genomic integrity and ultrastructural features of ejaculated spermatozoa contributing to the assessment of gamete fertility potential in patients with asthenozoospermia are discussed. The proportion of TUNEL-positive cells was significantly higher in the semen of patients with low sperm motility (n=40; p<0.01) as compared to men with normal sperm motility (n=54). Sperm DNA fragmentation negatively correlated (n=94) with sperm motility, sperm concentration, and integrity of the sperm cellular membrane (HOS-test). Two categories of patients were distinguished: (1) patients (23 out of 94 subjects) with < or = 4% of TUNEL-positive cells and (2) patients (71 subjects) with 4% of TUNEL-positive cells. A significant difference was noted in the sperm motility and HOS-test results between patients from both groups. Large numbers of immature spermatozoa with extensive cytoplasmic retention, ultrastructural chromatin and midpiece abnormalities, and conglomerates containing sperm fragments were present more frequently in the semen of asthenozoospermic subjects with >4% of TUNEL-positive sperm cells. Low sperm motility seems to be accompanied by serious defects of gamete chromatin expressed as diminished sperm genomic integrity and abnormal DNA condensation and by defects of sperm midpiece. These abnormalities may reflect developmental failure during the spermatogenic remodeling process. The DNA fragmentation test may be considered as an additional assay for the evaluation of spermatozoa beside standard analysis and taken together with electron microscopy may help to determine the actual number of "healthy" spermatozoa thereby playing an important role during diagnosis and treatment of male infertility.

  3. Noncoding RNAs: Possible Players in the Development of Fluorosis.

    PubMed

    Daiwile, Atul P; Sivanesan, Saravanadevi; Izzotti, Alberto; Bafana, Amit; Naoghare, Pravin K; Arrigo, Patrizio; Purohit, Hemant J; Parmar, Devendra; Kannan, Krishnamurthi

    2015-01-01

    Fluorosis is caused by excess of fluoride intake over a long period of time. Aberrant change in the Runt-related transcription factor 2 (RUNX2) mediated signaling cascade is one of the decisive steps during the pathogenesis of fluorosis. Up to date, role of fluoride on the epigenetic alterations is not studied. In the present study, global expression profiling of short noncoding RNAs, in particular miRNAs and snoRNAs, was carried out in sodium fluoride (NaF) treated human osteosarcoma (HOS) cells to understand their possible role in the development of fluorosis. qPCR and in silico hybridization revealed that miR-124 and miR-155 can be directly involved in the transcriptional regulation of Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor κ-B ligand (RANKL) genes. Compared to control, C/D box analysis revealed marked elevation in the number of UG dinucleotides and D-box sequences in NaF exposed HOS cells. Herein, we report miR-124 and miR-155 as the new possible players involved in the development of fluorosis. We show that the alterations in UG dinucleotides and D-box sequences of snoRNAs could be due to NaF exposure.

  4. Noncoding RNAs: Possible Players in the Development of Fluorosis

    PubMed Central

    Daiwile, Atul P.; Sivanesan, Saravanadevi; Izzotti, Alberto; Bafana, Amit; Naoghare, Pravin K.; Arrigo, Patrizio; Purohit, Hemant J.; Parmar, Devendra; Kannan, Krishnamurthi

    2015-01-01

    Fluorosis is caused by excess of fluoride intake over a long period of time. Aberrant change in the Runt-related transcription factor 2 (RUNX2) mediated signaling cascade is one of the decisive steps during the pathogenesis of fluorosis. Up to date, role of fluoride on the epigenetic alterations is not studied. In the present study, global expression profiling of short noncoding RNAs, in particular miRNAs and snoRNAs, was carried out in sodium fluoride (NaF) treated human osteosarcoma (HOS) cells to understand their possible role in the development of fluorosis. qPCR and in silico hybridization revealed that miR-124 and miR-155 can be directly involved in the transcriptional regulation of Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor κ-B ligand (RANKL) genes. Compared to control, C/D box analysis revealed marked elevation in the number of UG dinucleotides and D-box sequences in NaF exposed HOS cells. Herein, we report miR-124 and miR-155 as the new possible players involved in the development of fluorosis. We show that the alterations in UG dinucleotides and D-box sequences of snoRNAs could be due to NaF exposure. PMID:26339601

  5. Oncolytic virotherapy for osteosarcoma using midkine promoter-regulated adenoviruses.

    PubMed

    Takagi-Kimura, M; Yamano, T; Tagawa, M; Kubo, S

    2014-03-01

    Oncolytic virotherapy using adenoviruses has potential therapeutic benefits for a variety of cancers. We recently developed MOA5, a tumor-specific midkine promoter-regulated oncolytic vector based on human adenovirus serotype 5 (Ad5). We modified the binding tropism of MOA5 by replacing the cell-binding domain of the Ad5 fiber knob with that from another adenovirus serotype 35 (Ad35); the resulting vector was designated MOA35. Here we evaluated the therapeutic efficacies of MOA5 and MOA35 for human osteosarcoma. Midkine mRNA expression and its promoter activity was significantly high in five human osteosarcoma cell lines, but was restricted in normal cells. Very low levels of adenovirus cellular receptor coxsackievirus/adenovirus receptor (CAR) (Ad5 receptor) expression were observed in MNNG-HOS and MG-63 cells, whereas high levels of CAR expression were seen in the other osteosarcoma cell lines. By contrast, CD46 (Ad35 receptor) was highly expressed in all osteosarcoma cell lines. Infectivity and in vitro cytocidal effect of MOA35 was significantly enhanced in MNNG-HOS and MG-63 cells compared with MOA5, although the cytocidal effects of MOA5 were sometimes higher in high CAR-expressing cell lines. In MG-63 xenograft models, MOA35 significantly enhanced antitumor effects compared with MOA5. Our findings indicate that MOA5 and MOA35 allow tailored virotherapy and facilitate more effective treatments for osteosarcoma.

  6. Deciphering the Biophysical Effects of Oxidizing Sulfur-Containing Amino Acids in Interferon-beta-1a using MS and HDX-MS

    NASA Astrophysics Data System (ADS)

    Houde, Damian J.; Bou-Assaf, George M.; Berkowitz, Steven A.

    2017-02-01

    Introduction of a chemical change to one or more amino acids in a protein's polypeptide chain can result in various effects on its higher-order structure (HOS) and biophysical behavior (or properties). These effects range from no detectable change to significant structural or conformational alteration that can greatly affect the protein's biophysical properties and its resulting biological function. The ability to reliably detect the absence or presence of such changes is essential to understanding the structure-function relationship in a protein and in the successful commercial development of protein-based drugs (biopharmaceuticals). In this paper, we focus our attention on the latter by specifically elucidating the impact of oxidation on the HOS, structural dynamics, and biophysical properties of interferon beta-1a (IFNβ-1a). Oxidation is a common biochemical modification that occurs in many biopharmaceuticals, specifically in two naturally-occurring sulfur-containing amino acids, methionine and cysteine. To carry out this work, we used combinations of hydrogen peroxide and pH to differentially oxidize IFNβ-1a (to focus on only methionine oxidation versus methionine and cysteine oxidation). We then employed several analytical and biophysical techniques to acquire information about the differential impact of these two oxidation scenarios on IFNβ-1a. In particular, the use of MS-based techniques, especially HDX-MS, play a dominant role in revealing the differential effects.

  7. Characterizing the auto-bispectrum as a detector of nonlinearity in structural systems

    NASA Astrophysics Data System (ADS)

    Nichols, Jonathan M.; Milanese, Attilio; Marzocca, Pier

    2007-04-01

    Higher-order spectra (HOS) appear often in the analysis and identification of nonlinear systems. The auto-bispectrum is one example of a HOS and is frequently used in the analysis of stationary structural response data to detect the presence of certain types structural nonlinearities. In this work we use a closed-form expression for the auto-bispectrum, derived previously by the authors, to find the bispectral frequency most sensitive to the nonlinearity. We then explore the properties of nonlinearity detectors based on estimates of the magnitude of the auto-bispectrum at this frequency. We specifically consider the case where the bispectrum is estimated using the direct method based on the Fourier Transform. The performance of the detector is quantified using a Receiver Operator Characteristic (ROC) curve illustrating the trade-off between Type-I error and power of detection (1-Type-II error). Theoretically derived ROC curves are compared to those obtained via numerical simulation. Results are presented for different levels of nonlinearity. Possible consequences are discussed with regard to the detection of damage-induced nonlinearities in structures.

  8. Assessment of the structure of pegylated-recombinant protein therapeutics by the NMR fingerprint assay.

    PubMed

    Hodgson, Derek J; Aubin, Yves

    2017-05-10

    A number of recombinant protein therapeutic products, such as filgrastim (methionyl granulocyte colony stimulating factor [Met-GCSF] used to boost the immune system in chemotherapy treated cancer patients), and interferon alpha-2 (used for the treatment of various viral infections), have been chemically modified with the addition of a polyethylene glycol (PEG) chain. This modification prolongs residency of the drug in the body and reduces metabolic degradation, which allows less frequent administration of the products. Here we show how NMR spectroscopy methods can assess the higher order structure (HOS) of pegylated-filgrastim (Neulasta®), pegylated interferon-α2a (Pegasys®) pegylated interferon-α2b (PEG-Intron®) purchased from the marketplace. The addition of the PEG moiety effectively doubles the molecular weight of the three products. This presents a significant challenge for the application of NMR techniques. Nevertheless, the results showed that high-resolution spectra could be recorded for two of the three products. Comparison of the spectra of the pegylated protein and the non-pegylated protein shows that the chemical modification did not alter the HOS of these proteins.

  9. TPR-MET oncogenic rearrangement: Detection by polymerase chain reaction amplification of the transcript and expression in human tumor cells lines

    SciTech Connect

    Soman, N.R.; Wogan, G.N. ); Rhim, J.S. )

    1990-01-01

    Activation of the MET protooncogene by a rearrangement involving the fusion of TPR and MET specific gene sequences has been observed in a human osteosarcoma cell line (HOS) treated in vitro with N-methyl-N{prime}-nitro-N-nitrosoguanidine (MNNG). No information has been available about the possible occurrence of this rearrangement in human tumors. To facilitate rapid screening of human cell lines and tumor samples for this specific gene rearrangement; the authors developed a sensitive detection method based on polymerase chain reaction (PCR) amplification of TPR-MET mRNA. cDNA was generated from cellular transcripts by using one of the PCR primers, which was then used as a template for PCR amplification of a 205-base-pair region carrying the breakpoint. An end-labeled internal probe was hybridized in solution to an aliquot of the PCR product for detecting amplification. Cells could be directly screened by the assay without prior isolation of RNA. A 205-base-pair DNA fragment characteristic of the TRP-MET rearrangement was detected in cell lines previously known to contain this altered sequence. The rearrangement was also detected at very low levels in the parental (nontransformed) cell line, HOS TE-85. A preliminary survey of cell lines derived from a variety of human tumors indicates that TPR-MET rearrangement occurred and was expressed at very low frequencies by cells from 7 of 14 tumors of nonhematopoietic origin.

  10. Tricetin inhibits human osteosarcoma cells metastasis by transcriptionally repressing MMP-9 via p38 and Akt pathways.

    PubMed

    Chang, Pin-Yu; Hsieh, Ming-Ju; Hsieh, Yih-Shou; Chen, Pei-Ni; Yang, Jia-Sin; Lo, Fang-Cheng; Yang, Shun-Fa; Lu, Ko-Hsiu

    2017-08-01

    Tricetin, a dietary flavonoid, has cytostatic properties and anti-metastasis activities in various cancer cells. However, the detailed impacts and underlying mechanisms of tricetin on human osteosarcoma cell metastasis are still unclear. Here, the hypothesis that tricetin possesses the anti-metastatic effects on human osteosarcoma cells was tested. The effects of tricetin on cell viability, motility, migration, and invasion in human osteosarcoma U2OS and HOS cells were investigated. Gelatin zymography, western blotting, polymerase chain reaction (PCR), and the luciferase assay were used to further explore the underlying mechanisms involved in anti-metastatic effects in U2OS cells. Their results showed that Tricetin, up to 80 μM without cytotoxicity, attenuated U2OS and HOS cells motility, invasiveness, and migration by reducing matrix metalloproteinase (MMP)-9 enzyme activities. In U2OS cells, tricetin decreased MMP-9 protein and mRNA expressions, which was confirmed by real-time PCR. Next, tricetin reduced phosphorylation of p38 and Akt, but no effect on phosphorylation of ERK1/2 and JNK. In conclusion, tricetin possesses the anti-metastatic activity of osteosarcoma cells by transcriptionally repressing MMP-9 via p38 and Akt signaling pathways. This may be potentially useful as anti-metastatic agents for osteosarcoma chemotherapy. © 2016 Wiley Periodicals, Inc.

  11. Properties of sediment NOM collected from a drinking water reservoir in South China, and its association with THMs and HAAs formation

    NASA Astrophysics Data System (ADS)

    Hong, H. C.; Huang, F. Q.; Wang, F. Y.; Ding, L. X.; Lin, H. J.; Liang, Y.

    2013-01-01

    SummaryThe natural organic matter (NOM) from the sediment elutriate, which was obtained from a drinking water reservoir in South China, was fractionated into four fractions by using XAD-8 and XAD-4 resin. Dissolved organic carbon (DOC) as well as UV absorbance at 254 nm (UV254) and specific UV254 (SUV254) were used to quantify and characterize the NOM of raw sediment elutriate and the fractions. Formation of disinfection by-products (DBPs), i.e. trihalomethanes (THMs) and haloacetic acids (HAAs) were also investigated. Results showed that lots of organic matter can be liberated from the sediment during suspension. Hydrophilic organic matter (HiM) accounted for 50.7% of the DOC, followed by hydrophobic acid (HoA) (21.3%), transphilic organic matter (TPH) (15.2%) and other hydrophobic substances (HoS) (12.9%). Different from DOC distribution, the highest UV254 and SUV254 were detected in HoA, while the least were observed in HiM. All the organic fractions were good DBPs precursors. The hydrophobic fractions (HoS and HoA) were more important precursors of CHCl3 and TCAA as compared to other fractions, and UV254 was a good indicator for trichloroacetic acid (TCAA) formation. While for the hydrophilic fraction, relative higher dichloroacetic acid (DCAA) yields were observed, and DOC were good index for its formation.

  12. Semiclassical quantization of highly excited scar states

    NASA Astrophysics Data System (ADS)

    Vergini, Eduardo G.

    2017-04-01

    The semiclassical quantization of Hamiltonian systems with classically chaotic dynamics is restricted to low excited states, close to the ground state, because the number of required periodic orbits grows exponentially with energy. Nevertheless, here we demonstrate that it is possible to find eigenenergies of highly excited states scarred by a short periodic orbit. Specifically, by using 18146 homoclinic orbits (HO)s of the shortest periodic orbit of the hyperbola billiard, we find eigenenergies of the strongest scars over a range which includes 630 even eigenfunctions. The analysis of data reveals that the used semiclassical formula presents two regimes. First, when all HOs with excursion time smaller than the Heisenberg time t H are included, the error is around 3.3% of the mean level spacing. Second, in the energy region defined by \\tilde{t}/ tH > 0.13 , where \\tilde{t} is the maximum excursion time included in the calculation, the error is around 15% of the mean level spacing.

  13. Wind growth and wave breaking in higher-order spectral phase resolved wave models

    NASA Astrophysics Data System (ADS)

    Leighton, R.; Walker, D. T.

    2016-02-01

    Wind growth and wave breaking are a integral parts of the wave evolution. Higher-OrderSpectral models (HoS) describing the non-linear evolution require empirical models for these effects. In particular, the assimilation of phase-resolved remotesensing data will require the prediction and modeling of wave breaking events.The HoS formulation used in this effort is based on fully nonlinear model of O. Nwogu (2009). The model for wave growth due to wind is based on the early normal and tangential stress model of Munk (1947). The model for wave breaking contains two parts. The first part initiates the breaking events based on the local wave geometry and the second part is a model for the pressure field, which acting against the surface normal velocity extracts energy from the wave. The models are tuned to balance the wind energy input with the breaking wave losses and to be similarfield observations of breaking wave coverage. The initial wave field, based on a Pierson-Moskowitz spectrum for 10 meter wind speed of 5-15 m/s, defined over a region of up to approximate 2.5 km on a side with the simulation running for several hundreds of peak wave periods. Results will be presented describing the evolution of the wave field.Sponsored by Office of Naval Research, Code 322

  14. Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast.

    PubMed

    Wirén, Marianna; Silverstein, Rebecca A; Sinha, Indranil; Walfridsson, Julian; Lee, Hang-Mao; Laurenson, Patricia; Pillus, Lorraine; Robyr, Daniel; Grunstein, Michael; Ekwall, Karl

    2005-08-17

    We have conducted a genomewide investigation into the enzymatic specificity, expression profiles, and binding locations of four histone deacetylases (HDACs), representing the three different phylogenetic classes in fission yeast (Schizosaccharomyces pombe). By directly comparing nucleosome density, histone acetylation patterns and HDAC binding in both intergenic and coding regions with gene expression profiles, we found that Sir2 (class III) and Hos2 (class I) have a role in preventing histone loss; Clr6 (class I) is the principal enzyme in promoter-localized repression. Hos2 has an unexpected role in promoting high expression of growth-related genes by deacetylating H4K16Ac in their open reading frames. Clr3 (class II) acts cooperatively with Sir2 throughout the genome, including the silent regions: rDNA, centromeres, mat2/3 and telomeres. The most significant acetylation sites are H3K14Ac for Clr3 and H3K9Ac for Sir2 at their genomic targets. Clr3 also affects subtelomeric regions which contain clustered stress- and meiosis-induced genes. Thus, this combined genomic approach has uncovered different roles for fission yeast HDACs at the silent regions in repression and activation of gene expression.

  15. Effect of long-term administration of zinc after scrotal heating on mice spermatozoa and subsequent offspring quality.

    PubMed

    Ghasemi, N; Babaei, H; Azizallahi, S; Kheradmand, A

    2009-08-01

    This study was set to investigate whether the adverse effects of heat on spermatozoa and subsequent foetuses could be prevented by long-term zinc administration. The scrotums of animals were immersed in water at either 43 degrees C (heat group) or 23 degrees C (control group). Half of the heat and control mice were given 10 mg kg(-1) zinc every other day for 60 days and the others received sterile saline instead of zinc. Heat stress significantly reduced sperm motility, concentration, hypoosmotic swelling-water test (HOS-WT) positive and chromomycin A(3) (CMA(3)) negative spermatozoa at the first 15 days, and the greatest decrease occurred at 30 days (P < 0.05). Sperm motility, concentration and HOS-WT positive spermatozoa were also reduced initially in the zinc administered group, but we did not observe any further decrease in the above mentioned parameters on day 30 (P < 0.05). The weight of foetuses obtained from the females mated with paternal heat treatment males was significantly lower than that of the control group (P < 0.05) and long-term zinc therapy caused a partial recovery (P > 0.05). This study demonstrates that the adverse effects of hyperthermia on semen parameters may be prevented by zinc therapy. Likewise, long-term administration of zinc could improve quality of litter obtained from the females mated with scrotal heat treatment males.

  16. Physical Therapy Protocol After Hip Arthroscopy

    PubMed Central

    Domb, Benjamin G.; Sgroi, Terrance A.; VanDevender, Jeremy C.

    2016-01-01

    Context: Femoroacetabular impingement (FAI) was first described by Ganz in 2003 and is a significant cause of decreased function and mobility. Femoroacetabular impingement must be treated in an individualized, goal-oriented, stepwise fashion. This protocol was developed with biomechanical considerations of soft tissue and bony structures surrounding the hip joint. Evidence Acquisition: The PubMed database was searched for scientific and review articles from the years 2000 to 2015 utilizing the search terms: hip rehabilitation, femoroacetabular impingement, and arthroscopy. Study Design: Clinical review. Level of Evidence: Level 5. Results: Five hundred ninety-five of 738 patients were available for follow-up showing improvement from preoperative to 2-year follow-up of 61.29 to 82.02 for modified Harris Hip Score (mHHS), 62.79 to 83.04 for Hip Outcome Score–Activities of Daily Living (HOS-ADL), 40.96 to 70.07 for Hip Outcome Score–Sport-Specific Subscale (HOS-SSS), and 57.97 to 80.41 for Non-Arthritic Hip Score (NAHS); visual analog scale (VAS) scores decreased from 5.86 preoperatively to 2.94 postoperatively. Conclusion: Following a structured, criteria-based program, appropriate patients undergoing hip arthroscopy may achieve excellent outcomes and return to full independent activities of daily living as well as sport. PMID:27173983

  17. Coherent quantum squeezing due to the phase space noncommutativity

    NASA Astrophysics Data System (ADS)

    Bernardini, Alex E.; Mizrahi, Salomon S.

    2015-06-01

    The effects of general noncommutativity of operators on producing deformed coherent squeezed states is examined in phase space. A two-dimensional noncommutative (NC) quantum system supported by a deformed mathematical structure, similar to that of Hadamard billiard, is obtained and the components behaviour is monitored in time. It is assumed that the independent degrees of freedom are two free 1D harmonic oscillators (HOs), so the system Hamiltonian does not contain interaction terms. Through the NC deformation parameterized by a Seiberg-Witten transform on the original canonical variables, one gets the standard commutation relations for the new ones, such that the obtained, new, Hamiltonian represents two interacting 1D HOs. By admitting that one HO is inverted relatively to the other, we show that their effective interaction induces a squeezing dynamics for initial coherent states imaged in the phase space. A suitable pattern of logarithmic spirals is obtained and some relevant properties are discussed in terms of Wigner functions, which are essential to put in evidence the effects of the noncommutativity.

  18. Flight Test of the F/A-18 Active Aeroelastic Wing Airplane

    NASA Technical Reports Server (NTRS)

    Voracek, David

    2007-01-01

    A viewgraph presentation of flight tests performed on the F/A active aeroelastic wing airplane is shown. The topics include: 1) F/A-18 AAW Airplane; 2) F/A-18 AAW Control Surfaces; 3) Flight Test Background; 4) Roll Control Effectiveness Regions; 5) AAW Design Test Points; 6) AAW Phase I Test Maneuvers; 7) OBES Pitch Doublets; 8) OBES Roll Doublets; 9) AAW Aileron Flexibility; 10) Phase I - Lessons Learned; 11) Control Law Development and Verification & Validation Testing; 12) AAW Phase II RFCS Envelopes; 13) AAW 1-g Phase II Flight Test; 14) Region I - Subsonic 1-g Rolls; 15) Region I - Subsonic 1-g 360 Roll; 16) Region II - Supersonic 1-g Rolls; 17) Region II - Supersonic 1-g 360 Roll; 18) Region III - Subsonic 1-g Rolls; 19) Roll Axis HOS/LOS Comparison Region II - Supersonic (open-loop); 20) Roll Axis HOS/LOS Comparison Region II - Supersonic (closed-loop); 21) AAW Phase II Elevated-g Flight Test; 22) Region I - Subsonic 4-g RPO; and 23) Phase II - Lessons Learned

  19. Hypo-osmotic test in cat spermatozoa.

    PubMed

    Comercio, E A; Monachesi, N E; Loza, M E; Gambarotta, M; Wanke, M M

    2013-10-01

    The hypo-osmotic (HOS) test has been used in other species as an indicator of the fertilising capacity of spermatozoa. The aims of this study were to assess the response of domestic cat spermatozoa to the hypo-osmotic test, to determine the type of solution, concentration and time of incubation needed to obtain a maximum percentage of swelling, to correlate the selected combination with the percentages of progressive motility and to evaluate whether dilution of the ejaculate alters the results. Incubation for 30 and 45 min in solutions of fructose and of citrate of 50 and 100 mOsmol kg⁻¹ was evaluated. The highest percentage of swelling was obtained using the 50 mOsmol kg⁻¹ solution, and no significant differences were observed between the times of exposure to the solutions. A positive correlation was observed between the percentage of individual progressive motility and the percentage of sperm swelling in a 50 mOsmol kg⁻¹ fructose solution, with no significant differences being observed between raw and diluted semen samples. The results of this study suggest that the HOS test could be useful for evaluating membrane function in domestic cat spermatozoa, both in raw semen and in samples diluted in the EZ Mixin® commercial extender, and thus could be incorporated into routine semen evaluation protocols.

  20. Deciphering the Biophysical Effects of Oxidizing Sulfur-Containing Amino Acids in Interferon-beta-1a using MS and HDX-MS

    NASA Astrophysics Data System (ADS)

    Houde, Damian J.; Bou-Assaf, George M.; Berkowitz, Steven A.

    2017-05-01

    Introduction of a chemical change to one or more amino acids in a protein's polypeptide chain can result in various effects on its higher-order structure (HOS) and biophysical behavior (or properties). These effects range from no detectable change to significant structural or conformational alteration that can greatly affect the protein's biophysical properties and its resulting biological function. The ability to reliably detect the absence or presence of such changes is essential to understanding the structure-function relationship in a protein and in the successful commercial development of protein-based drugs (biopharmaceuticals). In this paper, we focus our attention on the latter by specifically elucidating the impact of oxidation on the HOS, structural dynamics, and biophysical properties of interferon beta-1a (IFNβ-1a). Oxidation is a common biochemical modification that occurs in many biopharmaceuticals, specifically in two naturally-occurring sulfur-containing amino acids, methionine and cysteine. To carry out this work, we used combinations of hydrogen peroxide and pH to differentially oxidize IFNβ-1a (to focus on only methionine oxidation versus methionine and cysteine oxidation). We then employed several analytical and biophysical techniques to acquire information about the differential impact of these two oxidation scenarios on IFNβ-1a. In particular, the use of MS-based techniques, especially HDX-MS, play a dominant role in revealing the differential effects.

  1. Stearic acids at sn-1, 3 positions of TAG are more efficient at limiting fat deposition than palmitic and oleic acids in C57BL/6 mice.

    PubMed

    Gouk, Shiou-Wah; Cheng, Sit-Foon; Ong, Augustine Soon-Hock; Chuah, Cheng-Hock

    2014-04-14

    In the present study, we investigated the effect of long-acyl chain SFA, namely palmitic acid (16:0) and stearic acid (18:0), at sn-1, 3 positions of TAG on obesity. Throughout the 15 weeks of the experimental period, C57BL/6 mice were fed diets fortified with cocoa butter, sal stearin (SAL), palm mid fraction (PMF) and high-oleic sunflower oil (HOS). The sn-1, 3 positions were varied by 16:0, 18:0 and 18:1, whilst the sn-2 position was preserved with 18:1. The HOS-enriched diet was found to lead to the highest fat deposition. This was in accordance with our previous postulation. Upon normalisation of total fat deposited with food intake to obtain the fat:feed ratio, interestingly, mice fed the SAL-enriched diet exhibited significantly lower visceral fat/feed and total fat/feed compared with those fed the PMF-enriched diet, despite their similarity in SFA-unsaturated fatty acid-SFA profile. That long-chain SFA at sn-1, 3 positions concomitantly with an unsaturated FA at the sn-2 position exert an obesity-reducing effect was further validated. The present study is the first of its kind to demonstrate that SFA of different chain lengths at sn-1, 3 positions exert profound effects on fat accretion.

  2. The use of the history of science as a motivational tool in middle school science

    NASA Astrophysics Data System (ADS)

    Chapel, Fredrick Milton

    In science classrooms, the content of science is usually taught as sets of facts to be learned as they are, with little understanding as to how those facts were discovered, verified, and challenged by the scientific community (American Association for the Advancement of Science, 1990). Additionally, laboratory activities are not used to challenge those established facts, but only verify them (Roth & Roychoudhury, 1993). The result is science devoid of inherent interest for students, creating a downward spiral of decreasing engagement and achievement, a conclusion supported by recent national and international assessment measures (Schmidt, McKnight, Cogan, Jakwerth, & Houang, 1999). The challenge is to create classroom environments in middle school science that support and motivate students to become and remain engaged in productive learning activities. The objective of this study was to determine the effectiveness of using the history of science (HOS) as a motivational tool in middle school science education. The behaviors and work samples of students were observed and analyzed in relation to three research questions: (1) What patterns of motivated student behavior emerge during a unit of instruction? (2) What evidence of student conceptual change can be observed during a unit of instruction? (3) What is the role of the HOS in the science classroom in regard to student motivation? This naturalistic, ethnographic case study examined four eighth-grade science classrooms in an inner-city charter middle school. The data collected included transcripts of classroom dialogue, student work samples (notes, essays, projects), daily anecdotal notes of the teacher, and observations of the classroom by educational consultants and school personnel. Data analysis was based upon specialized forms of discourse and task analysis with ethnomethodological and phenomenological sensitivity as to how students make meaning of what they are learning. The findings identified patterns of

  3. Patient-reported outcome instruments for femoroacetabular impingement and hip labral pathology: a systematic review of the clinimetric evidence.

    PubMed

    Lodhia, Parth; Slobogean, Gerard P; Noonan, Vanessa K; Gilbart, Michael K

    2011-02-01

    The purpose of this study is to systematically review the content and clinimetric evidence (rigor of rating scales and indexes for the description of clinical phenomena) of published patient-reported outcome (PRO) instruments used to assess femoroacetabular impingement (FAI) and labral hip pathology. We used Medical Subject Heading terms related to FAI and labrum/labral tears to search the Medline, Embase, and Cochrane databases for studies of FAI and labral hip pathology. Studies with hip-related PRO instruments, with any operative intervention except total hip arthroplasty, were included. We excluded studies with a skeletally immature population, revision surgeries in more than 10% of cases, or a primary diagnosis of hip osteoarthritis. We conducted a second review using the same databases for studies reporting clinimetric properties of at least 1 of the PRO instruments identified previously. Articles were selected in an independent, stepwise manner by 2 reviewers. Selected articles were evaluated to determine the presence and quality of measurement properties of the outcome instruments. We found 5 articles assessing 3 PRO instruments: the Hip Outcome Score (HOS), the Non-Arthritic Hip Score, and the 12-item modified Western Ontario and McMaster Universities Osteoarthritis Index. The HOS had the highest positive rating for internal consistency, construct validity, agreement, responsiveness, lack of floor/ceiling effect, and interpretability. The Non-Arthritic Hip Score showed evidence for validity and lack of floor/ceiling effect. The modified Western Ontario and McMaster Universities Osteoarthritis Index was only strong for internal consistency and was indeterminate for construct validity. Only 3 PRO instruments have shown clinimetric evidence to support their use to measure outcomes in FAI and labral pathology patients. The HOS has the greatest amount of clinimetric evidence and is the most proven instrument for use in this population. This review shows that

  4. Physical activity in chronic home-living and sub-acute hospitalized stroke patients using objective and self-reported measures.

    PubMed

    Vanroy, Christel; Vissers, Dirk; Vanlandewijck, Yves; Feys, Hilde; Truijen, Steven; Michielsen, Marc; Cras, Patrick

    2016-04-01

    Despite confirmed reduced physical activity (PA) after stroke in various stages of recovery, the type of activities stroke patients executed and the time spent at different activity levels have not been sufficiently verified with stroke-validated assessment tools. Observational study. To determine PA of sub-acute stroke patients hospitalized in a rehabilitation centre (HOS) compared to chronic home-living stroke patients (HOM) using objective and self-reported measures during 2 weekdays and 1 weekend day. Fifteen HOS and 15 HOM patients wore a Sense Wear Pro 2 accelerometer (METs*minutes/24 h) and a knee-worn pedometer Yamax Digi Walker SW 200 (steps) and filled in a coded activity diary (kcal/24 h; METs*minutes/24 h) during three consecutive days. In HOM significantly more steps (stepstotal HOM = 18722.6 ± 10063.6; stepstotal HOS = 7097.8 ± 5850.5) and higher energy expenditure (EE) levels (EEtotal HOM = 7759.34 ± 2243.04; EEtotal HOS = 5860.15 ± 1412.78) were measured. In this group less moderate activity (≥3-6 ≤ METs) was performed on a weekday (pday1 = 0.006; pday2 = 0.027) and in total (p = 0.037). Few therapy hours (physical, occupational and speech therapy, and psychological support) were provided in HOM compared to HOS (p < 0.001). Vigorous activities were only seen in HOM. In both groups few patients executed sport activities. In HOM significantly more steps were performed and higher EE values were measured. However, participation in moderate activities and time spent on therapy were less in HOM. Evaluating PA with quantitative measures is feasible in both chronic home-living and sub-acute hospitalized patients with stroke.

  5. Are Short-term Outcomes of Hip Arthroscopy in Patients 55 Years and Older Inferior to Those in Younger Patients?

    PubMed

    Bryan, Andrew J; Krych, Aaron J; Pareek, Ayoosh; Reardon, Patrick J; Berardelli, Rebecca; Levy, Bruce A

    2016-10-01

    Hip arthroscopy for young patients with femoroacetabular impingement (FAI) has been successful, but the efficacy of hip arthroscopy in older patients is not clearly defined. To evaluate the clinical outcomes of patients 55 years and older who are undergoing hip arthroscopy and to compare outcomes with those of patients younger than 55 years. Cohort study; Level of evidence, 3. A total of 201 (63 male, 138 female) patients undergoing primary hip arthroscopy for FAI without radiographic arthritis (Tönnis grade <3) were isolated from a prospective database and stratified by age to <55-year and ≥55-year groups. Patients were evaluated preoperatively and 1 and 2 years postoperatively using the modified Harris Hip Score (mHHS) and Hip Outcome Score (HOS: functional scores, as well as Activities of Daily Living [ADL] and Sport subscales). A Wilcoxon signed rank sum test was used to evaluate the differences in outcome scores between the cohorts at each interval. The <55-year group included 174 patients (mean age, 37 ± 12 years), and the ≥55-year group included 27 patients (mean age, 61 ± 5 years). The minimum follow-up time was 2 years in each group. Preoperative Tönnis grades and mHHS scores (59 vs 59; P = .75) were similar between groups. The ≥55-year cohort underwent labral debridement more frequently (78% vs 36%; P =.02) and were more likely to have full-thickness cartilage defects (22% vs 4%; P = .04). Despite this, the mHHS in both groups improved significantly from baseline, without significant differences at 1 year (86 [≥55 years] vs 81 [<55 years]; P = .53) or 2 years (73.88 [≥55 years] vs 79.54 [<55 years]; P = .06). However, at a minimum 2-year follow-up, patients <55 years had significant improvements over patients ≥55 years in the HOS subscales for ADL score (85.6 vs 75.2; P = .03), ADL rating (80.1 vs 70.0; P = .004), Sport score (70.2 vs 55.6; P = .04), and Sport rating (70.2 vs 58.0; P = .04). Although younger patients had superior HOS

  6. Gold(I) Complexes of 9-Deazahypoxanthine as Selective Antitumor and Anti-Inflammatory Agents

    PubMed Central

    Vančo, Ján; Gáliková, Jana; Hošek, Jan; Dvořák, Zdeněk; Paráková, Lenka; Trávníček, Zdeněk

    2014-01-01

    The gold(I) mixed-ligand complexes involving O-substituted derivatives of 9-deazahypoxanthine (HLn) and triphenylphosphine (PPh3) with the general formula [Au(Ln)(PPh3)] (1–5) were prepared and thoroughly characterized by elemental analysis, FT-IR and multinuclear NMR spectroscopy, ESI+ mass spectrometry, single crystal X-ray (HL5 and complex 2) and TG/DTA analyses. Complexes 1–5 were evaluated for their in vitro antitumor activity against nine human cancer lines, i.e. MCF7 (breast carcinoma), HOS (osteosarcoma), A549 (adenocarcinoma), G361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) and THP-1 (monocytic leukaemia), for their in vitro anti-inflammatory activity using a model of LPS-activated macrophages, and for their in vivo antiedematous activity by λ-carrageenan-induced hind paw edema model on rats. The results showed that the complexes 1–5 exhibit selective in vitro cytotoxicity against MCF7, HOS, 22Rv1, A2780 and A2780R, with submicromolar IC50 values for 2 against the MCF7 (0.6 µM) and HOS (0.9 µM). The results of in vitro cytotoxicity screening on primary culture of human hepatocytes (HEP220) revealed up to 30-times lower toxicity of compounds against healthy cells as compared with cancer cells. Additionally, the complexes 1–5 significantly influence the secretion and expression of pro-inflammatory cytokines TNF-α and IL-1β by a similar manner as a commercially used anti-arthritic drug Auranofin. The tested complexes also significantly influence the rate and overall volume of the edema, caused by the intraplantar application of λ-carrageenan polysaccharide to rats. Based on these promising results, the presented compounds could qualify to become feasible candidates for advanced testing as potential antitumor and anti-inflammatory drug-like compounds. PMID:25333949

  7. Crystallographic and spectroscopic insights into heme degradation by Mycobacterium tuberculosis MhuD.

    PubMed

    Graves, Amanda B; Morse, Robert P; Chao, Alex; Iniguez, Angelina; Goulding, Celia W; Liptak, Matthew D

    2014-06-16

    Mycobacterium heme utilization degrader (MhuD) is a heme-degrading protein from Mycobacterium tuberculosis responsible for extracting the essential nutrient iron from host-derived heme. MhuD has been previously shown to produce unique organic products compared to those of canonical heme oxygenases (HOs) as well as those of the IsdG/I heme-degrading enzymes from Staphylococcus aureus. Here, we report the X-ray crystal structure of cyanide-inhibited MhuD (MhuD-heme-CN) as well as detailed (1)H nuclear magnetic resonance (NMR), UV/vis absorption, and magnetic circular dichroism (MCD) spectroscopic characterization of this species. There is no evidence for an ordered network of water molecules on the distal side of the heme substrate in the X-ray crystal structure, as was previously reported for canonical HOs. The degree of heme ruffling in the crystal structure of MhuD is greater than that observed for HO and less than that observed for IsdI. As a consequence, the Fe 3dxz-, 3dyz-, and 3dxy-based MOs are very close in energy, and the room-temperature (1)H NMR spectrum of MhuD-heme-CN is consistent with population of both a (2)Eg electronic state with a (dxy)(2)(dxz,dyz)(3) electron configuration, similar to the ground state of canonical HOs, and a (2)B2g state with a (dxz,dyz)(4)(dxy)(1) electron configuration, similar to the ground state of cyanide-inhibited IsdI. Variable temperature, variable field MCD saturation magnetization data establishes that MhuD-heme-CN has a (2)B2g electronic ground state with a low-lying (2)Eg excited state. Our crystallographic and spectroscopic data suggest that there are both structural and electronic contributions to the α-meso regioselectivity of MhuD-catalyzed heme cleavage. The structural distortion of the heme substrate observed in the X-ray crystal structure of MhuD-heme-CN is likely to favor cleavage at the α- and γ-meso carbons, whereas the spin density distribution may favor selective oxygenation of the α-meso carbon.

  8. A New Automatic Subsurface Gas Monitoring System for Seismogeochemical Studies, Installed in Haruno Borehole, Shizuoka Prefecture, Central Japan

    NASA Astrophysics Data System (ADS)

    Miyakawa, Kazuya; Takama, Ruka; Kawabe, Iwao; Kariya, Shinnichi; Yamauchi, Tsuneo

    2010-12-01

    The results of subsurface gas monitoring by application of gas chromatography (GC) to the gas composition of bubbles associated with groundwater for seismogeochemical studies are reported. An automated gas monitoring system was used to determine gas compositions in a 500-m borehole at the Haruno Crustal Movement Observation Site (HOS), central Japan during period 1, from December 1999 to December 2000. The average ± two standard deviation (2SD) compositions of gases in this period were He = 82 ± 29 ppmV, H2 = 170 ± 62 ppmV, Ar = 0.05 ± 0.07%, N2 = 50 ± 8%, and CH4 = 45 ± 6%. A new automated gas monitoring system equipped with a micro-GC was installed in the borehole at the HOS, and gas bubbles from the borehole were monitored during period 2, from December 2006 to March 2007. The average ± two standard deviation (2SD) compositions of gases in this period were He = 8 ± 7 ppmV, H2 = 13 ± 15 ppmV, Ar = 0.6 ± 0.3%, N2 = 66 ± 7%, and CH4 = 14 ± 14%. The gas concentration ratios (He/Ar, H2/Ar, N2/Ar, and CH4/Ar) fluctuated significantly over time and repeatedly showed abrupt spike-like increases during period 2. The gas compositions obtained in period 1 and 2 were markedly different. Over the period from 2006 to 2007, the gas bubbles were depleted in He, H2, and CH4 of deep origin, but enriched in Ar and N2 of atmospheric origin. This difference can be interpreted as being due to an irreversible change of the aquifer/gas system. The present deep component in the HOS gas is estimated to have composition He = 63 ppmV, H2 = 37 ppmV, Ar = 0.17%, N2 = 63%, and CH4 = 37%. The new monitoring system is able to analyze the gas composition using a smaller volume of sample gas and with greater precision than the previous system. During the 3-month monitoring period 2, the separation capacity of the capillary column of the micro-GC was sufficiently maintained to determine gas-chromatographic peak areas for the five gaseous species examined. This study confirms that the

  9. A Technique for Determining the Nozzle-Flow Properties of Air in an Equilibrium, Nonequilibrium, or Frozen State

    NASA Technical Reports Server (NTRS)

    Hayman, Lovick O.; Stewart, Roger B.

    1961-01-01

    One of the problems associated with the development of high-enthalpy hypersonic test facilities hos been the determination of nozzle flow properties. This note presents a technique for determining the flow properties of air in an equilibrium, non-equilibrium, or frozen state using two test section measurements. A knowledge of two stagnation properties is required before the technique can be applied. The stagnation pressure can be measured, and reference 1 offers a method for determining stagnation enthalpy. Results of the calculations using the method of reference 1 are presented in reference 2 in a chart (chart 21) which can be readily used to determine the stagnation enthalpy from measurements of stagnation pressure, mass flow of air through the tunnel, and throat diameter.

  10. Bispectrum of stator phase current for fault detection of induction motor.

    PubMed

    Treetrong, Juggrapong; Sinha, Jyoti K; Gu, Fengshu; Ball, Andrew

    2009-07-01

    A number of research studies has shown that faults in a stator or rotor generally show sideband frequencies around the mains frequency (50 Hz) and at higher harmonics in the spectrum of the Motor Current Signature Analysis (MCSA). However in the present experimental studies such observations have not been seen, but any fault either in the stator or the rotor may distort the sinusoidal response of the motor RPM and the mains frequency so the MCSA response may contain a number of harmonics of the motor RPM and the mains frequency. Hence the use of a higher order spectrum (HOS), namely the bispectrum of the MCSA has been proposed here because it relates both amplitude and phase of number of the harmonics in a signal. It has been observed that it not only detects early faults but also indicates the severity of the fault to some extent.

  11. Short communication: Progressive motility of frozen-thawed canine semen is highest five minutes after thawing.

    PubMed

    Karger, S; Geiser, B; Grau, M; Heuwieser, W; Arlt, S P

    2017-04-01

    Progressive motility is usually estimated by visual inspection using a light contrast microscope at X 100 immediately after semen collection or immediately after thawing frozen semen. Standard operating procedures have never been established for this test. The objective of this experiment was to examine time-dependent changes of motility after thawing cryopreserved canine semen. Semen of 35 dogs was collected, and volume, concentration, progressive motility, morphology, membrane integrity and HOS test were evaluated. For cryopreservation, CaniPRO(®) Freeze A&B was used. Semen was thawed and diluted using CaniPRO(®) culture medium. After thawing, semen was evaluated as before. In addition, every sample was evaluated for progressively motile sperm cells 0, 5, 20 and 60 min after thawing. Progressive semen motility was significantly highest five minutes after thawing.

  12. EEG signal analysis: a survey.

    PubMed

    Subha, D Puthankattil; Joseph, Paul K; Acharya U, Rajendra; Lim, Choo Min

    2010-04-01

    The EEG (Electroencephalogram) signal indicates the electrical activity of the brain. They are highly random in nature and may contain useful information about the brain state. However, it is very difficult to get useful information from these signals directly in the time domain just by observing them. They are basically non-linear and nonstationary in nature. Hence, important features can be extracted for the diagnosis of different diseases using advanced signal processing techniques. In this paper the effect of different events on the EEG signal, and different signal processing methods used to extract the hidden information from the signal are discussed in detail. Linear, Frequency domain, time - frequency and non-linear techniques like correlation dimension (CD), largest Lyapunov exponent (LLE), Hurst exponent (H), different entropies, fractal dimension(FD), Higher Order Spectra (HOS), phase space plots and recurrence plots are discussed in detail using a typical normal EEG signal.

  13. Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells

    SciTech Connect

    Komm, B.S.; Terpening, C.M.; Benz, D.J.; Graeme, K.A.; Gallegos, A.; Korc, M.; Greene, G.L.; O'Malley, B.W.; Haussler, M.R.

    1988-07-01

    High specific activity estradiol labeled with iodine-125 was used to detect approximately 200 saturable, high-affinity (dissociation constant approximately equal to 1.0 nM) nuclear binding sites in rat (ROS 17/2.8) and human (HOS TE85) clonal osteoblast-like osteosarcoma cells. Of the steroids tested, only testosterone exhibited significant cross-reactivity with estrogen binding. RNA blot analysis with a complementary DNA probe to the human estrogen receptor revealed putative receptor transcripts of 6 to 6.2 kilobases in both rat and human osteosarcoma cells. Type I procollagen and transforming growth factor-beta messenger RNA levels were enhanced in cultured human osteoblast-like cells treated with 1 nM estradiol. Thus, estrogen can act directly on osteoblasts by a receptor-mediated mechanism and thereby modulate the extracellular matrix and other proteins involved in the maintenance of skeletal mineralization and remodeling.

  14. Support vector machine-based expert system for reliable heartbeat recognition.

    PubMed

    Osowski, Stanislaw; Hoai, Linh Tran; Markiewicz, Tomasz

    2004-04-01

    This paper presents a new solution to the expert system for reliable heartbeat recognition. The recognition system uses the support vector machine (SVM) working in the classification mode. Two different preprocessing methods for generation of features are applied. One method involves the higher order statistics (HOS) while the second the Hermite characterization of QRS complex of the registered electrocardiogram (ECG) waveform. Combining the SVM network with these preprocessing methods yields two neural classifiers, which have been combined into one final expert system. The combination of classifiers utilizes the least mean square method to optimize the weights of the weighted voting integrating scheme. The results of the performed numerical experiments for the recognition of 13 heart rhythm types on the basis of ECG waveforms confirmed the reliability and advantage of the proposed approach.

  15. [Age of the woman and spontaneous and induced abortions].

    PubMed

    Gizicki, Z

    1972-04-01

    From 1960 to 1970, 4710 women were admitted to the Zywiec County Hos pital, 2655 for spontaneous abortion and 2055 to have artificial abortio n performed. A significant difference between the age ranges of these 2 groups(chi square = 51.0; p less than .001). Differences were noted in 3 age classes: 21-25 years (U=3.75, p less than .001), 26-30 years (U=2.62, p less than .001), and 31-35 years (U=3.838, p less than .001). Spontaneous abortions prevail in teh 1st group, while in the other 2 groups, artificial abortions are more frequent. In the 3rd group, the number of spontaneous abortions and artificial abortions are almost equal. A high frequency of both types of abortions was noted in the middle group (26-30).

  16. Etude structurale des sulfotellurures de terres rares ( LS) 2Te 1 + x ( L = Tb, Dy, Ho, Er, Tm et Y). II. Surstructure des phases ordonnées. Macles d'ordre

    NASA Astrophysics Data System (ADS)

    Ghémard, Geneviève; Etienne, Jean; Schiffmacher, Gérard; Flahaut, Jean

    1982-11-01

    The ( LS) 2Te 1 + x compounds have an orthorhombic subcell, with a layered structure and vacant Te sites, and a monoclinic superstructure ( a = b = 6.658, c = 13.657 Å, γ = 102°43' for (HoS) 2Te 1.34). The order-disorder transition occurs at about 450°C. In the superstructure Te planes between ( L4S) tetrahedra layers are ordered with {B2}/{m} symmetry; however, some sites remain partially vacant. The S atoms conserve mmm symmetry, but the metallic atoms are slightly displaced from their substructure position ( R = 0.037). Ordering occurs so that each Te plane can be oriented in two different ways. Therefore, there are two kinds of domains, with respect to a twinning rule. These domains are observed by direct-imaging high-resolution electronic microscopy and are about 100 Å wide.

  17. Towards non-cooperative standoff biometrics using extremely low frequency (ELF) processing

    NASA Astrophysics Data System (ADS)

    Byrd, Kenneth A.; Szu, Harold; Wardlaw, Michael J.

    2009-04-01

    Earth's Field Nuclear Magnetic Resonance (⊕-NMR) is a novel detection technique that exploits the uniformity of the earth's magnetic field to measure precessing magnetizations of isotope-having objects such as human beings. The ability to provide standoff medical surveillance will increase the Biomedical Wellness (BMW) of not only aging American citizens but also persons we seek to track from healthy to diseased states. Taking advantage of the uniform field in the earth, spatio-temporal integration (3 orders due to time and 4 orders due to space) and Higher Order Statistics (HOS), namely, change detection via kurtosis (ΔK), SNR and the ability to make non-locality measurements may be increased to at least the level of the typical hospital NMR devices. Moreover, we present theoretical calculations of magnitude and consider time dynamics of the resonant/relaxing magnetic fields as a function of 3D human motion and distance.

  18. Outcomes of Hip Arthroscopic Surgery in Patients With Tönnis Grade 1 Osteoarthritis With a Minimum 2-Year Follow-up: Evaluation Using a Matched-Pair Analysis With a Control Group With Tönnis Grade 0.

    PubMed

    Chandrasekaran, Sivashankar; Gui, Chengcheng; Darwish, Nader; Lodhia, Parth; Suarez-Ahedo, Carlos; Domb, Benjamin G

    2016-07-01

    There are limited studies on the effect of mild osteoarthritis (OA) on outcomes of hip arthroscopic surgery. To conduct a matched-pair analysis with a minimum 2-year follow-up to evaluate outcomes after hip arthroscopic surgery in patients with Tönnis grade 1 OA. Cohort study; Level of evidence, 3. Data were prospectively collected on patients who underwent hip arthroscopic surgery between April 2008 and December 2012. Patients were excluded if they had previous hip conditions. The remaining patients were divided into either Tönnis 0 or 1 grade OA groups and were matched in a 1-to-1 ratio according to age within 5 years, sex, body mass index category, labral treatment, and capsular treatment. Four patient-reported outcome (PRO) scores, as well as the visual analog scale (VAS) score for pain, patient satisfaction, and rates of revision arthroscopic surgery and conversion to total hip arthroplasty (THA), were recorded. A total of 1412 hip arthroscopic procedures were performed during the study period, of which 1036 met the inclusion criteria and 892 (86.1%) had 2-year follow-up. There were 738 and 154 patients with Tönnis grade 0 and 1, respectively; 93 patients were matched in each group. The Tönnis grade 0 group had a mean follow up of 28.7 months (range, 23.5-67.9 months), and the Tönnis grade 1 group had a mean follow up of 31.5 months (range, 23.6-63.5 months). Both groups demonstrated a significant improvement in all PROs and the VAS at a minimum 2-year follow-up. For the Tönnis grade 0 group, the improvements (in points) in the PROs were as follows: modified Harris Hip Score (mHHS), 15.51; Nonarthritic Hip Score (NAHS), 20.65; Hip Outcome Score-Activities of Daily Living (HOS-ADL), 16.83; and Hip Outcome Score-Sport-Specific Subscale (HOS-SSS), 20.91. The VAS score for the Tönnis grade 0 group decreased by 2.82 points. For the Tönnis grade 1 group, the improvements (in points) in the PROs were as follows: mHHS, 19.52; NAHS, 20.96; HOS-ADL, 18.20; and

  19. Exposure to high fluoride concentration in drinking water will affect spermatogenesis and steroidogenesis in male albino rats.

    PubMed

    Pushpalatha, T; Srinivas, M; Sreenivasula Reddy, P

    2005-06-01

    Sodium fluoride (NaF) administered orally to adult male rats at a dose level of 4.5 ppm and 9.0 ppm for 75 days caused significant decrease in the body weight, brain index and testicular index. A significant decrease in sperm count, sperm motility, sperm viability and sperm function (HOS positive) with increased sperm abnormalities was also observed in NaF-exposed male rats. The activity levels of testicular steroidogenic marker enzymes 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) were significantly decreased in NaF-treated rats indicating decreased steroidogenesis and in turn spermatogenesis in rats exposed to NaF.

  20. Genetic Algorithms for solving SVM-ICA

    NASA Astrophysics Data System (ADS)

    Górriz, J. M.; Puntonet, C. G.

    2004-11-01

    In this paper we solve the well known ill-posed problem called Independent Component Analysis using the Support Vector Machines (SVM) methodology and proposing a genetic algorithm to minimize a nonconvex and nonlinear cost function based on statistical estimators. In this way a novel method for blindly separating unobservable independent component signals from their linear and non linear (using mapping functions) mixtures is devised. The GA presented in this work is able to extract independent components with faster rate than the previous independent component analysis algorithms based on Higher Order Statistics (HOS) as input space dimension increases showing significant accuracy and robustness. Using a suitable mathematically notation we derive independent functions equivalent to the Maximum Entropy principle.

  1. An Improved Fast Photochemical Oxidation of Proteins (FPOP) Platform for Protein Therapeutics

    NASA Astrophysics Data System (ADS)

    Zhang, Ying; Rempel, Don L.; Zhang, Hao; Gross, Michael L.

    2015-03-01

    Unlike small-molecule drugs, the size and dynamics of protein therapeutics challenge existing methods for assessing their high order structures (HOS). To extend fast photochemical oxidation of proteins (FPOP) to protein therapeutics, we modified its platform by introducing a mixing step prior to laser irradiation to minimize unwanted H2O2-induced oxidation. This improvement plus standardizing each step yield better reproducibility as determined by a fitting process whereby we used a non-FPOP spectrum as a template to report the unmodified level. We also tested different buffer systems for this modified FPOP platform with cytochrome c. The outcome is a standard oxidation profile that can be compared between different laboratories and regulatory agencies that wish to adopt FPOP for quality control purposes.

  2. Pile Transfer Function,

    DTIC Science & Technology

    2007-11-02

    J i/ (1) B dt ii d Ci/B _fi nA ClB (2) dt T where: fi Bi/B n = neutron flux I - mean life of a neutron Bi= % of group-i fission neutrons B = % of...ratio of the Laplace transforms of the output and input. It consists of K = a constant, or frequency invariant portion, and G(s) = the frequency variant...B J dt - AECD-326o Substituting in (1) and using (3): dn _(• 1)n f i n- jd(Ci/B3 (8) B dt ii dt By (4) i(5): ýLn = hoS ý n’ 8 - n f in _ d(i/ (9)Sdn

  3. An improved fast photochemical oxidation of proteins (FPOP) platform for protein therapeutics.

    PubMed

    Zhang, Ying; Rempel, Don L; Zhang, Hao; Gross, Michael L

    2015-03-01

    Unlike small-molecule drugs, the size and dynamics of protein therapeutics challenge existing methods for assessing their high order structures (HOS). To extend fast photochemical oxidation of proteins (FPOP) to protein therapeutics, we modified its platform by introducing a mixing step prior to laser irradiation to minimize unwanted H(2)O(2)-induced oxidation. This improvement plus standardizing each step yield better reproducibility as determined by a fitting process whereby we used a non-FPOP spectrum as a template to report the unmodified level. We also tested different buffer systems for this modified FPOP platform with cytochrome c. The outcome is a standard oxidation profile that can be compared between different laboratories and regulatory agencies that wish to adopt FPOP for quality control purposes.

  4. Classification of epilepsy using high-order spectra features and principle component analysis.

    PubMed

    Du, Xian; Dua, Sumeet; Acharya, Rajendra U; Chua, Chua Kuang

    2012-06-01

    The classification of epileptic electroencephalogram (EEG) signals is challenging because of high nonlinearity, high dimensionality, and hidden states in EEG recordings. The detection of the preictal state is difficult due to its similarity to the ictal state. We present a framework for using principal components analysis (PCA) and a classification method for improving the detection rate of epileptic classes. To unearth the nonlinearity and high dimensionality in epileptic signals, we extract principal component features using PCA on the 15 high-order spectra (HOS) features extracted from the EEG data. We evaluate eight classifiers in the framework using true positive (TP) rate and area under curve (AUC) of receiver operating characteristics (ROC). We show that a simple logistic regression model achieves the highest TP rate for class "preictal" at 97.5% and the TP rate on average at 96.8% with PCA variance percentages selected at 100%, which also achieves the most AUC at 99.5%.

  5. 10,000-Hour Cyclic Oxidation Behavior at 982 C (1800 F) of 68 High-Temperature Co-, Fe-, and Ni-Base Alloys

    NASA Technical Reports Server (NTRS)

    Barrett, Charles A.

    1997-01-01

    Sixty-eight high temperature Co-, Fe-, and Ni-base alloys were tested for 10-one thousand hour cycles in static air at 982 C (1800 F). The oxidation behavior of the test samples was evaluated by specific weight change/time data, x-ray diffraction of the post-test samples, and their final appearance. The gravimetric and appearance data were combined into a single modified oxidation parameter, KB4 to rank the cyclic oxidation resistance from excellent to catastrophic. The alloys showing the 'best' resistance with no significant oxidation attack were the alumina/aluminate spinel forming Ni-base turbine alloys: U-700, NASA-VIA and B-1900; the Fe-base ferritic alloys with Al: TRW-Valve, HOS-875, NASA-18T, Thermenol and 18SR; and the Ni-base superalloy IN-702.

  6. Relationship of death anxiety/fear to health-seeking beliefs and behaviors.

    PubMed

    Knight, K H; Elfenbein, M H

    1996-01-01

    The relationship of death anxiety/fear to health beliefs and behaviors was examined. One hundred and three college students completed the modified Death Anxiety Scale (DAS), the Death Anxiety Questionnaire (DAQ), the Death Attitude Profile (DAP), the Health Opinion Survey (HOS), and an item asking whether the participant had visited a physician at least once a year for a routine examination. The results indicated that those scoring higher on the DAS were less likely to be actively involved in their health care. Males were found to be less likely to prefer health information and to visit the doctor for an annual routine examination than females. In addition, females with high death anxiety (DAQ) were more likely to prefer health information than males with high death anxiety. These results underscore the need to examine the relationship of gender role to health-related beliefs.

  7. Siegenberg Germany Gunnery Range, Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

    DTIC Science & Technology

    1971-10-28

    PERrORMING OGANZ𔃺.. %k.4E A% tD ADODESS b E t E’ U SAFETAC/OL-A A .6_q 1 S 5 Air Force Environmental Technical Appl. Center Scott AFB IL 62225 1% ’K...INNERY RANGE 64070 JUL S51ONSAT-CV NAE YER S=N PERCENTAGE FREQUENCY OF OCCURRENCE OF WEATHER CONDZTIONS FROM HOURLY OBSERVATIONS MONTH HOS T .RAIN...10 !1 - .6 17 . 21 22 - 27 28 -33 34 40 Al - 48 55 >$6 % WIND DIR. AS " S EE D N. 7! 00 Is 798_--4,61’T NN ENE td ;1 _____ 1 - 3j~Z~ SSE $61 . -_ 1

  8. The Semen pH Affects Sperm Motility and Capacitation.

    PubMed

    Zhou, Ji; Chen, Li; Li, Jie; Li, Hongjun; Hong, Zhiwei; Xie, Min; Chen, Shengrong; Yao, Bing

    2015-01-01

    As the chemical environment of semen can have a profound effect on sperm quality, we examined the effect of pH on the motility, viability and capacitation of human sperm. The sperm in this study was collected from healthy males to avoid interference from other factors. The spermatozoa cultured in sperm nutrition solution at pH 5.2, 6.2, 7.2 and 8.2 were analyzed for sperm total motility, progressive motility (PR), hypo-osmotic swelling (HOS) rate, and sperm penetration. Our results showed that these parameters were similar in pH 7.2 and 8.2 sperm nutrition solutions, but decreased in pH 5.2 and 6.2 solutions. The HOS rate exhibited positive correlation with the sperm total motility and PR. In addition, the sperm Na(+)/K(+)-ATPase activity at different pHs was measured, and the enzyme activity was significantly lower in pH 5.2 and 6.2 media, comparing with that in pH 8.2 and pH 7.2 solutions. Using flow cytometry (FCM) and laser confocal scanning microscopy (LCSM) analysis, the intracellular Ca2(+ )concentrations of sperm cultured in sperm capacitation solution at pH 5.2, 6.2, 7.2 and 8.2 were determined. Compared with that at pH 7.2, the mean fluorescence intensity of sperm in pH 5.2 and 6.2 media decreased significantly, while that of pH 8.2 group showed no difference. Our results suggested that the declined Na(+)/K(+)-ATPase activity at acidic pHs result in decreased sperm movement and capacitation, which could be one of the mechanisms of male infertility.

  9. Application of power spectrum, cepstrum, higher order spectrum and neural network analyses for induction motor fault diagnosis

    NASA Astrophysics Data System (ADS)

    Liang, B.; Iwnicki, S. D.; Zhao, Y.

    2013-08-01

    The power spectrum is defined as the square of the magnitude of the Fourier transform (FT) of a signal. The advantage of FT analysis is that it allows the decomposition of a signal into individual periodic frequency components and establishes the relative intensity of each component. It is the most commonly used signal processing technique today. If the same principle is applied for the detection of periodicity components in a Fourier spectrum, the process is called the cepstrum analysis. Cepstrum analysis is a very useful tool for detection families of harmonics with uniform spacing or the families of sidebands commonly found in gearbox, bearing and engine vibration fault spectra. Higher order spectra (HOS) (also known as polyspectra) consist of higher order moment of spectra which are able to detect non-linear interactions between frequency components. For HOS, the most commonly used is the bispectrum. The bispectrum is the third-order frequency domain measure, which contains information that standard power spectral analysis techniques cannot provide. It is well known that neural networks can represent complex non-linear relationships, and therefore they are extremely useful for fault identification and classification. This paper presents an application of power spectrum, cepstrum, bispectrum and neural network for fault pattern extraction of induction motors. The potential for using the power spectrum, cepstrum, bispectrum and neural network as a means for differentiating between healthy and faulty induction motor operation is examined. A series of experiments is done and the advantages and disadvantages between them are discussed. It has been found that a combination of power spectrum, cepstrum and bispectrum plus neural network analyses could be a very useful tool for condition monitoring and fault diagnosis of induction motors.

  10. CXCR4 antibody treatment suppresses metastatic spread to the lung of intratibial human osteosarcoma xenografts in mice.

    PubMed

    Brennecke, Patrick; Arlt, Matthias J E; Campanile, Carmen; Husmann, Knut; Gvozdenovic, Ana; Apuzzo, Tiziana; Thelen, Marcus; Born, Walter; Fuchs, Bruno

    2014-03-01

    Current combined surgical and neo-adjuvant chemotherapy of primary metastatic osteosarcoma (OS) is ineffective, reflected by a 5-year survival rate of affected patients of less than 20 %. Studies in experimental OS metastasis models pointed to the CXCR4/CXCL12 homing axis as a novel target for OS metastasis-suppressive treatment. The present study investigated for the first time the CXCR4-blocking principle in a spontaneously metastasizing human 143B OS cell line-derived orthotopic xenograft mouse model. The highly metastatic 143B cells, unlike the parental non-metastatic HOS cells, express functional CXCR4 receptors at the cell surface, as revealed in this study by RT/PCR of gene transcripts, by FACS analysis with the monoclonal anti CXCR4 antibody 12G5 (mAb 12G5) and by CXCL12 time- and dose-dependent stimulation of AKT and ERK phosphorylation. A significantly (p < 0.05) higher CXCL12 dose-dependent chemotactic response of 143B compared to HOS cells in a Boyden chamber trans-well migration assay suggested a crucial role of the CXCL12/CXCR4 homing axis in 143B cell lung metastasis. Repetitive treatment of mice with 143B cell-derived intratibial tumors given intravenous bolus injections of mAb12G5 indeed inhibited significantly (p < 0.01) the number of X-gal-stainable lung micrometastases of lacZ-transduced 143B cells. Antibody treatment had also a mild inhibitory effect on primary tumor growth associated with remarkably less osteolysis, but it did not affect the number of developing lung macrometastases. In conclusion, these results demonstrate considerable potential of high-affinity CXCR4-blocking agents for OS tumor cell homing suppressive treatment in metastasizing OS complementary to current (neo)-adjuvant chemotherapy.

  11. MiR-34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene

    PubMed Central

    Pu, Youguang; Zhao, Fangfang; Wang, Haiyan; Cai, Shanbao

    2017-01-01

    MiR-34a-5p has been implicated in the tumorigenesis and progression of several types of cancer. However, the role of miR-34a-5p in osteosarcoma (OS) remains largely unknown. This study was performed in two multi-chemosensitive (G-292 and MG63.2) and two resistant (SJSA-1 and MNNG/HOS) OS cell lines. MiR-34a-5p promotes OS multi-chemoresistance via its repression of the Delta-like ligand 1 (DLL1) gene, the ligand of the Notch pathway, and thus negatively correlates with OS chemoresistance. The siRNA-mediated repression of the DLL1 gene suppressed cell apoptosis and de-sensitized G-292 and MG63.2 cells, while overexpression of DLL1 sensitized SJSA-1 and MNNG/HOS cells to drug-induced cell death. In agreement with the changes in the drug-induced cell death, the activity of the ATF2/ATF3/ATF4 signaling pathway was significantly altered by a forced reversal of miR-34a-5p or DLL1 levels in OS cells. DLL1 is a target of miR-34a-5p and negatively regulates the multi-chemoresistance of OS. This study suggested that miR-34a-5p, DLL1 and the ATF2/ATF3/ATF4 signaling pathway-associated genes are the potential diagnostic and/or therapeutic targets for an effective chemotherapy of OS. Our results also provide novel insights into the effective chemotherapy for OS patients. PMID:28281638

  12. Highly and Broad-Spectrum In Vitro Antitumor Active cis-Dichloridoplatinum(II) Complexes with 7-Azaindoles

    PubMed Central

    Štarha, Pavel; Dvořák, Zdeněk; Trávníček, Zdeněk

    2015-01-01

    The cis-[PtCl2(naza)2] complexes (1–3) containing monosubstituted 7-azaindole halogeno-derivatives (naza), showed significantly higher activity than cisplatin towards ovarian carcinoma A2780, its cisplatin-resistant variant A2780R, osteosarcoma HOS, breast carcinoma MCF7 and cervix carcinoma HeLa cell lines, with the IC50 values of 3.8, 3.5, 4.5, 2.7, and 9.2 μM, respectively, obtained for the most active complex 3. As for 4 and 5 having disubstituted 7-azaindoles in their molecule, the significant cytotoxicity was detected only for 4 against A2780 (IC50 = 4.8 μM), A2780R (IC50 = 3.8 μM) and HOS (IC50 = 4.3 μM), while 5 was evaluated as having only moderate antiproliferative effect against the mentioned cancer cell lines with IC50 = 33.4, 24.7 and 46.7 μM, respectively. All the studied complexes 1–5 effectively avoided the acquired resistance of ovarian carcinoma cell line. On the other hand, the complexes did not reveal any inhibition activity on the purified 20S proteasome from the A2780 cells. The representative complexes 3 and 5 showed low ability to be hydrolysed, but their stability was markedly lowered in the presence of physiological sulphur-containing biomolecule glutathione (GSH), as proved by the 1H NMR spectroscopy and mass spectrometry studies. A rate of interaction of the studied complexes with GSH was affected by an addition of another mechanistically relevant biomolecule guanosine monophosphate. The differences in interactions of 3 and 5 with GSH correlate well with their different cytotoxicity profiles. PMID:26309251

  13. Radiation exposure from depleted uranium: The radiation bystander effect.

    PubMed

    Miller, Alexandra C; Rivas, Rafael; Tesoro, Leonard; Kovalenko, Gregor; Kovaric, Nikola; Pavlovic, Peter; Brenner, David

    2017-09-15

    Depleted uranium (DU) is a radioactive heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalized human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. In vivo studies have also demonstrated that DU is leukemogenic and genotoxic. DU possesses both a radiological (alpha particle) and chemical (metal) component but is generally considered a chemical biohazard. Studies have shown that alpha particle radiation does play a role in DU's toxic effects. Evidence has accumulated that non-irradiated cells in the vicinity of irradiated cells can have a response to ionization events. The purpose of this study was to determine if these "bystander effects" play a role in DU's toxic and neoplastic effects using HOS cells. We investigated the bystander responses between DU-exposed cells and non-exposed cells by co-culturing the two equal populations. Decreased cell survival and increased neoplastic transformation were observed in the non-DU exposed cells following 4 or 24h co-culture. In contrast Ni (II)- or Cr(VI)- exposed cells were unable to alter those biological effects in non-Ni(II) or non-Cr(VI) exposed co-cultured cells. Transfer experiments using medium from the DU-exposed and non-exposed co-cultured cells was able to cause adverse biological responses in cells; these results demonstrated that a factor (s) is secreted into the co-culture medium which is involved in this DU-associated bystander effect. This novel effect of DU exposure could have implications for radiation risk and for health risk assessment associated with DU exposure. Copyright © 2017. Published by Elsevier Inc.

  14. Ischiofemoral impingement and hamstring dysfunction as a potential pain generator after ischial tuberosity apophyseal fracture non-union/malunion.

    PubMed

    Spencer-Gardner, Luke; Bedi, Asheesh; Stuart, Michael J; Larson, Christopher M; Kelly, Bryan T; Krych, Aaron J

    2017-01-01

    The purpose of this study was to describe the occurrence of ischiofemoral impingement (IFI) and hamstring dysfunction following malunion or non-union of ischial tuberosity apophyseal avulsion fractures and report the short-term outcomes of surgical treatment with regard to alleviating symptomatic extra-articular impingement. All patients who underwent surgery for recalcitrant hip and buttock pain in the setting of prior ischial tuberosity avulsion fracture at three tertiary-level hip preservation centres were included for this review. A total of ten patients met our inclusion criteria and underwent sciatic neurolysis, resection of the ischial tuberosity fragment and hamstring reattachment. Clinical outcomes scores were collected post-operatively including the Modified Harris Hip Score (mHHS) and the Hip Outcomes Score (HOS). Ten patients with a mean age of 18 years (range 14-28) underwent surgery for symptomatic ischiofemoral impingement after ischial tuberosity avulsion fracture. At a mean of 2.2-year follow-up (range 1.7-3.5), the median post-operative mHHS was 89.7 (65.7-96.8) and HOS ADL and Sport subscales were 90 % or greater in all cases. Five patients (50 %) rated their hip as normal, and five patients (50 %) rated their hip as near normal. Malunion or non-union following ischial tuberosity apophyseal fracture can lead to IFI and hamstring dysfunction. Clinically, the resultant pain and dysfunction is often chronic, and can be debilitating. In select cases, a reliable surgical technique is presented to improve hamstring function and correct ischiofemoral impingement in this setting with good-to-excellent outcomes in the majority of cases at short-term follow-up. IV.

  15. Performance improvement of junctionless field effect transistors using p-GaAs/AlGaAs heterostructure

    NASA Astrophysics Data System (ADS)

    Bajelan, F.; Goharrizi, A. Yazdanpanah; Faez, R.; Darvish, G.

    2017-10-01

    The performance analysis of junctionless (JL) gate-all-around (GAA) metal oxide semiconductor field effect transistors (MOSFETs) is investigated using the Non-Equilibrium Green's Function (NEGF) formalism. The main problem of JL transistors is found to be the OFF-state current. In the present work, the OFF-state current of such devices is decreased by choosing channel materials with a large band gap and heavy effective mass. Our simulation results show that the OFF-state current of JL transistors with p-type GaAs is less than that of n-type GaAs. Plus, the heterostructure (HES) channel is proposed in this study for improving the device characteristics of JL-FETs as compared to homostructure (HOS). Therefore, p-type GaAs and GaAs/AlGaAs are used as the channel material for HOS and HES devices, respectively. The simulation is performed for different thicknesses of GaAs and AlGaAs with a fixed diameter of 5 nm for the nanowire. It is shown that the optimum electronic characteristics of HES devices is achieved when the thicknesses of GaAs and AlGaAs layers are chosen to be 0.5 nm and 4 nm, respectively. OFF-state current (IOFF) of 5.32 × 10-16 A, ON-state current (ION) of 6.44 × 10-6 A, ON/OFF current ratio (ION/IOFF) of 1.21 × 1010, subthreshold slope (SS) of 60.8 mV/dec, drain induced barrier lowering (DIBL) of 4.6 mV/V, and threshold voltage (VTH) of 330 mV are obtained for the proposed HES JL-GAA-FET.

  16. Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication.

    PubMed

    Merli, Marcelo L; Cirulli, Brenda A; Menéndez-Bravo, Simón M; Cricco, Julia A

    2017-06-27

    Trypanosoma cruzi, the causative agent of Chagas disease, presents a complex life cycle and adapts its metabolism to nutrients' availability. Although T. cruzi is an aerobic organism, it does not produce heme. This cofactor is acquired from the host and is distributed and inserted into different heme-proteins such as respiratory complexes in the parasite's mitochondrion. It has been proposed that T. cruzi's energy metabolism relies on a branched respiratory chain with a cytochrome c oxidase-type aa3 (CcO) as the main terminal oxidase. Heme A, the cofactor for all eukaryotic CcO, is synthesized via two sequential enzymatic reactions catalyzed by heme O synthase (HOS) and heme A synthase (HAS). Previously, TcCox10 and TcCox15 (Trypanosoma cruzi Cox10 and Cox15 proteins) were identified in T. cruzi They presented HOS and HAS activity, respectively, when they were expressed in yeast. Here, we present the first characterization of TcCox15 in T. cruzi, confirming its role as HAS. It was differentially detected in the different T. cruzi stages, being more abundant in the replicative forms. This regulation could reflect the necessity of more heme A synthesis, and therefore more CcO activity at the replicative stages. Overexpression of a non-functional mutant caused a reduction in heme A content. Moreover, our results clearly showed that this hindrance in the heme A synthesis provoked a reduction on CcO activity and, in consequence, an impairment on T. cruzi survival, proliferation and infectivity. This evidence supports that T. cruzi depends on the respiratory chain activity along its life cycle, being CcO an essential terminal oxidase. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  17. Seasonal changes in semen quality and freezability in the Warmblood stallion.

    PubMed

    Janett, F; Thun, R; Niederer, K; Burger, D; Hässig, M

    2003-08-01

    The objective of this study was to investigate seasonal changes in stallion semen quality and to determine the best time for semen cryopreservation. Experiments were performed using 10 Warmblood stallions from the National Stud Farm in Avenches (Switzerland). Ejaculates were collected and frozen every other week during 1 year from January to December 1999. Volume, concentration, and motility, and the number of morphologically normal sperm and sperm with major defects (abnormal heads, acrosome defects, nuclear vacuoles, proximal droplets, abnormal midpieces) were evaluated. For all frozen-thawed semen samples motility as well as viability (SYBR-14/PI) was tested, and the hypoosmotic swelling test (HOS) was performed. To analyze seasonal differences 4 periods of 3 months each were defined: autumn (September, October, November), winter (December, January, February), spring (March, April, May) and summer (June, July, August). During the 1 year experiment all semen quality parameters showed a clear seasonal pattern. The volume, total sperm count and motility in fresh semen were significantly higher (P<0.05) in summer than in winter, while sperm concentration was significantly lower in summer compared to the other seasons. Regarding morphology, normal sperm was significantly lower (P<0.05) in summer than at any other time of the year and higher values (P<0.05) were found for major defects in summer than in spring and autumn. In frozen-thawed semen motility was significantly (P<0.05) improved in autumn when compared to spring and summer. Viability was lowest in summer and differed significantly (P<0.05) from other seasons. The HOS test revealed significantly more (P<0.05) membrane damaged spermatozoa in winter than in spring, summer and autumn. Our results demonstrate that in our climatic conditions clear seasonal differences occur in semen quality of fresh and frozen-thawed semen and that cryopreservation of stallion semen should preferably be performed in autumn.

  18. ActiveSeismoPick3D - automatic first arrival determination for large active seismic arrays

    NASA Astrophysics Data System (ADS)

    Paffrath, Marcel; Küperkoch, Ludger; Wehling-Benatelli, Sebastian; Friederich, Wolfgang

    2016-04-01

    We developed a tool for automatic determination of first arrivals in active seismic data based on an approach, that utilises higher order statistics (HOS) and the Akaike information criterion (AIC), commonly used in seismology, but not in active seismics. Automatic picking is highly desirable in active seismics as the number of data provided by large seismic arrays rapidly exceeds of what an analyst can evaluate in a reasonable amount of time. To bring the functionality of automatic phase picking into the context of active data, the software package ActiveSeismoPick3D was developed in Python. It uses a modified algorithm for the determination of first arrivals which searches for the HOS maximum in unfiltered data. Additionally, it offers tools for manual quality control and postprocessing, e.g. various visualisation and repicking functionalities. For flexibility, the tool also includes methods for the preparation of geometry information of large seismic arrays and improved interfaces to the Fast Marching Tomography Package (FMTOMO), which can be used for the prediction of travel times and inversion for subsurface properties. Output files are generated in the VTK format, allowing the 3D visualization of e.g. the inversion results. As a test case, a data set consisting of 9216 traces from 64 shots was gathered, recorded at 144 receivers deployed in a regular 2D array of a size of 100 x 100 m. ActiveSeismoPick3D automatically checks the determined first arrivals by a dynamic signal to noise ratio threshold. From the data a 3D model of the subsurface was generated using the export functionality of the package and FMTOMO.

  19. Application of higher order cumulant features for cardiac health diagnosis using ECG signals.

    PubMed

    Martis, Roshan Joy; Acharya, U Rajendra; Lim, Choo Min; Mandana, K M; Ray, A K; Chakraborty, Chandan

    2013-08-01

    Electrocardiogram (ECG) is the electrical activity of the heart indicated by P, Q-R-S and T wave. The minute changes in the amplitude and duration of ECG depicts a particular type of cardiac abnormality. It is very difficult to decipher the hidden information present in this nonlinear and nonstationary signal. An automatic diagnostic system that characterizes cardiac activities in ECG signals would provide more insight into these phenomena thereby revealing important clinical information. Various methods have been proposed to detect cardiac abnormalities in ECG recordings. Application of higher order spectra (HOS) features is a seemingly promising approach because it can capture the nonlinear and dynamic nature of the ECG signals. In this paper, we have automatically classified five types of beats using HOS features (higher order cumulants) using two different approaches. The five types of ECG beats are normal (N), right bundle branch block (RBBB), left bundle branch block (LBBB), atrial premature contraction (APC) and ventricular premature contraction (VPC). In the first approach, cumulant features of segmented ECG signal were used for classification; whereas in the second approach cumulants of discrete wavelet transform (DWT) coefficients were used as features for classifiers. In both approaches, the cumulant features were subjected to data reduction using principal component analysis (PCA) and classified using three layer feed-forward neural network (NN) and least square-support vector machine (LS-SVM) classifiers. In this study, we obtained the highest average accuracy of 94.52%, sensitivity of 98.61% and specificity of 98.41% using first approach with NN classifier. The developed system is ready clinically to run on large datasets.

  20. T-box family of transcription factor-TBX5, insights in development and disease.

    PubMed

    Zhu, Ting; Qiao, Longwei; Wang, Qian; Mi, Rui; Chen, Jinnan; Lu, Yaojuan; Gu, Junxia; Zheng, Qiping

    2017-01-01

    The T-box gene family refers to a group of transcription factors that share a highly conserved, sequence-specific DNA-binding domain (T-box) containing around 180-amino acids. According to HUGO gene nomenclature committee (HGNC), there are 18 T-box family members. These T-box genes have been implicated essential roles during embryogenesis and cardiac development, given their specific expression pattern in developing mammalian heart for several T-box genes, including TBX5. TBX5 is consisted of three transcriptional variants which cover 9 exons and encode two distinct isoforms that differ in N-terminus. TBX5 is probably the most frequently studied T-box gene over the past decade due to the typical cardiac defects observed in Holt-Oram syndrome (HOS), which is caused by TBX5 mutation. Most of the mutations are within exons 3-7 where locate sequence coding for the T-box domain. Notably, a variety of cardiac defects, as well as abnormalities in limb and other organs have been seen in HOS syndrome with different kinds of TBX5 mutations, suggesting a heterogeneous disease mechanism. We have performed a meta-analysis of TBX5 and found a significant correlation between its single nucleotide polymorphism (SNP) rs3825214 (A to G), and risk of atrial fibrillation and its subtypes, supporting TBX5 as a master transcription factor for cardiac development. In addition, bioinformatics analysis of this SNP identified several TFs that may be affected for their binding affinity with TBX5. Identification and characterization of more TBX5 mutations and SNPs hold promise for therapeutic strategy targeting TBX5 associated developmental abnormalities and diseases.

  1. Selection of viable human spermatozoa with low levels of DNA fragmentation from an immotile population using density gradient centrifugation and magnetic-activated cell sorting.

    PubMed

    Zhang, H; Xuan, X; Yang, S; Li, X; Xu, C; Gao, X

    2017-05-03

    We aimed to determine whether density gradient centrifugation and magnetic-activated cell sorting (DGC-MACS) could select viable spermatozoa, with lower levels of DNA fragmentation, from an immotile population. Analysis involved sixteen patients, each with a sperm count ≥10(7) /mL. All samples were immotile despite exhibiting a live population >40%. Spermatozoa were prepared using DGC-MACS and selected spermatozoa evaluated for membrane and DNA integrity using the hypo-osmotic swelling (HOS) test, vital staining and the TUNEL test. The mean proportion of spermatozoa with an intact membrane in control, DGC and DGC-MACS populations, was 52.5 ± 12.21%, 69.38 ± 7.87% and 81.81 ± 5.29%. The mean proportion of live spermatozoa in control, DGC and DGC-MACS populations, was 65.88 ± 12.77%, 77.25 ± 7.39% and 85.81 ± 5.2%. DGC-MACS reduced the within-sample discrepancy between HOS test and vital stain results from 13.18% to 4.12%. The mean proportion of spermatozoa exhibiting DNA damage in control, DGC and DGC-MACS populations, was 9.56 ± 3.39%, 5.25 ± 1.61% and 2.75 ± 1.13%. Finally, analysis showed that 71.23% of the DNA-fragmented spermatozoa in unprocessed samples were removed following DGC-MACS and that the addition of MACS to an existing DGC protocol reduced fragmented spermatozoa by a further 26.15% compared to DGC alone. Consequently, DGC-MACS is a clinically viable method able to select viable spermatozoa with lower levels of DNA fragmentation from an immotile population. © 2017 Blackwell Verlag GmbH.

  2. Increased electrocatalyzed performance through hairpin oligonucleotide aptamer-functionalized gold nanorods labels and graphene-streptavidin nanomatrix: Highly selective and sensitive electrochemical biosensor of carcinoembryonic antigen.

    PubMed

    Wen, Wei; Huang, Jing-Yi; Bao, Ting; Zhou, Jun; Xia, Hong-Xing; Zhang, Xiu-Hua; Wang, Sheng-Fu; Zhao, Yuan-Di

    2016-09-15

    We report a triplex signal amplification strategy for sensitive biosensing of cancer biomarker by taking advantage of hairpin-shaped oligonucleotide-functionalized gold nanorods (HO-GNRs), graphene and the avidin-biotin reation. The strategy expands electrochemical detection of carcinoembryonic antigen (CEA) by using an aptamer as biosensor's recognition element and HO-GNRs as signal enhancer. To construct this biosensor, the GNR was used as a carrier of horseradish peroxidase (HRP) and HO aptamer with a biotin at the 3'-end and a thiol at the 5'-end, which amplified the electrochemical response because of a large molar ratio of HRP to HO. In the presence of target CEA, the binding reactions of CEA with the loop portions of the HOs caused HOs' loop-stem structure opened and exposed the biotins, and then HRP-GNRs-HO conjugates were captured on graphene and streptavidin modified electrodes via the reaction between the exposed biotins and preimmobilized streptavidins. The accumulation of HRP effectively catalyzed the hydrogen peroxide-mediated oxidation of o-phenylenediamine to generate an electrochemical reduction current for CEA detection. Under optimal conditions, the electrochemical biosensor exhibited a wide dynamic range of 5pgmL(-1) and 50ngmL(-1) toward CEA standards with a low detection limit of 1.5pgmL(-1) (signal-to-noise ratio of 3). The proposed biosensor accurately detected CEA concentration in 8 human serum samples from patients with lung diseases, showing excellent correlations with standard chemiluminescence immunoassay. Furthermore, these results of target DNA detection made it abundantly clear that the proposed strategy can also be extended for detection of other relative biomarkers using different functional DNA structures, which shows great prospects in single-nucleotide polymorphisms analysis, biomedical sensing and application for accurate clinical diseases diagnostic.

  3. Designing Hydrologic Observatories as a Community Resource

    NASA Astrophysics Data System (ADS)

    Hooper, R. P.; Duncan, J. M.

    2004-12-01

    CUAHSI convened a workshop in August 2004 to explore what makes a successful hydrologic observatory. Because of their high cost, only a small number of observatories will be operated, at least initially. (CUAHSI has recommended a pilot network of 5 observatories to develop operational experience and an eventual network of approximately 15 sites.) Because hydrologic scientists can work "in their backyard" (unlike oceanographers or astronomers), hydrologic observatories must offer significant advantages over current methods of field work to successfully attract researchers. Twenty-four teams of scientists submitted "prospectuses" of potential locations for hydrologic observatories for consideration by network attendees. These documents (available at http://www.cuahsi.org) were marketing documents to the workshop participants, who voted for a hypothetical network of 5 observatories from the 24 proposed sites. This network formed the basis for a day of discussions on necessary attributes of core data and how to form a network of observatories from a collection of sites that are designed and implemented individually. Key findings included: 1) Core data must be balanced among disciplines. Although the hydrologic cycle is an organizing principle for the design of HOs, physical data cannot dominate the core data; chemical and biological data, although more expensive to collect, must be given equal footing. 2) New data collection must strategically leverage existing data. Resources are always limited, so that a successful HO must carefully target gaps in existing data, as determined by an explicitly stated conceptual model, and fill them rather than designing an independent study. 3) Site logistics must support remote researchers. Significant resources will be necessary for on-site staff to handle housing, transportation, permitting and other needs. 4) Network-level hypotheses are required early in the implementation of HOs. A network will only emerge around hypotheses

  4. The tumor suppressive role of RASSF1A in osteosarcoma through the Wnt signaling pathway.

    PubMed

    Wang, Wei-Guo; Chen, Shi-Jie; He, Jin-Shen; Li, Jing-Song; Zang, Xiao-Fang

    2016-07-01

    Ras-association domain family 1 isoform A (RASSF1A) is a tumor suppressor gene and its expression is lost in numerous types of cancer cells, including primary osteosarcoma cells. However, its functional significance in osteosarcoma has not been well defined. The messenger RNA (mRNA) expression of RASSF1A in osteosarcoma tissues and corresponding non-tumoral tissues was measured by real-time PCR. Overexpression of RASSF1A was established by an adenoviral vector expressing RASSF1A. Cell migration and invasion were analyzed in transwells. Apoptosis and cell cycle were analyzed using flow cytometry. Wnt/β-catenin activity was measured by TCF reporter dual-luciferase assay. Cell viability was measured by MTT assay. Protein expression was detected by Western blot. RASSF1A mRNA expression was significantly lower in osteosarcoma tissues than that in the corresponding non-tumoral tissues. The lowered RASSF1A expression correlated with the clinical severity of osteosarcoma. rAd-RASSF1A injection significantly inhibited the growth of xenograft MNNG/HOS tumors in mice. Overexpression of RASSF1A resulted in significant inhibition of the proliferation, migration, and invasion; induced apoptosis; and arrested cell cycle at G0/G1 phase in both the MNNG/HOS and SaOS2 cells. Overexpression of RASSF1A inhibited the Wnt/β-catenin activity, decreased phosphorylation of Akt/glycogen synthase kinase-3-β (GSK3-β), and increased phosphorylation of mammalian sterile 20-like kinase 1 (MST1). Overexpression of RASSF1A downregulated the cyclin D1, c-Myc, and matrix metalloproteinase-7 (MMP-7) protein levels. RASSF1A functions as a tumor suppressor in osteosarcoma and exerts anti-cancer roles through regulating Akt/GSK-3-Wnt/β-catenin signaling.

  5. Imatinib Mesylate Exerts Anti-Proliferative Effects on Osteosarcoma Cells and Inhibits the Tumour Growth in Immunocompetent Murine Models

    PubMed Central

    Ory, Benjamin; Charrier, Céline; Brion, Régis; Blanchard, Frederic; Redini, Françoise; Heymann, Dominique

    2014-01-01

    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 status of patients

  6. Ultramicroscopic and biochemical changes in ram spermatozoa cryopreserved with trehalose-based hypertonic extenders.

    PubMed

    Aisen, E; Quintana, M; Medina, V; Morello, H; Venturino, A

    2005-06-01

    The ability of a range of extenders to cryopreserve ram spermatozoa was tested. The extenders were modified by the inclusion of citrate, Tris buffer, trehalose, and EDTA. Ejaculates from three Pampinta rams were evaluated and pooled at 30 degrees C. The semen was diluted to contain 1 x 10(9) cells/mL, cooled to 5 degrees C, loaded into 0.25-mL straws, frozen and stored in liquid nitrogen. Evaluation was based on the hypoosmotic swelling test (HOS test), electron microscopy, and biochemical parameters such as lipid peroxidation and reduced and total glutathione levels, all measured after thawing. The HOS test indicated that the percentage of intact plasma membranes after freezing and thawing was significantly higher for the hypertonic extender containing trehalose (T), compared with an extender containing trehalose+EDTA (TE) or an isotonic Tris extender (B) (p < 0.05). Membrane evaluation by ultramicroscopy also indicated better sperm cryopreservation in extender T compared with the others, and there was a significant reduction in the number of damaged membranes (27%, p < 0.0002). The level of reduced glutathione was significantly higher after sperm cryopreservation in either hypertonic diluent (T and TE) with respect to the isotonic extender B, immediately after thawing (12%) and after a 3-h post-thawing thermotolerance test at 37 degrees C (17%, p = 0.007). Total glutathione levels did not show statistical differences among the extenders. After 3h post-thawing incubation at 37 degrees C, lipid peroxide levels in spermatozoa were statistically lower for T than TE (35%) or isotonic extender B (44%) (p = 0.002). Taken together these results indicate a reduction in the oxidative stress provoked by freezing and thawing when semen is cryopreserved in extender T. The antioxidant properties of extender T may be related to its effectiveness in membrane cryopreservation.

  7. HIV-1 Vpu Promotes Release and Prevents Endocytosis of Nascent Retrovirus Particles from the Plasma Membrane

    PubMed Central

    Neil, Stuart J. D; Eastman, Scott W; Jouvenet, Nolwenn; Bieniasz, Paul D

    2006-01-01

    The human immunodeficiency virus (HIV) type-1 viral protein U (Vpu) protein enhances the release of diverse retroviruses from human, but not monkey, cells and is thought to do so by ablating a dominant restriction to particle release. Here, we determined how Vpu expression affects the subcellular distribution of HIV-1 and murine leukemia virus (MLV) Gag proteins in human cells where Vpu is, or is not, required for efficient particle release. In HeLa cells, where Vpu enhances HIV-1 and MLV release approximately 10-fold, concentrations of HIV-1 Gag and MLV Gag fused to cyan fluorescent protein (CFP) were initially detected at the plasma membrane, but then accumulated over time in early and late endosomes. Endosomal accumulation of Gag-CFP was prevented by Vpu expression and, importantly, inhibition of plasma membrane to early endosome transport by dominant negative mutants of Rab5a, dynamin, and EPS-15. Additionally, accumulation of both HIV and MLV Gag in endosomes required a functional late-budding domain. In human HOS cells, where HIV-1 and MLV release was efficient even in the absence of Vpu, Gag proteins were localized predominantly at the plasma membrane, irrespective of Vpu expression or manipulation of endocytic transport. While these data indicated that Vpu inhibits nascent virion endocytosis, Vpu did not affect transferrin endocytosis. Moreover, inhibition of endocytosis did not restore Vpu-defective HIV-1 release in HeLa cells, but instead resulted in accumulation of mature virions that could be released from the cell surface by protease treatment. Thus, these findings suggest that a specific activity that is present in HeLa cells, but not in HOS cells, and is counteracted by Vpu, traps assembled retrovirus particles at the cell surface. This entrapment leads to subsequent endocytosis by a Rab5a- and clathrin-dependent mechanism and intracellular sequestration of virions in endosomes. PMID:16699598

  8. Influence of substrate modification and C-terminal truncation on the active site structure of substrate-bound heme oxygenase from Neisseriae meningitidis; A 1H NMR study†

    PubMed Central

    Peng, Dungeng; Satterlee, James D.; Ma, Li-Hua; Dallas, Jerry L.; Smith, Kevin M.; Zhang, Xuhong; Sato, Michihiko; La Mar, Gerd N.

    2011-01-01

    Heme oxygenase, HO, from the pathogenic bacterium N. meningitidis, NmHO, which secures host iron, shares many properties with mammalian HOs, but also exhibits some key differences. The crystal structure appears more compact and the crystal-undetected C-terminus interacts with substrate in solution. The unique nature of substrate-protein, specifically pyrrole-I/II-helix-2, peripheral interactions in NmHO are probed by 2D 1H NMR to reveal unique structural features controlling substrate orientation. The thermodynamics of substrate orientational isomerism are mapped for substrates with individual vinyl → methyl → hydrogen substitutions and with enzyme C-terminal deletions. NmHO exhibits significantly stronger orientational preference, reflecting much stronger and selective pyrrole-I/II interactions with the protein matrix, than in mammalian HOs. Thus, replacing bulky vinyls with hydrogens results in a 180° rotation of substrate about the α,γ-meso axis in the active site. A "collapse" of the substrate pocket as substrate size decreases is reflected in movement of helix-2 toward the substrate as indicated by significant and selective increased NOESY cross peak intensity, increase in steric Fe-CN tilt reflected in the orientation of the major magnetic axis, and decrease in steric constraints controlling the rate of aromatic ring reorientation. The active site of NmHO appears "stressed" for native protohemin and its "collapse" upon replacing vinyls by hydrogen leads to a factor ~102 increase in substrate affinity. Interaction of the C-terminus with the active site destabilizes the crystallographic protohemin orientation by ~0.7 kcal/mol, which is consistent with optimizing the His207-Asp27 H-bond. Implications of the active site "stress" for product release are discussed. PMID:21870860

  9. Wnt/β-catenin Signaling Activates Expression of the Bone-related Transcription Factor RUNX2 in Select Human Osteosarcoma Cell Types.

    PubMed

    Vega, Oscar A; Lucero, Claudia M J; Araya, Hector F; Jerez, Sofia; Tapia, Julio C; Antonelli, Marcelo; Salazar-Onfray, Flavio; Las Heras, Facundo; Thaler, Roman; Riester, Scott M; Stein, Gary S; van Wijnen, Andre J; Galindo, Mario A

    2017-03-28

    Osteosarcoma is the most common malignant bone tumor in children and adolescents. Metastasis and poor responsiveness to chemotherapy in osteosarcoma correlates with over-expression of the runt-related transcription factor RUNX2, which normally plays a key role in osteogenic lineage commitment, osteoblast differentiation and bone formation. Furthermore, WNT/β-catenin signaling is over-activated in osteosarcoma and promotes tumor progression. Importantly, the WNT/β-catenin pathway normally activates RUNX2 gene expression during osteogenic lineage commitment. Therefore, we examined whether the WNT/β-catenin pathway controls the tumor-related elevation of RUNX2 expression in osteosarcoma. We analyzed protein levels and nuclear localization of β-catenin and RUNX2 in a panel of human osteosarcoma cell lines (SAOS, MG63, U2OS, HOS, G292 and 143B). In all six cell lines, β-catenin and RUNX2 are expressed to different degrees and localized in the nucleus and/or cytoplasm. SAOS cells have the highest levels of RUNX2 protein that is localized in the nucleus, while MG63 cells have the lowest RUNX2 levels which is mostly localized in the cytoplasm. Levels of β-catenin and RUNX2 protein are enhanced in HOS, G292 and 143B cells after treatment with the GSK3β inhibitor SB216763. Furthermore, small interfering RNA (siRNA)-mediated depletion of β-catenin inhibits RUNX2 expression in G292 cells. Thus, WNT/β-catenin activation is required for RUNX2 expression in at least some osteosarcoma cell types, where RUNX2 is known to promote expression of metastasis related genes. This article is protected by copyright. All rights reserved.

  10. Evaluation of the Spermicidal and Contraceptive Activity of Platycodin D, a Saponin from Platycodon grandiflorum

    PubMed Central

    Lu, Zongliang; Wang, Leiguang; Zhou, Rui; Qiu, Yi; Yang, Liuna; Zhang, Chanyu; Cai, Min; Mi, Mantian; Xu, Hongxia

    2013-01-01

    Background The extract of Platycodon grandiflorum has been reported to have effective spermicidal activity. This study was designed to evaluate the spermicidal and contraceptive activity, as well as the safety, of Platycodin D (PD), a major saponin in Platycodon grandiflorum. Methods Using the computer-aided sperm analysis (CASA) test criteria, the sperm-immobilizing activity of PD was studied using highly motile human sperm. The sperm viability was assessed by fluorescent staining using SYBR-14 (living sperm) and propidium iodide (dead sperm). The sperm membrane integrity was assessed by evaluating the hypo-osmotic swelling (HOS) and examinations by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The in vivo contraceptive efficacy was evaluated in rats using post-intrauterine PD application. The comet assay was employed to determine whether PD caused DNA damage in the sperm. Vaginal biopsies were also performed to determine whether the PD gel induced vaginal inflammation. Results A dose-dependent effect of PD on the sperm motility and viability was observed. The maximum spermicidal effect was observed with a 0.25 mM concentration of PD. More than 70% of the PD-treated sperm lost their HOS responsiveness at a concentration of 0.20 mM PD, indicating that PD caused injury to the sperm plasma membrane. TEM and SEM revealed significant damage to both the head and tail membranes of the sperm. PD decreased the fertility to zero in rats, was non-DNA damaging and was not harmful to the vaginal tissue in the rats. Conclusion PD has significant spermicidal activity that should be explored in further studies. PMID:24303079

  11. Decay of sperm obtained from epididymes of wild ruminants depending on postmortem time.

    PubMed

    Martinez-Pastor, F; Guerra, C; Kaabi, M; Diaz, A R; Anel, E; Herraez, P; de Paz, P; Anel, L

    2005-01-01

    We have carried out a study on the effect of postmortem time (PT) in some characteristics of epididymal sperm salvaged from hunted Iberian red deer and roe deer. Testis were collected, identified, refrigerated down to 5 degrees C, and sent to our laboratory by the wardens of the hunting reserves. This way, samples were delivered at different times postmortem. Sperm were extracted from the cauda epididymis by means of cuts. Analyzed parameters were: osmolality, pH, motility-both subjectively and with CASA, HOS test reactivity, acrosomal status and viability (assessed with propidium iodide). Osmolality and pH rose with prolonged postmortem time, possibly due to tissue decomposition. Most sperm quality parameters negatively correlated with PT. Besides, when comparing PT classes (groups of 24 h for red deer and 30 h for roe deer), we could appreciate that motility was more affected by PT than other quality variables. Progressive motility was especially impaired. We also classified the samples in high, medium and low quality for each PT group (considering progressive motility, intact acrosomes and reactivity to the HOS test), and it was clear that after 2 days the number of high quality samples was testimonial, and after several days, we almost found only low quality samples. In conclusion, epididymal sperm from Iberian red deer and roe deer undergo a decrease of quality with PT, but it could stay acceptable within many hours postmortem. There are implications for wildlife conservation programs, as epididymal sperm is a good source of germplasm. If valuable animals die and it is not possible to process their sperm immediately, it may still be possible to obtain viable spermatozoa many hours later.

  12. T-box family of transcription factor-TBX5, insights in development and disease

    PubMed Central

    Zhu, Ting; Qiao, Longwei; Wang, Qian; Mi, Rui; Chen, Jinnan; Lu, Yaojuan; Gu, Junxia; Zheng, Qiping

    2017-01-01

    The T-box gene family refers to a group of transcription factors that share a highly conserved, sequence-specific DNA-binding domain (T-box) containing around 180-amino acids. According to HUGO gene nomenclature committee (HGNC), there are 18 T-box family members. These T-box genes have been implicated essential roles during embryogenesis and cardiac development, given their specific expression pattern in developing mammalian heart for several T-box genes, including TBX5. TBX5 is consisted of three transcriptional variants which cover 9 exons and encode two distinct isoforms that differ in N-terminus. TBX5 is probably the most frequently studied T-box gene over the past decade due to the typical cardiac defects observed in Holt-Oram syndrome (HOS), which is caused by TBX5 mutation. Most of the mutations are within exons 3-7 where locate sequence coding for the T-box domain. Notably, a variety of cardiac defects, as well as abnormalities in limb and other organs have been seen in HOS syndrome with different kinds of TBX5 mutations, suggesting a heterogeneous disease mechanism. We have performed a meta-analysis of TBX5 and found a significant correlation between its single nucleotide polymorphism (SNP) rs3825214 (A to G), and risk of atrial fibrillation and its subtypes, supporting TBX5 as a master transcription factor for cardiac development. In addition, bioinformatics analysis of this SNP identified several TFs that may be affected for their binding affinity with TBX5. Identification and characterization of more TBX5 mutations and SNPs hold promise for therapeutic strategy targeting TBX5 associated developmental abnormalities and diseases. PMID:28337273

  13. Effects of the Molecular Weight and the Degree of Deacetylation of Chitosan Oligosaccharides on Antitumor Activity

    PubMed Central

    Park, Jae Kweon; Chung, Mi Ja; Choi, Ha Na; Park, Yong Il

    2011-01-01

    Effects of the degree of deacetylation (DDA) and the molecular mass of chitosan oligosaccharides (CTS-OS), obtained from the enzymatic hydrolysis of high molecular weight chitosan (HMWC), on antitumor activity was explored. The DDA and molecular weights of CTS-OS were determined by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-TOF MS) analysis. The CTS-OS were found to be a mixture of mainly dimers (18.8%), trimers (24.8%), tetramers (24.9%), pentamers (17.7%), hexamers (7.1%), heptamers (3.3%), and octamers (3.4%). The CTS-OS were further fractionated by gel-filtration chromatography into two major fractions: (1) COS, consisting of glucosamine (GlcN)n, n = 3–5 with DDA 100%; and (2) HOS, consisting of (GlcN)5 as the minimum residues and varying number of N-acetylglucosamine (GlcNAc)n, n = 1–2 with DDA about 87.5% in random order. The cytotoxicities, expressed as the concentration needed for 50% cell death (CC50), of CTS-OS, COS, and HOS against PC3 (prostate cancer cell), A549 (lung cancer cell), and HepG2 (hepatoma cell), were determined to be 25 μg·mL−1, 25 μg·mL−1, and 50 μg·mL−1, respectively. The HMWC was approximately 50% less effective than both CTS-OS and COS. These results demonstrate that the molecular weight and DDA of chitosan oligosaccharides are important factors for suppressing cancer cell growth. PMID:21339986

  14. Do Patients With Borderline Dysplasia Have Inferior Outcomes After Hip Arthroscopic Surgery for Femoroacetabular Impingement Compared With Patients With Normal Acetabular Coverage?

    PubMed

    Cvetanovich, Gregory L; Levy, David M; Weber, Alexander E; Kuhns, Benjamin D; Mather, Richard C; Salata, Michael J; Nho, Shane J

    2017-07-01

    The literature contains conflicting reports regarding whether outcomes of hip arthroscopic surgery for patients with borderline dysplasia are inferior to outcomes in patients with normal acetabular coverage. To assess differences in the outcomes of hip arthroscopic surgery for femoroacetabular impingement (FAI) in groups of patients with borderline dysplasia and normal coverage. Cohort study; Level of evidence, 3. A registry of consecutive patients who had undergone primary hip arthroscopic surgery with capsular plication for FAI between January 2012 and January 2014 were divided based on the preoperative lateral center-edge angle (LCEA) into 2 distinct groups: (1) borderline dysplasia (LCEA 18°-25°) and (2) normal acetabular coverage (LCEA 25.1°-40°). There were 36 patients in the borderline dysplastic group and 312 patients in the normal coverage group. The primary outcome measure was the Hip Outcome Score-Activities of Daily Living (HOS-ADL) at a minimum of 2 years postoperatively. Secondary outcome measures included the HOS-Sports and modified Harris Hip Score (mHHS). The mean preoperative LCEA differed significantly between groups (23.4° ± 1.5° for borderline dysplastic, 32.5° ± 3.8° for normal coverage; P < .001). The borderline dysplastic group had a higher percentage of female patients than the normal coverage group (27/36 [75%] vs 177/312 [57%], respectively; P = .048). There were no differences in other preoperative demographics and radiographic parameters. At a minimum 2 years after hip arthroscopic surgery (mean follow-up, 2.6 ± 0.6 years), both groups demonstrated significant improvements in all patient-reported outcome scores ( P < .001 in all cases). There were no significant differences between the borderline dysplastic and normal coverage groups in final outcome scores, score improvements, or percentage of patients experiencing clinically significant improvements. One patient in the borderline dysplastic group (3%) underwent revision hip

  15. Teaching Elderly Adults to Use the Internet to Access Health Care Information: Before-After Study

    PubMed Central

    Nolfi, David A

    2005-01-01

    Background Much has been written about the Internet's potential to revolutionize health care delivery. As younger populations increasingly utilize Internet-based health care information, it will be essential to ensure that the elderly become adept at using this medium for health care purposes, especially those from minority, low income, and limited educational backgrounds. Objective This paper presents the results of a program designed to teach elderly adults to use the Internet to access health care information. The objective was to examine whether the training led to changes in participant's perceptions of their health, perceptions of their interactions with health care providers, health information–seeking behaviors, and self-care activities. Methods Participants attended a 5-week training course held in public libraries and senior community centers within the greater Pittsburgh and Allegheny County region. Classes within each seminar lasted 2 hours and consisted of lecture and hands-on training. Baseline surveys were administered prior to the course, 5-week follow-up surveys were administered immediately after the course, and final surveys were mailed 1 year later. Instruments included the Multidimensional Health Locus of Control (MHLC) Scale, which measures three domains of locus of control (internal, external, and chance); the Krantz Health Opinion Survey (HOS); and the Lau, Hartman, and Ware Health Value Survey. Two additional questionnaires included multiple choice and qualitative questions designed to measure participants' Internet utilization and levels of health care participation. The Health Participation Survey was administered with the baseline survey. The Internet Use Survey was administered at the 1-year mark and contained several items from the Health Participation Survey, which allowed comparison between baseline and 1-year responses. Results Of the 60 elderly adults who began the training course, 42 (mean age 72) completed the entire 5-week

  16. TRAF4 enhances osteosarcoma cell proliferation and invasion by Akt signaling pathway.

    PubMed

    Yao, Weitao; Wang, Xin; Cai, Qiqing; Gao, Songtao; Wang, Jiaqiang; Zhang, Peng

    2014-01-01

    TRAF4, or tumor necrosis factor receptor-associated factor 4, is overexpressed in several cancers, suggesting a specific role in cancer progression. However, its functions in osteosarcoma are unclear. This study aimed to explore the expression of TRAF4 in osteosarcoma tissues and cells, the correlation of TRAF4 to clinical pathology of osteosarcoma, as well as the role and mechanism of TRAF4 in osteosarcoma metastasis. The protein expression levels of TRAF4 in osteosarcoma tissues and three osteosarcoma cell lines, MG-63, HOS, and U2OS, were assessed. Constructed TRAF4 overexpression vectors and established TRAF4 overexpression of the U2OS cell line. Cell proliferation, cell invasion, protein levels, and TRAF4 phosphorylations were assessed following TRAF4 transfection, as well as the effects of TRAF4 siRNA on cell proliferation and invasion. The results show that TRAF4 protein levels in osteosarcoma tissues were significantly higher than that in normal bone tissues. Importantly, an obvious upregulation of TRAF4 was found in carcinoma tissues from patients with lung metastasis compared with patients without lung metastasis. Consistently, a similar increase in TRAF4 mRNA and protein was also demonstrated in the osteosarcoma cell lines MG-63, HOS, and U2OS compared to normal bone cells, hFOB1.19. When TRAF4 was overexpressed in U2OS cells, cell proliferation was significantly enhanced, accompanied by an increase in Ki67 expression and colony formation. Compared with the control and vector-treated groups, TRAF4 transfection increased the invasion potential of U2OS cells (p < 0.05). Interestingly, TRAF4 transfection significantly enhanced the phosphorylation of Akt. After blocking Akt with its specific siRNA, TRAF4-induced cell proliferation and invasion were dramatically attenuated. In summary, our findings demonstrated that TRAF4 enhances osteosarcoma cell proliferation and invasion partially by the Akt pathway. This work suggests that TRAF4 might be an important

  17. Intermediate clinical and radiological results of cervical TDR (Mobi-C®) with up to 2 years of follow-up

    PubMed Central

    Beaurain, J.; Bernard, P.; Dufour, T.; Fuentes, J. M.; Hovorka, I.; Huppert, J.; Steib, J. P.; Vital, J. M.; Aubourg, L.

    2009-01-01

    The interest in cervical total disc replacement (TDR) as an alternative to the so-far gold standard in the surgical treatment of degenerative disc disease (DDD), e.g anterior cervical discectomy and fusion (ACDF), is growing very rapidly. Many authors have established the fact that ACDF may result in progressive degeneration in adjacent segments. On the contrary, but still theoretically, preservation of motion with TDR at the surgically treated level may potentially reduce the occurrence of adjacent-level degeneration (ALD). The authors report the intermediate results of an undergoing multicentre prospective study of TDR with Mobi-C® prosthesis. The aim of the study was to assess the safety and efficacy of the device in the treatment of DDD and secondary to evaluate the radiological status of adjacent levels and the occurrence of ossifications, at 2-year follow-up (FU). 76 patients have performed their 2-year FU visit and have been analyzed clinically and radiologically. Clinical outcomes (NDI, VAS, SF-36) and ROM measurements were analyzed pre-operatively and at the different post-operative time-points. Complications and re-operations were also assessed. Occurrences of heterotopic ossifications (HOs) and of adjacent disc degeneration radiographic changes have been analyzed from 2-year FU X-rays. The mean NDI and VAS scores for arm and neck are reduced significantly at each post-operative time-point compared to pre-operative condition. Motion is preserved over the time at index levels (mean ROM = 9° at 2 years) and 85.5% of the segments are mobile at 2 years. HOs are responsible for the fusion of 6/76 levels at 2 years. However, presence of HO does not alter the clinical outcomes. The occurrence rate of radiological signs of ALD is very low at 2 years (9.1%). There has been no subsidence, no expulsion and no sub-luxation of the implant. Finally, after 2 years, 91% of the patients assume that they would undergo the procedure again. These intermediate

  18. Intermediate clinical and radiological results of cervical TDR (Mobi-C) with up to 2 years of follow-up.

    PubMed

    Beaurain, J; Bernard, P; Dufour, T; Fuentes, J M; Hovorka, I; Huppert, J; Steib, J P; Vital, J M; Aubourg, L; Vila, T

    2009-06-01

    The interest in cervical total disc replacement (TDR) as an alternative to the so-far gold standard in the surgical treatment of degenerative disc disease (DDD), e.g anterior cervical discectomy and fusion (ACDF), is growing very rapidly. Many authors have established the fact that ACDF may result in progressive degeneration in adjacent segments. On the contrary, but still theoretically, preservation of motion with TDR at the surgically treated level may potentially reduce the occurrence of adjacent-level degeneration (ALD). The authors report the intermediate results of an undergoing multicentre prospective study of TDR with Mobi-C prosthesis. The aim of the study was to assess the safety and efficacy of the device in the treatment of DDD and secondary to evaluate the radiological status of adjacent levels and the occurrence of ossifications, at 2-year follow-up (FU). 76 patients have performed their 2-year FU visit and have been analyzed clinically and radiologically. Clinical outcomes (NDI, VAS, SF-36) and ROM measurements were analyzed pre-operatively and at the different post-operative time-points. Complications and re-operations were also assessed. Occurrences of heterotopic ossifications (HOs) and of adjacent disc degeneration radiographic changes have been analyzed from 2-year FU X-rays. The mean NDI and VAS scores for arm and neck are reduced significantly at each post-operative time-point compared to pre-operative condition. Motion is preserved over the time at index levels (mean ROM = 9 degrees at 2 years) and 85.5% of the segments are mobile at 2 years. HOs are responsible for the fusion of 6/76 levels at 2 years. However, presence of HO does not alter the clinical outcomes. The occurrence rate of radiological signs of ALD is very low at 2 years (9.1%). There has been no subsidence, no expulsion and no sub-luxation of the implant. Finally, after 2 years, 91% of the patients assume that they would undergo the procedure again. These intermediate results

  19. Acetabular labral reconstruction with an iliotibial band autograft: outcome and survivorship analysis at minimum 3-year follow-up.

    PubMed

    Geyer, Mark R; Philippon, Marc J; Fagrelius, Theodore S; Briggs, Karen K

    2013-08-01

    Injury to the acetabular labrum results from multiple causes including femoroacetabular impingement, dysplasia, and acute trauma. The patient's labrum can be reconstructed utilizing an iliotibial band autograft that is tubularized and fixed to the acetabular rim, substituting for the patient's own labrum. Purpose/ The purpose of this study was to evaluate the midterm results of this technique with a follow-up from 3 to 6 years after reconstruction. The hypothesis was that midterm results would show excellent patient-reported outcomes and high patient satisfaction with outcome. Case series; Level of evidence, 4. A retrospective review of a prospectively collected registry was undertaken that identified 75 patients (76 hips) who underwent arthroscopic labral reconstruction using an iliotibial band autograft by a single surgeon from February 2005 to August 2008. Modified Harris Hip Score (mHHS), Hip Outcome Score (HOS), and patient satisfaction level (on a scale of 1-10) were recorded preoperatively and postoperatively annually. Survivorship analysis curves were created to evaluate the effectiveness of this technique. Among 76 hips, 19 progressed to total hip arthroplasty at an average of 28 months from the procedure. Mean survivor time (no arthroplasty) was 59.1 months (95% CI, 53.9-64.4). Follow-up on the surviving hips was available for 49 patients (86%) with a mean follow-up time of 49 months (range, 36-70 months). The mHHS significantly increased from a preoperative mean of 58.9 to the most recent follow-up score averaging 83 (P = .0001); HOS values in the sports and the activities of daily living subscales also increased significantly (P = .0001 and P = .001, respectively). Median patient satisfaction with outcome was 8. A joint space of ≤2 mm was found to be a poor prognostic factor for survival of the hip. Arthroscopic labral reconstruction using an iliotibial band autograft resulted in a survivorship of 56 months. Of the 76% of patients who did not require

  20. Discovering miRNA Regulatory Networks in Holt–Oram Syndrome Using a Zebrafish Model

    PubMed Central

    D’Aurizio, Romina; Russo, Francesco; Chiavacci, Elena; Baumgart, Mario; Groth, Marco; D’Onofrio, Mara; Arisi, Ivan; Rainaldi, Giuseppe; Pitto, Letizia; Pellegrini, Marco

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in the post-transcriptional regulation of gene expression. miRNAs are involved in the regulation of many biological processes such as differentiation, apoptosis, and cell proliferation. miRNAs are expressed in embryonic, postnatal, and adult hearts, and they have a key role in the regulation of gene expression during cardiovascular development and disease. Aberrant expression of miRNAs is associated with abnormal cardiac cell differentiation and dysfunction. Tbx5 is a member of the T-box gene family, which acts as transcription factor involved in the vertebrate heart development. Alteration of Tbx5 level affects the expression of hundreds of genes. Haploinsufficiency and gene duplication of Tbx5 are at the basis of the cardiac abnormalities associated with Holt–Oram syndrome (HOS). Recent data indicate that miRNAs might be an important part of the regulatory circuit through which Tbx5 controls heart development. Using high-throughput technologies, we characterized genome-widely the miRNA and mRNA expression profiles in WT- and Tbx5-depleted zebrafish embryos at two crucial developmental time points, 24 and 48 h post fertilization (hpf). We found that several miRNAs, which are potential effectors of Tbx5, are differentially expressed; some of them are already known to be involved in cardiac development and functions, such as miR-30, miR-34, miR-190, and miR-21. We performed an integrated analysis of miRNA expression data with gene expression profiles to refine computational target prediction approaches by means of the inversely correlation of miRNA–mRNA expressions, and we highlighted targets, which have roles in cardiac contractility, cardiomyocyte proliferation/apoptosis, and morphogenesis, crucial functions regulated by Tbx5. This approach allowed to discover complex regulatory circuits involving novel miRNAs and protein coding genes not considered before in the HOS such as miR-34a and

  1. Male contraceptive efficacy of Ricinus communis L. extract.

    PubMed

    Nath, Sushmita; Dutta Choudhury, Manabendra; Roychoudhury, Shubhadeep; Talukdar, Anupam Das; Misro, Man Mohan

    2013-08-26

    Ricinus communis L. (Rc), of Euphorbiaceae family is a widespread plant in tropical regions and it is used in traditional medicines as an antifertility agent in India and different parts of the world. The aim of the present study is to revalidate the ethnobotanical knowledge by evaluating the activity of only crude stem bark extracts of Rc. In this study, effects of extracts on male contraceptive efficacy were experimented in vitro with human sperm sample. The work is based on primordial and contemporary therapeutic uses of this plant. In this study, dose of petroleum ether extract, ethyl acetate extract, acetone extract and lyophilised aqueous extract of Rc were added to fresh human semen in 1:1 volumetric ratio. As the aqueous extract showed a promising result in 1:1 ratio, therefore, the Hypo-osmotic swelling test (HOS), Nuclear chromatin decondensation test (NCD) and Acrosomal status and function test (AFT) were also carried out with the aqueous extract of Rc. The sperm immobilisation effects of the extract appeared immediately in a dose-dependent manner when the samples were treated with four different extracts of this plant. At a concentration of 100mg/mL, 100% (p<0.001 and p<0.05) sperms lost their progressive motility. At a concentration of 300 mg/mL, 100% (p<0.001 and p<0.05) became immotile when treated with aqueous extract. There was 88% (p<0.001 and p<0.05) morphological deformities in sperm sample due the effect of aqueous extract when they were tested for HOS and 91% (p<0.05) sperms behaved against NCD as compared to control group. Also there was a distinct decline (p<0.05) in AFT with increase in dosage concentration. The findings of the study revealed that aqueous stem bark extract of the plant showed dose dependent loss of sperm motility by influencing the morphological deformation, blockage in nuclear envelope and distinct declination in acrosomal status of spermatozoa. This research, thus, opens up scope for future exploration of bark of the

  2. Synthesis, metabolism, and biological activity of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3.

    PubMed

    Takano, Masashi; Yasuda, Kaori; Higuchi, Erika; Tohyama, Eri; Takeuchi, Akiko; Sakaki, Toshiyuki; Kittaka, Atsushi

    2016-11-01

    Recently, we found that 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D3 showed higher osteocalcin promoter transactivation activity in human osteosarcoma (HOS) cells and a greater therapeutic effect in ovariectomized (OVX) rats in vivo than those of active vitamin D3, 1α,25(OH)2D3. We were interested in introducing a heterocyclic ring to the C2 position of the seco-steroidal structure via an alkyl linker, and four novel C2-(3-tetrazolylpropyl) substituted 1α,25-dihydroxy-19-norvitamin D3 analogs, 2α-[3-(tetrazol-1-yl)propyl]-, 2β-[3-(tetrazol-1-yl)propyl]-, 2α-[3-(tetrazol-2-yl)propyl]-, and 2β-[3-(tetrazol-2-yl)propyl]-19-nor-1α,25(OH)2D3 were synthesized. Among them, 2α-[3-(tetrazol-1-yl)propyl]-19-nor-1α,25(OH)2D3 showed weak binding affinity for human vitamin D receptor (hVDR) (2.6% of 1α,25(OH)2D3 and ca. 15% of 19-nor-1α,25(OH)2D3) and weak VDR transactivation activity in HOS cells (EC50 7.3nM, when 1α,25(OH)2D30.23nM). Although the other three compounds could not act as VDR binders by evaluation of the competition assays, 2α-[3-(tetrazol-2-yl)propyl]-19-nor-1α,25(OH)2D3 showed weak transactivation activity (EC50 12.5nM). Metabolic stability of the 2α-substituted compounds 2α-[3-(tetrazol-1-yl)propyl]- and 2α-[3-(tetrazol-2-yl)propyl]-19-nor-1α,25(OH)2D3 was higher than that of the 2β-substituted counterparts 2β-[3-(tetrazol-1-yl)propyl]- and 2β-[3-(tetrazol-2-yl)propyl]-19-nor-1α,25(OH)2D3 against human CYP24A1. Introduction of a tetrazole ring to the C2-position of the 19-norvitamin D3 skeleton with the propyl linker led to weak VDR agonistic activity with stability against CYP24A1 metabolism. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Association between adverse mental health and an unhealthy lifestyle in rural-to-urban migrant workers in Shanghai.

    PubMed

    Yang, Hua; Gao, Jian; Wang, Tianhao; Yang, Lihong; Liu, Yao; Shen, Yao; Gong, Jian; Dai, Wei; Zhou, Jing; Gu, Jie; Pan, Zhigang; Zhu, Shanzhu

    2017-02-01

    The association between adverse mental health and unhealthy lifestyle behaviors in migrant workers remains poorly defined in Chinese rural-to-urban migrants. A cross-sectional study was conducted regarding health-related behaviors in 5484 migrants (51.3% males) employed in Shanghai for at least 6 months. The Chinese version of the Symptom Checklist-90-Revised (SCL-90-R) was used to assess migrant mental health status. Logistic regression was applied to determine the contribution of adverse mental health to lifestyle behaviors. Of the 5484 migrants, 21.1% had potential mental health problems and 63.1% had an unhealthy lifestyle. The three most prevalent mental disorders were obsessions-compulsions (O-C; 13.7%; 751/5484), interpersonal sensitivity (I-S; 11.0%; 603/5484), and hostility (HOS; 10.8%; 590/5484). Compared with the male participants, the female participants exhibited significantly increased mean scores for phobic anxiety (PHOB) and anxiety (ANX) (p < 0.001). Logistic regression indicated that after adjustment for potential confounding factors in both genders, an unhealthy lifestyle score was significantly associated with all nine subscales of the SCL-90-R. The male participants with psychoticism [PSY; odds ratio (OR) = 4.908, 95% confidence interval (CI) 2.474-9.735], ANX (OR = 4.022, 95% CI 2.151-7.518), or depression (DEP; OR = 3.378, 95% CI 2.079-5.487) were the most likely to have an unhealthy lifestyle. In the female participants, an unhealthy lifestyle was most associated with HOS (OR = 2.868, 95% CI 2.155-3.819), PSY (OR = 2.783, 95% CI 1.870-4.141), or DEP (OR = 2.650, 95% CI 1.960-3.582). Lifestyle behaviors were significantly associated with mental health in rural-to-urban migrant workers, and these findings indicate the need to develop targeted psychological interventions to foster healthy lifestyles in migrants. Copyright © 2016. Published by Elsevier B.V.

  4. Novel iron complexes bearing N6-substituted adenosine derivatives: synthesis, magnetic, 57Fe Mössbauer, DFT, and in vitro cytotoxicity studies.

    PubMed

    Trávnícek, Zdenek; Mikulík, Jirí; Cajan, Michal; Zboril, Radek; Popa, Igor

    2008-09-15

    Iron complexes (1-7) involving N6-benzyladenosine derivatives of the predominant composition [Fe(L(n))Cl(3)].H(2)O {where L(1)=N6-(2-fluorobenzyl)adenosine (1), L(2)=N6-(4-fluorobenzyl)adenosine (2), L(3)=N6-(2-trifluoromethylbenzyl)adenosine (3), L(4)=N6-(3-trifluoromethylbenzyl)adenosine (4), L(5)=N6-(4-trifluoromethylbenzyl)adenosine (5), L(6)=N6-(4-trifluoromethoxybenzyl)adenosine (6), and L(7)=N6-(4-chlorobenzyl)adenosine (7)} have been synthesized. The compounds have been characterized by elemental analysis, variable-temperature and in-field 57Fe Mössbauer, ES+ MS, FTIR, 1H and 13C NMR spectroscopies, magnetochemical and conductivity measurements, thermal (TGA/DSC/DTA) analyses, and DFT calculations. It has been found that the organic molecule is coordinated to iron via N7 atom of the appropriate adenosine derivative and the products are represented by mixtures of complexes with various iron oxidation (Fe(III)/Fe(II)) and spin states (S=5/2, 4/2, 3/2, 2/2) and geometries (tetrahedral or trigonal bipyramidal). It is caused by the fact that partial redox processes proceed during the reactions due to the presence of a ribose moiety, which is oxidized to the corresponding 5'-ribotic acid, and simultaneously, a portion of Fe(III) cations is reduced to Fe(II) ones. Moreover, a significant effect of crystal water molecules on stereochemistry, and hence, on magnetic and spectral properties of the prepared complexes has been found. The compounds have been tested for their in vitro cytotoxicity against the following human cancer cell lines: malignant melanoma (G-361), osteogenic sarcoma (HOS), chronic myelogenous leukemia (K-562), and breast adenocarcinoma (MCF-7). The most important results have been obtained for complex 2 with IC(50) values 8-16 microM against HOS, K-562, and MCF-7 cell lines, and for complex 6 with IC(50) value 4 microM against MCF-7 cell line.

  5. The transcription factor Sox9 is involved in BMP-2 signaling.

    PubMed

    Zehentner, B K; Dony, C; Burtscher, H

    1999-10-01

    We investigated the regulation of Sox9, a transcription factor known to play a role in chondrogenesis, by bone morphogenetic protein-2 (BMP-2) and hedgehog proteins in order to better understand their signaling function in endochondral bone formation. The mesenchymal progenitor cell line C3H10T1/2 was stimulated with BMP-2. Sox9 expression levels were measured by quantitative reverse transcriptase-polymerase chain reaction and Northern analysis. We found that Sox9 was up-regulated by BMP-2 in a dose-dependent manner. The expression of Col2a1, a downstream response gene of Sox9, was also significantly increased upon BMP-2 addition. We also monitored Sox9 expression after the addition of BMP-2 to osteosarcoma cell lines; BMP-2 treatment increased Sox9 mRNA levels in MG63, considered to be early osteoblast-like, but not in human osteogenic sarcoma (HOS) cells, which are thought to be more advanced in the osteoblastic lineage. This response seems to be influenced by differences in BMP receptor expression; MG63 cells express BMP receptor IA (BMPR-IA), whereas HOS cells express BMPR-IA and BMPR-IB. We also saw an increase in Sox9 mRNA levels in BMP-2-treated primary human bone cells (HBCs) derived from femoral heads. We found that in addition to BMP-2, Sonic and Indian hedgehog can increase Sox9 expression in C3H10T1/2 and primary HBCs. Time course studies with C3H10T1/2 cells after BMP-2 stimulation showed increasing expression of cartilage markers, decrease of collagen I mRNA, and a late induction of osteocalcin expression. Moreover, the treatment of C3H10T1/2 cells with Sox9 antisense oligonucleotides revealed that Sox9 is a downstream mediator of BMP-2 affecting the expression of chondrocyte and osteoblast marker genes. Our data show that Sox9 is an important downstream mediator of the BMP-2 and hedgehog signaling pathways in osteogenic cells.

  6. Chlorophytum borivilianum (Safed Musli) root extract prevents impairment in characteristics and elevation of oxidative stress in sperm of streptozotocin-induced adult male diabetic Wistar rats.

    PubMed

    Giribabu, Nelli; Kumar, Kilari Eswar; Rekha, Somesula Swapna; Muniandy, Sekaran; Salleh, Naguib

    2014-08-08

    We hypothesized that C. borivilianum root, known to improve male reproductive performance, prevents impairment in characteristics, morphology and elevation of oxidative stress in sperm of diabetics. We therefore investigated the effect of aqueous root extract of C. borivilianum on these parameters in diabetic rat model. C. borivilianum root aqueous extract (250 and 500 mg/kg/day) or glibenclamide (600 μg/kg/day) were administered to streptozotocin (STZ)-induced diabetic male rats for 28 consecutive days. At the end of treatment, animals were sacrificed and sperm were collected. Sperm count and percentages of forward motility, viability, hypoosmotic swelling (HOS) tail-coiled and abnormal sperm were evaluated. Sperm lipid peroxidation product (LPO), hydrogen peroxide (H2O2) and nitric oxide (NO) levels, total antioxidant capacity (TAC), activity levels of endogenous antioxidant enzymes (superoxide dismutase-SOD, catalase-CAT and glutathione peroxidase-GPx), epididymal sperm density, serum fasting blood glucose (FBG) and HbA1c levels were measured. The expression of sperm caspase-3 was assessed. Meanwhile, in-vitro free radical scavenging activity of C. borivilianum root extract was determined and the root extract was analyzed for the presence of bioactive compounds by FTIR spectroscopy. C. borivilianum root aqueous extract prevents the decrease in sperm count, percentages of forward motility, viability, HOS and the increase in abnormal sperm percentage and caspase-3 level in diabetic rats. Sperm LPO, H2O2 and NO levels, FBG and HbA1c were lower while TAC, SOD, CAT, GPx and epididymal sperm density were higher in diabetic rats receiving C. borivilianum root extract treatment. C. borivilianum root exhibited strong in-vitro free radical scavenging activity which may be due to the phenolic compound. C. borivilianum root extract prevents impairment in sperm characteristics and morphology via preventing elevation of oxidative stress, apoptosis and free radicals levels of

  7. A liquid biopsy-based method for the detection and quantification of circulating tumor cells in surgical osteosarcoma patients.

    PubMed

    Zhang, Haoqiang; Gao, Peng; Xiao, Xin; Heger, Michal; Geng, Lei; Fan, Bo; Yuan, Yulin; Huang, Chen; Chen, Guojing; Liu, Yao; Hu, Yongchen; Yu, Xiuchun; Wu, Sujia; Wang, Ling; Wang, Zhen

    2017-03-08

    A method for the enumeration and quantification of osteosarcoma (OS) circulating tumor cells (CTCs) is currently not available. A correlation between the number of CTCs and progression-free survival (PFS) has been established for other cancers, but not for OS CTCs. A method was therefore developed for CTC quantification in OS and validated in a prospective cohort of surgical patients with primary and recurrent/metastatic OS (N=23). Human OS cells, acting as CTCs, were enumerated from spiked human peripheral blood (PB) following erythrocyte and leukocyte depletion. The OS cells were quantified microscopically based on aneuploidy and a CK18-/CD45- phenotype. Aneuploidy was assayed by fluorescence in situ hybridization (FISH) using fluorescence-labeled alpha-satellite probes for the centromeres of chromosome (CEP 8). CK18 and CD45 phenotyping was performed with immunocytochemistry. HOS cells in spiked PB could be effectively retrieved with the FISH-based enumeration method, which was subsequently employed in an OS patient cohort. PB of recurrent/metastatic OS patients contained more CTCs than the PB of primary OS patients. OS patients with ≥2 CTCs per 7.5 ml of PB had worse PFS than patients whose PB contained <2 CTCs. In 2 cases, CTCs were present in PB of OS patients with negative X-ray and chest CT scans. In conclusion, our method was able to quantitate CTCs in liquid biopsies of OS patients. The number of CTCs has diagnostic and prognostic value.

  8. Protective Effect of Chitin Urocanate Nanofibers against Ultraviolet Radiation.

    PubMed

    Ito, Ikuko; Yoneda, Toshikazu; Omura, Yoshihiko; Osaki, Tomohiro; Ifuku, Shinsuke; Saimoto, Hiroyuki; Azuma, Kazuo; Imagawa, Tomohiro; Tsuka, Takeshi; Murahata, Yusuke; Ito, Norihiko; Okamoto, Yoshiharu; Minami, Saburo

    2015-12-19

    Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils (NFs). We typically obtain NFs by hydrolyzing chitin with acetic acid. However, in the present study, we used urocanic acid to prepare urocanic acid chitin NFs (UNFs) and examined its protective effect against UVB radiation. Hos: HR-1 mice coated with UNFs were UVB irradiated (302 nm, 150 mJ/cm²), and these mice showed markedly lower UVB radiation-induced cutaneous erythema than the control. Additionally, sunburn cells were rarely detected in the epidermis of UNFs-coated mice after UVB irradiation. Although the difference was not as significant as UNFs, the number of sunburn cells in mice treated with acetic acid chitin nanofibrils (ANFs) tended to be lower than in control mice. These results demonstrate that ANFs have a protective effect against UVB and suggest that the anti-inflammatory and antioxidant effects of NFs influence the protective effect of ANFs against UVB radiation. The combination of NFs with other substances that possess UV-protective effects, such as urocanic acid, may provide an enhanced protective effect against UVB radiation.

  9. Hybrid Collagenase Nanocapsules for Enhanced Nanocarrier Penetration in Tumoral Tissues.

    PubMed

    Villegas, María Rocío; Baeza, Alejandro; Vallet-Regí, María

    2015-11-04

    Poor penetration of drug delivery nanocarriers within dense extracellular matrices constitutes one of the main liabilities of current nanomedicines. The conjugation of proteolytic enzymes on the nanoparticle surface constitutes an attractive alternative. However, the scarce resistance of these enzymes against the action of proteases or other aggressive agents present in the bloodstream strongly limits their application. Herein, a novel nanodevice able to transport proteolytic enzymes coated with an engineered pH-responsive polymeric is presented. This degradable coat protects the housed enzymes against proteolytic attack at the same time that it triggers their release under mild acidic conditions, usually present in many tumoral tissues. These enzyme nanocapsules have been attached on the surface of mesoporous silica nanoparticles, as nanocarrier model, showing a significatively higher penetration of the nanoparticles within 3D collagen matrices which housed human osteosarcoma cells (HOS). This strategy can improve the therapeutic efficacy of the current nanomedicines, allowing a more homogeneous and deeper distribution of the therapeutic nanosystems in cancerous tissues.

  10. The unified ICE-CBF pathway provides a transcriptional feedback control of freezing tolerance during cold acclimation in Arabidopsis.

    PubMed

    Kim, Ye Seul; Lee, Minyoung; Lee, Jae-Hyung; Lee, Hyo-Jun; Park, Chung-Mo

    2015-09-01

    During cold acclimation, C-repeat binding factors (CBFs) activate downstream targets, such as cold-regulated genes, leading to the acquisition of freezing tolerance in plants. Inducer of CBF expression 1 (ICE1) plays a key role by activating CBF3 expression in shaping the cold-induced transcriptome. While the ICE1-CBF3 regulon constitutes a major cold acclimation pathway, gene regulatory networks governing the CBF signaling are poorly understood. Here, we demonstrated that ICE1 and its paralog ICE2 induce CBF1, CBF2, and CBF3 by binding to the gene promoters. ICE2, like ICE1, was ubiquitinated by the high expression of osmotically responsive gene 1 (HOS1) E3 ubiquitin ligase. Whereas ICE2-defective ice2-2 mutant did not exhibit any discernible freezing-sensitive phenotypes, ice1-2 ice2-2/+ plant, which is defective in ICE1 and has a heterozygotic ice2 mutation, exhibited significantly reduced freezing tolerance. Accordingly, all three CBF genes were markedly down-regulated in the ice1-2 ice2-2/+ plant, indicating that ICE1 and ICE2 are functionally redundant with different implementations in inducing CBF genes. Together with the negative regulation of CBF3 by CBF2, we propose that the unified ICE-CBF pathway provides a transcriptional feedback of freezing tolerance to sustain plant development and survival during cold acclimation.

  11. Wellness engineering for better quality of life of aging baby boomer

    NASA Astrophysics Data System (ADS)

    Szu, Harold

    2007-04-01

    Current health care system serving 78M aging baby-boomers is no longer sustainable, as the cost about 1/5 GDP will reach 1/4 GDT when all is retired in decades, unless the system is changed. We design a high-tech safe net to enhance the timeliness of early correct treatment execution (otherwise, causing 1/4 mortality associated with an escalating legal fee waste). We follow the common sense that "a stitch in time saves nine," and adopt the military surveillance know-how in designing early warning health management system, comprising of smart sensor pairs for point-care surveillance. However, the grand plan of affordable smart sensors hardware for households requires an ODM & OEM teaming to conduct parallel designing and sequential marketing strategy. The military software strategy combating a treacherous adversary enemy match well with point cares surveillance overcoming real world microorganism variability. Moreover, such smart military software provides self-reference change detection, not by traditional cohort ensemble average, but by individual own higher order statistics (HOS) independent component analysis (ICA), which take the advantage of known initial condition for each individual and desirable over-sampling daily dynamics. The triggering of warning follows the military algorithms comprising of Receiver Operation Characteristics (ROC) and Automatic Target Recognition (ATR). To further reduce the unwanted false negative rate, a benchmarked is made against the traditional cohort-ensemble baseline average & the upper & lower bounds of variance as adopted by the gatekeepers - Medical Doctors (MD) and Nurses.

  12. Reactions occurring during the sulfation of sodium chloride deposited on alumina substrates

    NASA Technical Reports Server (NTRS)

    Wu, C. S.; Birks, N.

    1986-01-01

    The reaction between solid NaCl and air containing 1 pct SO2 has been studied between 500 and 700 C. The reaction product, Na2SO4, forms not only on the surface of the NaCl but also on surrounding areas of the substrate due to the volatility of the NaCl at these temperatures. At the higher temperatures, the vapor pressure of NaCl is so high that the majority of the reaction product is distributed on the substrate. Above 625 C, the reaction product is a liquid solution of NaCl and Na2SO4 that exists only so long as NaCl is supplied from the original crystal source. Eventually, the liquid solidifies by constitutional solidification as the NaCl is converted to Na2SO4. While it exists, the liquid NaCl-Na2SO4 solution is shown to be highly corrosive to Al2O3 and, on a scale of Al2O3 growing on alloy HOS 875, particularly attacks the grain boundaries of the scale at preferred sites where chromium and iron oxides and sulfides rapidly develop. This is proposed as one mechanism by which NaCl deposition contributes to the initiation of low temperature hot corrosion.

  13. Lack of rearranged Tpr-met mRNA expression in human gastric cancer cell lines and gastric mucosa and carcinoma.

    PubMed

    Osaki, M; Miyata, H; Hayashi, A; Gomyo, Y; Tatebe, S; Ito, H

    1996-01-01

    The met protooncogene was activated by a rearrangement involving the fusion of tpr (1q25) and met (7q21-31) gene sequence in a human osteosarcoma cell line (HOS) incubated in vitro with N-methyl-N-nitro-N-nitrosoguanidine (MNNG). We examined the expression of tpr-met mRNA by means of the reverse transcription-nested polymerase chain reaction (RT-nested PCR) in human two gastric cell lines (MKN-1 and MKN-45), T-cell acute lymphocytic leukemia cell line (MOLT-4), and in gastric tissue samples including normal mucosa, intestinal metaplasia and carcinoma from three surgical specimens. A DNA fragment of 88-bp was amplified in MKN-1 and MOLT-4, 96-bp in MKN-45 and of 58-bp in all nine tissue samples including gastric carcinomas. The amplified DNA sequences were not homologous with the rearranged tpr-met gene. Our study indicated that rearranged tpr-met mRNA is not expressed either in human gastric carcinoma cell lines or in gastric mucosa and carcinoma.

  14. The role of thermal shock in cyclic oxidation

    NASA Technical Reports Server (NTRS)

    Lowell, C. E.; Deadmore, D. L.

    1978-01-01

    The effect of thermal shock on the spalling of oxides from the surfaces of several commercial alloys was determined. The average cooling rate was varied from approximately 240 C per second to less than 1.0 C per second during cyclic oxidation tests in air. The tests consisted of one hundred cycles of one hour at the maximum temperature (1100 or 1200 C). The alloys were HOS-875, TD-Ni, TD-NiCrAl, IN-601, IN-702, and B-1900 plus Hf. All of these alloys exhibited partial spalling within the oxide rather than total oxide loss down to bare metal. Thermal shock resulted in deformation of the metal which in turn resulted, in most cases, in changing the oxide failure mode from compressive to tensile. Tensile failures were characterized by cracking of the oxide and little loss, while compressive failures were characterized by explosive loss of platelets of oxide. This behavior was confirmed by examination of mechanically stressed oxide scales. The thermally shocked oxides spalled less than the slow cooled samples with the exception of TD-NiCrAl. This material failed in a brittle manner rather than by plastic deformation.

  15. Synthesis and spectral characterization of silver/magnesium co-substituted hydroxyapatite for biomedical applications

    NASA Astrophysics Data System (ADS)

    Gopi, D.; Shinyjoy, E.; Kavitha, L.

    2014-06-01

    The present work is aimed at the synthesis of antibacterial and bioactive silver/magnesium co-substituted hydroxyapatite (Ag/Mg-HAP) powders. For this purpose, firstly, different concentrations (0.5, 1.5, 2.5 wt.%) of silver substituted HAP (Ag-HAP) powders were prepared by ultrasonic irradiation technique and were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDAX). Secondly, magnesium (Mg) is co-substituted as secondary material into Ag-HAP to offset the potential cytotoxicity of Ag, as higher concentration of Ag is toxic. The antibacterial activity of as-synthesized powders was evaluated by Escherichia coli (E. coli) and was found to be effectively high against bacterial colonization. Also, the in vitro cell-material interaction is evaluated with human osteosarcoma MG63 (HOS MG63) cells for cell proliferation. The results showed the evidence of cytotoxic effects of the higher concentration of Ag-HAP characterized by poor cellular viability whereas, Ag/Mg-HAP showed better cell viability indicating that co-substitution of Mg in Ag-HAP effectively offset the negative effects of Ag and improve performance compared with pure HAP. Thus, the as synthesized Ag/Mg-HAP will serve as a better candidate for biomedical applications with good antibacterial property and bone bonding ability.

  16. Stb3 plays a role in the glucose-induced transition from quiescence to growth in Saccharomyces cerevisiae.

    PubMed

    Liko, Dritan; Conway, Michael K; Grunwald, Douglas S; Heideman, Warren

    2010-07-01

    Addition of glucose to quiescent Saccharomyces cerevisiae cells causes the immediate induction of approximately 1000 genes. These genes include ribosomal proteins (RP) and non-RP genes needed for ribosome production and other growth processes. RRPE sequence elements are commonly found 5' of non-RP growth gene ORFs, and Stb3 has recently been identified as an RRPE binding protein. Stb3 overexpression (Stb3OE) produces a slow growth phenotype that is associated with reduced expression of non-RP genes and a drop in the rate of amino acid incorporation. Genes affected by Stb3 are associated with a TGAAAAA motif. Stb3 is restricted to the nucleus in quiescent cells and is immediately released into the cytoplasm after glucose repletion. The Stb3OE slow growth phenotype is reversed by loss of Hos2 histone deactylase activity, consistent with the idea that repression involves histone deacetylation. SCH9 overexpression or PPH22 deletion, mutations that activate target of rapamycin (Tor) nutrient sensing pathways, also reverse the Stb3OE phenotype. Inhibition of Tor signaling makes the phenotype more severe and restricts Stb3 to the nucleus. The results support a model in which Stb3 is one of the components that repress a large set of growth genes as nutrients are depleted. This repression is ended by glucose.

  17. Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib

    PubMed Central

    Rimassa, Lorenza; Abbadessa, Giovanni; Personeni, Nicola; Porta, Camillo; Borbath, Ivan; Daniele, Bruno; Salvagni, Stefania; Van Laethem, Jean-Luc; Van Vlierberghe, Hans; Trojan, Jörg; De Toni, Enrico N.; Weiss, Alan; Miles, Steven; Gasbarrini, Antonio; Lencioni, Monica; Lamar, Maria E.; Wang, Yunxia; Shuster, Dale; Schwartz, Brian E.; Santoro, Armando

    2016-01-01

    ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82%) versus before (40%) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials. PMID:27579536

  18. TRIM66 overexpresssion contributes to osteosarcoma carcinogenesis and indicates poor survival outcome.

    PubMed

    Chen, Yu; Guo, Yongfei; Yang, Haisong; Shi, Guodong; Xu, Guohua; Shi, Jiangang; Yin, Na; Chen, Deyu

    2015-09-15

    TRIM66 belongs to the family of tripartite motif (TRIM)-containing proteins. Alterations in TRIM proteins have been implicated in several malignancies. This study was aimed at elucidating the expression and biological function of TRIM66 in osteosarcoma. Here, TRIM66 expression level was higher in osteosarcoma tissues than in normal tissues. High TRIM66 expression was correlated with high rate of local recurrence and lung metastasis, and short survival time. Then, we found that knockdown of TRIM66 in two osteosarcoma cell lines, MG63 and HOS, significantly inhibited cell proliferation and induced G1-phase arrest. Moreover, inhibition of TRIM66 in osteosarcoma cells significantly induced cell apoptosis, while remarkably inhibited cell migration, invasion as well as tumorigenicity in nude mice. Gene set enrichment analysis in Gene Expression Omnibus dataset revealed that apoptosis, epithelial-mesenchymal transition (EMT) and transforming growth factor-β (TGF-β) signaling pathway-related genes were enriched in TRIM66 higher expression patients, which was confirmed by western blot analysis in osteosarcoma cells with TRIM66 silenced. In conclusion, TRIM66 may act as an oncogene through suppressing apoptosis pathway and promoting TGF-β signaling in osteosarcoma carcinogenesis. TRIM66 may be a prognostic factor and potential therapeutic target in osteosarcoma.

  19. Inhibition of hyaluronan retention by 4-methylumbelliferone suppresses osteosarcoma cells in vitro and lung metastasis in vivo.

    PubMed

    Arai, E; Nishida, Y; Wasa, J; Urakawa, H; Zhuo, L; Kimata, K; Kozawa, E; Futamura, N; Ishiguro, N

    2011-12-06

    Hyaluronan (HA) plays crucial roles in the tumourigenicity of many types of malignant tumours. 4-Methylumbelliferone (MU) is an inhibitor of HA synthesis. Several studies have shown its inhibitory effects on malignant tumours; however, none have focused on its effects on osteosarcoma. We investigated the effects of MU on HA accumulation and tumourigenicity of highly metastatic murine osteosarcoma cells (LM8) that have HA-rich cell-associated matrix, and human osteosarcoma cell lines (MG-63 and HOS). In vitro, MU inhibited HA retention, thereby reducing the formation of functional cell-associated matrices, and also inhibited cell proliferation, migration, and invasion. Akt phosphorylation was suppressed by MU (1.0 mM). In vivo, although MU showed only a mild inhibitory effect on the growth of the primary tumour, it markedly inhibited (75% reduction) the development of lung metastasis. Hyaluronan retention in the periphery of the primary tumour was markedly suppressed by MU. These findings suggested that MU suppressed HA retention and cell-associated matrix formation in osteosarcoma cells, resulting in a reduction of tumourigenicity, including lung metastasis. 4-Methylumbelliferone is a promising therapeutic agent targeting both primary tumours and distant metastasis of osteosarcoma, possibly via suppression of HA retention.

  20. Set3 contributes to heterochromatin integrity by promoting transcription of subunits of Clr4-Rik1-Cul4 histone methyltransferase complex in fission yeast

    PubMed Central

    Yu, Yao; Zhou, Huan; Deng, Xiaolong; Wang, Wenchao; Lu, Hong

    2016-01-01

    Heterochromatin formation in fission yeast depends on RNAi machinery and histone-modifying enzymes. One of the key histone-modifying complexes is Clr4-Rik1-Cul4 methyltransferase complex (CLRC), which mediates histone H3K9 methylation, a hallmark for heterochromatin. CLRC is composed of the Clr4 histone methyltransferase, Rik1, Raf1, Raf2 and Pcu4. However, transcriptional regulation of the CLRC subunits is not well understood. In this study, we identified Set3, a core subunit of the Set3/Hos2 histone deacetylase complex (Set3C), as a contributor to the integrity and silencing of heterochromatin at centromeres, telomeres and silent mating-type locus. This novel role of Set3 relies on its PHD finger, but is independent of deacetylase activity or structural integrity of Set3C. Set3 is not located to the centromeric region. Instead, Set3 is targeted to the promoters of clr4+ and rik1+, probably through its PHD finger. Set3 promotes transcription of clr4+ and rik1+. Consistently, the protein levels of Clr4 and Rik1 were reduced in the set3Δ mutant. The heterochromatin silencing defect in the set3Δ mutant could be rescued by overexpressing of clr4+ or rik1+. Our study suggests transcriptional activation of essential heterochromatin factors underlies the tight regulation of heterochromatin integrity. PMID:27538348

  1. Different concentrations of cysteamine and ergothioneine improve microscopic and oxidative parameters in ram semen frozen with a soybean lecithin extender.

    PubMed

    Najafi, Abozar; Kia, Hossein Daghigh; Mohammadi, Hossein; Najafi, Mir Hossein; Zanganeh, Zaynab; Sharafi, Mohsen; Martinez-Pastor, Felipe; Adeldust, Hamideh

    2014-08-01

    The aim of this study was to evaluate the effects of ergothioneine and cysteamine as antioxidant supplements in a soybean lecithin extender for freezing ram semen. Twenty-four ejaculates were collected from four rams and diluted with extenders (1.5% soybean lecithin, 7% glycerol) containing no supplements (control) and cysteamine or ergothioneine (2, 4, 6 or 8mM). Motility by CASA, viability, plasma membrane functionality (HOS test), total abnormality, lipid peroxidation, glutathione peroxidase (GPx) activity and capacitation status (CTC staining) were assessed after thawing. Using 6mM of either antioxidant improved total motility. Cysteamine at 6mM and ergothioneine at 4 and 6mM improved viability and reduced lipid peroxidation (malondialdehyde concentration). Both antioxidants improved membrane functionality significantly, except at 8mM. Progressive motility, kinematic parameters, GPx activity, capacitation status and sperm abnormalities were not influenced by the antioxidant supplements. In conclusion, cysteamine at 6mM and ergothioneine at 4 or 6mM seem to improve the post-thawing quality of ram semen cryopreserved in a soybean lecithin extender.

  2. New Treatment Options for Osteosarcoma - Inactivation of Osteosarcoma Cells by Cold Atmospheric Plasma.

    PubMed

    Gümbel, Denis; Gelbrich, Nadine; Weiss, Martin; Napp, Matthias; Daeschlein, Georg; Sckell, Axel; Ender, Stephan A; Kramer, Axel; Burchardt, Martin; Ekkernkamp, Axel; Stope, Matthias B

    2016-11-01

    Cold atmospheric plasma has been shown to inhibit tumor cell growth and induce tumor cell death. The aim of the study was to investigate the effects of cold atmospheric plasma treatment on proliferation of human osteosarcoma cells and to characterize the underlying cellular mechanisms. Human osteosarcoma cells (U2-OS and MNNG/HOS) were treated with cold atmospheric plasma and seeded in culture plates. Cell proliferation, p53 and phospho-p53 protein expression and nuclear morphology were assessed. The treated human osteosarcoma cell lines exhibited attenuated proliferation rates by up to 66%. The cells revealed an induction of p53, as well as phospho-p53 expression, by 2.3-fold and 4.5-fold, respectively, compared to controls. 4',6-diamidino-2-phenylindole staining demonstrated apoptotic nuclear condensation following cold atmospheric plasma treatment. Cold atmospheric plasma treatment significantly attenuated cell proliferation in a preclinical in vitro osteosarcoma model. The resulting increase in p53 expression and phospho-activation in combination with characteristic nuclear changes indicate this was through induction of apoptosis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Anti-Inflammatory Effect of Angelica gigas via Heme Oxygenase (HO)-1 Expression.

    PubMed

    Cho, Joon Hyeong; Kwon, Jung Eun; Cho, Youngmi; Kim, Inhye; Kang, Se Chan

    2015-06-15

    Angelica gigas (AG) is effective against various medical conditions such as bacterial infection, inflammation, and cancer. It contains a number of coumarin compounds and the group of interest is the pyranocoumarin, which comprises decursin and decursinol angelate. This group has an effect on controlling inflammation, which is caused by excessive nitric oxide (NO) production. Heme oxygenases (HOs), particularly HO-1, play a role in regulating the production of NO. Thus, this study aimed to investigate the anti-inflammatory effects of AG by measuring HO-1 expression. Treatments with CH2Cl2 layer and Angelica gigas extract (AGE) showed the highest NO inhibition effects. Decursin, decursinol angelate, and nodakenin were isolated from the CH2Cl2 layer of AGE. Decursin also demonstrated the highest anti-oxidative effect among the coumarins. Although decursin had the best NO inhibition and anti-oxidative effects, the effects of AGE treatment far surpassed that of decursin. This is owing to the combination effect of the coumarins present within AGE, which is a solvent extract of AG. The expression of HO-1 is an effective indicator of the anti-inflammatory effects of AG. Based on the results of the coumarin compounds, HO-1 expression was found to be dose dependent and specific to decursin.

  4. Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes

    PubMed Central

    Govind, Chhabi K.; Qiu, Hongfang; Ginsburg, Daniel S.; Ruan, Chun; Hofmeyer, Kimberly; Hu, Cuihua; Swaminathan, Venkatesh; Workman, Jerry L.; Li, Bing; Hinnebusch, Alan G.

    2010-01-01

    Methylation of histone H3 by Set1 and Set2 is required for deacetylation of nucleosomes in coding regions by histone deacetylase complexes (HDACs) Set3C and Rpd3C(S), respectively. We report that Set3C and Rpd3C(S) are co-transcriptionally recruited in the absence of Set1 and Set2, but in a manner stimulated by Pol II CTD kinase Cdk7/Kin28. Consistently, Rpd3C(S) and Set3C interact with Ser5-phosphorylated Pol II and histones in extracts, but only the histone interactions require H3 methylation. Moreover, reconstituted Rpd3C(S) binds specifically to Ser5-phosphorylated CTD peptides in vitro. Hence, whereas interaction with methylated H3 residues is required for Rpd3C(S) and Set3C deacetylation activities, their co-transcriptional recruitment is stimulated by the phosphorylated CTD. We further demonstrate that Rpd3, Hos2, and Hda1 have overlapping functions in deacetylating histones and suppressing co-transcriptional histone eviction. A strong correlation between increased acetylation and lower histone occupancy in HDA mutants implies that histone acetylation is a key determinant of nucleosome eviction. PMID:20670892

  5. Antileukemic Effect of Tualang Honey on Acute and Chronic Leukemia Cell Lines.

    PubMed

    Nik Man, Nik Muhd Khuzaimi; Hassan, Rosline; Ang, Cheng Yong; Abdullah, Abu Dzarr; Mohd Radzi, Muhammad Amiro Rasheeq; Sulaiman, Siti Amrah

    2015-01-01

    Complementary medicine using natural product as antitumor is on the rise. Much research has been performed on Tualang Honey and it was shown to have therapeutic potential in wound healing, and antimicrobial activity and be antiproliferative against several cancer models such as human osteosarcoma (HOS), human breast (MCF-7 and MDA-MB-231), and cervical (HeLa) cancer cell lines. To date, there was limited study on antileukemic properties of Tualang (Koompassia excelsa) Honey. The aim of this study was to evaluate the antileukemic effect of Tualang Honey on acute and chronic leukemia cell lines. Leukemia cell lines (K562 and MV4-11) and human mononuclear cell isolated from peripheral blood were grown in RPM1 1640 culture medium. The cells were incubated with increasing concentrations of Tualang Honey. After incubation, the evaluation of viability and apoptosis was performed. The morphological changes of leukemia cells were the presence of cytoplasmic blebs followed by apoptotic bodies and round shape of cells. IC50 against K562 and MV4-11 was determined. Tualang Honey gave 53.9% and 50.6% apoptosis activity on K562 and MV4-11, respectively, while on human mononuclear cell it was 37.4%. Tualang Honey has the apoptosis-inducing ability for acute and chronic myeloid leukemia (K562 and MV4-11) cell lines.

  6. Biophysical effects on the interannual variation in carbon dioxide exchange of an alpine meadow on the Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Liu, Huizhi; Sun, Jihua; Shao, Yaping

    2017-04-01

    Eddy covariance measurements from 2012 to 2015 were used to investigate the interannual variation in carbon dioxide exchange and its control over an alpine meadow on the south-east margin of the Tibetan Plateau. The annual net ecosystem exchange (NEE) in the 4 years from 2012 to 2015 was -114.2, -158.5, -159.9 and -212.6 g C m-2 yr-1, and generally decreased with the mean annual air temperature (MAT). An exception occurred in 2014, which had the highest MAT. This was attributed to higher ecosystem respiration (RE) and similar gross primary production (GPP) in 2014 because the GPP increased with the MAT, but became saturated due to the limit in photosynthetic capacity. In the spring (March to May) of 2012, low air temperature (Ta) and drought events delayed grass germination and reduced GPP. In the late wet season (September to October) of 2012 and 2013, the low Ta in September and its negative effects on vegetation growth caused earlier grass senescence and significantly lower GPP. This indicates that the seasonal pattern of Ta has a substantial effect on the annual total GPP, which is consistent with results obtained using the homogeneity-of-slopes (HOS) model. The model results showed that the climatic seasonal variation explained 48.6 % of the GPP variability, while the percentages explained by climatic interannual variation and the ecosystem functional change were 9.7 and 10.6 %, respectively.

  7. Reactions occurring during the sulfation of sodium chloride deposited on alumina substrates

    NASA Technical Reports Server (NTRS)

    Wu, C. S.; Birks, N.

    1986-01-01

    The reaction between solid NaCl and air containing 1 pct SO2 has been studied between 500 and 700 C. The reaction product, Na2SO4, forms not only on the surface of the NaCl but also on surrounding areas of the substrate due to the volatility of the NaCl at these temperatures. At the higher temperatures, the vapor pressure of NaCl is so high that the majority of the reaction product is distributed on the substrate. Above 625 C, the reaction product is a liquid solution of NaCl and Na2SO4 that exists only so long as NaCl is supplied from the original crystal source. Eventually, the liquid solidifies by constitutional solidification as the NaCl is converted to Na2SO4. While it exists, the liquid NaCl-Na2SO4 solution is shown to be highly corrosive to Al2O3 and, on a scale of Al2O3 growing on alloy HOS 875, particularly attacks the grain boundaries of the scale at preferred sites where chromium and iron oxides and sulfides rapidly develop. This is proposed as one mechanism by which NaCl deposition contributes to the initiation of low temperature hot corrosion.

  8. Synthesis and spectral characterization of silver/magnesium co-substituted hydroxyapatite for biomedical applications.

    PubMed

    Gopi, D; Shinyjoy, E; Kavitha, L

    2014-06-05

    The present work is aimed at the synthesis of antibacterial and bioactive silver/magnesium co-substituted hydroxyapatite (Ag/Mg-HAP) powders. For this purpose, firstly, different concentrations (0.5, 1.5, 2.5wt.%) of silver substituted HAP (Ag-HAP) powders were prepared by ultrasonic irradiation technique and were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDAX). Secondly, magnesium (Mg) is co-substituted as secondary material into Ag-HAP to offset the potential cytotoxicity of Ag, as higher concentration of Ag is toxic. The antibacterial activity of as-synthesized powders was evaluated by Escherichia coli (E. coli) and was found to be effectively high against bacterial colonization. Also, the in vitro cell-material interaction is evaluated with human osteosarcoma MG63 (HOS MG63) cells for cell proliferation. The results showed the evidence of cytotoxic effects of the higher concentration of Ag-HAP characterized by poor cellular viability whereas, Ag/Mg-HAP showed better cell viability indicating that co-substitution of Mg in Ag-HAP effectively offset the negative effects of Ag and improve performance compared with pure HAP. Thus, the as synthesized Ag/Mg-HAP will serve as a better candidate for biomedical applications with good antibacterial property and bone bonding ability.

  9. Sulfonated polyaniline-based organic electrodes for controlled electrical stimulation of human osteosarcoma cells.

    PubMed

    Min, Yong; Yang, Yanyin; Poojari, Yadagiri; Liu, Yidong; Wu, Jen-Chieh; Hansford, Derek J; Epstein, Arthur J

    2013-06-10

    Electrically conducting polymers (CPs) were found to stimulate various cell types such as neurons, osteoblasts, and fibroblasts in both in vitro and in vivo studies. However, to our knowledge, no studies have been reported on the utility of CPs in stimulation of cancer or tumor cells in the literature. Here we report a facile fabrication method of self-doped sulfonated polyaniline (SPAN)-based interdigitated electrodes (IDEs) for controlled electrical stimulation of human osteosarcoma (HOS) cells. Increased degree of sulfonation was found to increase the SPAN conductivity, which in turn improved the cell attachment and cell growth without electrical stimulation. However, an enhanced cell growth was observed under controlled electrical (AC) stimulation at low applied voltage and frequency (≤800 mV and ≤1 kHz). The cell growth reached a maximum threshold at an applied voltage or frequency and beyond which pronounced cell death was observed. We believe that these organic electrodes may find utility in electrical stimulation of cancer or tumor cells for therapy and research and may also provide an alternative to the conventional metal-based electrodes.

  10. Dissecting DNA damage response pathways by analyzing protein localization and abundance changes during DNA replication stress

    PubMed Central

    Tkach, Johnny M.; Yimit, Askar; Lee, Anna Y.; Riffle, Michael; Costanzo, Michael; Jaschob, Daniel; Hendry, Jason A.; Ou, Jiongwen; Moffat, Jason; Boone, Charles; Davis, Trisha N.; Nislow, Corey; Brown, Grant W.

    2012-01-01

    Re-localization of proteins is a hallmark of the DNA damage response. We use high-throughput microscopic screening of the yeast GFP fusion collection to develop a systems-level view of protein re-organization following drug-induced DNA replication stress. Changes in protein localization and abundance reveal drug-specific patterns of functional enrichments. Classification of proteins by sub-cellular destination allows the identification of pathways that respond to replication stress. We analyzed pairwise combinations of GFP fusions and gene deletion mutants to define and order two novel DNA damage responses. In the first, Cmr1 forms subnuclear foci that are regulated by the histone deacetylase Hos2 and are distinct from the typical Rad52 repair foci. In a second example, we find that the checkpoint kinases Mec1/Tel1 and the translation regulator Asc1 regulate P-body formation. This method identifies response pathways that were not detected in genetic and protein interaction screens, and can be readily applied to any form of chemical or genetic stress to reveal cellular response pathways. PMID:22842922

  11. Anti-Inflammatory Effect of Angelica gigas via Heme Oxygenase (HO)-1 Expression

    PubMed Central

    Cho, Joon Hyeong; Kwon, Jung Eun; Cho, Youngmi; Kim, Inhye; Kang, Se Chan

    2015-01-01

    Angelica gigas (AG) is effective against various medical conditions such as bacterial infection, inflammation, and cancer. It contains a number of coumarin compounds and the group of interest is the pyranocoumarin, which comprises decursin and decursinol angelate. This group has an effect on controlling inflammation, which is caused by excessive nitric oxide (NO) production. Heme oxygenases (HOs), particularly HO-1, play a role in regulating the production of NO. Thus, this study aimed to investigate the anti-inflammatory effects of AG by measuring HO-1 expression. Treatments with CH2Cl2 layer and Angelica gigas extract (AGE) showed the highest NO inhibition effects. Decursin, decursinol angelate, and nodakenin were isolated from the CH2Cl2 layer of AGE. Decursin also demonstrated the highest anti-oxidative effect among the coumarins. Although decursin had the best NO inhibition and anti-oxidative effects, the effects of AGE treatment far surpassed that of decursin. This is owing to the combination effect of the coumarins present within AGE, which is a solvent extract of AG. The expression of HO-1 is an effective indicator of the anti-inflammatory effects of AG. Based on the results of the coumarin compounds, HO-1 expression was found to be dose dependent and specific to decursin. PMID:26083119

  12. Ovarian tumor characterization and classification: a class of GyneScan™ systems.

    PubMed

    Acharya, U Rajendra; Sree, Vinitha S; Saba, Luca; Molinari, Filippo; Guerriero, Stefano; Suri, Jasjit S

    2012-01-01

    In this work, we have developed an adjunct Computer Aided Diagnostic (CAD) technique that uses 3D acquired ultrasound images of the ovary and data mining algorithms to accurately characterize and classify benign and malignant ovarian tumors. In this technique, we extracted image-texture based and Higher Order Spectra (HOS) based features from the images. The significant features were then selected and used to train and test the Decision Tree (DT) classifier. The proposed technique was validated using 1000 benign and 1000 malignant images, obtained from 10 patients with benign and 10 with malignant disease, respectively. On evaluating the classifier with 10-fold stratified cross validation, we observed that the DT classifier presented a high accuracy of 95.1%, sensitivity of 92.5% and specificity of 97.7%. Thus, the four significant features could adequately quantify the subtle changes and nonlinearities in the pixel intensities. The preliminary results presented in this paper indicate that the proposed technique can be reliably used as an adjunct tool for ovarian tumor classification since the system is accurate, completely automated, cost-effective, and can be easily written as a software application for use in any computer.

  13. Induction of a specific CD8+ T-cell response to cancer/testis antigens by demethylating pre-treatment against osteosarcoma.

    PubMed

    Li, Binghao; Zhu, Xiaobing; Sun, Lingling; Yuan, Li; Zhang, Jian; Li, Hengyuan; Ye, Zhaoming

    2014-11-15

    Conventional non-surgical therapeutic regimens against osteosarcoma are subject to chemoresistance and tumor relapse, and immunotherapy may be promising for this tumor. However, it's hard to find satisfactory epitopes for immunotherapy against osteosarcoma. Cancer/testis antigens (CTAs), such as MAGE-A family and NY-ESO-1, the potential antigens that almost exclusively express in tumor cells and immune-privileged sites, have been found expressed in osteosarcoma also. Nevertheless, the expression of CTAs is downregulated in many tumors, constraining the application of immunotherapy. In this article, we demonstrate that the expression of MAGE-A family and NY-ESO-1 in osteosarcoma cells can be upregulated following treatment with demethylating agent 5-aza-2'-deoxycytidine and consequently induces a CTA specific CD8+ T-cell response against osteosarcoma in vitro and in vivo. The in vivo imaging was realized by using luciferase-transfected HOS cells and DiR labeled T-cells in severely combined immunodeficiency mouse models. Cytotoxic T cells specifically recognizing MAGE-A family and NY-ESO-1 clustered at the tumor site in mice pre-treated with DAC and resulted in tumor growth suppression, while it was not observed in mice without DAC pre-treatment. This study is important for more targeted therapeutic approaches and suggests that adoptive immunotherapy, combined with demethylating treatment, has the potential for non-surgical therapeutic strategy against osteosarcoma.

  14. Mapping the Binding Interface of VEGF and a Monoclonal Antibody Fab-1 Fragment with Fast Photochemical Oxidation of Proteins (FPOP) and Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zhang, Ying; Wecksler, Aaron T.; Molina, Patricia; Deperalta, Galahad; Gross, Michael L.

    2017-05-01

    We previously analyzed the Fab-1:VEGF (vascular endothelial growth factor) system described in this work, with both native top-down mass spectrometry and bottom-up mass spectrometry (carboxyl-group or GEE footprinting) techniques. This work continues bottom-up mass spectrometry analysis using a fast photochemical oxidation of proteins (FPOP) platform to map the solution binding interface of VEGF and a fragment antigen binding region of an antibody (Fab-1). In this study, we use FPOP to compare the changes in solvent accessibility by quantitating the extent of oxidative modification in the unbound versus bound states. Determining the changes in solvent accessibility enables the inference of the protein binding sites (epitope and paratopes) and a comparison to the previously published Fab-1:VEGF crystal structure, adding to the top-down and bottom-up data. Using this method, we investigated peptide-level and residue-level changes in solvent accessibility between the unbound proteins and bound complex. Mapping these data onto the Fab-1:VEGF crystal structure enabled successful characterization of both the binding region and regions of remote conformation changes. These data, coupled with our previous higher order structure (HOS) studies, demonstrate the value of a comprehensive toolbox of methods for identifying the putative epitopes and paratopes for biotherapeutic antibodies.

  15. Intelligent Case Based Decision Support System for Online Diagnosis of Automated Production System

    NASA Astrophysics Data System (ADS)

    Ben Rabah, N.; Saddem, R.; Ben Hmida, F.; Carre-Menetrier, V.; Tagina, M.

    2017-01-01

    Diagnosis of Automated Production System (APS) is a decision-making process designed to detect, locate and identify a particular failure caused by the control law. In the literature, there are three major types of reasoning for industrial diagnosis: the first is model-based, the second is rule-based and the third is case-based. The common and major limitation of the first and the second reasonings is that they do not have automated learning ability. This paper presents an interactive and effective Case Based Decision Support System for online Diagnosis (CB-DSSD) of an APS. It offers a synergy between the Case Based Reasoning (CBR) and the Decision Support System (DSS) in order to support and assist Human Operator of Supervision (HOS) in his/her decision process. Indeed, the experimental evaluation performed on an Interactive Training System for PLC (ITS PLC) that allows the control of a Programmable Logic Controller (PLC), simulating sensors or/and actuators failures and validating the control algorithm through a real time interactive experience, showed the efficiency of our approach.

  16. Small scale contact and adhesion of soft materials in nano- and bio-systems

    NASA Astrophysics Data System (ADS)

    Cao, Yifang

    This dissertation presents the results obtained from recent experimental, theoretical and computational studies of small scale contact and adhesion of soft materials in both the nano- and bio-systems. These include: stamped flexible/organic electronic devices, and polydimethylsiloxane (PDMS) and biological human osteoscarcoma (HOS) cells. Following a presentation of a method for determining the initial contact point and nanoindentation load-indentation depth characteristics for soft materials, adhesion and contact-induced phenomena are discussed for the processing of organic electronics structures. These include experiments and models that provide new insights into metallic electrode cold welding and organic material pattern transfer processes that are being explored for the fabrication of small organic structures that are relevant to flexible bioelectronics and bioMEMS. Subsequently, a shear assay technique and cell spreading study are presented for the characterization of cell viscoelastic properties and cell prestress. These then present new evidence of how contact guidance (alignment of cells) occurs along microgrooved PDMS structures that have the potential to reduce the overall levels of scar tissue formation. The implications of the results are also assessed for cell biophysics, and potential applications in flexible bioMEMS structures.

  17. Propagation of 3D nonlinear waves over complex bathymetry using a High-Order Spectral method

    NASA Astrophysics Data System (ADS)

    Gouin, Maïté; Ducrozet, Guillaume; Ferrant, Pierre

    2016-04-01

    Scattering of regular and irregular surface gravity waves propagating over a region of arbitrary three-dimensional varying bathymetry is considered here. The three-dimensional High-Order Spectral method (HOS) with an extension to account for a variable bathymetry is used. The efficiency of the model has been proved to be conserved even with this extension. The method is first applied to a bathymetry consisting of an elliptical lens, as used in the Vincent and Briggs (1989) experiment. Incident waves passing across the lens are transformed and a strong convergence region is observed after the elliptical mound. The wave amplification depends on the incident wave. Numerical results for regular and irregular waves are analysed and compared with other methods and experimental data demonstrating the efficiency and practical applicability of the present approach. Then the method is used to model waves propagating over a real bathymetry: the canyons of Scripps/La Jolla in California. The implementation of this complex bathymetry in the model is presented, as well as the first results achieved. They will be compared to the ones obtained with another numerical model.

  18. Hydrophilic polymer drug from a derivative of salicylic acid: synthesis, controlled release studies and biological behavior.

    PubMed

    Rodríguez, Gema; Gallardo, Alberto; Fernández, Mar; Rebuelta, Mercedes; Buján, Julia; Bellón, Juan María; Honduvilla, Natalio G; Escudero, Cristina; San Román, Julio

    2004-06-25

    Hydrophilic polymeric drugs bearing "Triflusal" (4-trifluoromethylsalicylic acid), a drug widely used as antithrombogenic agent (Disgren), have been prepared by free radical copolymerization of methacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)] benzoate (HTRF) and N,N'-dimethylacrylamide (DMA). The reactivity ratios of both monomers have been determined by 1H NMR spectra by applying non-linear least square treatments to the copolymerization equation (terminal model), and the kinetic parameters obtained indicated that the microstructure of copolymer chains is homogeneous, with a random distribution of the active HTRF units along the copolymer chains. That means that for the copolymer system THDMA22 used in this work, HTRF units are mainly isolated in relatively long DMA sequences. Therefore, in this structure the intramolecular interactions between adjacent HTRF units are negligible. Release of Triflusal from THDMA22 has been studied in vitro using buffered solutions at pH = 2, 7.4 and 10 and 37 degrees C. The system showed an interesting pseudo-zero order release profile at pH = 7.4 during several months. It has been also evaluated the pharmacological activity and the behavior of the system in contact with biological media. In this sense, we have carried out some in vitro studies about the antiaggregant properties and biocompatibility of THDMA22. Results demonstrate that this copolymer inhibits platelet aggregation in its macromolecular form and presents a good biocompatibility with Human Osteoblastic Cells (HOS).

  19. Heme reversibly damps PERIOD2 rhythms in mouse suprachiasmatic nucleus explants.

    PubMed

    Guenthner, C J; Bickar, D; Harrington, M E

    2009-12-01

    The hypothalamic suprachiasmatic nucleus (SCN), which in mammals serves as the master circadian pacemaker by synchronizing autonomous clocks in peripheral tissues, is composed of coupled single-cell oscillators that are driven by interlocking positive/negative transcriptional/translational feedback loops. Several studies have suggested that heme, a common prosthetic group that is synthesized and degraded in a circadian manner in the SCN, may modulate the function of several feedback loop components, including the REV-ERB nuclear receptors and PERIOD2 (PER2). We found that ferric heme (hemin, 3-100 microM) dose-dependently and reversibly damped luminescence rhythms in SCN explants from mice expressing a PER2::LUCIFERASE (PER2::LUC) fusion protein. Inhibitors of heme oxygenases (HOs, which degrade heme to biliverdin, carbon monoxide, and iron) mimicked heme's effects on PER2 rhythms. In contrast, heme and HO inhibition did not damp luminescence rhythms in thymus and esophagus explants and had only a small effect on PER2::LUC damping in spleen explants, suggesting that heme's effects are tissue-specific. Analysis of the effects of heme's degradation products on SCN PER2::LUC rhythms indicated that they probably were not responsible for heme's effects on rhythms. The heme synthesis inhibitor N-methylprotoporphyrinIX (NMP) lengthened the circadian period of SCN PER2::LUC rhythms by about an hour. These data are consistent with an important role for heme in the circadian system.

  20. Electrospun 3D composite scaffolds for craniofacial critical size defects.

    PubMed

    Chakrapani, V Yogeshwar; Kumar, T S Sampath; Raj, Deepa K; Kumary, T V

    2017-08-01

    Critical size defects in the craniofacial region can be effectively treated using three dimensional (3D) composite structures mimicking natural extra cellular matrix (ECM) and incorporated with bioactive ceramics. In this study we have shown that the dynamic liquid bath collector can be used to form electrospun polycaprolactone (PCL)-hydroxyapatite (HA) composite structure as unique 3D scaffold. The structure was found to have three distinct sections (base, stem and head) based on the mechanism of its formation and morphology. The size of the head portion was around 15 mm and was found to vary with the process parameters. Scanning electron microscopy (SEM) analysis revealed that the base had random fibres while the fibres in stem and head sections were aligned but perpendicular to each other. X-ray diffraction (XRD) analysis also showed an increase in the crystallinity index of the fibres from base to head section. Cytotoxicity and cytocompatibility studies using human osteosarcoma (HOS) cells showed good cell adhesion and proliferation indicating the suitability of the 3D structure for craniofacial graft applications.

  1. Protective role of Centella asiatica on lead-induced oxidative stress and suppressed reproductive health in male rats.

    PubMed

    Sainath, S B; Meena, R; Supriya, Ch; Reddy, K Pratap; Reddy, P Sreenivasula

    2011-09-01

    Centella asiatica has been mentioned in ancient ayurvedic text of the Indian system of medicine for its properties to promote intelligence. The objective of the present study was to investigate the beneficial effects of C. asiatica on lead-induced oxidative stress and suppressed reproductive performance in male rats. Significant decrease in the weights of testes and epididymis were observed in lead treated animals. Exposure to lead acetate significantly increased malondialdehyde levels with a significant decrease in the superoxide dismutase and catalase activities in the liver, brain, kidneys and testes of rats. Epididymal sperm count, viable sperms, motile sperms and HOS-tail coiled sperms decreased significantly in lead-exposed rats. Testicular steroidogenic enzyme activities also decreased significantly in lead-exposed rats. No significant changes in the selected reproductive variables were observed in the plant extract alone treated rats. Whereas, co-administration of aqueous extracts of C. asiatica to lead exposed rats showed a significant increase in the weights of reproductive organs, reduction in lead-induced oxidative stress in the tissues and improvement in selected reproductive parameters over lead-exposed rats indicating the beneficial role of C. asiatica to counteract lead-induced oxidative stress and to restore the suppressed reproduction in male rats. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Tumor Suppressor WWOX inhibits osteosarcoma metastasis by modulating RUNX2 function.

    PubMed

    Del Mare, Sara; Aqeilan, Rami I

    2015-08-10

    Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. This malignant osteoid forming tumor is characterized by its metastatic potential, mainly to lungs. We recently demonstrated that WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human OS and that WWOX restoration in WWOX-negative OS cells suppresses tumorigenicity. Of note, WWOX levels are reduced in paired OS samples of post-treatment metastastectomies as compared to pre-treatment biopsies suggesting that decreased WWOX levels are associated with a more aggressive phenotype at the metastatic site. Nevertheless, little is known about WWOX function in OS metastasis. Here, we investigated the role of tumor suppressor WWOX in suppressing pulmonary OS metastasis both in vitro and in vivo. We demonstrated that ectopic expression of WWOX in OS cells, HOS and LM-7, inhibits OS invasion and cell migration in vitro. Furthermore, WWOX expression reduced tumor burden in vivo and inhibited metastases' seeding and colonization. Mechanistically, WWOX function is associated with reduced levels of RUNX2 metastatic target genes implicated in adhesion and motility. Our results suggest that WWOX plays a critical role in determining the aggressive phenotype of OS, and its expression could be an attractive therapeutic target to combat this devastating adolescent disease.

  3. Frequent Attenuation of the WWOX Tumor Suppressor in Osteosarcoma is Associated with Increased Tumorigenicity and Aberrant RUNX2 Expression

    PubMed Central

    Kurek, Kyle; Del Mare, Sara; Salah, Zaidoun; Abdeen, Suhaib; Sadiq, Hussain; Lee, Sukhee; Gaudio, Eugenio; Zanesi, Nicola; Jones, Kevin B.; DeYoung, Barry; Amir, Gail; Gebhardt, Mark; Warman, Matthew; Stein, Gary S.; Stein, Janet L.; Lian, Jane B.; Aqeilan, Rami I.

    2011-01-01

    The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is deleted or attenuated in most human tumors. Wwox-deficient mice develop osteosarcoma (OS), an aggressive bone tumor with poor prognosis that often metastasizes to lung. On the basis of these observations, we examined the status of WWOX in human OS specimens and cell lines. In human OS clinical samples, WWOX expression was absent or reduced in 58% of tumors examined (P< 0.0001). Compared to the primary tumors, WWOX levels frequently increased in tumors resected following chemotherapy. In contrast, tumor metastases to lung often exhibited reduced WWOX levels, relative to the primary tumor. In human OS cell lines having reduced WWOX expression, ectopic expression of WWOX inhibited proliferation and attenuated invasion in vitro, and suppressed tumorgenicity in nude mice. Expression of WWOX was associated with reduced RUNX2 expression in OS cell lines, whereas Runx2 levels were elevated in femurs of Wwox-deficient mice. Furthermore, WWOX reconstitution in HOS cells was associated with downregulation of RUNX2 levels and RUNX2 target genes, consistent with the ability of WWOX to suppress RUNX2 transactivation activity. In clinical samples, RUNX2 was expressed in the majority of primary tumors and undetectable in most tumors resected following chemotherapy, whereas most metastases were RUNX2 positive. Our results deepen the evidence of a tumor suppressor role for WWOX in OS, furthering its prognostic and therapeutic significance in this disease. PMID:20530675

  4. Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression.

    PubMed

    Kurek, Kyle C; Del Mare, Sara; Salah, Zaidoun; Abdeen, Suhaib; Sadiq, Hussain; Lee, Suk-Hee; Gaudio, Eugenio; Zanesi, Nicola; Jones, Kevin B; DeYoung, Barry; Amir, Gail; Gebhardt, Mark; Warman, Matthew; Stein, Gary S; Stein, Janet L; Lian, Jane B; Aqeilan, Rami I

    2010-07-01

    The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is deleted or attenuated in most human tumors. Wwox-deficient mice develop osteosarcoma (OS), an aggressive bone tumor with poor prognosis that often metastasizes to lung. On the basis of these observations, we examined the status of WWOX in human OS specimens and cell lines. In human OS clinical samples, WWOX expression was absent or reduced in 58% of tumors examined (P < 0.0001). Compared with the primary tumors, WWOX levels frequently increased in tumors resected following chemotherapy. In contrast, tumor metastases to lung often exhibited reduced WWOX levels relative to the primary tumor. In human OS cell lines having reduced WWOX expression, ectopic expression of WWOX inhibited proliferation and attenuated invasion in vitro, and suppressed tumorigenicity in nude mice. Expression of WWOX was associated with reduced RUNX2 expression in OS cell lines, whereas RUNX2 levels were elevated in femurs of Wwox-deficient mice. Furthermore, WWOX reconstitution in HOS cells was associated with downregulation of RUNX2 levels and RUNX2 target genes, consistent with the ability of WWOX to suppress RUNX2 transactivation activity. In clinical samples, RUNX2 was expressed in the majority of primary tumors and undetectable in most tumors resected following chemotherapy, whereas most metastases were RUNX2 positive. Our results deepen the evidence of a tumor suppressor role for WWOX in OS, furthering its prognostic and therapeutic significance in this disease.

  5. Tumor Suppressor WWOX inhibits osteosarcoma metastasis by modulating RUNX2 function

    PubMed Central

    Del Mare, Sara; Aqeilan, Rami I.

    2015-01-01

    Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. This malignant osteoid forming tumor is characterized by its metastatic potential, mainly to lungs. We recently demonstrated that WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human OS and that WWOX restoration in WWOX-negative OS cells suppresses tumorigenicity. Of note, WWOX levels are reduced in paired OS samples of post-treatment metastastectomies as compared to pre-treatment biopsies suggesting that decreased WWOX levels are associated with a more aggressive phenotype at the metastatic site. Nevertheless, little is known about WWOX function in OS metastasis. Here, we investigated the role of tumor suppressor WWOX in suppressing pulmonary OS metastasis both in vitro and in vivo. We demonstrated that ectopic expression of WWOX in OS cells, HOS and LM-7, inhibits OS invasion and cell migration in vitro. Furthermore, WWOX expression reduced tumor burden in vivo and inhibited metastases’ seeding and colonization. Mechanistically, WWOX function is associated with reduced levels of RUNX2 metastatic target genes implicated in adhesion and motility. Our results suggest that WWOX plays a critical role in determining the aggressive phenotype of OS, and its expression could be an attractive therapeutic target to combat this devastating adolescent disease. PMID:26256646

  6. Measles Edmonston Vaccine Strain Derivatives have Potent Oncolytic Activity against Osteosarcoma

    PubMed Central

    Musibay, Evidio Domingo; Allen, Cory; Kurokawa, Cheyne; Hardcastle, Jayson J.; Aderca, Ileana; Msaouel, Pavlos; Bansal, Aditya; Jiang, Huailei; DeGrado, Timothy R.; Galanis, Evanthia

    2015-01-01

    Osteosarcoma is the most common primary bone tumor affecting children and young adults, and development of metastatic disease is associated with poor prognosis. The purpose of this study was to evaluate the antitumor efficacy of virotherapy with engineered measles virus (MV) vaccine strains in the treatment of osteosarcoma. Cell lines derived from pediatric patients with osteosarcoma (HOS, MG63, 143B, KHOS-312H, U2-OS and SJSA1) were examined for MV-GFP and MV-NIS gene expression and cytotoxicity as defined by syncytial formation, cell death, and eradication of cell monolayers: significant antitumor activity was demonstrated. Findings were correlated with in vivo efficacy in subcutaneous, orthotopic (tibial bone), and lung metastatic osteosarcoma xenografts treated with the MV derivative MV-NIS via the intratumoral (IT) or intravenous (IV) route. Following treatment, we observed decrease in tumor growth of subcutaneous xenografts (p=0.0374) and prolongation of survival in mice with orthotopic (p<0.0001) and pulmonary metastatic osteosarcoma tumors (p=0.0207). Expression of the NIS transgene in MV-NIS infected tumors allowed for SPECT-CT and PET-CT imaging of virus infected tumors in vivo. Our data support the translational potential of MV-based virotherapy approaches in the treatment of recurrent and metastatic osteosarcoma. PMID:25394505

  7. Unraveling Site-Specific and Combinatorial Histone Modifications Using High-Resolution Mass Spectrometry in Histone Deacetylase Mutants of Fission Yeast.

    PubMed

    Abshiru, Nebiyu; Rajan, Roshan Elizabeth; Verreault, Alain; Thibault, Pierre

    2016-07-01

    Histone deacetylases (HDACs) catalyze the removal of acetylation marks from lysine residues on histone and nonhistone substrates. Their activity is generally associated with essential cellular processes such as transcriptional repression and heterochromatin formation. Interestingly, abnormal activity of HDACs has been reported in various types of cancers, which makes them a promising therapeutic target for cancer treatment. In the current study, we aim to understand the mechanisms underlying the function of HDACs using an in-depth quantitative analysis of changes in histone acetylation levels in Schizosaccharomyces pombe (S. pombe) lacking major HDAC activities. We employed a targeted quantitative mass spectrometry approach to profile changes of acetylation and methylation at multiple lysine residues on the N-terminal tail of histones H3 and H4. Our analyses identified a number of histone acetylation sites that are significantly affected by S. pombe HDAC mutations. We discovered that mutation of the Class I HDAC known as Clr6 causes a major increase in the abundance of triacetylated H4 molecules at K5, K8, and K12. A clr6-1 hypomorphic mutation also increased the abundance of multiple acetyl-lysines in histone H3. In addition, our study uncovered a few crosstalks between histone acetylation and methylation upon deletion of HDACs Hos2 and Clr3. We anticipate that the results from this study will greatly improve our current understanding of the mechanisms involved in HDAC-mediated gene regulation and heterochromatin assembly.

  8. The association of depressive symptoms and ischemic heart disease in older adults is not moderated by gender, marital status or education.

    PubMed

    Mittag, Oskar; Meyer, Thorsten

    2012-02-01

    To investigate whether the association of depression and ischemic heart disease (IHD) is moderated by gender, marital status or education. Data from the 1998 Medicare Health Outcome Survey (HOS) with a 2 year follow-up were re-analyzed. 63,965 older adults who had not reported IHD at baseline were included. Logistic regression analysis modelled the effects of depression, somatic risk factors, and demographic variables on IHD after 2 years. Two year reported incidence of IHD was 6.2%. Depression was associated with a 1.53-fold risk of developing IHD after controlling for somatic risk factors and demographic variables. Male gender, lower than high-school education, and being married were associated with IHD. Neither of these variables yielded significant interactions with depression, nor did any of the higher-order interaction terms. The association of depression and IHD seems independent from pivotal demographic variables. Possibly the impact of psychosocial factors in this sample of older people is weak compared to medical conditions and age. Also the possibility exists that a common factor such as a shared genetic vulnerability contributes to both depressive symptoms and IHD.

  9. Cell cycle arrest and apoptosis induced by aspidin PB through the p53/p21 and mitochondria-dependent pathways in human osteosarcoma cells.

    PubMed

    Wan, Daqian; Jiang, Chaoyin; Hua, Xin; Wang, Ting; Chai, Yimin

    2015-10-01

    Aspidin PB is a natural product extracted from Dryopteris fragrans (L.) Schott, which has been characterized for its various biological activities. We reported that aspidin PB induced cell cycle arrest and apoptosis through the p53/p21 and mitochondria-dependent pathways in human osteosarcoma cells. Aspidin PB inhibited the proliferation of Saos-2, U2OS, and HOS cells in a dose-dependent and time-dependent manner. Aspidin PB induced changes in the cell cycle regulators (cyclin A, pRb, CDK2, p53, and p21), which caused cell cycle arrest in the S phase. We also explored the role of siRNA targeted to p53; it led to a dose-dependent attenuation of aspidin PB-induced apoptosis signaling. Moreover, after treatment with aspidin PB, the p21-silenced cells decreased significantly at the S phase. Aspidin PB increased the percentage of cells with mitochondrial membrane potential disruption. Western blot analysis showed that aspidin PB inhibited Bcl-2 expression and induced Bax expression to disintegrate the outer mitochondrial membrane and caused cytochrome C release. Mitochondrial cytochrome C release was associated with the activation of caspase-9 and caspase-3 cascades. Furthermore, the double-stranded DNA breaks and reactive oxygen species signaling were both involved in aspidin PB-induced DNA damage. In addition, aspidin PB inhibited tumor growth significantly in U2OS xenografts. Above all, we conclude that aspidin PB represents a valuable natural source and may potentially be applicable in osteosarcoma therapy.

  10. Blind deconvolution and source separation in acoustics

    NASA Astrophysics Data System (ADS)

    Sibul, Leon H.; Roan, Michael J.; Coviello, Christian M.

    2005-09-01

    Blind deconvolution (BDC) and blind source separation (BSS) are active research topics with many important applications in acoustics. The goal of deconvolution is to recover original input signal from the output of a convolution filter. In blind deconvolution details of the convolution filter and input signals are not known. The fundamental assumption in BDC is that the input signal is a non-Gaussian stochastic process. A topic closely related to BDC is BSS. BSS is a process that is an inverse operation to a mixing process. In BSS it is assumed that inputs to the mixing systems are statistically independent stochastic processes, where only one input may be Gaussian, others must be non-Gaussian. Standard criterion functions for BDC and BSS are reviewed. Limitations of the second-order statistics and need for higher-order statistics (HOS) or information theoretic criteria that lead to nonlinear optimization algorithms are pointed out. Advantages of various information theoretic criteria for BDC and BSS are discussed. Because gradients of these criteria are nonlinear, resulting optimization algorithms are nonlinear. Linear and non-linear algorithms for BDC and BSS are examined. [Work supported by ONR Codes 321US and 333.

  11. First report of ivermectin resistance in field populations of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) in Punjab districts of India.

    PubMed

    Singh, Nirbhay Kumar; Singh, Harkirat; Jyoti; Prerna, Mranalini; Rath, Shitanshu S

    2015-11-30

    The larval immersion test (LIT) was used on the progenies of Rhipicephalus (Boophilus) microplus collected from four districts of the Punjab state, India to test the resistance to ivermectin. The regression graphs of probit mortality of larval ticks plotted against log values of increasing concentrations of ivermectin were utilized for the determination of slope of mortality, lethal concentration for 50%(LC50), 95%(LC95), resistance ratios (RR50, RR95) and the resistance levels (RL). Values of the coefficient of determination (R(2)) for LIT ranged from 0.900 to 0.978, and the RR50 and RR95 values against ivermectin ranged from 2.97 to 8.85 and 2.42 to 8.47, respectively, indicating resistance status in all field isolates. On the basis of RR values, three field isolates (BAT, GUR, HOS) showed level II, whereas PTK isolate showed presence of level I resistance status against ivermectin. This appears to be the first report of ivermectin resistance in R. (B.) microplus from Punjab, India.

  12. Topical royal jelly alleviates symptoms of pruritus in a murine model of allergic contact dermatitis

    PubMed Central

    Yamaura, Katsunori; Tomono, Ayana; Suwa, Eriko; Ueno, Koichi

    2013-01-01

    Background: Royal jelly is widely used as a health tonic, especially in Asia. Royal jelly is commonly used in cosmetics as well as in dietary supplements and beverages. Little is known, however, about the pharmacologic efficacy of topical royal jelly. Therefore, we investigated the antipruritic activity of topical royal jelly on chronic pruritus in experimental allergic contact dermatitis in mice. Materials and Methods: Hairless mice (HOS: HR-1), with chronic allergic contact dermatitis induced by 5 weeks of repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the entire back skin were treated topically with royal jelly (0.01% or 1%) for 5 weeks after sensitization with TNCB. The effects of royal jelly on pruritus and inflammation were evaluated by measurement of scratching behavior and skin inflammation score, respectively. Results: Repeated application of TNCB to the back skin of mice elicited frequent scratching behavior immediately and 24h after challenge. Topical royal jelly (0.01% or 1%) and betamethasone (0.01%) significantly ameliorated this chronic pruritus throughout the experimental period. The level of nerve growth factor mRNA in back skin was increased in the mice with dermatitis and reduced by betamethasone, but not by royal jelly. Conclusion: The inhibitory effect of royal jelly on chronic pruritus may occur through different mechanisms from those of betamethasone. Topical application of royal jelly, as used in cosmetics, might be beneficial for the alleviation of chronic pruritus. PMID:23661987

  13. The advantages of using a combination of LDL and glutamine in comparison with TRIS egg yolk and Equex® STAMP extenders in the cryopreservation of canine semen.

    PubMed

    Bencharif, Djemil; Amirat-Briand, Lamia; Garand, Annabelle; Anton, Marc; Schmitt, Eric; Desherces, Serge; Delhomme, Guy; Langlois, Marie-Laure; Barrière, Paul; Destrumelle, Sandrine; Vera-Munoz, Oscar; Tainturier, Daniel

    2012-08-01

    Twenty semen samples taken from 5 dogs were frozen in liquid nitrogen at -196 °C in four different extenders: one control extender based on 20% egg yolk, 6% LDL alone (low density lipoproteins: the active cryoprotective principle in chicken egg yolk), 6% LDL combined with 20 mmol glutamine, and Equex® (a reference extender that we wish to compare with the LDL-glutamine combination). After thawing, spermatozoal motility was evaluated using a HAMILTON THORNE CERROS 12 image analyzer; the percentage of motile spermatozoa was 27.7% in the egg yolk extender (p<0.05), 49.9% with 6% LDL alone (p>0.05), 54.7% in the 6% LDL+20 mmol glutamine extender, and 47.9% with Equex® (p>0.05). The motility parameters (VAP, VCL, VSL and ALH) were also superior in the 6% LDL+20 mmol glutamine extender in comparison with the other extenders. Finally, the spermatozoa were generally better protected during freezing with the 6% LDL+20 mmol glutamine association than with the egg yolk, 6% LDL, or Equex extenders in terms of the flagellar plasma membrane (HOS test), DNA (Acridine orange test), and acrosome integrity (Spermac® test: no significant difference). The Equex® extender obtained the best results for the acrosome, followed by 6% LDL+20 mmol glutamine (FITC-PSA test: p<0.05 between each extender). Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Metformin displays in vitro and in vivo antitumor effect against osteosarcoma

    PubMed Central

    Ko, Yunmi; Choi, Aery; Lee, Minyoung

    2016-01-01

    Purpose Patients with unresectable, relapsed, or refractory osteosarcoma need a novel therapeutic agent. Metformin is a biguanide derivative used in the treatment of type II diabetes, and is recently gaining attention in cancer research. Methods We evaluated the effect of metformin against human osteosarcoma. Four osteosarcoma cell lines (KHOS/NP, HOS, MG-63, U-2 OS) were treated with metformin and cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were evaluated using flow cytometric analysis, and migration and wound healing assay were performed. Fourteen female Balb/c-nude mice received KHOS/NP cell grafts in their thigh, and were allowed access to metformin containing water (2 mg/mL) ad libitum. Tumor volume was measured every 3–4 days for a period of 4 weeks. Results Metformin had a significant antiproliferative effect on human osteosarcoma cells. In particular, metformin inhibited the proliferation and migration of KHOS/NP cells by activation of AMP-activated protein kinase and consequent inhibition of the mammalian target of rapamycin pathway. It also inhibited the proliferation of cisplatin-resistant KHOS/NP clone cells. Analysis of KHOS/NP xenograft Balb/c-nude models indicated that metformin displayed potent in vivo antitumor effects. Conclusion Further studies are necessary to explore metformin's therapeutic potential and the possibilities for its use as an adjuvant agent for osteosarcoma. PMID:27721842

  15. [Hip arthroscopy in males younger than 40 with femoroacetabular impingement: short-term outcomes].

    PubMed

    Más Martínez, J; Morales-Santías, M; Bustamante Suarez Suarez de Puga, D; Sanz-Reig, J

    2014-01-01

    Femoroacetabular impingement is probably the most common mechanism that leads to the development of early cartilage and labral damage in the non-dysplastic hip. The objective was to evaluate the outcomes of hip arthroscopy as a treatment for femoroacetabular impingement in patients with high level of function. A prospective study was performed on 41 patients younger than 40 years old undergoing hip arthroscopy for femoroacetabular impingement. Modified Harris Hip Score and HOS and IHOT questionnaires were used for clinical assessment. Radiological evaluation was made for joint space and alpha angle. The mean age of patients was 32.7 years. Labrum injury was detected in 78%, and acetabular cartilage injury in 56% of cases. The average follow-up was 31.3 months. There was a significantly improvement in the mean score in the clinical questionnaires. Radiologically there was no change in the mean joint space, with significantly reduction to normal values of the alpha angle. All patients returned to sports at their pre-injury level of function. Hip arthroscopy resulted in improvement in hip functional outcomes with correction of the underlying osseous deformity and treatment of the associated labral and cartilage pathology, with the return of patients to their pre-injury sports. Further follow-up is essential to confirm the stability of the clinical and radiological outcomes. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  16. Histone deacetylases and phosphorylated polymerase II C-terminal domain recruit Spt6 for cotranscriptional histone reassembly.

    PubMed

    Burugula, Bala Bharathi; Jeronimo, Célia; Pathak, Rakesh; Jones, Jeffery W; Robert, François; Govind, Chhabi K

    2014-11-15

    Spt6 is a multifunctional histone chaperone involved in the maintenance of chromatin structure during elongation by RNA polymerase II (Pol II). Spt6 has a tandem SH2 (tSH2) domain within its C terminus that recognizes Pol II C-terminal domain (CTD) peptides phosphorylated on Ser2, Ser5, or Try1 in vitro. Deleting the tSH2 domain, however, only has a partial effect on Spt6 occupancy in vivo, suggesting that more complex mechanisms are involved in the Spt6 recruitment. Our results show that the Ser2 kinases Bur1 and Ctk1, but not the Ser5 kinase Kin28, cooperate in recruiting Spt6, genome-wide. Interestingly, the Ser2 kinases promote the association of Spt6 in early transcribed regions and not toward the 3' ends of genes, where phosphorylated Ser2 reaches its maximum level. In addition, our results uncover an unexpected role for histone deacetylases (Rpd3 and Hos2) in promoting Spt6 interaction with elongating Pol II. Finally, our data suggest that phosphorylation of the Pol II CTD on Tyr1 promotes the association of Spt6 with the 3' ends of transcribed genes, independently of Ser2 phosphorylation. Collectively, our results show that a complex network of interactions, involving the Spt6 tSH2 domain, CTD phosphorylation, and histone deacetylases, coordinate the recruitment of Spt6 to transcribed genes in vivo. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  17. Histone Deacetylases and Phosphorylated Polymerase II C-Terminal Domain Recruit Spt6 for Cotranscriptional Histone Reassembly

    PubMed Central

    Burugula, Bala Bharathi; Jeronimo, Célia; Pathak, Rakesh; Jones, Jeffery W.; Robert, François

    2014-01-01

    Spt6 is a multifunctional histone chaperone involved in the maintenance of chromatin structure during elongation by RNA polymerase II (Pol II). Spt6 has a tandem SH2 (tSH2) domain within its C terminus that recognizes Pol II C-terminal domain (CTD) peptides phosphorylated on Ser2, Ser5, or Try1 in vitro. Deleting the tSH2 domain, however, only has a partial effect on Spt6 occupancy in vivo, suggesting that more complex mechanisms are involved in the Spt6 recruitment. Our results show that the Ser2 kinases Bur1 and Ctk1, but not the Ser5 kinase Kin28, cooperate in recruiting Spt6, genome-wide. Interestingly, the Ser2 kinases promote the association of Spt6 in early transcribed regions and not toward the 3′ ends of genes, where phosphorylated Ser2 reaches its maximum level. In addition, our results uncover an unexpected role for histone deacetylases (Rpd3 and Hos2) in promoting Spt6 interaction with elongating Pol II. Finally, our data suggest that phosphorylation of the Pol II CTD on Tyr1 promotes the association of Spt6 with the 3′ ends of transcribed genes, independently of Ser2 phosphorylation. Collectively, our results show that a complex network of interactions, involving the Spt6 tSH2 domain, CTD phosphorylation, and histone deacetylases, coordinate the recruitment of Spt6 to transcribed genes in vivo. PMID:25182531

  18. Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes.

    PubMed

    Govind, Chhabi K; Qiu, Hongfang; Ginsburg, Daniel S; Ruan, Chun; Hofmeyer, Kimberly; Hu, Cuihua; Swaminathan, Venkatesh; Workman, Jerry L; Li, Bing; Hinnebusch, Alan G

    2010-07-30

    Methylation of histone H3 by Set1 and Set2 is required for deacetylation of nucleosomes in coding regions by histone deacetylase complexes (HDACs) Set3C and Rpd3C(S), respectively. We report that Set3C and Rpd3C(S) are cotranscriptionally recruited in the absence of Set1 and Set2, but in a manner stimulated by Pol II CTD kinase Cdk7/Kin28. Consistently, Rpd3C(S) and Set3C interact with Ser5-phosphorylated Pol II and histones in extracts, but only the histone interactions require H3 methylation. Moreover, reconstituted Rpd3C(S) binds specifically to Ser5-phosphorylated CTD peptides in vitro. Hence, whereas interaction with methylated H3 residues is required for Rpd3C(S) and Set3C deacetylation activities, their cotranscriptional recruitment is stimulated by the phosphorylated CTD. We further demonstrate that Rpd3, Hos2, and Hda1 have overlapping functions in deacetylating histones and suppressing cotranscriptional histone eviction. A strong correlation between increased acetylation and lower histone occupancy in HDA mutants implies that histone acetylation is important for nucleosome eviction. Copyright 2010 Elsevier Inc. All rights reserved.

  19. A Histone Deacetylase Complex Mediates Biofilm Dispersal and Drug Resistance in Candida albicans

    PubMed Central

    Fox, Emily P.; Hartooni, Nairi; Mitchell, Kaitlin F.; Hnisz, Denes; Andes, David R.; Kuchler, Karl; Johnson, Alexander D.

    2014-01-01

    ABSTRACT Biofilms are resilient, surface-associated communities of cells with specialized properties (e.g., resistance to drugs and mechanical forces) that are distinct from those of suspension (planktonic) cultures. Biofilm formation by the opportunistic human fungal pathogen Candida albicans is medically relevant because C. albicans infections are highly correlated with implanted medical devices, which provide efficient substrates for biofilm formation; moreover, biofilms are inherently resistant to antifungal drugs. Biofilms are also important for C. albicans to colonize diverse niches of the human host. Here, we describe four core members of a conserved histone deacetylase complex in C. albicans (Set3, Hos2, Snt1, and Sif2) and explore the effects of their mutation on biofilm formation. We find that these histone deacetylase complex members are needed for proper biofilm formation, including dispersal of cells from biofilms and multifactorial drug resistance. Our results underscore the importance of the physical properties of biofilms in contributing to drug resistance and dispersal and lay a foundation for new strategies to target biofilm dispersal as a potential antifungal intervention. PMID:24917598

  20. Inhibition of hyaluronan retention by 4-methylumbelliferone suppresses osteosarcoma cells in vitro and lung metastasis in vivo

    PubMed Central

    Arai, E; Nishida, Y; Wasa, J; Urakawa, H; Zhuo, L; Kimata, K; Kozawa, E; Futamura, N; Ishiguro, N

    2011-01-01

    Background: Hyaluronan (HA) plays crucial roles in the tumourigenicity of many types of malignant tumours. 4-Methylumbelliferone (MU) is an inhibitor of HA synthesis. Several studies have shown its inhibitory effects on malignant tumours; however, none have focused on its effects on osteosarcoma. Methods: We investigated the effects of MU on HA accumulation and tumourigenicity of highly metastatic murine osteosarcoma cells (LM8) that have HA-rich cell-associated matrix, and human osteosarcoma cell lines (MG-63 and HOS). Results: In vitro, MU inhibited HA retention, thereby reducing the formation of functional cell-associated matrices, and also inhibited cell proliferation, migration, and invasion. Akt phosphorylation was suppressed by MU (1.0 m). In vivo, although MU showed only a mild inhibitory effect on the growth of the primary tumour, it markedly inhibited (75% reduction) the development of lung metastasis. Hyaluronan retention in the periphery of the primary tumour was markedly suppressed by MU. Conclusion: These findings suggested that MU suppressed HA retention and cell-associated matrix formation in osteosarcoma cells, resulting in a reduction of tumourigenicity, including lung metastasis. 4-Methylumbelliferone is a promising therapeutic agent targeting both primary tumours and distant metastasis of osteosarcoma, possibly via suppression of HA retention. PMID:22045192

  1. Surveying the Impact of Work Hours and Schedules on Commercial Motor Vehicle Driver Sleep.

    PubMed

    Hege, Adam; Perko, Michael; Johnson, Amber; Yu, Chong Ho; Sönmez, Sevil; Apostolopoulos, Yorghos

    2015-06-01

    Given the long hours on the road involving multiple and interacting work stressors (i.e., delivery pressures, irregular shifts, ergonomic hazards), commercial drivers face a plethora of health and safety risks. Researchers goal was to determine whether and to what extent long-haul trucker work schedules influence sleep duration and quality. Survey and biometric data collected from male long-haul truck drivers at a major truckstop in central North Carolina over a six month period. Daily hours worked (mean = 11 hours, 55 minutes) and frequency of working over government-mandated daily HOS regulations (23.8% "frequently or always") were statistically significant predictors of sleep duration. Miles driven per week (mean = 2,812.61), irregular daily hours worked (63.8%), and frequency of working over the daily hour limit (23.8% "frequently or always") were statistically significant predictors of sleep quality. Implications of findings suggest a comprehensive review of the regulations and operational conditions for commercial motor vehicle drivers be undertaken.

  2. The anti-tumor effect of pachymic acid on osteosarcoma cells by inducing PTEN and Caspase 3/7-dependent apoptosis.

    PubMed

    Wen, Huilong; Wu, Zhong; Hu, Huidong; Wu, Yixiong; Yang, Gang; Lu, Jiajun; Yang, Guang; Guo, Gang; Dong, Qirong

    2017-08-30

    Pachymic acid (PA) is a lanostane type triterpenoid isolated from Poria cocos, which possesses an anti-tumor effect in breast cancer, prostate cancer, lung cancer, and bladder cancer cells. In this study, we investigated the effect of PA on the growth and apoptosis of human immortalized cell line (HOS) and primary osteosarcoma cells by a Cell Counting Kit-8 (CCK-8) and Annexin V and propidium iodide (PI) staining, respectively. Western blot was used to measure the expression of cleaved Caspase 3, PTEN, and AKT, as well as the AKT phosphorylation. The Caspase 3 activity was determined using the Caspase-3 Colorimetric Assay Kit. From the results, PA significantly reduced cell proliferation in a concentration- and time-dependent manner. PA also induced cell apoptosis in a dose-dependent fashion. PA treatment led to increased Caspase 3 activation and PTEN expression, as well as reduced AKT phosphorylation. Moreover, Ac-DEVD-CHO (a Caspase 3/7 inhibitor) pre-treatment or PTEN knockdown partially blocked the effects of PA on cell proliferation and apoptosis. Caspase 3/7 inhibitor had an additive effect with PTEN knockdown. Collectively, our results suggested that induction of apoptosis by PA was mediated in part by PTEN/AKT signaling and Caspase 3/7 activity. This study provides evidence that PA might be useful in the treatment of human osteosarcoma.

  3. A new 2D monolayer BiXene, M2C (M = Mo, Tc, Os).

    PubMed

    Sun, Weiwei; Li, Yunguo; Wang, Baotian; Jiang, Xue; Katsnelson, Mikhail I; Korzhavyi, Pavel; Eriksson, Olle; Di Marco, Igor

    2016-08-25

    The existence of BiXenes, a new family of 2D monolayers, is hereby predicted. Theoretically, BiXenes have 1H symmetry (P6[combining macron]m2) and can be formed from the 4d/5d binary carbides. As the name suggests, they are close relatives of MXenes, which instead have 1T symmetry (P3[combining macron]m1). The newly found BiXenes, as well as some new MXenes, are shown to have formation energies close to that of germanene, which suggests that these materials should be possible to be synthesised. Among them, we illustrate that 1H-Tc2C and 1T-Mo2C are dynamically stable at 0 K, while 1H-Mo2C, 1T-Tc2C, 1H-Os2C, and 1T-Rh2C are likely to be stabilised via strain or temperature. In addition, the nature of the chemical bonding is analysed, emphasizing that the covalency between the transition metal ions and carbon is much stronger in BiXenes than in MXenes. The emergence of BiXenes can not only open up a new era of conducting 2D monolayers, but also provide good candidates for carrier materials aimed at energy storage and spintronic devices that have already been unveiled in MXenes.

  4. The Heme-Oxygenase Family Required for Phytochrome Chromophore Biosynthesis Is Necessary for Proper Photomorphogenesis in Higher Plants1

    PubMed Central

    Davis, Seth J.; Bhoo, Seong Hee; Durski, Adam M.; Walker, Joseph M.; Vierstra, Richard D.

    2001-01-01

    The committed step in the biosynthesis of the phytochrome chromophore phytochromobilin involves the oxidative cleavage of heme by a heme oxygenase (HO) to form biliverdin IXα. Through positional cloning of the photomorphogenic mutant hy1, the Arabidopsis HO (designated AtHO1) responsible for much of phytochromobilin synthesis recently was identified. Using the AtHO1 sequence, we identified families of HO genes in a number of plants that cluster into two subfamilies (HO1- and HO2-like). The tomato (Lycopersicon esculentum) yg-2 and Nicotiana plumbaginifolia pew1 photomorphogenic mutants are defective in specific HO genes. Phenotypic analysis of a T-DNA insertion mutant of Arabidopsis HO2 revealed that the second HO subfamily also contributes to phytochromobilin synthesis. Homozygous ho2-1 plants show decreased chlorophyll accumulation, reduced growth rate, accelerated flowering time, and reduced de-etiolation. A mixture of apo- and holo-phyA was detected in etiolated ho2-1 seedlings, suggesting that phytochromobilin is limiting in this mutant, even in the presence of functional AtHO1. The patterns of Arabidopsis HO1 and HO2 expression suggest that the products of both genes overlap temporally and spatially. Taken together, the family of HOs is important for phytochrome-mediated development in a number of plants and that each family member may uniquely contribute to the phytochromobilin pool needed to assemble holo-phytochromes. PMID:11402195

  5. Bipolar disorders in Australia. A population-based study of excess costs.

    PubMed

    Fisher, Laura J; Goldney, Robert D; Dal Grande, Eleonora; Taylor, Anne W; Hawthorne, Graeme

    2007-02-01

    To estimate the excess costs associated with bipolar disorders in Australia, based on prevalence (using the Mood Disorder Questionnaire (MDQ)) and associated excess burden-of-illness costs. Using data from the 2004 South Australian Health Omnibus Survey (HOS), a weighted cross-sectional survey of 3,015 adults, excess costs were estimated from health service utilisation. There was a 2.5% lifetime prevalence of bipolar disorders, delineated by the MDQ. Those persons (MDQ positive) reported a significantly greater use of services and a poorer health status and quality of life than those who were MDQ negative. Using the service provision perspective, excess costs of bipolar disorders in Australia were approx $3.97-$4.95 billion. These results from an Australian population demonstrate the significant economic burden of bipolar disorders. Our findings emphasise the need for further evaluation of the cost-effectiveness of different treatments, or alternative means of reducing the burden borne by individuals, the health system and the general community.

  6. Antileukemic Effect of Tualang Honey on Acute and Chronic Leukemia Cell Lines

    PubMed Central

    Nik Man, Nik Muhd Khuzaimi; Hassan, Rosline; Ang, Cheng Yong; Abdullah, Abu Dzarr; Mohd Radzi, Muhammad Amiro Rasheeq; Sulaiman, Siti Amrah

    2015-01-01

    Complementary medicine using natural product as antitumor is on the rise. Much research has been performed on Tualang Honey and it was shown to have therapeutic potential in wound healing, and antimicrobial activity and be antiproliferative against several cancer models such as human osteosarcoma (HOS), human breast (MCF-7 and MDA-MB-231), and cervical (HeLa) cancer cell lines. To date, there was limited study on antileukemic properties of Tualang (Koompassia excelsa) Honey. The aim of this study was to evaluate the antileukemic effect of Tualang Honey on acute and chronic leukemia cell lines. Leukemia cell lines (K562 and MV4-11) and human mononuclear cell isolated from peripheral blood were grown in RPM1 1640 culture medium. The cells were incubated with increasing concentrations of Tualang Honey. After incubation, the evaluation of viability and apoptosis was performed. The morphological changes of leukemia cells were the presence of cytoplasmic blebs followed by apoptotic bodies and round shape of cells. IC50 against K562 and MV4-11 was determined. Tualang Honey gave 53.9% and 50.6% apoptosis activity on K562 and MV4-11, respectively, while on human mononuclear cell it was 37.4%. Tualang Honey has the apoptosis-inducing ability for acute and chronic myeloid leukemia (K562 and MV4-11) cell lines. PMID:26613081

  7. Spermicidal efficacy of VRP, a synthetic cationic antimicrobial peptide, inducing apoptosis and membrane disruption.

    PubMed

    Ghosh, Prasanta; Bhoumik, Arpita; Saha, Sudipta; Mukherjee, Sandipan; Azmi, Sarfuddin; Ghosh, Jimut K; Dungdung, Sandhya R

    2017-04-14

    Presently available contraceptives are mostly hormonal or detergent in nature with numerous side effects like irritation, lesion, inflammation in vagina, alteration of body homeostasis, etc. Antimicrobial peptides with spermicidal activity but without adverse effects may be suitable alternatives. In the present study, spermicidal activity of a cationic antimicrobial peptide VRP on human spermatozoa has been elucidated. Progressive forward motility of human spermatozoa was instantly stopped after 100 μM VRP treatment and at 350 μM, all kinds of sperm motility ceased within 20 s as assessed by the Sander-Cramer assay. The spermicidal effect was confirmed by eosin-nigrosin assay and HOS test. VRP treatment (100 μM) in human spermatozoa induced both the intrinsic and extrinsic pathways of apoptosis. TUNEL assay showed VRP treatment significantly disrupted the DNA integrity and changed the mitochondrial membrane permeability as evident from MPTP assay. AFM and SEM results depicted ultra structural changes including disruption of the acrosomal cap and plasma membrane of the head and midpiece region after treatment with 350 μM VRP. MTT assay showed after treatments with 100 and 350 μM of VRP for 24 hr, a substantial amount of Lactobacillus acidophilus (about 90% and 75%, respectively) remained viable. Hence, VRP being a small synthetic peptide with antimicrobial and spermicidal activity but tolerable to normal vaginal microflora, may be a suitable target for elucidating its contraceptive potentiality. © 2017 Wiley Periodicals, Inc.

  8. Protection of male reproductive toxicity in rats exposed to di-n-butyl phthalate during embryonic development by testosterone.

    PubMed

    Giribabu, Nelli; Reddy, Pamanji Sreenivasula

    2017-03-01

    Di-n-butyl phthalate (DBP) widely spread industrial chemical that made drastic alteration in male reproductive system. The present study elucidates the protective role of testosterone on reproductive toxicity in prenatal DBP exposed adult male rats. Pregnant rats were injected with corn oil or 100 and 500mg/kg body weight of DBP on gestation day (GD) 1, 7 and 14. F1 male rats were weaned, injected with either testosterone or vehicle. On postnatal day (PND) 100 F1 adult male rats were cohabited with untreated female rats. Then rats were sacrificed and analyzed for other reproductive end points. Prenatal DBP exposed male rat testes, seminal vesicle weight, sperm count, motility, viability and HOS tail coiled sperm were significantly decreased with increased sperm morphological abnormalities. The levels of testicular 3β, 17βHSD, serum testosterone were significantly decreased with increased FSH, LH levels in experimental rats. The fertility studies revealed that increased pre, post-implantation losses and resorptions in normal females cohabited with experimental rats. Higher testicular LPO with lower SOD, CAT and GPx activity levels in experimental rats. Administration of testosterone to prenatal DBP treated male rats showed significant protection in above all parameters. In conclusions, testosterone deteriorates prenatal DBP induced reproductive and fertility toxicity by decreased oxidative stress and increased testicular antioxidant enzymes.

  9. An Automatic Prediction of Epileptic Seizures Using Cloud Computing and Wireless Sensor Networks.

    PubMed

    Sareen, Sanjay; Sood, Sandeep K; Gupta, Sunil Kumar

    2016-11-01

    Epilepsy is one of the most common neurological disorders which is characterized by the spontaneous and unforeseeable occurrence of seizures. An automatic prediction of seizure can protect the patients from accidents and save their life. In this article, we proposed a mobile-based framework that automatically predict seizures using the information contained in electroencephalography (EEG) signals. The wireless sensor technology is used to capture the EEG signals of patients. The cloud-based services are used to collect and analyze the EEG data from the patient's mobile phone. The features from the EEG signal are extracted using the fast Walsh-Hadamard transform (FWHT). The Higher Order Spectral Analysis (HOSA) is applied to FWHT coefficients in order to select the features set relevant to normal, preictal and ictal states of seizure. We subsequently exploit the selected features as input to a k-means classifier to detect epileptic seizure states in a reasonable time. The performance of the proposed model is tested on Amazon EC2 cloud and compared in terms of execution time and accuracy. The findings show that with selected HOS based features, we were able to achieve a classification accuracy of 94.6 %.

  10. Mobile phones affect multiple sperm quality traits: a meta-analysis

    PubMed Central

    Dama, Madhukar Shivajirao

    2013-01-01

    As mobile phone usage is growing rapidly, there is a need for a comprehensive analysis of the literature to inform scientific debates about the adverse effects of mobile phone radiation on sperm quality traits. Therefore, we conducted a meta-analysis of the eligible published research studies on human males of reproductive age. Eleven studies were eligible for this analysis. Based on the meta-analysis, mobile phone use was significantly associated with deterioration in semen quality (Hedges’s g = -0.547; 95% CI: -0.713, -0.382; p < 0.001). The traits particularly affected adversely were sperm concentration, sperm morphology, sperm motility, proportion of non-progressive motile sperm (%), proportion of slow progressive motile sperm (%), and sperm viability. Direct exposure of spermatozoa to mobile phone radiation with in vitro study designs also significantly deteriorated the sperm quality (Hedges’s g = -2.233; 95% CI: -2.758, -1.708; p < 0.001), by reducing straight line velocity, fast progressive motility, Hypo-osmotic swelling (HOS) test score, major axis (µm), minor axis (µm), total sperm motility, perimeter (µm), area (µm 2), average path velocity, curvilinear velocity, motile spermatozoa, and  acrosome reacted spermatozoa (%). The strength of evidence for the different outcomes varied from very low to very high. The analysis shows that mobile phone use is possibly associated with a number of deleterious effects on the spermatozoa. PMID:24327874

  11. Effect of lecithin nanoliposome or soybean lecithin supplemented by pomegranate extract on post-thaw flow cytometric, microscopic and oxidative parameters in ram semen.

    PubMed

    Mehdipour, Mahdieh; Daghigh Kia, Hossein; Nazari, Maryam; Najafi, Abouzar

    2017-10-01

    This investigation was carried out to study the effect of soybean lecithin 1.5% (wt/vol) (0, 2.5, 5 and 7.5 mg l(-1) pomegranate extract (PE)) or PE-loaded lecithin nanoliposome (0, 2.5, 5 and 7.5 mg l(-1)) to Tris-based extender. Sperm motility (CASA), viability, membrane integrity (HOS test), abnormalities, mitochondrial activity, apoptosis status, lipid peroxidation, total antioxidant capacity (TAC)) and antioxidant activities (GPX, SOD) were investigated following freeze-thawing. No significant differences were detected in motility parameters, viability, membrane integrity, and mitochondria activity after thawing sperm between soybean lecithin and lecithin nanoliposomes. It was shown that PE5 significantly improved sperm total and progressive motility, membrane integrity, viability, mitochondria activity, TAC and reduced lipid peroxidation (malondialdehyde concentration). Moreover, the percentage of apoptotic sperm in PE5 extenders was significantly the lowest among other treatments. Sperm abnormalities, SOD and GPX were not affected by the antioxidant supplements. For apoptotic status, no differences were observed between soybean lecithin and lecithin nanoliposome. We showed that lecithin nanoliposome extender can be a beneficial alternative extender to protect ram sperm during cryopreservation without any adverse effects. It was also observed that regarding pomegranate concentration, PE5 can improve the quality of ram semen after thawing. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications.

    PubMed

    Ryter, Stefan W; Alam, Jawed; Choi, Augustine M K

    2006-04-01

    The heme oxygenases, which consist of constitutive and inducible isozymes (HO-1, HO-2), catalyze the rate-limiting step in the metabolic conversion of heme to the bile pigments (i.e., biliverdin and bilirubin) and thus constitute a major intracellular source of iron and carbon monoxide (CO). In recent years, endogenously produced CO has been shown to possess intriguing signaling properties affecting numerous critical cellular functions including but not limited to inflammation, cellular proliferation, and apoptotic cell death. The era of gaseous molecules in biomedical research and human diseases initiated with the discovery that the endothelial cell-derived relaxing factor was identical to the gaseous molecule nitric oxide (NO). The discovery that endogenously produced gaseous molecules such as NO and now CO can impart potent physiological and biological effector functions truly represented a paradigm shift and unraveled new avenues of intense investigations. This review covers the molecular and biochemical characterization of HOs, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by environmental stress. Furthermore, the current understanding of the functional significance of HO shall be discussed from the perspective of each of the metabolic by-products, with a special emphasis on CO. Finally, this presentation aspires to lay a foundation for potential future clinical applications of these systems.

  13. Oridonin synergizes with Nutlin-3 in osteosarcoma cells by modulating the levels of multiple Bcl-2 family proteins.

    PubMed

    Wang, Xiao-Hui; Zhang, Shu-Feng; Bao, Jun-Tao; Liu, Fu-Yun

    2017-06-01

    The small-molecule inhibitors of p53-murine double minute 2 interaction, such as Nutlin-3, are effective against cancers bearing wild-type p53. However, murine double minute 2 inhibitors often are unable to completely eliminate solid tumor cells. To address this issue, we investigated the anticancer effects of Nutlin-3 in combination with Oridonin in osteosarcoma cells. We found that Oridonin at sub-toxic concentrations synergistically enhanced Nutlin-3-mediated cell viability inhibition in wild-type p53 U2OS and SJSA-1, but not in p53-mutant MNNG/HOS and in null-p53 Saos-2 osteosarcoma cell lines. Importantly, in the presence of Oridonin, Nutlin-3 could completely abolish cell viability in the wild-type p53 osteosarcoma cell lines. Western blotting analysis showed that Oridonin treatment rapidly and distinctly increased the levels of all three forms of Bim and also markedly reduced the levels of Bcl-2 and Bcl-xl in osteosarcoma cells. Western blotting analysis further showed that Oridonin considerably enhanced Nutlin-3-triggered activation of caspases-9 and -3 and poly(ADP-ribose) polymerase cleavage. Flow cytometry assay showed that Oridonin significantly enhanced Nutlin-3-mediated apoptosis in wild-type p53 osteosarcoma cells. Overall, our results suggest that the combined treatment of Nutlin-3 plus Oridonin may offer a novel therapeutic strategy for osteosarcoma.

  14. TRIM66 overexpresssion contributes to osteosarcoma carcinogenesis and indicates poor survival outcome

    PubMed Central

    Chen, Yu; Guo, Yongfei; Yang, Haisong; Shi, Guodong; Xu, Guohua; Shi, Jiangang; Na, Yin; Chen, Deyu

    2015-01-01

    TRIM66 belongs to the family of tripartite motif (TRIM)-containing proteins. Alterations in TRIM proteins have been implicated in several malignancies. This study was aimed at elucidating the expression and biological function of TRIM66 in osteosarcoma. Here, TRIM66 expression level was higher in osteosarcoma tissues than in normal tissues. High TRIM66 expression was correlated with high rate of local recurrence and lung metastasis, and short survival time. Then, we found that knockdown of TRIM66 in two osteosarcoma cell lines, MG63 and HOS, significantly inhibited cell proliferation and induced G1-phase arrest. Moreover, inhibition of TRIM66 in osteosarcoma cells significantly induced cell apoptosis, while remarkably inhibited cell migration, invasion as well as tumorigenicity in nude mice. Gene set enrichment analysis in Gene Expression Omnibus dataset revealed that apoptosis, epithelial-mesenchymal transition (EMT) and transforming growth factor-β (TGF-β) signaling pathway-related genes were enriched in TRIM66 higher expression patients, which was confirmed by western blot analysis in osteosarcoma cells with TRIM66 silenced. In conclusion, TRIM66 may act as an oncogene through suppressing apoptosis pathway and promoting TGF-β signaling in osteosarcoma carcinogenesis. TRIM66 may be a prognostic factor and potential therapeutic target in osteosarcoma. PMID:26247633

  15. Response of goat sperm to hypoosmotic steps modelled probit analysis.

    PubMed

    Leboeuf, B; Le Vern, Y; Furstoss, V; Kerboeuf, D; Guillouet, P; Magistrini, M

    2006-02-01

    Hypoosmotic swelling test (HOS) has been proposed by many authors to evaluate the functional integrity of the sperm membrane. Our approach in this experiment has consisted in exposing spermatozoa to a wide range of osmotic pressures then evaluating the reacted sperm cells by flow cytometry and finally modelling the sperm cell responses. Semen samples were diluted in skim milk or NPPC (native phosphocaseinate) extenders, and stored at 4 degrees C for 3 days. At D0 and D3 aliquots from each ejaculate (n=12) were submitted to seven hypoosmotic solutions varying from 230 to 10mOsm/kg. Sperm samples were analyzed using flow cytometry to determine two populations of spermatozoa identified by propidium iodide (PI): PI+ (including PI, red fluorescence) and PI- (excluding PI, no fluorescence). Spermatozoa PI+ were considered as spermatozoa with membrane damages. PI+ exhibited a high variation from 230 to 10mOsm/kg which was considered as a dose-response curve. Data were modelled using Mixed procedure and probit analysis to a sigmoid curve. Each model curve characterized the profile of response of the variable PI+ to the range of osmotic pressure from 230 to 10mOsm/kg. The estimated parameters modelling the sigmoid curves are discussed in order to evaluate the effect of extender (skim milk versus NPPC) and duration of preservation (D0 versus D3). Such modelling could help to differentiate storage method ejaculates within males or between male, contributing therefore to improve semen technology.

  16. Genomic and Epidemiological Evidence for Community Origins of Hospital-Onset Methicillin-Resistant Staphylococcus aureus Bloodstream Infections.

    PubMed

    Popovich, Kyle J; Snitkin, Evan S; Hota, Bala; Green, Stefan J; Pirani, Ali; Aroutcheva, Alla; Weinstein, Robert A

    2017-06-01

    We examined whether disparities existed in hospital-onset (HO) Staphylococcus aureus bloodstream infections (BSIs) and used whole-genome sequencing (WGS) to identify factors associated with USA300 transmission networks. We evaluated HO methicillin-susceptible S. aureus (MSSA) and HO methicillin-resistant S. aureus (MRSA) BSIs for 2009-2013 at 2 hospitals and used an adjusted incidence for modeling. WGS and phylogenetic analyses were performed on a sample of USA300 BSI isolates. Epidemiologic data were analyzed in the context of phylogenetic reconstructions. On multivariate analysis, male sex, African-American race, and non-Hispanic white race/ethnicity were significantly associated with HO-MRSA BSIs whereas Hispanic ethnicity was negatively associated (rate ratio, 0.41; P = .002). Intermixing of community-onset and HO-USA300 strains on the phylogenetic tree indicates that these strains derive from a common pool. African-American race was the only factor associated with genomic clustering of isolates. In a multicenter assessment of HO-S. aureus BSIs, African-American race was significantly associated with HO-MRSA but not MSSA BSIs. There appears to be a nexus of USA300 community and hospital transmission networks, with a community factor being the primary driver. Our data suggest that HO-USA300 BSIs likely are due to colonizing strains acquired in the community before hospitalization. Therefore, prevention efforts may need to extend to the community for maximal benefit.

  17. Mapping the Binding Interface of VEGF and a Monoclonal Antibody Fab-1 Fragment with Fast Photochemical Oxidation of Proteins (FPOP) and Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zhang, Ying; Wecksler, Aaron T.; Molina, Patricia; Deperalta, Galahad; Gross, Michael L.

    2017-03-01

    We previously analyzed the Fab-1:VEGF (vascular endothelial growth factor) system described in this work, with both native top-down mass spectrometry and bottom-up mass spectrometry (carboxyl-group or GEE footprinting) techniques. This work continues bottom-up mass spectrometry analysis using a fast photochemical oxidation of proteins (FPOP) platform to map the solution binding interface of VEGF and a fragment antigen binding region of an antibody (Fab-1). In this study, we use FPOP to compare the changes in solvent accessibility by quantitating the extent of oxidative modification in the unbound versus bound states. Determining the changes in solvent accessibility enables the inference of the protein binding sites (epitope and paratopes) and a comparison to the previously published Fab-1:VEGF crystal structure, adding to the top-down and bottom-up data. Using this method, we investigated peptide-level and residue-level changes in solvent accessibility between the unbound proteins and bound complex. Mapping these data onto the Fab-1:VEGF crystal structure enabled successful characterization of both the binding region and regions of remote conformation changes. These data, coupled with our previous higher order structure (HOS) studies, demonstrate the value of a comprehensive toolbox of methods for identifying the putative epitopes and paratopes for biotherapeutic antibodies.

  18. Synthesis, characterization, DNA interaction and cleavage, and in vitro cytotoxicity of copper(II) mixed-ligand complexes with 2-phenyl-3-hydroxy-4(1H)-quinolinone.

    PubMed

    Buchtík, Roman; Trávníček, Zdeněk; Vančo, Ján; Herchel, Radovan; Dvořák, Zdeněk

    2011-10-07

    A series of mixed-ligand complexes [Cu(qui)(L)]NO(3)·xH(2)O (1-6), where Hqui = 2-phenyl-3-hydroxy-4(1H)-quinolinone, L = 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), bis(2-pyridyl)amine (ambpy) (3), 5-methyl-1,10-phenanthroline (mphen) (4), 5-nitro-1,10-phenanthroline (nphen) (5) and bathophenanthroline (bphen) (6), have been synthesized and fully characterized. The X-ray structures of [Cu(qui)(phen)]NO(3)·H(2)O (2) and [Cu(qui)(ambpy)]NO(3) (3a) show a slightly distorted square-planar geometry in the vicinity of the central copper(II) atom. An in vitro cytotoxicity study of the complexes found significant activity against human osteosarcoma (HOS) and human breast adenocarcinoma (MCF7) cell lines, with the best results for complex 6, where IC(50) equals to 2.1 ± 0.2 μM, and 2.2 ± 0.4 μM, respectively. The strong interactions of the complexes with calf thymus DNA (CT-DNA) and high ability to cleave pUC19 DNA plasmid were found. A correlation has been found between the in vitro cytotoxicity and DNA cleavage studies of the complexes.

  19. Targeting the Pro-Survival Protein MET with Tivantinib (ARQ 197) Inhibits Growth of Multiple Myeloma Cells12

    PubMed Central

    Zaman, Shadia; Shentu, Shujun; Yang, Jing; He, Jin; Orlowski, Robert Z.; Stellrecht, Christine M.; Gandhi, Varsha

    2015-01-01

    The hepatocyte growth factor (HGF)/MNNG HOS transforming gene (MET) pathway regulates cell growth, survival, and migration. MET is mutated or amplified in several malignancies. In myeloma, MET is not mutated, but patients have high plasma concentrations of HGF, high levels of MET expression, and gene copy number, which are associated with poor prognosis and advanced disease. Our previous studies demonstrated that MET is critical for myeloma cell survival and its knockdown induces apoptosis. In our current study, we tested tivantinib (ARQ 197), a small-molecule pharmacological MET inhibitor. At clinically achievable concentrations, tivantinib induced apoptosis by > 50% in all 12 human myeloma cell lines tested. This biologic response was associated with down-regulation of MET signaling and inhibition of the mitogen-activated protein kinase and phosphoinositide 3-kinase pathways, which are downstream of the HGF/MET axis. Tivantinib was equally effective in inducing apoptosis in myeloma cell lines resistant to standard chemotherapy (melphalan, dexamethasone, bortezomib, and lenalidomide) as well as in cells that were co-cultured with a protective bone marrow microenvironment or with exogenous cytokines. Tivantinib induced apoptosis in CD138 + plasma cells from patients and demonstrated efficacy in a myeloma xenograft mouse model. On the basis of these data, we initiated a clinical trial for relapsed/refractory multiple myeloma (MM). In conclusion, MET inhibitors may be an attractive target-based strategy for the treatment of MM. PMID:25810013

  20. Targeting the pro-survival protein MET with tivantinib (ARQ 197) inhibits growth of multiple myeloma cells.

    PubMed

    Zaman, Shadia; Shentu, Shujun; Yang, Jing; He, Jin; Orlowski, Robert Z; Stellrecht, Christine M; Gandhi, Varsha

    2015-03-01

    The hepatocyte growth factor (HGF)/MNNG HOS transforming gene (MET) pathway regulates cell growth, survival, and migration. MET is mutated or amplified in several malignancies. In myeloma, MET is not mutated, but patients have high plasma concentrations of HGF, high levels of MET expression, and gene copy number, which are associated with poor prognosis and advanced disease. Our previous studies demonstrated that MET is critical for myeloma cell survival and its knockdown induces apoptosis. In our current study, we tested tivantinib (ARQ 197), a small-molecule pharmacological MET inhibitor. At clinically achievable concentrations, tivantinib induced apoptosis by >50% in all 12 human myeloma cell lines tested. This biologic response was associated with down-regulation of MET signaling and inhibition of the mitogen-activated protein kinase and phosphoinositide 3-kinase pathways, which are downstream of the HGF/MET axis. Tivantinib was equally effective in inducing apoptosis in myeloma cell lines resistant to standard chemotherapy (melphalan, dexamethasone, bortezomib, and lenalidomide) as well as in cells that were co-cultured with a protective bone marrow microenvironment or with exogenous cytokines. Tivantinib induced apoptosis in CD138+ plasma cells from patients and demonstrated efficacy in a myeloma xenograft mouse model. On the basis of these data, we initiated a clinical trial for relapsed/refractory multiple myeloma (MM). In conclusion, MET inhibitors may be an attractive target-based strategy for the treatment of MM. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Surveying the Impact of Work Hours and Schedules on Commercial Motor Vehicle Driver Sleep

    PubMed Central

    Hege, Adam; Perko, Michael; Johnson, Amber; Yu, Chong Ho; Sönmez, Sevil; Apostolopoulos, Yorghos

    2015-01-01

    Background Given the long hours on the road involving multiple and interacting work stressors (i.e., delivery pressures, irregular shifts, ergonomic hazards), commercial drivers face a plethora of health and safety risks. Researchers goal was to determine whether and to what extent long-haul trucker work schedules influence sleep duration and quality. Methods Survey and biometric data collected from male long-haul truck drivers at a major truckstop in central North Carolina over a six month period. Results Daily hours worked (mean = 11 hours, 55 minutes) and frequency of working over government-mandated daily HOS regulations (23.8% “frequently or always”) were statistically significant predictors of sleep duration. Miles driven per week (mean = 2,812.61), irregular daily hours worked (63.8%), and frequency of working over the daily hour limit (23.8% “frequently or always”) were statistically significant predictors of sleep quality. Conclusion Implications of findings suggest a comprehensive review of the regulations and operational conditions for commercial motor vehicle drivers be undertaken. PMID:26106509

  2. Silencing near tRNA genes is nucleosome-mediated and distinct from boundary element function

    PubMed Central

    Good, Paul D.; Kendall, Ann; Ignatz-Hoover, James; Miller, Erin L.; Pai, Dave A.; Rivera, Sara R.; Carrick, Brian; Engelke, David R.

    2013-01-01

    Transfer RNA (tRNA) genes and other RNA polymerase III transcription units are dispersed in high copy throughout nuclear genomes, and can antagonize RNA polymerase II transcription in their immediate chromosomal locus. Previous work in Saccharomyces cerevisiae found that this local silencing required subnuclear clustering of the tRNA genes near the nucleolus. Here we show that the silencing also requires nucleosome participation, though the nature of the nucleosome interaction appears distinct from other forms of transcriptional silencing. Analysis of an extensive library of histone amino acid substitutions finds a large number of residues that affect the silencing, both in the histone N-terminal tails and on the nucleosome disk surface. The residues on the disk surfaces involved are largely distinct from those affecting other regulatory phenomena. Consistent with the large number of histone residues affecting tgm silencing, survey of chromatin modification mutations shows that several enzymes known to affect nucleosome modification and positioning are also required. The enzymes include an Rpd3 deacetylase complex, Hos1 deacetylase, Glc7 phosphatase, and the RSC nucleosome remodeling activity, but not multiple other activities required for other silencing forms or boundary element function at tRNA gene loci. Models for communication between the tRNA gene transcription complexes and local chromatin are discussed. PMID:23707796

  3. Silencing near tRNA genes is nucleosome-mediated and distinct from boundary element function.

    PubMed

    Good, Paul D; Kendall, Ann; Ignatz-Hoover, James; Miller, Erin L; Pai, Dave A; Rivera, Sara R; Carrick, Brian; Engelke, David R

    2013-08-15

    Transfer RNA (tRNA) genes and other RNA polymerase III transcription units are dispersed in high copy throughout nuclear genomes, and can antagonize RNA polymerase II transcription in their immediate chromosomal locus. Previous work in Saccharomyces cerevisiae found that this local silencing required subnuclear clustering of the tRNA genes near the nucleolus. Here we show that the silencing also requires nucleosome participation, though the nature of the nucleosome interaction appears distinct from other forms of transcriptional silencing. Analysis of an extensive library of histone amino acid substitutions finds a large number of residues that affect the silencing, both in the histone N-terminal tails and on the nucleosome disk surface. The residues on the disk surfaces involved are largely distinct from those affecting other regulatory phenomena. Consistent with the large number of histone residues affecting tgm silencing, survey of chromatin modification mutations shows that several enzymes known to affect nucleosome modification and positioning are also required. The enzymes include an Rpd3 deacetylase complex, Hos1 deacetylase, Glc7 phosphatase, and the RSC nucleosome remodeling activity, but not multiple other activities required for other silencing forms or boundary element function at tRNA gene loci. Models for communication between the tRNA gene transcription complexes and local chromatin are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Detection of Neovascularization Based on Fractal and Texture Analysis with Interaction Effects in Diabetic Retinopathy

    PubMed Central

    Lee, Jack; Zee, Benny Chung Ying; Li, Qing

    2013-01-01

    Diabetic retinopathy is a major cause of blindness. Proliferative diabetic retinopathy is a result of severe vascular complication and is visible as neovascularization of the retina. Automatic detection of such new vessels would be useful for the severity grading of diabetic retinopathy, and it is an important part of screening process to identify those who may require immediate treatment for their diabetic retinopathy. We proposed a novel new vessels detection method including statistical texture analysis (STA), high order spectrum analysis (HOS), fractal analysis (FA), and most importantly we have shown that by incorporating their associated interactions the accuracy of new vessels detection can be greatly improved. To assess its performance, the sensitivity, specificity and accuracy (AUC) are obtained. They are 96.3%, 99.1% and 98.5% (99.3%), respectively. It is found that the proposed method can improve the accuracy of new vessels detection significantly over previous methods. The algorithm can be automated and is valuable to detect relatively severe cases of diabetic retinopathy among diabetes patients. PMID:24358105

  5. Accessible solitons in complex Ginzburg-Landau media

    NASA Astrophysics Data System (ADS)

    He, Yingji; Malomed, Boris A.

    2013-10-01

    We construct dissipative spatial solitons in one- and two-dimensional (1D and 2D) complex Ginzburg-Landau (CGL) equations with spatially uniform linear gain; fully nonlocal complex nonlinearity, which is proportional to the integral power of the field times the harmonic-oscillator (HO) potential, similar to the model of “accessible solitons;” and a diffusion term. This CGL equation is a truly nonlinear one, unlike its actually linear counterpart for the accessible solitons. It supports dissipative spatial solitons, which are found in a semiexplicit analytical form, and their stability is studied semianalytically, too, by means of the Routh-Hurwitz criterion. The stability requires the presence of both the nonlocal nonlinear loss and diffusion. The results are verified by direct simulations of the nonlocal CGL equation. Unstable solitons spontaneously spread out into fuzzy modes, which remain loosely localized in the effective complex HO potential. In a narrow zone close to the instability boundary, both 1D and 2D solitons may split into robust fragmented structures, which correspond to excited modes of the 1D and 2D HOs in the complex potentials. The 1D solitons, if shifted off the center or kicked, feature persistent swinging motion.

  6. Interferon but not MxB inhibits foamy retroviruses.

    PubMed

    Bähr, Ariane; Singer, Anna; Hain, Anika; Vasudevan, Ananda Ayyappan Jaguva; Schilling, Mirjam; Reh, Juliane; Riess, Maximilian; Panitz, Sylvia; Serrano, Vanessa; Schweizer, Matthias; König, Renate; Chanda, Sumit; Häussinger, Dieter; Kochs, Georg; Lindemann, Dirk; Münk, Carsten

    2016-01-15

    Foamy viruses (FV) are retroviruses that are widely distributed in primate and non-primate animal species. We tested here FV with capsids of simian and non-simian origin for sensitivity to interferon-β (IFN-β). Our data show significant inhibition of FV by IFN-β early in infection of human HOS and THP-1 but not of HEK293T cells. The post-entry restriction of FV was not mediated by the interferon-induced MxB protein that was recently identified as a capsid-interacting restriction factor targeting Human immunodeficiency virus (HIV) before integration. Neither the ectopic expression of MxA or MxB in HEK293T cells nor the lack of MxB expression in CRISPR/CAS MxB THP-1 knockout cells impacted the infection of the tested FV. IFN-β treated THP-1 and THP-1 KO MxB cells showed the same extend of restriction to FV. Together, the data demonstrate that IFN-β inhibits FV early in infection and that MxB is not a restriction factor of FV.

  7. Enhancement of autoregressive model based gear tooth fault detection technique by the use of minimum entropy deconvolution filter

    NASA Astrophysics Data System (ADS)

    Endo, H.; Randall, R. B.

    2007-02-01

    This paper proposes the use of the minimum entropy deconvolution (MED) technique to enhance the ability of the existing autoregressive (AR) model based filtering technique to detect localised faults in gears. The AR filter technique has been proven superior for detecting localised gear tooth faults than the traditionally used residual analysis technique. The AR filter technique is based on subtracting a regular gearmesh signal, as represented by the toothmesh harmonics and immediately adjacent sidebands, from the spectrum of a signal from one gear obtained by the synchronous signal averaging technique (SSAT). The existing AR filter technique performs well but is based on autocorrelation measurements and is thus insensitive to phase relationships which can be used to differentiate noise from impulses. The MED technique can make a use of the phase information by means of the higher-order statistical (HOS) characteristics of the signal, in particular the kurtosis, to enhance the ability to detect emerging gear tooth faults. The experimental results presented in this paper validate the superior performance of the combined AR and MED filtering techniques in detecting spalls and tooth fillet cracks in gears.

  8. A liquid biopsy-based method for the detection and quantification of circulating tumor cells in surgical osteosarcoma patients

    PubMed Central

    Zhang, Haoqiang; Gao, Peng; Xiao, Xin; Heger, Michal; Geng, Lei; Fan, Bo; Yuan, Yulin; Huang, Chen; Chen, Guojing; Liu, Yao; Hu, Yongchen; Yu, Xiuchun; Wu, Sujia; Wang, Ling; Wang, Zhen

    2017-01-01

    A method for the enumeration and quantification of osteosarcoma (OS) circulating tumor cells (CTCs) is currently not available. A correlation between the number of CTCs and progression-free survival (PFS) has been established for other cancers, but not for OS CTCs. A method was therefore developed for CTC quantification in OS and validated in a prospective cohort of surgical patients with primary and recurrent/metastatic OS (N=23). Human OS cells, acting as CTCs, were enumerated from spiked human peripheral blood (PB) following erythrocyte and leukocyte depletion. The OS cells were quantified microscopically based on aneuploidy and a CK18−/CD45− phenotype. Aneuploidy was assayed by fluorescence in situ hybridization (FISH) using fluorescence-labeled alpha-satellite probes for the centromeres of chromosome (CEP 8). CK18 and CD45 phenotyping was performed with immunocytochemistry. HOS cells in spiked PB could be effectively retrieved with the FISH-based enumeration method, which was subsequently employed in an OS patient cohort. PB of recurrent/metastatic OS patients contained more CTCs than the PB of primary OS patients. OS patients with ≥2 CTCs per 7.5 ml of PB had worse PFS than patients whose PB contained <2 CTCs. In 2 cases, CTCs were present in PB of OS patients with negative X-ray and chest CT scans. In conclusion, our method was able to quantitate CTCs in liquid biopsies of OS patients. The number of CTCs has diagnostic and prognostic value. PMID:28350107

  9. Automated diagnosis of dry eye using infrared thermography images

    NASA Astrophysics Data System (ADS)

    Acharya, U. Rajendra; Tan, Jen Hong; Koh, Joel E. W.; Sudarshan, Vidya K.; Yeo, Sharon; Too, Cheah Loon; Chua, Chua Kuang; Ng, E. Y. K.; Tong, Louis

    2015-07-01

    Dry Eye (DE) is a condition of either decreased tear production or increased tear film evaporation. Prolonged DE damages the cornea causing the corneal scarring, thinning and perforation. There is no single uniform diagnosis test available to date; combinations of diagnostic tests are to be performed to diagnose DE. The current diagnostic methods available are subjective, uncomfortable and invasive. Hence in this paper, we have developed an efficient, fast and non-invasive technique for the automated identification of normal and DE classes using infrared thermography images. The features are extracted from nonlinear method called Higher Order Spectra (HOS). Features are ranked using t-test ranking strategy. These ranked features are fed to various classifiers namely, K-Nearest Neighbor (KNN), Nave Bayesian Classifier (NBC), Decision Tree (DT), Probabilistic Neural Network (PNN), and Support Vector Machine (SVM) to select the best classifier using minimum number of features. Our proposed system is able to identify the DE and normal classes automatically with classification accuracy of 99.8%, sensitivity of 99.8%, and specificity if 99.8% for left eye using PNN and KNN classifiers. And we have reported classification accuracy of 99.8%, sensitivity of 99.9%, and specificity if 99.4% for right eye using SVM classifier with polynomial order 2 kernel.

  10. Anticancer Activity, Antioxidant Activity, and Phenolic and Flavonoids Content of Wild Tragopogon porrifolius Plant Extracts

    PubMed Central

    Rishmawi, Suzi; Ariqat, Sharehan H.; Khalid, Mahmoud F.; Warad, Ismail; Salah, Zaidoun

    2016-01-01

    Tragopogon porrifolius, commonly referred to as white salsify, is an edible herb used in folk medicine to treat cancer. Samples of Tragopogon porrifolius plant grown wild in Palestine were extracted with different solvents: water, 80% ethanol, and 100% ethanol. The extracts were analyzed for their total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity (AA). Four different antioxidant assays were used to evaluate AA of the extracts: two measures the reducing power of the extracts (ferric reducing antioxidant power (FRAP) and cupric reducing antioxidant power (CUPRAC)), while two other assays measure the scavenging ability of the extracts (2,2-azino-di-(3-ethylbenzothialozine-sulphonic acid (ABTS)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH)). Anticancer activity of the plant extracts were also tested on HOS and KHOS osteosarcoma cell lines. The results revealed that the polarity of the extraction solvent affects the TPC, TFC, and AA. It was found that both TPC and AA are highest for plant extracted with 80% ethanol, followed by water, and finally with 100% ethanol. TFC however was the highest in the following order: 80% ethanol > 100% ethanol > water. The plant extracts showed anticancer activities against KHOS cancer cell lines; they reduced total cell count and induced cell death in a drastic manner. PMID:27999608

  11. In vitro antibacterial efficacy of tetracycline hydrochloride adsorbed onto Bio-Oss bone graft.

    PubMed

    Dashti, A; Ready, D; Salih, V; Knowles, J C; Barralet, J E; Wilson, M; Donos, N; Nazhat, S N

    2010-05-01

    Local delivery of antibiotics may provide the advantage of reducing the potential side effects associated with their systemic administration. This study assessed, in vitro, the antimicrobial efficacy of tetracycline hydrochloride (TCH) adsorbed onto Bio-Oss bone grafts against a range of pathogenic bacteria. Various levels of TCH were adsorbed onto Bio-Oss granules by immersing in TCH aqueous solutions of different initial concentrations for 48 h at room temperature. TCH release was assessed in phosphate buffered saline at 37 degrees C, and its antimicrobial efficacy, up to 96 h, was tested against two Gram-negative bacteria associated with periodontal diseases: Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans, and Porphyromonas gingivalis, and one Gram-positive bacterium associated with soft-tissue and bone infections: Staphylococcus aureus. The range of TCH concentrations studied was also assessed for cytotoxicity against osteoblast-like human osteosarcoma cell lines. The amount of TCH adsorbed and released from Bio-Oss was concentration dependent. All TCH adsorbed Bio-Oss resulted in a reduction of A. actinomycetemcomitans, P. gingivalis, and S. aureus and higher concentrations were generally more effective in reducing or eliminating bacterial growth. The proliferation of HOS cells was not substantially reduced except for the maximum concentration of TCH. In addition to its osteoconductive role, TCH adsorbed Bio-Oss could also be functional in negating systemically antibiotic prophylactic treatment in the prevention of implant or biomaterial related infections. (c) 2010 Wiley Periodicals, Inc.

  12. Mechanosensitivity of human osteosarcoma cells and phospholipase C {beta}2 expression

    SciTech Connect

    Hoberg, M. . E-mail: Maik.Hoberg@med.uni-tuebingen.de; Gratz, H.-H.; Noll, M.; Jones, D.B.

    2005-07-22

    Bone adapts to mechanical load by osteosynthesis, suggesting that osteoblasts might respond to mechanical stimuli. We therefore investigated cell proliferation and phospholipase C (PLC) expression in osteoblasts. One Hertz uniaxial stretching at 4000 {mu}strains significantly increased the proliferation rates of human osteoblast-like osteosarcoma cell line MG-63 and primary human osteoblasts. However, U-2/OS, SaOS-2, OST, and MNNG/HOS cells showed no significant changes in proliferation rate. We investigated the expression pattern of different isoforms of PLC in these cell lines. We were able to detect PLC {beta}1, {beta}3, {gamma}1, {gamma}2, and {delta}1 in all cells, but PLC {beta}2 was only detectable in the mechanosensitive cells. We therefore investigated the possible role of PLC {beta}2 in mechanotransduction. Inducible antisense expression for 24 h inhibited the translation of PLC {beta}1 in U-2/OS cells by 35% and PLC {beta}2 in MG-63 by 29%. Fluid shear flow experiments with MG-63 lacking PLC {beta}2 revealed a significantly higher level of cells losing attachment to coverslips and a significantly lower number of cells increasing intracellular free calcium.

  13. John Collins Warren and his act of conscience: a brief narrative of the trial and triumph of a great surgeon.

    PubMed Central

    Moore, F D

    1999-01-01

    On examination of the correspondence among the principals involved, as well as the original patent application being prepared by Morton, it has become possible to reconstruct some of the remarkable details attending the first use of ether anesthesia at the Massachusetts General Hos pital in the autumn of 1846. At the time that Warren invited Morton to demonstrate the use of his "ethereal vapor" for anesthesia in a minor operation on Oct. 16, 1846, the exact chemical composition of the agent used was being held secret by Morton; Warren was clearly disturbed by this unethical use of a secret "nostrum." When the time arrived 3 weeks later for its possible use for a serious "capital" operation, Warren employed a simple stratagem of public confrontation to discover from Morton the true nature of the substance to be used. On being informed that it was pure unadulterated sulfuric ether, not some mysterious new discovery labeled "Letheon," Warren gave approval for its first use in a "capital" operation (low thigh amputation) on Nov. 7, 1846. Despite this revelation to the immediate participants, a veil of secrecy continued to surround the substance for many months, an anomalous situation evidently traceable to Morton's desire for personal reward from the discovery. It was this matter of secrecy, rather than priority for its discovery, that surrounded the early use of ether anesthesia with controversy and recrimination both in this country and abroad. Images Figure 2. PMID:10024099

  14. Hypocretin/Orexin Peptides Excite Rat Neuroendocrine Dopamine Neurons through Orexin 2 Receptor-Mediated Activation of a Mixed Cation Current

    PubMed Central

    Lyons, David J.; Hellysaz, Arash; Ammari, Rachida; Broberger, Christian

    2017-01-01

    Hypocretin/Orexin (H/O) neurons of the lateral hypothalamus are compelling modulator candidates for the chronobiology of neuroendocrine output and, as a consequence, hormone release from the anterior pituitary. Here we investigate the effects of H/O peptides upon tuberoinfundibular dopamine (TIDA) neurons – cells which control, via inhibition, the pituitary secretion of prolactin. In whole cell recordings performed in male rat hypothalamic slices, application of H/O-A, as well as H/O-B, excited oscillating TIDA neurons, inducing a reversible depolarising switch from phasic to tonic discharge. The H/O-induced inward current underpinning this effect was post-synaptic (as it endured in the presence of tetrodotoxin), appeared to be carried by a Na+-dependent transient receptor potential-like channel (as it was blocked by 2-APB and was diminished by removal of extracellular Na+), and was a consequence of OX2R receptor activation (as it was blocked by the OX2R receptor antagonist TCS OX2 29, but not the OX1R receptor antagonist SB 334867). Application of the hormone, melatonin, failed to alter TIDA membrane potential or oscillatory activity. This first description of the electrophysiological effects of H/Os upon the TIDA network identifies cellular mechanisms that may contribute to the circadian rhythmicity of prolactin secretion. PMID:28145492

  15. Triggering of apoptosis in osteosarcoma cells by graphene/single-walled carbon nanotube hybrids via the ROS-mediated mitochondrial pathway.

    PubMed

    Yan, Xinxin; Yang, Wen; Shao, Zengwu; Yang, Shuhua; Liu, Xianzhe

    2017-02-01

    Carbon nanomaterials are increasingly significant in the biological and medical fields, especially becoming promising candidates in treating difficult and complicated disease. Graphene/single-walled carbon nanotubes (G/SWCNT) hybrids is 3D structure which has been constructed by combining 1D single-walled carbon nanotubes (SWCNTs) and 2D graphene. However, the effects of the nanomaterial on biological systems are limited. In this study, we report a systematic investigation of the cytotoxicity and in vivo biodistribution of G/SWCNT hybrids on osteosarcoma cells (HOS and U2OS). The CCK-8, neutral red, and lactic dehydrogenase assays demonstrated that the cytotoxicity of G/SWCNT hybrids exhibits a dose-dependent behavior on osteosarcoma cells. In our conditions, the hybrids were less cytotoxic than graphene and single-walled carbon nanotubes. The results also showed the apoptosis of osteosarcoma cells induced by G/SWCNT hybrids was through the increase of intracellular reactive oxygen species, the decrease of mitochondrial membrane potential, the alternation of apoptosis-related proteins, and then triggered the ROS-mediated mitochondrial pathway. Moreover, the in vivo biodistribution of G/SWCNT hybrids was observed by histological analysis of major organs in mice, and showed that organs were neither damaged nor inflammatory. This study demonstrated that G/SWCNT hybrids could serve as a potential platform in anticancer therapy. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 443-453, 2017.

  16. The synergistic effect of SaOS-2 cell extract and other bone-inducing agents on human bone cell cultivation.

    PubMed

    Saif, Ashraf; Wende, Kristian; Lindequist, Ulrike

    2012-12-01

    Human osteosarcoma cell line SaOS-2 is an osteoblastic cell model that contains factors like bone morphogenetic proteins necessary for initiating bone formation. The cell line also expresses high levels of osteoinductive activity. In contrast to highly complicated and expensive ways to identify, purify, and separate specific bone-inducing agents from SaOS-2 cells, lysate can be used as an alternative to isolated bone-stimulating factors. Lysates of SaOS-2 stimulate the activity of the alkaline phosphatase of human osteoblastic cells HOS 58 in vitro. In other words, they probably possess osteoinductive activity. Different serial concentrations of substances like dexamethasone and insulin were tested with and without a lysate of SaOS-2 cells to assay their synergistic action. Results showed that a lysate of the SaOS-2 cell line acts as a synergistic agent and increases the osteoinductive activity of known bone-inducing agents. SaOS-2 cell lysate could be used in the future as a clinical agent to promote bone repair and possibly enhance osteointegration. Using SaOS-2 total cellular extract offers the possibility of lowering the effective dose of other bone-inducing agents.

  17. Role of mesenchymal stem cells in osteosarcoma and metabolic reprogramming of tumor cells

    PubMed Central

    Bonuccelli, Gloria; Avnet, Sofia; Grisendi, Giulia; Salerno, Manuela; Granchi, Donatella; Dominici, Massimo; Kusuzaki, Katsuyuki; Baldini, Nicola

    2014-01-01

    The tumor microenvironment plays an important role in cancer progression. Here, we focused on the role of reactive mesenchymal stem cells (MSC) in osteosarcoma (OS), and used human adipose MSC and a panel of OS cell lines (Saos-2, HOS, and 143B) to investigate the mutual effect of normal-cancer cell metabolic programming. Our results showed that MSC are driven by oxidative stress induced by OS cells to undergo Warburg metabolism, with increased lactate production. Therefore, we analyzed the expression of lactate monocarboxylate transporters. By real time PCR and immunofluorescence, in MSC we detected the expression of MCT-4, the transporter for lactate efflux, whereas MCT-1, responsible for lactate uptake, was expressed in OS cells. In agreement, silencing of MCT-1 by siRNA significantly affected the ATP production in OS cancer cells. Thus, cancer cells directly increase their mitochondrial biogenesis using this energy-rich metabolite that is abundantly provided by MSC as an effect of the altered microenvironmental conditions induced by OS cells. We also showed that lactate produced by MSC promotes the migratory ability of OS cells. These data provide novel information to be exploited for cancer therapies targeting the mutual metabolic reprogramming of cancer cells and their stroma. PMID:25277190

  18. Ethylene glycol, but not DMSO, could replace glycerol inclusion in soybean lecithin-based extenders in ram sperm cryopreservation.

    PubMed

    Najafi, Abouzar; Daghigh-Kia, Hossein; Dodaran, Hossein Vaseghi; Mehdipour, Mahdieh; Alvarez-Rodriguez, Manuel

    2017-02-01

    The aim of this study was to evaluate the effects of glycerol, ethylene glycol or DMSO in a soybean lecithin extender for freezing ram semen. In this study, 20 ejaculates were collected from four Ghezel rams and diluted with soybean lecithin extender with glycerol (7%), ethylene glycol (3%, 5% and 7%) or DMSO (3%, 5% and 7%). Sperm motility (CASA), membrane integrity (HOS test), viability, total abnormality, mitochondrial activity (Rhodamine 123) and apoptotic features (Annexin V/Propidium iodide) were assessed after thawing. There was no significant difference between glycerol and ethylene glycol at different concentrations (3% and 5%) regarding sperm total and progressive motility, viability, and membrane integrity. The least percentages of mitochondrial functionality were observed in samples frozen with all different DMSO concentrations tested (P<0.05). Moreover, the percentage of post-thawed dead sperm was the greatest for all the DMSO concentrations compared with other groups (P<0.05). Thus, DMSO had an adverse effect on the post thaw ram sperm parameters. In contrast, ethylene glycol could be a desirable substitute of glycerol in the freezing extender, in view of similar results obtained in post-thaw quality of ram semen cryopreserved in a soybean lecithin extender. We propose that glycerol in a soybean lecithin based extender could be replaced by ethylene glycol at 3% or 5% concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Protective Effect of Chitin Urocanate Nanofibers against Ultraviolet Radiation

    PubMed Central

    Ito, Ikuko; Yoneda, Toshikazu; Omura, Yoshihiko; Osaki, Tomohiro; Ifuku, Shinsuke; Saimoto, Hiroyuki; Azuma, Kazuo; Imagawa, Tomohiro; Tsuka, Takeshi; Murahata, Yusuke; Ito, Norihiko; Okamoto, Yoshiharu; Minami, Saburo

    2015-01-01

    Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils (NFs). We typically obtain NFs by hydrolyzing chitin with acetic acid. However, in the present study, we used urocanic acid to prepare urocanic acid chitin NFs (UNFs) and examined its protective effect against UVB radiation. Hos: HR-1 mice coated with UNFs were UVB irradiated (302 nm, 150 mJ/cm2), and these mice showed markedly lower UVB radiation-induced cutaneous erythema than the control. Additionally, sunburn cells were rarely detected in the epidermis of UNFs-coated mice after UVB irradiation. Although the difference was not as significant as UNFs, the number of sunburn cells in mice treated with acetic acid chitin nanofibrils (ANFs) tended to be lower than in control mice. These results demonstrate that ANFs have a protective effect against UVB and suggest that the anti-inflammatory and antioxidant effects of NFs influence the protective effect of ANFs against UVB radiation. The combination of NFs with other substances that possess UV-protective effects, such as urocanic acid, may provide an enhanced protective effect against UVB radiation. PMID:26703629

  20. Molecular cloning, characterization, and expression of an alfalfa (Medicago sativa L.) heme oxygenase-1 gene, MsHO1, which is pro-oxidants-regulated.

    PubMed

    Fu, Guang-Qing; Xu, Sheng; Xie, Yan-Jie; Han, Bin; Nie, Li; Shen, Wen-Biao; Wang, Ren

    2011-07-01

    It has been documented that plant heme oxygenase-1 (HO-1; EC 1.14.99.3) is both development- and stress-regulated, thus it plays a vital role in light signalling and stress responses. In this study, an alfalfa (Medica sativa L.) HO-1 gene MsHO1 was isolated and sequenced. It contains four exons and three introns within genomic DNA sequence and encodes a polypeptide with 283 amino acids. MsHO1 had a conserved HO signature sequence and showed high similarity to other HOs in plants, especially HO-1 isoform. The MsHO1:GFP fusion protein was localized in the chloroplast. Further biochemical activity analysis of mature MsHO1, which was expressed in Escherichia coli, showed that the Vmax was 48.78 nmol biliverdin-IXα (BV) h⁻¹ nmol⁻¹ protein with an apparent Km value for hemin of 2.33 μM, and the optimum Tm and pH were 37 °C and 7.2, respectively. Results of semi-quantitative RT-PCR and western blot showed that the expressions of MsHO1 were higher in alfalfa stems and leaves than those in germinating seeds and roots. Importantly, MsHO1 gene expression and protein level were induced significantly by some pro-oxidant compounds, including hemin and nitric oxide (NO) donor sodium nitroprusside (SNP). In conclusion, MsHO1 may play an important role in oxidative responses.

  1. Anti-proliferative, pro-apoptotic and anti-invasive effect of EC/EV system in human osteosarcoma

    PubMed Central

    Punzo, Francesca; Tortora, Chiara; Di Pinto, Daniela; Manzo, Iolanda; Bellini, Giulia; Casale, Fiorina; Rossi, Francesca

    2017-01-01

    Osteosarcoma is the most common and aggressive bone tumor in children. The Endocannabinoid/Endovanilloid system has been proposed as anticancer target in tumor of different origins. This system is composed of two receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel and their ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells. We investigated the effects of JWH-133 (CB2 agonist) and RTX (TRPV1 agonist) in six human Osteosarcoma cell lines: MG-63, U-2OS, MNNG/HOS, Saos-2, KHOS/NP, Hs888Lu, by Apoptosis and Migration-Assay. We also compared the effects of these compounds on Caspase-3, AKT, MMP-2 and Notch-1 regulation by Q-PCR and Western Blotting. We observed an anti-proliferative, pro-apoptotic, anti-invasive effect. Our results show that both CB2 stimulation and TRPV1 activation, in different Osteosarcoma cell lines, can act on the same pathways to obtain the same effect, indicating the Endocannabinoid/Endovanilloid system as a new therapeutic target in Osteosarcoma. PMID:28903355

  2. Growth modulation of human cells in vitro by mild oxidative stress and 1,4-dihydropyridine derivative antioxidants.

    PubMed

    Lovaković, Tomislava; Poljak-Blazi, Marija; Duburs, Gunars; Cipak, Ana; Cindrić, Marina; Vigante, Brigita; Bisenieks, Egils; Jaganjac, Morana; Mrakovcić, Lidija; Dedić, Azra; Zarković, Neven

    2011-03-01

    Reactive oxygen species and lipid peroxidation products are not only cytotoxic but may also modulate signal transduction in cells. Accordingly, antioxidants may be considered as modifiers of cellular redox signaling. Therefore, the effects of two novel synthetic antioxidants, analogues of 1,4-dihydropyridine derivatives, cerebrocrast and Z41-74 were analysed in vitro on human osteosarcoma cell line HOS, the growth of which can be modulated by lipid peroxidation. The cells were pretreated with either cerebrocrast or Z41-74 and afterwards exposed to mild, copper induced lipid peroxidation or to 4-hydroxynonenal (HNE), the end product of lipid peroxidation. The results obtained have shown that both antioxidants exert growth modulating effects interfering with the lipid peroxidation. Namely, cells treated with antioxidants showed increased metabolic rate and cell growth, thereby attenuating the effects of lipid peroxidation. Such biomodulating effects of cerebrocrast and Z41-74 resembled growth modulating effects of HNE, suggesting that the antioxidants could eventually promote cellular adaptation to oxidative stress interacting with redox signaling and hydroxynonenal HNE-signal transduction pathways. This may be of particular relevance for better understanding the beneficial role of hydroxynonenal HNE in cell growth control. Therefore, cerebrocrast and Z41-74 could be convenient to study further oxidative homeostasis involving lipid peroxidation.

  3. Relative efficacy of egg yolk and soya milk-based extenders for cryopreservation (-196°C) of buffalo semen.

    PubMed

    Chaudhari, D V; Dhami, A J; Hadiya, K K; Patel, J A

    2015-02-01

    The aim was to compare commercially available soybean milk-based extenders, viz. Bioxcell(®) and Optixcell(®) (IMV, France) with standard Tris-citrate-fructose-egg yolk-glycerol (TFYG) extender for cryopreservation of buffalo semen. Semen was collected twice a week in artificial vagina from six sexually mature, 4-6 years old, healthy breeding bulls of Surti buffalo breed. In all 48 qualifying ejaculates (8 per bull) having initial motility >70% were split into three equal aliquots and were diluted (at 34°C keeping 100×10(6) sperm ml(-1)) in TFYG, Bioxcell and Optixcell extenders. The French mini straws filled from each aliquot were gradually cooled to 4-5°C, equilibrated at 4°C for 4 h and frozen in liquid nitrogen 2 vapor using programmable biofreezer. Just before freezing (post-equilibration) and 24 h after frozen storage, the samples were evaluated for various sperm quality parameters using standard protocols. Frozen semen straws were thawed in a water bath at 37°C for 30 s. The post-thaw incubation survival (37°C for 1 h) was assessed through motility rating at 0, 30 and 60 min of incubation. The mean percentages of prefreeze sperms in TFYG, Bioxcell and Optixcell extenders in terms of progressive motility (69.48±0.37, 68.02±0.49, 70.94±0.38), viability (79.21±0.39, 77.38±0.48, 81.58±0.38), total abnormalities (7.90±0.14, 8.60±0.16, 7.08±0.15), intact acrosome (89.54± 0.18, 88.58±0.22, 90.52±0.21) and hypoosmotic swelling (HOS) reactivity (67.96±0.32, 65.65±0.42, 70.23±0.37) varied significantly (p<0.05) between extenders. Similar pattern of significant (p<0.05) variations between these extenders for post-thaw sperm progressive motility (47.71±0.79, 44.38±0.85, 49.90±0.90), viability (57.19±0.79, 53.85±0.84, 59.67±0.91), total abnormalities (12.33±0.17, 12.75±0.21, 11.27±0.18), intact acrosome (76.83±0.23, 75.90± 0.27, 78.50±0.25) and HOS reactivity (45.02±0.84, 42.31±0.82, 47.81±0.90) was also observed for TFYG, Bioxcell

  4. Relative efficacy of egg yolk and soya milk-based extenders for cryopreservation (−196°C) of buffalo semen

    PubMed Central

    Chaudhari, D.V.; Dhami, A. J.; Hadiya, K. K.; Patel, J. A.

    2015-01-01

    Aim: The aim was to compare commercially available soybean milk-based extenders, viz. Bioxcell® and Optixcell® (IMV, France) with standard Tris-citrate-fructose-egg yolk-glycerol (TFYG) extender for cryopreservation of buffalo semen. Materials and Methods: Semen was collected twice a week in artificial vagina from six sexually mature, 4-6 years old, healthy breeding bulls of Surti buffalo breed. In all 48 qualifying ejaculates (8 per bull) having initial motility >70% were split into three equal aliquots and were diluted (at 34°C keeping 100×106 sperm ml−1) in TFYG, Bioxcell and Optixcell extenders. The French mini straws filled from each aliquot were gradually cooled to 4-5°C, equilibrated at 4°C for 4 h and frozen in liquid nitrogen 2 vapor using programmable biofreezer. Just before freezing (post-equilibration) and 24 h after frozen storage, the samples were evaluated for various sperm quality parameters using standard protocols. Frozen semen straws were thawed in a water bath at 37°C for 30 s. The post-thaw incubation survival (37°C for 1 h) was assessed through motility rating at 0, 30 and 60 min of incubation. Results: The mean percentages of prefreeze sperms in TFYG, Bioxcell and Optixcell extenders in terms of progressive motility (69.48±0.37, 68.02±0.49, 70.94±0.38), viability (79.21±0.39, 77.38±0.48, 81.58±0.38), total abnormalities (7.90±0.14, 8.60±0.16, 7.08±0.15), intact acrosome (89.54± 0.18, 88.58±0.22, 90.52±0.21) and hypoosmotic swelling (HOS) reactivity (67.96±0.32, 65.65±0.42, 70.23±0.37) varied significantly (p<0.05) between extenders. Similar pattern of significant (p<0.05) variations between these extenders for post-thaw sperm progressive motility (47.71±0.79, 44.38±0.85, 49.90±0.90), viability (57.19±0.79, 53.85±0.84, 59.67±0.91), total abnormalities (12.33±0.17, 12.75±0.21, 11.27±0.18), intact acrosome (76.83±0.23, 75.90± 0.27, 78.50±0.25) and HOS reactivity (45.02±0.84, 42.31±0.82, 47.81±0.90) was

  5. Effect of antioxidant supplementation in semen extenders on semen quality and reactive oxygen species of chilled canine spermatozoa.

    PubMed

    Michael, A J; Alexopoulos, C; Pontiki, E A; Hadjipavlou-Litina, D J; Saratsis, P; Ververidis, H N; Boscos, C M

    2009-05-01

    The objective of this study was to evaluate quality of chilled dog semen processed with extenders containing various antioxidants. Single ejaculates from five dogs were always pooled and evaluated for concentration, sperm motility, progressive motility (RSF-movement), viability, acrosomal integrity and by the hypo-osmotic swelling (HOS)-test. Also, superoxide (O(2)(-)) production, hydroxyl radicals (OH) and total reactive oxygen species (tROS) were determined. Pooled semen was divided in seven aliquots (for control and test conditions), which were diluted to a final concentration of 67x10(6)spermatozoa/ml with TRIS-glucose-egg yolk extender with or without the following supplements: control (without antioxidants), vitamin C (0.5mM), N-acetyl-l-cysteine (NAC; 0.5mM), taurine (0.2mM), catalase (100u/ml), vitamin E (0.1mM) and 5-(4-dimethylamino-phenyl)-2-phenyl-penta-2,4-dienoic acid (B16; 0.1mM). The semen aliquots were chilled and preserved at 4 degrees C. Portions of chilled semen were removed at 24 and 72h, and semen quality was evaluated after rewarming. At 24h the mean (+/-S.E.M.) sperm motility was higher (p<0.001) when vitamin E, taurine and B16 were added in the extender, whereas more spermatozoa with RSF-movement were observed (p<0.001) in the vitamin E, catalase, B16 and taurine groups. Sperm viability was higher (p=0.040) in B16 and vitamin E groups and the percentage of swollen spermatozoa was higher (p=0.002) only in the B16 group. Acrosomal integrity and OH were not significantly influenced by any of the antioxidants tested. Superoxide production was significantly lower when vitamin C, B16 and vitamin E were added in semen extenders compared with the control (p=0.017). All antioxidant groups, except vitamin C and NAC, contained less tROS compared to the control group, but only the B16 group value differed significantly (p=0.05). At 72h sperm motility was higher (p<0.001) when vitamin E, catalase, B16, taurine and NAC were added in the extender. More

  6. Nonlinearity detection for condition monitoring utilizing higher-order spectral analysis diagnostics

    NASA Astrophysics Data System (ADS)

    Park, Hyeonsu

    In this dissertation, we investigate the theory and application of higher-order spectral analysis techniques to condition monitoring in shipboard electrical power systems. Monitoring and early detection of faults in rotating machines, such as induction motors, are essential for both preventive maintenance and to avoid potentially severe damage. As machines degrade, they often tend to become more nonlinear. This increased nonlinearity results in the introduction of new frequencies which satisfy particular frequency selection rules; the exact selection rule depends on the order of the nonlinearity. In addition, the phases of the newly generated frequencies satisfy a similar phase selection rule. This results in a phase coherence, or phase coupling, between the "original" interacting frequencies and the "new" frequencies. This phase coupling is a true signature of nonlinearity. Since the classical auto-power spectrum contains no phase information, the phase coupling signature associated with nonlinear interactions is not available. However, various higher-order spectra (HOS) are capable of detecting such nonlinear-induced phase coupling. The efficacy of the various proposed HOS-based methodologies is investigated using real-world vibration time-series data from a faulted induction motor driving a dc generator. The fault is controlled by varying a resistor placed in one phase of the three-phase line to the induction motor. First, we propose a novel method using a bispectral change detection (BCD) for condition monitoring. Even though the bicoherence is dominant and powerful in the detection of phase coupling of nonlinearly interacting frequencies, it has some difficulties in its application to machine condition monitoring. Basically, the bicoherence may not be able to distinguish between intrinsic nonlinearities associated with healthy machines and fault-induced nonlinearities. Therefore, the ability to discriminate the fault-only nonlinearities from the intrinsic

  7. Assessment of semen quality in pure and crossbred Jersey bulls

    PubMed Central

    Kumar, Umesh; Gawande, Ajay P.; Sahatpure, Sunil K.; Patil, Manoj S.; Lakde, Chetan K.; Bonde, Sachin W.; Borkar, Pradnyankur L.; Poharkar, Ajay J.; Ramteke, Baldeo R.

    2015-01-01

    Aim: To compare the seminal attributes of neat, pre-freeze (at equilibration), and post-freeze (24 h after freezing) semen in pure and crossbred Jersey bulls. Materials and Methods: Total 36 ejaculates (3 ejaculates from each bull) were collected from 6 pure Jersey and 6 crossbred Jersey bulls and evaluated for various seminal attributes during neat, pre-freeze, and post-freeze semen. Results: The mean (±standard error [SE]) values of neat semen characteristics in pure and crossbred Jersey bulls were recorded such as volume (ml), color, consistency, mass activity (scale: 0-5), and sperm concentration (millions/ml). The extended semen was further investigated at pre-freeze and post-freeze stages and the mean (±SE) values recorded at neat, pre-freeze, and post-freeze semen were compared between pure and crossbred Jersey bulls; sperm motility (80.55±1.70%, 62.77±1.35%, 46.11±1.43% vs. 80.00±1.80%, 65.00±1.66%, 47.22±1.08%), live sperm count (83.63±1.08%, 71.72±1.09%, 58.67±1.02% vs. 80.00±1.08%, 67.91±1.20%, 51.63±0.97%), total abnormal sperm count (8.38±0.32%, 12.30±0.39%, 16.75±0.42% vs. 9.00±0.45%, 12.19±0.48%, 18.11±0.64%), hypo-osmotic swelling (HOS) reacted spermatozoa (71.88±0.77%, 62.05±0.80%, 47.27±1.05% vs. 72.77±1.02%, 62.11±0.89%, 45.94±1.33%), acrosome integrity (89.05±0.83%, 81.33±0.71%, 71.94±0.86% vs. 86.55±0.57%, 78.66±0.42%, 69.38±0.53%), and DNA integrity (99.88±0.07%, 100, 99.66±0.11% vs. 99.94±0.05%, 100, 99.44±0.18%,). The volume, color, consistency, sperm concentration, and initial motility in pure and crossbred Jersey bulls did not differ significantly (p>0.05). The mass activity was significantly (p<0.05) higher in pure Jersey as compare to crossbred Jersey bulls. Live sperm percentage and acrosome integrity was significantly (p<0.01) higher in pure Jersey bulls as compared to crossbred Jersey bulls. However, no statistical difference (p>0.05) was observed in abnormal sperm; HOS reacted spermatozoa and DNA

  8. Modelization of highly nonlinear waves in coastal regions

    NASA Astrophysics Data System (ADS)

    Gouin, Maïté; Ducrozet, Guillaume; Ferrant, Pierre

    2015-04-01

    The proposed work deals with the development of a highly non-linear model for water wave propagation in coastal regions. The accurate modelization of surface gravity waves is of major interest in ocean engineering, especially in the field of marine renewable energy. These marine structures are intended to be settled in coastal regions where the effect of variable bathymetry may be significant on local wave conditions. This study presents a numerical model for the wave propagation with complex bathymetry. It is based on High-Order Spectral (HOS) method, initially limited to the propagation of non-linear wave fields over flat bottom. Such a model has been developed and validated at the LHEEA Lab. (Ecole Centrale Nantes) over the past few years and the current developments will enlarge its application range. This new numerical model will keep the interesting numerical properties of the original pseudo-spectral approach (convergence, efficiency with the use of FFTs, …) and enable the possibility to propagate highly non-linear wave fields over long time and large distance. Different validations will be provided in addition to the presentation of the method. At first, Bragg reflection will be studied with the proposed approach. If the Bragg condition is satisfied, the reflected wave generated by a sinusoidal bottom patch should be amplified as a result of resonant quadratic interactions between incident wave and bottom. Comparisons will be provided with experiments and reference solutions. Then, the method will be used to consider the transformation of a non-linear monochromatic wave as it propagates up and over a submerged bar. As the waves travel up the front slope of the bar, it steepens and high harmonics are generated due to non-linear interactions. Comparisons with experimental data will be provided. The different test cases will assess the accuracy and efficiency of the method proposed.

  9. Absence of tpr-met and expression of c-met in human gastric mucosa and carcinoma.

    PubMed

    Heideman, D A; Snijders, P J; Bloemena, E; Meijer, C J; Offerhaus, G J; Meuwissen, S G; Gerritsen, W R; Craanen, M E

    2001-08-01

    The c-met proto-oncogene, encoding the hepatocyte growth factor receptor, can be activated by various mechanisms. These include, among others, gene amplification with concomitant overexpression and the tpr-met oncogenic rearrangement. In the case of gastric cancer, contradictory results on the presence of the tpr-met oncogenic rearrangement have been published. The current study aimed therefore to assess the prevalence of tpr-met expression in Caucasian gastric adenocarcinomas, to evaluate the importance of this oncogene in their carcinogenesis. In addition, the level of c-met expression was determined, to evaluate the role of this alternative mode of activation of the proto-oncogene. A series of Caucasian gastric adenocarcinomas (n=43) and normal gastric mucosal samples (n=14) was analysed for tpr-met and c-met expression. Expression of tpr-met mRNA in the samples was performed by two reverse transcriptase polymerase chain reaction (RT-PCR) assays, with excellent correlation. The specificity of both methods was confirmed by direct sequencing of the PCR products of the MNNG-HOS cell line, which is known to contain the rearrangement. The level of c-met expression was assessed using semi-quantitative RT-PCR assays and immunohistochemistry (IHC). None of the normal gastric mucosal or gastric adenocarcinoma samples expressed tpr-met mRNA, as determined by both RT-PCR assays. Seventy per cent of the adenocarcinomas showed overexpression of c-met, according to elevated c-met mRNA levels, compared with the expression level of normal gastric mucosa. A significant correlation was found between the level of c-met mRNA and protein expression. In conclusion, these results strongly suggest that tpr-met activation does not play a role in Caucasian gastric carcinogenesis, while overexpression of the c-met gene occurs in the majority of Caucasian gastric adenocarcinomas. Copyright 2001 John Wiley & Sons, Ltd.

  10. Induction of G2/M phase cell cycle arrest and apoptosis by ginsenoside Rf in human osteosarcoma MG‑63 cells through the mitochondrial pathway.

    PubMed

    Shangguan, Wen-Ji; Li, He; Zhang, Yue-Hui

    2014-01-01

    Ginsenosides, extracted from the traditional Chinese herb ginseng, are a series of novel natural anticancer products known for their favorable safety and efficacy profiles. The present study aimed to investigate the cytotoxicity of ginsenoside Rf to human osteosarcoma cells and to explore the anticancer molecular mechanisms of ginsenoside Rf. Five human osteosarcoma cell lines (MG-63, OS732, U-2OS, HOS and SAOS-2) were employed to investigate the cytotoxicity of ginsenoside Rf by MTT and colony forming assays. After treatment with ginsenoside Rf, MG-63 cells which were the most sensitive to ginsenoside Rf, were subjected to flow cytometry to detect cell cycle distribution and apoptosis, and nuclear morphological changes were visualized by Hoechst 33258 staining. Caspase-3, -8 and -9 activities were also evaluated. The expression of cell cycle markers including cyclin B1 and Cdk1 was detected by RT-PCR and western blotting. The expression of apoptotic genes Bcl-2 and Bax and the release of cytochrome c were also examined by western blotting. Change in the mitochondrial membrane potential was observed by JC-1 staining in situ. Our results demonstrated that the cytotoxicity of ginsenoside Rf to these human osteosarcoma cell lines was dose-dependent, and the MG-63 cells were the most sensitive to exposure to ginsenoside Rf. Additionally, ginsenoside Rf induced G2/M phase cell cycle arrest and apoptosis in MG-63 cells. Furthermore, we observed upregulation of Bax and downregulation of Bcl-2, Cdk1 and cyclin B1, the activation of caspase-3 and -9 and the release of cytochrome c in MG-63 cells following treatment with ginsenoside Rf. Our findings demonstrated that ginsenoside Rf induces G2/M phase cell cycle arrest and apoptosis in human osteosarcoma MG-63 cells through the mitochondrial pathway, suggesting that ginsenoside Rf, as an effective natural product, may have a therapeutic effect on human osteosarcoma.

  11. A zinc(II) quinolinone complex (Et3NH)[Zn(qui)Cl2]: Synthesis, X-ray structure, spectral properties and in vitro cytotoxicity

    NASA Astrophysics Data System (ADS)

    Buchtík, Roman; Nemec, Ivan; Trávníček, Zdeněk

    2014-02-01

    A new zinc(II) complex with 2-phenyl-3-hydroxy-4(1H)-quinolinone (Hqui) of the composition (Et3NH)[Zn(qui)Cl2] was prepared and characterized by elemental analysis, FT IR, 1D and 2D NMR, and fluorescence spectroscopy, mass spectrometry and single crystal X-ray analysis. The molecular structure is composed of the triethylammonium (Et3NH+) cations and tetrahedral [ZnII(qui)Cl2]- complex anions, in which the Zn(II) atoms are bidentate coordinated by one qui ligand through keto (OK) and phenolate (OP) oxygen atoms and by two chlorido ligands, thus forming the {O2Cl2} donor set, with Zn-OK = 1.9860(14) Å, Zn-OP 1.9961(14) Å and Zn-Cl = 2.2509(6) Å and 2.2266(6) Å. The complex cations are aligned into 1D supramolecular chains through the NH⋯Cl hydrogen bonding between the amine group of the quinolinone ligand and the chlorido ligand of the adjacent complex anion. The amine group from the Et3NH+ cations provides the NH⋯OP hydrogen bond with the phenolate oxygen atoms from the complex anion. Screening of in vitro cytotoxicity of the compound was studied on human osteosarcoma (HOS) and human breast adenocarcinoma (MCF7) cell lines, with IC50 > 50 μM. The fluorescence study showed that the complex exhibits a relatively high integral intensity (29%) as compared to the standard quinine sulfate, and 1.6-fold enhancement of emission with respect to free Hqui.

  12. Methotrexate-mediated inhibition of RAD51 expression and homologous recombination in cancer cells.

    PubMed

    Du, Li-Qing; Du, Xiao-Qing; Bai, Jian-Qiang; Wang, Yan; Yang, Qing-Shan; Wang, Xiao-Chun; Zhao, Peng; Wang, Hong; Liu, Qiang; Fan, Fei-Yue

    2012-05-01

    Methotrexate is an inhibitor of folic acid metabolism. Homologous recombination is one of the most important ways to repair double-stranded breaks in DNA and influence the radio- and chemosensitivity of tumor cells. But the relationship between methotrexate and homologous recombination repair has not been elucidated. Induction of double-strand breaks by methotrexate in HOS cells is assessed by the neutral comet assay. Inhibition of subnuclear repair foci by methotrexate is measured by immunofluorescence. Western blot and quantitative real-time PCR are conducted to detect whether methotrexate affects the expression level of genes involved in homologous recombination. In addition, we used a pCMV3xnls-I-SceI construct to determine whether methotrexate directly inhibits the process of homologous recombinational repair in cells, and the sensitivity to methotrexate in the Ku80-deficient cells is detected using clonogenic survival assays. The result showed that methotrexate can regulate the repair of DNA double-strand breaks after radiation exposure, and methotrexate inhibition caused the complete inhibition of subnuclear repair foci in response to ionizing radiation. Mechanistic investigation revealed that methotrexate led to a significant reduction in the transcription of RAD51 genes. Treatment with methotrexate resulted in a decreased ability to perform homology-directed repair of I-SceI-induced chromosome breaks. In addition, enhancement of cell death was observed in Ku mutant cells compared to wild-type cells. These results demonstrate that methotrexate can affect homologous recombination repair of DNA double-strand breaks by controlling the expression of homologous recombination-related genes and suppressing the proper assembly of homologous recombination-directed subnuclear foci.

  13. Classification of oxidative stress based on its intensity

    PubMed Central

    Lushchak, Volodymyr I.

    2014-01-01

    In living organisms production of reactive oxygen species (ROS) is counterbalanced by their elimination and/or prevention of formation which in concert can typically maintain a steady-state (stationary) ROS level. However, this balance may be disturbed and lead to elevated ROS levels called oxidative stress. To our best knowledge, there is no broadly acceptable system of classification of oxidative stress based on its intensity due to which proposed here system may be helpful for interpretation of experimental data. Oxidative stress field is the hot topic in biology and, to date, many details related to ROS-induced damage to cellular components, ROS-based signaling, cellular responses and adaptation have been disclosed. However, it is common situation when researchers experience substantial difficulties in the correct interpretation of oxidative stress development especially when there is a need to characterize its intensity. Careful selection of specific biomarkers (ROS-modified targets) and some system may be helpful here. A classification of oxidative stress based on its intensity is proposed here. According to this classification there are four zones of function in the relationship between “Dose/concentration of inducer” and the measured “Endpoint”: I – basal oxidative stress (BOS); II – low intensity oxidative stress (LOS); III – intermediate intensity oxidative stress (IOS); IV – high intensity oxidative stress (HOS). The proposed classification will be helpful to describe experimental data where oxidative stress is induced and systematize it based on its intensity, but further studies will be in need to clear discriminate between stress of different intensity. PMID:26417312

  14. Eradication of osteosarcoma by fluorescence-guided surgery with tumor labeling by a killer-reporter adenovirus.

    PubMed

    Yano, Shuya; Miwa, Shinji; Kishimoto, Hiroyuki; Urata, Yasuo; Tazawa, Hiroshi; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2016-05-01

    In a previous study, we developed fluorescence-guided surgery (FGS) for osteosarcoma using an orthotopic model with 143B human osteosarcoma cells expressing red fluorescent protein (RFP) implanted into the intramedullary cavity of the tibia in nude mice. The FGS-treated mice had a significantly higher disease-free survival (DFS) rate than the bright-light surgery (BLS). However, although FGS significantly reduced the recurrence of the primary tumor, it did not reduce lung metastasis. In the present study, we utilized the OBP-401 telomerase-dependent killer-reporter adenovirus, carrying green fluorescent protein (GFP), to label human osteosarcoma in situ in orthotopic mouse models. OBP-401-illuminated human osteosarcoma cell lines, 143B and MNNG/HOS cells in vitro and in vivo. OBP-401 tumor illumination enabled effective FGS of the 143B-derived orthotopic mouse model of human osteosarcoma model as well as FGS eradication of residual cancer cells after BLS. OBP-401-assisted FGS significantly inhibited local recurrence and lung metastasis after surgery, thereby prolonging DFS and overall survival (OS), achieving a very important improvement of therapeutic outcomes over our previously reported FGS study. These therapeutic benefits of FGS were demonstrated using a clinically-viable methodology of direct labeling of human osteosarcoma in situ with the OBP-401 killer-reporter adenovirus in contrast with previous reports, which used genetically engineered labeled cells or antibody-based fluorescent labels for FGS. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:836-844, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. Tbx5 and Osr1 interact to regulate posterior second heart field cell cycle progression for cardiac septation

    PubMed Central

    Zhou, Lun; Liu, Jielin; Olson, Patrick; Zhang, Ke; Wynne, Joshua; Xie, Linglin

    2015-01-01

    Rationale Mutations of TBX5 cause Holt–Oram syndrome (HOS) in humans, a disease characterized by atrial or occasionally ventricular septal defects in the heart and skeletal abnormalities of the upper extremity. Previous studies have demonstrated that Tbx5 regulates Osr1 expression in the second heart field (SHF) of E9.5 mouse embryos. However, it is unknown whether and how Tbx5 and Osr1 interact in atrial septation. Objective To determine if and how Tbx5 and Osr1 interact in the posterior SHF for cardiac septation. Methods and Results In the present study, genetic inducible fate mapping showed that Osr1-expressing cells contribute to atrial septum progenitors between E8.0 and E11.0. Osr1 expression in the pSHF was dependent on the level of Tbx5 at E8.5 and E9.5 but not E10.5, suggesting that the embryo stage before E10.5 is critical for Tbx5 interacting with Osr1 in atrial septation. Significantly more atrioventricular septal defects (AVSDs) were observed in embryos with compound haploinsufficiency for Tbx5 and Osr1. Conditional compound haploinsufficiency for Tbx5 and Osr1 resulted in a significant cell proliferation defect in the SHF, which was associated with fewer cells in the G2 and M phases and a decreased level of Cdk6 expression. Remarkably, genetically targeted disruption of Pten expression in atrial septum progenitors rescued AVSDs caused by Tbx5 and Osr1 compound haploinsufficiency. There was a significant decrease in Smo expression, which is a Hedgehog (Hh) signaling pathway modulator, in the pSHF of Osr1 knockout embryos at E9.5, implying a role for Osr1 in regulating Hh signaling. Conclusions Tbx5 and Osr1 interact to regulate posterior SHF cell cycle progression for cardiac septation. PMID:25986147

  16. Investigation of the HD-sEMG probability density function shapes with varying muscle force using data fusion and shape descriptors.

    PubMed

    Al Harrach, Mariam; Boudaoud, Sofiane; Carriou, Vincent; Laforet, Jeremy; Letocart, Adrien J; Grosset, Jean-François; Marin, Frédéric

    2017-08-01

    This work presents an evaluation of the High Density surface Electromyogram (HD-sEMG) Probability Density Function (PDF) shape variation according to contraction level. On that account, using PDF shape descriptors: High Order Statistics (HOS) and Shape Distances (SD), we try to address the absence of a consensus for the sEMG non-Gaussianity evolution with force variation. This is motivated by the fact that PDF shape information are relevant in physiological assessment of the muscle architecture and function, such as contraction level classification, in complement to classical amplitude parameters. Accordingly, both experimental and simulation studies are presented in this work. For data fusion, the watershed image processing technique was used. This technique allowed us to find the dominant PDF shape variation profiles from the 64 signals. The experimental protocol consisted of three isometric isotonic contractions of 30, 50 and 70% of the Maximum Voluntary Contraction (MVC). This protocol was performed by six subjects and recorded using an 8 × 8 HD-sEMG grid. For the simulation study, the muscle modeling was done using a fast computing cylindrical HD-sEMG generation model. This model was personalized by morphological parameters obtained by sonography. Moreover, a set of the model parameter configurations were compared as a focused sensitivity analysis of the PDF shape variation. Further, monopolar, bipolar and Laplacian electrode configurations were investigated in both experimental and simulation studies. Results indicated that sEMG PDF shape variations according to force increase are mainly dependent on the Motor Unit (MU) spatial recruitment strategy, the MU type distribution within the muscle, and the used electrode arrangement. Consequently, these statistics can give us an insight into non measurable parameters and specifications of the studied muscle primarily the MU type distribution. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Effects of stress on mouse β-defensin-3 expression in the upper digestive mucosa.

    PubMed

    Kawashima, Rie; Shimizu, Tomoko; To, Masahiro; Saruta, Juri; Jinbu, Yoshinori; Kusama, Mikio; Tsukinoki, Keiichi

    2014-03-01

    Gastrointestinal integrity and immune surveillance are affected by stress. Stress also adversely affects mucosal barrier function. β-defensins constitute an integral component of the innate immune system as antimicrobial peptides, serving as the first line of defense against microbial pathogens at the epithelial surfaces of the upper digestive mucosa. The primary objective of this study was to determine the effects of stress on the expression profile of mouse β-defensin-3 in the upper digestive mucosa of mice with diabetes. We established a mouse model of restraint stress by using NSY/Hos mice with type 2 diabetes mellitus. We used real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry to investigate the effects of stress and glucocorticoid administration on mouse β-defensin-3 expression in the upper digestive mucosa of the gingiva, esophagus, and stomach. Mouse β-defensin-3 mRNA expression was higher in the esophagus than in the gingiva or stomach (p<0.05). In the esophagus, mouse β-defensin-3 mRNA expression was lower in stressed mice than in non-stressed mice (p<0.05). Furthermore, immunoreactivity to mouse β-defensin-3 protein was lower in the esophagus of stressed mice than non-stressed mice, consistent with the results of mRNA expression analysis. Systemic glucocorticoid administration also downregulated esophageal mouse β-defensin-3 mRNA expression. Our novel findings show that stress decreases mouse β-defensin-3 expression in the esophagus of mice with diabetes, possibly due to increased endogenous glucocorticoid production. It appears to be highly likely that stress management may normalize mucosal antimicrobial defenses in patients with diabetes.

  18. A Bulk Segregant Gene Expression Analysis of a Peach Population Reveals Components of the Underlying Mechanism of the Fruit Cold Response

    PubMed Central

    Pons, Clara; Martí, Cristina; Forment, Javier; Crisosto, Carlos H.; Dandekar, Abhaya M.; Granell, Antonio

    2014-01-01

    Peach fruits subjected for long periods of cold storage are primed to develop chilling injury once fruits are shelf ripened at room temperature. Very little is known about the molecular changes occurring in fruits during cold exposure. To get some insight into this process a transcript profiling analyses was performed on fruits from a PopDG population segregating for chilling injury CI responses. A bulked segregant gene expression analysis based on groups of fruits showing extreme CI responses indicated that the transcriptome of peach fruits was modified already during cold storage consistently with eventual CI development. Most peach cold-responsive genes have orthologs in Arabidopsis that participate in cold acclimation and other stresses responses, while some of them showed expression patterns that differs in fruits according to their susceptibility to develop mealiness. Members of ICE1, CBF1/3 and HOS9 regulons seem to have a prominent role in differential cold responses between low and high sensitive fruits. In high sensitive fruits, an alternative cold response program is detected. This program is probably associated with dehydration/osmotic stress and regulated by ABA, auxins and ethylene. In addition, the observation that tolerant siblings showed a series of genes encoding for stress protective activities with higher expression both at harvest and during cold treatment, suggests that preprogrammed mechanisms could shape fruit ability to tolerate postharvest cold-induced stress. A number of genes differentially expressed were validated and extended to individual genotypes by medium-throughput RT-qPCR. Analyses presented here provide a global view of the responses of peach fruits to cold storage and highlights new peach genes that probably play important roles in the tolerance/sensitivity to cold storage. Our results provide a roadmap for further experiments and would help to develop new postharvest protocols and gene directed breeding strategies to better

  19. Systematic review of cross-cultural adaptations of hip-specific patient-reported outcome measures in Spanish.

    PubMed

    Gómez-Valero, Sara; García-Pérez, Fernando; Flórez-García, Mariano Tomás; Miangolarra-Page, Juan Carlos

    2017-03-16

    The aim of this study was to conduct a systematic review of the quality of the transcultural adaptation procedure and the clinimetric properties of the self-administered hip-disability functional assessment questionnaires adapted for the Spanish population. We searched the MEDLINE, EMBASE, CINAHL and Web of Science databases (from inception until June 2016) to locate all the scales adapted to Spanish and to analyze the different phases of the adaptation process and its psychometric properties. Eight scales were identified, and were grouped into three sections, according to the type of diseases in which they can be used: a) lower limb: Lower Limb Functional Index (LLFI), Lower Extremity Functional Scale (LEFS) and Arthrosis of Membres Inférieurs et Qualité de vie (AMICAL); b) knee and/or hip: Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, Osteoarthritis Knee and Hip Quality of Life (OAKHQOL) and Hip and Knee Questionnaire (HKQ); and c) specific for hip: Hip Outcome Score (HOS) and International Hip Outcome Tool-33 (iHOT-33). The transcultural adaptation procedure was satisfactory in all cases, albeit somewhat less rigorous for the HKQ and LLFI than for the remaining questionnaires. No study evaluated all the psychometric properties. We currently have 8 hip-disability functional assessment questionnaires adapted to Spanish with satisfactory psychometric properties. We can measure the patient's perceived impact of his or her hip disease by selecting, among the different options, those alternatives that best fit our clinical or research objectives. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  20. Transformation of human osteoblast cells to the tumorigenic phenotype by depleted uranium-uranyl chloride.

    PubMed Central

    Miller, A C; Blakely, W F; Livengood, D; Whittaker, T; Xu, J; Ejnik, J W; Hamilton, M M; Parlette, E; John, T S; Gerstenberg, H M; Hsu, H

    1998-01-01

    Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Although the health effects of occupational uranium exposure are well known, limited data exist regarding the long-term health effects of internalized DU in humans. We established an in vitro cellular model to study DU exposure. Microdosimetric assessment, determined using a Monte Carlo computer simulation based on measured intracellular and extracellular uranium levels, showed that few (0.0014%) cell nuclei were hit by alpha particles. We report the ability of DU-uranyl chloride to transform immortalized human osteoblastic cells (HOS) to the tumorigenic phenotype. DU-uranyl chloride-transformants are characterized by anchorage-independent growth, tumor formation in nude mice, expression of high levels of the k-ras oncogene, reduced production of the Rb tumor-suppressor protein, and elevated levels of sister chromatid exchanges per cell. DU-uranyl chloride treatment resulted in a 9.6 (+/- 2.8)-fold increase in transformation frequency compared to untreated cells. In comparison, nickel sulfate resulted in a 7.1 (+/- 2.1)-fold increase in transformation frequency. This is the first report showing that a DU compound caused human cell transformation to the neoplastic phenotype. Although additional studies are needed to determine if protracted DU exposure produces tumors in vivo, the implication from these in vitro results is that the risk of cancer induction from internalized DU exposure may be comparable to other biologically reactive and carcinogenic heavy-metal compounds (e.g., nickel). Images Figure 1 Figure 2 Figure 3 PMID:9681973

  1. Oral chemoprevention of skin cancer in mice by benzophenone sunscreens dioxybenzone and octabenzone in drinking water.

    PubMed

    Rao, G Subba; Tokuda, Harukuni; Ichiishi, Eiichiro; Takasaki, Midori; Iida, Akira; Suzuki, Nobutaka; Konoshima, Takao; Kapadia, Govind J

    2013-06-01

    Sunscreen compounds with added benefit of skin cancer prevention have both public and commercial interests. Our earlier study using the Epstein-Barr virus early antigen in vitro assay reported on skin cancer chemoprevention potential of benzophenone sunscreens. We now report the in vivo antitumor activity of two of the benzophenone sunscreens which tested positively in the in vitro assay, octabenzone (UV-1) and dioxybenzone (UV-2), in the two-stage mouse skin carcinogenesis model using (±)-(E)-4-methyl-2-[-(E)-hydroxyamino]-5-nitro-6-methoxy-3-hexanamide (NOR-1) as inducer and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) as promoter. Pathogen-free, female hairless mice of HOS:HR-1 strain, 15 animals per control and test groups, were used. Skin tumors were induced by a single dose of NOR-1 (390 nmol in 100 μl of acetone). One week later, TPA (1.7 nmol in 100 μl of acetone) was applied to skin twice weekly for 20 weeks as tumor a promoter. The test compounds UV-I or UV-2 were administered at 0.0025% to mice through drinking water ad libitum, starting one week prior to and stopping one week after tumor initiation. All animals were examined weekly for the development of skin papillomas. In both UV-1- and UV-2-treated mice, a two-week delay in tumor appearance, and significant inhibition (p<0.001) of tumor incidence (50% and 60%, respectively) and tumor burden (papilloma inhibition/mouse, 50% and 70%, respectively) were observed when compared to the positive control group. UV-2 (dihydroxy derivative) was a more potent inhibitor of skin tumor than UV-1 (monohydroxy derivative), which followed their antioxidant activity ranking. The results affirm the skin cancer chemoprevention potential of orally-ingested benzophenone sunscreens in mice and warrant studies in humans to validate synergistic protection achievable by complementation of oral and topical sunscreen usage.

  2. Study on the description method of upper limb's muscle force levels during simulated in-orbit operations

    NASA Astrophysics Data System (ADS)

    Zhao, Yan; Li, DongXu; Liu, ZhiZhen; Liu, Liang

    2013-03-01

    The dexterous upper limb serves as the most important tool for astronauts to implement in-orbit experiments and operations. This study developed a simulated weightlessness experiment and invented new measuring equipment to quantitatively evaluate the muscle ability of the upper limb. Isometric maximum voluntary contractions (MVCs) and surface electromyography (sEMG) signals of right-handed pushing at the three positions were measured for eleven subjects. In order to enhance the comprehensiveness and accuracy of muscle force assessment, the study focused on signal processing techniques. We applied a combination method, which consists of time-, frequency-, and bi-frequency-domain analyses. Time- and frequency-domain analyses estimated the root mean square (RMS) and median frequency (MDF) of sEMG signals, respectively. Higher order spectra (HOS) of bi-frequency domain evaluated the maximum bispectrum amplitude ( B max), Gaussianity level (Sg) and linearity level (S l ) of sEMG signals. Results showed that B max, S l , and RMS values all increased as force increased. MDF and Sg values both declined as force increased. The research demonstrated that the combination method is superior to the conventional time- and frequency-domain analyses. The method not only described sEMG signal amplitude and power spectrum, but also deeper characterized phase coupling information and non-Gaussianity and non-linearity levels of sEMG, compared to two conventional analyses. The finding from the study can aid ergonomist to estimate astronaut muscle performance, so as to optimize in-orbit operation efficacy and minimize musculoskeletal injuries.

  3. Cell Cycle Arrest and Apoptosis Induced by Kinamycin F in Human Osteosarcoma Cells.

    PubMed

    Bavelloni, Alberto; Focaccia, Enrico; Piazzi, Manuela; Errani, Costantino; Blalock, William; Faenza, Irene

    2017-08-01

    Kinamycin F is a bacterial metabolite which contains an unusual and potentially reactive diazo group that is known for its ability to inhibit cell growth. In this study, the potential anti-tumor activity of kinamycin F was investigated in three human osteosarcoma cell lines, MG-63, U-2 OS and HOS as an antitumor agent with a potentially novel target. Proliferation and cell viability were measured in three human osteosarcoma cell lines by commercially available kits. We also evaluated the effects of the drug on cell cycle progression using the Muse™ Cell Analyzer. Caspase-3 activity was determined by a fluorometric EnzChek assay kit. Finally, following treatment with kinamycin F the protein levels of cyclin D3, cyclin A and cdK-2 were examined. Kinamycin F induced a concentration-dependent cell death in all the three cell lines. Flow cytometry revealed that kinamycin F treatment at 1 μM concentration significantly increased the cell population in the G2/M-phase (60-65%). Kinamycin F activated caspase 3 in all the three cell lines, clearly demonstrating that the growth inhibitory effect of kinamycin F can be attributed to apoptosis induction. Finally, kinamycin F suppressed osteosarcoma cell proliferation affecting cyclin A and D3 expression. Understanding the mechanism by which kinamycin F exerts its ability to inhibit cell growth may be a step forward in the development of new therapeutic strategies for the treatment of OS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma.

    PubMed

    Su, Y; Wagner, E R; Luo, Q; Huang, J; Chen, L; He, B-C; Zuo, G-W; Shi, Q; Zhang, B-Q; Zhu, G; Bi, Y; Luo, J; Luo, X; Kim, S H; Shen, J; Rastegar, F; Huang, E; Gao, Y; Gao, J-L; Yang, K; Wietholt, C; Li, M; Qin, J; Haydon, R C; He, T-C; Luu, H H

    2011-09-15

    Osteosarcoma (OS) is the most common primary malignancy of bone. There is a critical need to identify the events that lead to the poorly understood mechanism of OS development and metastasis. The goal of this investigation is to identify and characterize a novel marker of OS progression. We have established and characterized a highly metastatic OS subline that is derived from the less metastatic human MG63 line through serial passages in nude mice via intratibial injections. Microarray analysis of the parental MG63, the highly metastatic MG63.2 subline, as well as the corresponding primary tumors and pulmonary metastases revealed insulin-like growth factor binding protein 5 (IGFBP5) to be one of the significantly downregulated genes in the metastatic subline. Confirmatory quantitative RT-PCR on 20 genes of interest demonstrated IGFBP5 to be the most differentially expressed and was therefore chosen to be one of the genes for further investigation. Adenoviral mediated overexpression and knockdown of IGFBP5 in the MG63 and MG63.2 cell lines, as well as other OS lines (143B and MNNG/HOS) that are independent of our MG63 lines, were employed to examine the role of IGFBP5. We found that overexpression of IGFBP5 inhibited in vitro cell proliferation, migration and invasion of OS cells. Additionally, IGFBP5 overexpression promoted apoptosis and cell cycle arrest in the G1 phase. In an orthotopic xenograft animal model, overexpression of IGFBP5 inhibited OS tumor growth and pulmonary metastases. Conversely, siRNA-mediated knockdown of IGFBP5 promoted OS tumor growth and pulmonary metastases in vivo. Immunohistochemical staining of patient-matched primary and metastatic OS samples demonstrated decreased IGFBP5 expression in the metastases. These results suggest 1) a role for IGFBP5 as a novel marker that has an important role in the pathogenesis of OS, and 2) that the loss of IGFBP5 function may contribute to more metastatic phenotypes in OS.

  5. Long non-coding RNA tumor suppressor candidate 7 functions as a tumor suppressor and inhibits proliferation in osteosarcoma.

    PubMed

    Cong, Menglin; Li, Jianmin; Jing, Rui; Li, Zhenzhong

    2016-07-01

    Osteosarcoma is the most common malignant tumor of bone. Recent studies have proven long non-coding RNAs (lncRNAs) play important roles in the tumorigenesis and progression of cancer. However, few lncRNAs have been investigated in osteosarcoma. Here, we reported a novel lncRNA, tumor suppressor candidate 7 (TUSC7), was significantly downregulated in osteosarcoma tissues compared with paired non-tumor tissues and low expression of TUSC7 indicated poor survival (HR = 0.313, 95 % confidence interval (CI) 0.092-0.867) of osteosarcoma patients. Further analysis revealed that loss copy number of TUSC7 was correlated with low expression of TUSC7, and additionally, loss of TUSC7 copy number also indicated poor prognosis (HR = 3.994, 95 % CI 1.147-13.91) of osteosarcoma patients. Two osteosarcoma cell lines, HOS and MG63, were utilized to investigate biological function of TUSC7. Cell counting kit 8 (CCK-8) assay revealed that after silence of TUSC7, cell proliferation ability increased and the colony formation ability also increased. Further results showed that cell cycle was not affected by treatment of si-TUSC7, while the percentage of apoptotic cells decreased. Western blot showed that after silence of TUSC7, the proapoptotic Bcl2 expression was downregulated. Finally, we established xenograft tumor models in nude mice with MG63 cells. Compared with negative control group, silence of TUSC7 significantly promoted tumor growth in vivo. Thus, we demonstrated that TUSC7 could be a potential tumor suppressor in osteosarcoma.

  6. Arsine toxicity is induced by inhalation but not by percutaneous exposure in hairless mice.

    PubMed

    Kato, Koichi; Yamanaka, Kenzo; Shimoda, Yasuyo; Yamano, Yuko; Nagano, Kasuke; Hata, Akihisa; Endo, Yoko; Tachikawa, Mariko; Endo, Ginji

    2014-04-01

    Arsine (AsH₃) is used in many industries, but there is insufficient knowledge about the potential for percutaneous absorption. In order to examine possible percutaneous absorption of arsine, we conducted inhalation studies. Arsine was generated by reducing arsenic trioxide with NaBH₄. Male 5-week-old Hos:HR-1 hairless mice were subjected to a single percutaneous exposure or whole-body inhalation exposure of ca. 300 ppm arsine for 5 min. The examination was performed 0-6 hr after the exposure. Total arsenic in whole blood and hematocrit (Ht) values were measured. Generation of an arsenic-hemoglobin (As-Hb) adduct in the blood was detected using high-performance liquid chromatography with an inductively coupled plasma mass spectrometer (HPLC-ICP-MS). Ht values in the inhalation group significantly decreased after 3 hr, but those in the percutaneous exposure group did not. Total arsenic in the inhalation group was 9.0-14.2 mg/l, which was significantly higher than that in the percutaneous group. The As-Hb adduct was detected only in mice in the inhalation group. Histopathological changes were noted only in the inhalation group, with marked deposition of eosinophilic globules in the proximal convoluted tubules of the kidneys, the Kupffer cells of the liver, and the red pulp in the spleen, but not in the lungs. Immunohistochemically, these eosinophilic globules were stained positively by hemoglobin (Hb) antibody. In the present study, arsine-induced hemolysis and deposition of Hb occurred in the kidney via the inhalation route but not via percutaneous exposure. The presence of As-Hb adduct may be a useful indicator for confirming arsine poisoning.

  7. Variation of the oxidation state of verdoheme in the heme oxygenase reaction

    SciTech Connect

    Gohya, Tomohiko; Sato, Michihiko; Zhang Xuhong; Migita, Catharina T.

    2008-11-14

    Heme oxygenase (HO) converts hemin to biliverdin, CO, and iron applying molecular oxygen and electrons. During successive HO reactions, two intermediates, {alpha}-hydroxyhemin and verdoheme, have been generated. Here, oxidation state of the verdoheme-HO complexes is controversial. To clarify this, the heme conversion by soybean and rat HO isoform-1 (GmHO-1 and rHO-1, respectively) was compared both under physiological conditions, with oxygen and NADPH coupled with ferredoxin reductase/ferredoxin for GmHO-1 or with cytochrome P450 reductase for rHO-1, and under a non-physiological condition with hydrogen peroxide. EPR measurements on the hemin-GmHO-1 reaction with oxygen detected a low-spin ferric intermediate, which was undetectable in the rHO-1 reaction, suggesting the verdoheme in the six-coordinate ferric state in GmHO-1. Optical absorption measurements on this reaction indicated that the heme degradation was extremely retarded at verdoheme though this reaction was not inhibited under high-CO concentrations, unlike the rHO-1 reaction. On the contrary, the Gm and rHO-1 reactions with hydrogen peroxide both provided ferric low-spin intermediates though their yields were different. The optical absorption spectra suggested that the ferric and ferrous verdoheme coexisted in reaction mixtures and were slowly converted to the ferric biliverdin complex. Consequently, in the physiological oxygen reactions, the verdoheme is found to be stabilized in the ferric state in GmHO-1 probably guided by protein distal residues and in the ferrous state in rHO-1, whereas in the hydrogen peroxide reactions, hydrogen peroxide or hydroxide coordination stabilizes the ferric state of verdoheme in both HOs.

  8. The post-thaw irradiation of avian spermatozoa with He-Ne laser differently affects chicken, pheasant and turkey sperm quality.

    PubMed

    Iaffaldano, N; Paventi, G; Pizzuto, R; Passarella, S; Cerolini, S; Zaniboni, L; Marzoni, M; Castillo, A; Rosato, M P

    2013-11-30

    The effects of post-thaw Helium-Neon (He-Ne) laser irradiation on mobility and functional integrity of frozen/thawed chicken, pheasant and turkey spermatozoa were investigated. Cytochrome C oxidase (COX) activity was also determined as a measure of the effect of irradiation on mitochondrial bioenergetics. Semen samples from each species were collected, processed and frozen according to the pellet procedure. After thawing, each semen sample was divided into two subsamples: the first one was the control; the second one was irradiated with a single mode continuous He-Ne laser wave (wavelength 632.8 nm; 6 mW; 3.96 J/cm(2)). Then the samples were assessed for sperm mobility (Accudenz(®) swim-down test), viability (SYBR-14/PI staining), osmotic-resistance (HOS test) and COX activity. The irradiation was effective P<0.05 increasing sperm motility in the turkey semen (0.228 ± 0.01 compared with 0.294 ± 0.02). The irradiation also caused an increase (P<0.05) of the COX activity in pheasant (+135 ± 4%) and turkey (+116 ± 4%) sperm, without affecting viability and osmotic-resistance. The COX was positively correlated (P<0.05) with the viability of chicken sperm, however no significant interactions were found between mobility and COX activity in the three avian species. Due to the difference in energetic metabolism among avian species used in this study, the He-Ne laser irradiation has a differential action on bio-stimulation of turkey, chicken and pheasant spermatozoa. The present results are the first to elucidate the possibility for restoration of motility of cryopreserved avian spermatozoa by bio-stimulation provided via He-Ne laser irradiation. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. [Construction and identification of a multiple myeloma-specific APE1 siRNA expression vector].

    PubMed

    Yang, Zhen-zhou; Chen, Xing-hua; Wang, Dong; Wang, Ge; Xiang, De-bing

    2006-04-01

    To construct a multiple myeloma (MM)-specific APE1siRNA expression vector, and detect the specific knock-down effect of the siRNA on expression of APE1 protein. APE1siRNA cDNA sequence was designed, synthesized and inserted into pSilencer 2.0-U6 linear expression vector. pSilencer APE1siRNA was digested by enzyme EcoRI and BamHI, then linear vector and IgP fragments were conjugated by T4 DNA ligase. pSilencer IgP-APE1siRNA and pSilencer IE-IgP-APE1siRNA were digested by enzyme EcoRI or XhoI. Linear vector and IE or Kappa fragments were conjugated by T4 DNA ligase. Then a MM specific pSilencer K-IE-IgP-APE1siRNA was cloned. The recombinant products were identified by DNA sequencing and enzyme digestions at each step. pSilencer K-IE-IgP-APE1siRNA plasmid was transfected to KM3, HOS, MDA-231 cells by liposome. APE1 gene silence induced by RNAi was analysed by Western blot. APE1 protein in KM3 cells could be knocked down effectively and specifically by pSilencer K-IE-IgP-APE1siRNA vector. After 2 days, the level of APE1 protein in KM3 cells transfected with siRNA was 0.118 +/- 0.047, while that transfected with plasmid only was 0.988 +/- 0.029. The efficiency of gene silence was 90%. A MM specific APE1siRNA expression vector was successfully constructed.

  10. An integrated index for automated detection of infarcted myocardium from cross-sectional echocardiograms using texton-based features (Part 1).

    PubMed

    Sudarshan, Vidya K; Acharya, U Rajendra; Ng, E Y K; Tan, Ru San; Chou, Siaw Meng; Ghista, Dhanjoo N

    2016-04-01

    Cross-sectional view echocardiography is an efficient non-invasive diagnostic tool for characterizing Myocardial Infarction (MI) and stages of expansion leading to heart failure. An automated computer-aided technique of cross-sectional echocardiography feature assessment can aid clinicians in early and more reliable detection of MI patients before subsequent catastrophic post-MI medical conditions. Therefore, this paper proposes a novel Myocardial Infarction Index (MII) to discriminate infarcted and normal myocardium using features extracted from apical cross-sectional views of echocardiograms. The cross-sectional view of normal and MI echocardiography images are represented as textons using Maximum Responses (MR8) filter banks. Fractal Dimension (FD), Higher-Order Statistics (HOS), Hu's moments, Gabor Transform features, Fuzzy Entropy (FEnt), Energy, Local binary Pattern (LBP), Renyi's Entropy (REnt), Shannon's Entropy (ShEnt), and Kapur's Entropy (KEnt) features are extracted from textons. These features are ranked using t-test and fuzzy Max-Relevancy and Min-Redundancy (mRMR) ranking methods. Then, combinations of highly ranked features are used in the formulation and development of an integrated MII. This calculated novel MII is used to accurately and quickly detect infarcted myocardium by using one numerical value. Also, the highly ranked features are subjected to classification using different classifiers for the characterization of normal and MI LV ultrasound images using a minimum number of features. Our current technique is able to characterize MI with an average accuracy of 94.37%, sensitivity of 91.25% and specificity of 97.50% with 8 apical four chambers view features extracted from only single frame per patient making this a more reliable and accurate classification.

  11. BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma.

    PubMed

    Gobin, Bérengère; Huin, Marc Baud'; Lamoureux, François; Ory, Benjamin; Charrier, Céline; Lanel, Rachel; Battaglia, Séverine; Redini, Françoise; Lezot, Frédéric; Blanchard, Frédéric; Heymann, Dominique

    2015-02-15

    It has been established that disturbances in intracellular signaling pathways play a considerable part in the oncologic process. Phosphatidylinositol-3-kinase (PI3K) has become of key interest in cancer therapy because of its high mutation frequency and/or gain in function of its catalytic subunits in cancer cells. We investigated the therapeutic value of BYL719, a new specific PI3Kα inhibitor that blocks the ATP site, on osteosarcoma and bone cells. The in vitro effects of BYL719 on proliferation, apoptosis, and cell cycle were assessed in human and murine osteosarcoma cell. Its impact on bone cells was determined using human mesenchymal stem cells (hMSC) and human CD14+ osteoclast precursors. Two different murine preclinical models of osteosarcoma were used to analyze the in vivo biological activities of BYL719. BYL719 decreased cell proliferation by blocking cell cycle in G0/G1 phase with no outstanding effects on apoptosis cell death in HOS and MOS-J tumor cells. BYL719 inhibited cell migration and can thus be considered as a cytostatic drug for osteosarcoma. In murine preclinical models of osteosarcoma, BYL719 significantly decreased tumor progression and tumor ectopic bone formation as shown by a decrease of Ki67+ cells and tumor vascularization. To explore the maximum therapeutic potential of BYL719, the drug was studied in combination with conventional chemotherapeutic drugs, revealing promising efficacy with ifosfamide. BYL719 also exhibited dual activities on osteoblast and osteoclast differentiation. Overall, the present work shows that BYL719 is a promising drug in either a single or multidrug approach to curing bone sarcoma.

  12. Disproportionate growth between the spine and pelvis in patients with thoracic adolescent scoliosis: a new look into the pattern's growth.

    PubMed

    Bao, H; Liu, Z; Yan, P; Qiu, Y; Zhu, F

    2015-12-01

    A self-control ratio, the spine-pelvis index (SPI), was proposed for the assessment of patients with adolescent idiopathic scoliosis (AIS) in this study. The aim was to evaluate the disproportionate growth between the spine and pelvis in these patients using SPI. A total of 64 female patients with thoracic AIS were randomly enrolled between December 2010 and October 2012 (mean age 13 years, standard deviation (sd) 2.17; 9 to 18) and a further 73 healthy female patients with a mean age of 12.4 years (mean age 12.4 years, sd 2.24; 9 to 18), were randomly selected from a normal control database at our centre. The radiographic parameters measured included length of spine (LOS), height of spine (HOS), length of thoracic vertebrae (LOT), height of thoracic vertebrae (HOT), width of pelvis (WOP), height of pelvis (HOP) and width of thorax (WOT). SPI was defined as the ratio LOS/HOP. The SPI and LOT/HOP in patients with AIS showed a significant increase when compared with normal girls (p < 0.001 and p < 0.001 respectively), implying an abnormal pattern of growth of the spine relative to the pelvis in patients with AIS. No significant difference in SPI was found in different age groups in the control group, making the SPI an age-independent parameter with a mean value of 2.219 (2.164 to 2.239). We also found that the SPI was not related to maturity in the control group. This study, for the first time, used a self-control ratio to confirm the disproportionate patterns of growth of the spine and pelvis in patients with thoracic AIS, highlighting that the SPI is not affected by age or maturity.

  13. Spermicidal and Contraceptive Potential of Desgalactotigonin: A Prospective Alternative of Nonoxynol-9

    PubMed Central

    Chakraborty, Debanjana; Maity, Arindam; Jha, Tarun; Mondal, Nirup Bikash

    2014-01-01

    Crude decoction of Chenopodium album seed showed spermicidal effect at MIC 2 mg/ml in earlier studies. Systematic isolation, characterization and evaluation revealed that the major metabolite Desgalactotigonin (DGT) is the most effective principle in both in vitro and in vivo studies. The in vitro studies comprises (a) rat and human sperm motility and immobilizing activity by Sander-Cramer assay; (b) sperm membrane integrity was observed by HOS test and electron microscopy; (c) microbial potential was examined in Lactobacillus broth culture, and (d) the hemolytic index was determined by using rat RBCs. The in vivo contraceptive efficacy was evaluated by intra uterine application of DGT in rat. Lipid peroxidation and induction of apoptosis by DGT on human spermatozoa were also studied. The minimum effective concentration (MEC) of DGT that induced instantaneous immobilization in vitro was 24.18 µM for rat and 58.03 µM for human spermatozoa. Microbial study indicated DGT to be friendly to Lactobacillus acidophilus. Implantation was prevented in DGT treated uterine horn while no hindrance occurred in the untreated contra lateral side. At the level of EC50, DGT induced apoptosis in human spermatozoa as determined by increased labeling with Annexin-V and decreased polarization of sperm mitochondria. Desgalactotigonin emerged 80 and 2×104 times more potent than the decoction and Nonoxynol-9 respectively. It possesses mechanism based detrimental action on both human and rat spermatozoa and spares lactobacilli and HeLa cells at MEC which proves its potential as a superior ingredient for the formulation of a contraceptive safer/compatible to vaginal microflora. PMID:25243914

  14. Alleviating anastrozole induced bone toxicity by selenium nanoparticles in SD rats

    SciTech Connect

    Vekariya, Kiritkumar K.; Kaur, Jasmine; Tikoo, Kulbhushan

    2013-04-15

    Aromatase inhibitors like anastrozole play an undisputed key role in the treatment of breast cancer, but on the other hand, various side effects like osteoporosis and increased risk of bone fracture accompany the chronic administration of these drugs. Here we show for the first time that selenium nanoparticles, when given in conjugation to anastrozole, lower the bone toxicity caused by anastrozole and thus reduce the probable damage to the bone. Selenium nanoparticles at a dose of 5 μg/ml significantly reduced the cell death caused by anastrozole (1 μM) in HOS (human osteoblast) cells. In addition, our results also highlighted that in female SD rat model, SeNPs (0.25, 0.5, 1 mg/kg/day) significantly prevented the decrease in bone density and increase in biochemical markers of bone resorption induced by anastrozole (0.2 mg/kg/day) treatment. Histopathological examination of the femurs of SeNP treated group revealed ossification, mineralization, calcified cartilaginous deposits and a marginal osteoclastic activity, all of which indicate a marked restorative action, suggesting the protective action of the SeNPs. Interestingly, SeNPs (1 mg/kg/day) also exhibited protective effect in ovariectomized rat model, by preventing osteoporosis, which signifies that bone loss due to estrogen deficiency can be effectively overcome by using SeNPs. - Highlights: ► SeNPs significantly reduce bone toxicity in anastrozole treated rats. ► SeNPs successfully prevented osteoporosis in ovariectomized rats. ► SeNP treatment lowered the levels of TRAP and increased the levels of ALKP.

  15. Carbon Nanofiber/Polycaprolactone/Mineralized Hydroxyapatite Nanofibrous Scaffolds for Potential Orthopedic Applications.

    PubMed

    Elangomannan, Shinyjoy; Louis, Kavitha; Dharmaraj, Bhagya Mathi; Kandasamy, Venkata Saravanan; Soundarapandian, Kannan; Gopi, Dhanaraj

    2017-02-22

    Hydroxyapatite (Ca10 (PO4)6(OH)2, HAP), a multimineral substituted calcium phosphate is one of the most substantial bone mineral component that has been widely used as bone replacement materials because of its bioactive and biocompatible properties. However, the use of HAP as bone implants is restricted due to its brittle nature and poor mechanical properties. To overcome this defect and to generate suitable bone implant material, HAP is combined with biodegradable polymer (polycaprolactone, PCL). To enhance the mechanical property of the composite, carbon nanofibers (CNF) is incorporated to the composite, which has long been considered for hard and soft tissue implant due to its exceptional mechanical and structural properties. It is well-known that nanofibrous scaffold are the most-prominent material for the bone reconstruction. We have developed a new remarkable CNF/PCL/mineralized hydroxyapatite (M-HAP) nanofibrous scaffolds on titanium (Ti). The as-developed coatings were characterized by various techniques. The results indicate the formation and homogeneous distribution of components in the nanofibrous scaffolds. Incorporation of CNF into the PCL/M-HAP composite significantly improves the adhesion strength and elastic modulus of the scaffolds. Furthermore, the responses of human osteosarcoma (HOS MG63) cells cultured onto the scaffolds demonstrate that the viability of cells were considerably high for CNF-incorporated PCL/M-HAP than for PCL/M-HAP. In vivo analysis show the presence of soft fibrous tissue growth without any significant inflammatory signs, which suggests that incorporated CNF did not counteract the favorable biological roles of HAP. For load-bearing applications, research in various bone models is needed to substantiate the clinical availability. Thus, from the obtained results, we suggest that CNF/PCL/M-HAP nanofibrous scaffolds can be considered as potential candidates for orthopedic applications.

  16. Age- and Parkinson's disease-related evaluation of gait by General Tau Theory.

    PubMed

    Zhang, Shutao; Qian, Jinwu; Zhang, Zhen; Shen, Linyong; Wu, Xi; Hu, Xiaowu

    2016-10-01

    The degeneration of postural control in the elderly and patients with Parkinson's disease (PD) can be debilitating and may lead to increased fall risk. This study evaluated the changes in postural control during gait affected by PD and aging using a new method based on the General Tau Theory. Fifteen patients with PD, 11 healthy old adults (HOs), and 15 healthy young adults (HYs) were recruited. Foot trajectories of each participant were monitored during walking by a three-camera Optotrak Certus(®) motion capture system. The anteroposterior direction of foot movement during stepping was analyzed by tau-G and tau-J guidance strategies. Two linear regression analyses suggested that the tau of the step-gap was strongly coupled onto the tau-J guidance during walking. The regression slope K could estimate the coupling ratio in the tau-coupling equation which reflects the performance of postural control during gait. The mean K value for the PD group, which was highest among the three groups, was approximately 0.5. Therefore, participants in the PD group walked with the poorest postural control and exhibited a relatively hard contact with the endpoint during stepping when compared with those in the HO and HY groups. The HY and HO groups obtained mean K values significantly lower than 0.5, which indicated that the gait was well controlled and ended at low speed with low deceleration. However, the HO group showed a decreased tendency for postural control, in which the mean K value was significantly higher than that of the HY group. The K value was moderately positively correlated with the double support time and negatively correlated with the stride length and walking speed. The tau-J coupling ratio can provide additional insight into gait disturbances and may serve as a reliable, objective, and quantitative tool to evaluate dynamic postural control during walking.

  17. Development of an Adaptive Multi-Method Algorithm for Automatic Picking of First Arrival Times: Application to Near Surface Seismic Data

    NASA Astrophysics Data System (ADS)

    Khalaf, A.; Camerlynck, C. M.; Schneider, A. C.; Florsch, N.

    2015-12-01

    Accurate picking of first arrival times plays an important role in many seismic studies, particularly in seismic tomography and reservoirs or aquifers monitoring. Many techniques have been developed for picking first arrivals automatically or semi-automatically, but most of them were developed for seismological purposes which does not attain the accuracy objectives due to the complexity of near surface structures, and to usual low signal-to-noise ratio. We propose a new adaptive algorithm for near surface data based on three picking methods, combining multi-nested windows (MNW), Higher Order Statistics (HOS), and Akaike Information Criterion (AIC). They exploit the benefits of integrating many properties, which reveal the presence of first arrivals, to provide an efficient and robust first arrivals picking. This strategy mimics the human first-break picking, where at the beginning the global trend is defined. Then the exact first-breaks are searched in the vicinity of the now defined trend. In a multistage algorithm, three successive phases are launched, where each of them characterize a specific signal property. Within each phase, the potential picks and their error range are automatically estimated, and then used sequentially as leader in the following phase picking. The accuracy and robustness of the implemented algorithm are successfully validated on synthetic and real data which have special challenges for automatic pickers. The comparison of resulting P-wave arrival times with those picked manually, and other algorithms of automatic picking, demonstrated the reliable performance of the new scheme under different noisy conditions. All parameters of our multi-method algorithm are auto-adaptive thanks to the integration in series of each sub-algorithm results in the flow. Hence, it is nearly a parameter-free algorithm, which is straightforward to implement and demands low computational resources.

  18. Effects of SOST Gene Silencing on Proliferation, Apoptosis, Invasion, and Migration of Human Osteosarcoma Cells Through the Wnt/β-Catenin Signaling Pathway.

    PubMed

    Zou, Jian; Zhang, Wei; Li, Xiao-Lin

    2017-02-28

    Our study explored the effects of SOST gene silencing on the proliferation, apoptosis, invasion, and migration of human osteosarcoma cells through Wnt/β-catenin signaling pathway. Fresh tissues were obtained from 108 patients with osteosarcoma and 46 patients with osteochondroma. Human osteosarcoma cells (MG-63, U2-OS, HOS, and Saos-2) and normal osteoblast (hFoB1.19) were selected and cultured. Osteosarcoma cells were grouped randomly into the blank group, the scrambled control group, and the SOST-siRNA group. Cell proliferation was determined by MTT assay. Cell cycle and apoptosis were tested by flow cytometry. Transwell and scratch test were performed to determine cell invasion and migration. The qRT-PCR and Western blotting were used to detect mRNA and protein expression level of sclerostin, Wnt1, β-catenin, C-Myc, Cyclin D1, and MMP-7. The activity of caspase-3 was assessed by immunocytochemistry. Alkaline phosphatase (ALP) activity was measured using P-nitrophenylphosphate as a substrate. Low SOST mRNA and sclerostin protein expression levels were observed in osteosarcoma tissues and cells. Compared with the blank and scrambled control groups, sclerostin expression, apoptotic cells, ALP activity, and caspase-3 activity were down-regulated, while the proliferation, invasion, and migration abilities of osteosarcoma cells were evidently enhanced in the SOST-siRNA group. After SOST gene silencing, the mRNA and protein expression levels of Wnt1, β-catenin, C-Myc, Cyclin D1, and MMP-7 in osteosarcoma cells and β-catenin protein expression levels in the nucleus and cytoplasm were significantly elevated. SOST gene silencing promotes the proliferation, invasion, and migration, and inhibits apoptosis of osteosarcoma cells by activating Wnt/β-catenin signaling pathway.

  19. Heme Reversibly Damps PERIOD2 Rhythms in Mouse Suprachiasmatic Nucleus Explants

    PubMed Central

    Guenthner, Casey J.; Bickar, David; Harrington, Mary E.

    2009-01-01

    The hypothalamic suprachiasmatic nucleus (SCN), which in mammals serves as the master circadian pacemaker by synchronizing autonomous clocks in peripheral tissues, is composed of coupled single-cell oscillators that are driven by interlocking positive/negative transcriptional/translational feedback loops. Several studies have suggested that heme, a common prosthetic group that is synthesized and degraded in a circadian manner in the SCN, may modulate the function of several feedback loop components, including the REV-ERB nuclear receptors and PERIOD2 (PER2). We found that ferric heme (hemin, 3-100 μM) dose-dependently and reversibly damped luminescence rhythms in SCN explants from mice expressing a PER2∷LUCIFERASE (PER2∷LUC) fusion protein. Inhibitors of heme oxygenases (HOs, which degrade heme to biliverdin, carbon monoxide, and iron) mimicked heme’s effects on PER2 rhythms. In contrast, heme and HO inhibition did not damp luminescence rhythms in thymus and esophagus explants and had only a small effect on PER2∷LUC damping in spleen explants, suggesting that heme’s effects are tissue-specific. Analysis of the effects of heme’s degradation products on SCN PER2∷LUC rhythms indicated that they probably were not responsible for heme’s effects on rhythms. The heme synthesis inhibitor N-methylprotoporphyrin IX (NMP) lengthened the circadian period of SCN PER2∷LUC rhythms by about an hour. These data are consistent with an important role for heme in the circadian system. PMID:19698763

  20. Regulation of BMP-induced ectopic bone formation by Ahsg.

    PubMed

    Rittenberg, B; Partridge, E; Baker, G; Clokie, C; Zohar, R; Dennis, J W; Tenenbaum, H C

    2005-05-01

    alpha2-HS-glycoprotein (Ahsg), also known as fetuin is a serum and bone resident glycoprotein, which binds to TGF-beta superfamily members including bone morphogenetic proteins (BMP) and inhibits dexamethasone-induced osteogenesis in bone marrow cultures in vitro. Here we demonstrate that Ahsg reduces cytokine binding to its cognate receptor in HOS osteocyte cells and suppresses intracellular signaling, while in vivo, we test the hypothesis that Ahsg-deficient mice are hyper-responsive to BMP-induced osteogenesis. Human native BMP was implanted into the hindquarter muscles of Ahsg(+/+), Ahsg(+/-) and Ahsg(-/-) mice and 4 weeks later, ossicle formation was analyzed by radiography, bone density scanning (DEXA) and histomorphometry. Alkaline phosphatase (AP) activity was measured in ossicles as a marker for bone cell differentiation, and was significantly higher in Ahsg(-/-) versus Ahsg(+/-) and/or Ahsg(+/+) mice. Ectopic ossicle size in the Ahsg(+/-) mouse was 4-fold greater than that in the wild type (Ahsg(+/+)), and intermediate to that shown in Ahsg(-/-) mouse. Bone mineral density (BMD) was lower in the Ahsg(-/+) and Ahsg(-/-) mice compared to Ahsg(+/+) littermates. The ratio of cortical to cancellous bone was found to be >2-fold higher in Ahsg(-/-) mouse in comparison to the Ahsg(+/+) mice with no significant change in the Ahsg(-/+) mouse. Finally, a significantly higher incidence of satellite ossification; small islands of immature bone, was shown in Ahsg(-/-) mice as compared to Ahsg(+/+) mice. Although Ahsg binds to TGF-beta/BMP and blocks receptor signalling, it may also sequester cytokines in matrix, thereby acting as a reservoir of osteoinductive activity when released. This may explain the non-linear relationship between ectopic bone formation characteristics and Ahsg(+/+), Ahsg(+/-) and Ahsg(-/-) genotypes, although the increase in satellite bone formation might also explain this phenomenon. Our results suggest that Ahsg may be useful for prevention of

  1. Anti-Inflammatory Effect of Titrated Extract of Centella asiatica in Phthalic Anhydride-Induced Allergic Dermatitis Animal Model

    PubMed Central

    Park, Ju Ho; Choi, Ji Yeon; Son, Dong Ju; Park, Eun Kyung; Song, Min Jong; Hellström, Mats; Hong, Jin Tae

    2017-01-01

    Centella asiatica has potent antioxidant and anti-inflammatory properties. However, its anti-dermatitic effect has not yet been reported. In this study, we investigated the anti-dermatitic effects of titrated extract of Centella asiatica (TECA) in a phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. An AD-like lesion was induced by the topical application of five percent PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100 μL of 0.2% and 0.4% of TECA (40 μg or 80 μg/cm2) was spread on the dorsum of the ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and NF-κB activity, which were determined by electromobility shift assay (EMSA). We also measured TNF-α, IL-1β, IL-6, and IgE concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). TECA treatment attenuated the development of PA-induced atopic dermatitis. Histological analysis showed that TECA inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. TECA treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as the release of TNF-α, IL-1β, IL-6, and IgE. In addition, TECA (1, 2, 5 μg/mL) potently inhibited Lipopolysaccharide (LPS) (1 μg/mL)-induced NO production, expression of iNOS and COX-2, and NF-κB DNA binding activities in RAW264.7 macrophage cells. Our data demonstrated that TECA could be a promising agent for AD by inhibition of NF-κB signaling. PMID:28358324

  2. Anti-Inflammatory Effect of Titrated Extract of Centella asiatica in Phthalic Anhydride-Induced Allergic Dermatitis Animal Model.

    PubMed

    Park, Ju Ho; Choi, Ji Yeon; Son, Dong Ju; Park, Eun Kyung; Song, Min Jong; Hellström, Mats; Hong, Jin Tae

    2017-03-30

    Centella asiatica has potent antioxidant and anti-inflammatory properties. However, its anti-dermatitic effect has not yet been reported. In this study, we investigated the anti-dermatitic effects of titrated extract of Centella asiatica (TECA) in a phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. An AD-like lesion was induced by the topical application of five percent PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100 μL of 0.2% and 0.4% of TECA (40 μg or 80 μg/cm²) was spread on the dorsum of the ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and NF-κB activity, which were determined by electromobility shift assay (EMSA). We also measured TNF-α, IL-1β, IL-6, and IgE concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). TECA treatment attenuated the development of PA-induced atopic dermatitis. Histological analysis showed that TECA inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. TECA treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as the release of TNF-α, IL-1β, IL-6, and IgE. In addition, TECA (1, 2, 5 μg/mL) potently inhibited Lipopolysaccharide (LPS) (1 μg/mL)-induced NO production, expression of iNOS and COX-2, and NF-κB DNA binding activities in RAW264.7 macrophage cells. Our data demonstrated that TECA could be a promising agent for AD by inhibition of NF-κB signaling.

  3. Basic cardiopulmonary resuscitation knowledge of house-officers in a tertiary institution: factors determining accuracy

    PubMed Central

    Okonta, Kelechi Emmanuel; Okoh, Boma Alali Ngozi

    2014-01-01

    Background To assess the level of knowledge of CPR among House-Officers (HO) and some factors determining accuracy of knowledge. Methods A total of 50 structured questionnaires were administered to HO with 35 (70%) questionnaires duly filled and returned. Data on the participants’ brief biodata and the understanding of basic skills of BLS were collected and analyzed using International Business Machine SPSS Statistics version 21 for Windows. The t-test for independent samples was applied for the grouped data with P < 0.05 taken as level of significance. Results The age of the respondents ranged from 20-37 years with the mean age of 25.4 + SD2.7 years and the male/female ratio was 1:1.3. Eleven (31.4%) out of the 35 HO had no prior CPR training while 68.6% had prior training; Eighteen (51.4%) had training within the last 2 years. Twenty (57.1%) had performed CPR in a real situation, while 42.9% had not. Six (17.1%) HO scored above 50% while 82.9% scored below 50%. The female HO got more correct answers than the males (25% versus 6.7%, p = 0.167). The number of respondents who had prior CPR training had more correct answers than those who did not (25% versus 0%, p = 0.083) while those who had previously performed CPR had more correct answers than those who had not (33.3% versus 5%, P <0.05). Conclusion There was a general poor knowledge of the performance of basic CPR amongst HOs. However, previous experience of having performed CPR in real setting, or the use of mannequins, improved their theoretical knowledge of CPR. PMID:25419335

  4. HDAC8 mutations in Cornelia de Lange Syndrome affect the cohesin acetylation cycle

    PubMed Central

    Deardorff, Matthew A.; Bando, Masashige; Nakato, Ryuichiro; Watrin, Erwan; Itoh, Takehiko; Minamino, Masashi; Saitoh, Katsuya; Komata, Makiko; Katou, Yuki; Clark, Dinah; Cole, Kathryn E.; Baere, Elfride De; Decroos, Christophe; Donato, Nataliya Di; Ernst, Sarah; Francey, Lauren J.; Gyftodimou, Yolanda; Hirashima, Kyotaro; Hullings, Melanie; Ishikawa, Yuuichi; Jaulin, Christian; Kaur, Maninder; Kiyono, Tohru; Lombardi, Patrick M.; Magnaghi-Jaulin, Laura; Mortier, Geert R.; Nozaki, Naohito; Petersen, Michael B.; Seimiya, Hiroyuki; Siu, Victoria M.; Suzuki, Yutaka; Takagaki, Kentaro; Wilde, Jonathan J.; Willems, Patrick J.; Prigent, Claude; Gillessen-Kaesbach, Gabriele; Christianson, David W.; Kaiser, Frank J.; Jackson, Laird G.; Hirota, Toru; Krantz, Ian D.; Shirahige, Katsuhiko

    2012-01-01

    Cornelia de Lange syndrome (CdLS) is a dominantly inherited congenital malformation disorder caused by mutations in the cohesin-loading protein NIPBL1,2 for nearly 60% of individuals with classical CdLS3-5 and in the core cohesin components SMC1A (~5%) and SMC3 (<1%) for a smaller fraction of probands6,7. In humans, the multi-subunit complex cohesin is comprised of SMC1, SMC3, RAD21 and a STAG protein to form a ring structure proposed to encircle sister chromatids to mediate sister chromatid cohesion (SCC)8 as well as play key roles in gene regulation9. SMC3 is acetylated during S-phase to establish cohesiveness of chromatin-loaded cohesin10-13 and in yeast, HOS1, a class I histone deacetylase, deacetylates SMC3 during anaphase14-16. Here we report the identification of HDAC8 as the vertebrate SMC3 deacetylase as well as loss-of-function HDAC8 mutations in six CdLS probands. Loss of HDAC8 activity results in increased SMC3 acetylation (SMC3-ac) and inefficient dissolution of the “used” cohesin complex released from chromatin in both prophase and anaphase. While SMC3 with retained acetylation is loaded onto chromatin, ChIP-Seq analysis demonstrates decreased occupancy of cohesin localization sites that results in a consistent pattern of altered transcription seen in CdLS cell lines with either NIPBL or HDAC8 mutations. PMID:22885700

  5. A Comprehensive TALEN-Based Knockout Library for Generating Human Induced Pluripotent Stem Cell-Based Models for Cardiovascular Diseases.

    PubMed

    Karakikes, Ioannis; Termglinchan, Vittavat; Cepeda, Diana A; Lee, Jaecheol; Diecke, Sebastian; Hendel, Ayal; Itzhaki, Ilanit; Ameen, Mohamed; Shrestha, Rajani; Wu, Haodi; Ma, Ning; Shao, Ning-Yi; Seeger, Timon; Woo, Nicole A; Wilson, Kitchener D; Matsa, Elena; Porteus, Matthew H; Sebastiano, Vittorio; Wu, Joseph C

    2017-02-28

    Rationale: Targeted genetic engineering using programmable nucleases such as transcription activator-like effector nucleases (TALENs) is a valuable tool for precise, site-specific genetic modification in the human genome. Objective: The emergence of novel technologies such as human induced pluripotent stem cells (iPSCs) and nuclease-mediated genome editing represent a unique opportunity for studying cardiovascular diseases in vitro. Methods and Results: By incorporating extensive literature and database searches, we designed a collection of TALEN constructs to knockout (KO) eighty-eight human genes that are associated with cardiomyopathies and congenital heart diseases. The TALEN pairs were designed to induce double-strand DNA break near the starting codon of each gene that either disrupted the start codon or introduced a frameshift mutation in the early coding region, ensuring faithful gene KO. We observed that all the constructs were active and disrupted the target locus at high frequencies. To illustrate the general utility of the TALEN-mediated KO technique, six individual genes (TNNT2, LMNA/C, TBX5, MYH7, ANKRD1, and NKX2.5) were knocked out with high efficiency and specificity in human iPSCs. By selectively targeting a dilated cardiomyopathy (DCM)-causing mutation (TNNT2 p.R173W) in patient-specific iPSC-derived cardiac myocytes (iPSC-CMs), we demonstrated that the KO strategy ameliorates the DCM phenotype in vitro. In addition, we modeled the Holt-Oram syndrome (HOS) in iPSC-CMs in vitro and uncovered novel pathways regulated by TBX5 in human cardiac myocyte development. Conclusions: Collectively, our study illustrates the powerful combination of iPSCs and genome editing technology for understanding the biological function of genes and the pathological significance of genetic variants in human cardiovascular diseases. The methods, strategies, constructs and iPSC lines developed in this study provide a validated, readily available resource for cardiovascular

  6. Cost-effectiveness of the SEN-concept: Specialized Emergency Nurses (SEN) treating ankle/foot injuries.

    PubMed

    Derksen, Robert J; Coupé, Veerle Mh; van Tulder, Maurits W; Veenings, Bart; Bakker, Fred C

    2007-10-01

    Emergency Departments (EDs) are confronted with progressive overcrowding. As a consequence, the workload for ED physicians increases and waiting times go up with the risk of unnecessary complications and patient dissatisfaction. To cope with these problems, Specialized Emergency Nurses (SENs), regular ED-nurses receiving a short, injury-specific course, were trained to assess and treat minor injuries according to a specific protocol. An economic evaluation was conducted alongside a randomized controlled trial comparing House Officers (HOs) and SENs in their assessment of ankle and foot injuries. Cost prices were established for all parts of healthcare utilization involved. Total costs of health care utilization were computed per patient in both groups. Cost-effectiveness was investigated by comparing the difference in total cost between groups with the difference in sensitivity and specificity between groups in diagnosing fractures and severe sprains. Finally, cost-effectiveness ratios were calculated and presented on a cost-effectiveness plane. No significant differences were seen between treatment groups for any of the health care resources assessed. However, the waiting times for both first assessment by a treatment officer and time spent waiting between hearing the diagnosis and final treatment were significantly longer in the HO group. There was no statistically significant difference in costs between groups. The total costs were euro 186 (SD euro 623) for patients in the SEN group and euro 153 (SD euro 529) for patients in the HO group. The difference in total costs was euro 33 (95% CI: - euro 84 to euro 155). The incremental cost-effectiveness ratio was euro 27 for a reduction of one missed diagnosis and euro 18 for a reduction of one false negative. Considering the benefits of the SEN-concept in terms of decreased workload for the ED physicians, increased patient satisfaction and decreased waiting times, SENs appear to be a useful solution to the problem of

  7. Spectroscopic insights into axial ligation and active-site H-bonding in substrate-bound human heme oxygenase-2.

    PubMed

    Gardner, Jessica D; Yi, Li; Ragsdale, Stephen W; Brunold, Thomas C

    2010-09-01

    Heme oxygenases (HOs) are monooxygenases that catalyze the first step in heme degradation, converting heme to biliverdin with concomitant release of Fe(II) and CO from the porphyrin macrocycle. Two heme oxygenase isoforms, HO-1 and HO-2, exist that differ in several ways, including a complete lack of Cys residues in HO-1 and the presence of three Cys residues as part of heme-regulatory motifs (HRMs) in HO-2. HRMs in other heme proteins are thought to directly bind heme, or to otherwise regulate protein stability or activity; however, it is not currently known how the HRMs exert these effects on HO-2 function. To better understand the properties of this vital enzyme and to elucidate possible roles of its HRMs, various forms of HO-2 possessing distinct alterations to the HRMs were prepared. In this study, variants with Cys265 in a thiol form are compared with those with this residue in an oxidized (part of a disulfide bond or existing as a sulfenate moiety) form. Absorption and magnetic circular dichroism spectroscopic data of these HO-2 variants clearly demonstrate that a new low-spin Fe(III) heme species characteristic of thiolate ligation is formed when Cys265 is reduced. Additionally, absorption, magnetic circular dichroism, and resonance Raman data collected at different temperatures reveal an intriguing temperature dependence of the iron spin state in the heme-HO-2 complex. These findings are consistent with the presence of a hydrogen-bonding network at the heme's distal side within the active site of HO-2 with potentially significant differences from that observed in HO-1.

  8. Free radicals, reactive oxygen species, oxidative stress and its classification.

    PubMed

    Lushchak, Volodymyr I

    2014-12-05

    Reactive oxygen species (ROS) initially considered as only damaging agents in living organisms further were found to play positive roles also. This paper describes ROS homeostasis, principles of their investigation and technical approaches to investigate ROS-related processes. Especial attention is paid to complications related to experimental documentation of these processes, their diversity, spatiotemporal distribution, relationships with physiological state of the organisms. Imbalance between ROS generation and elimination in favor of the first with certain consequences for cell physiology has been called "oxidative stress". Although almost 30years passed since the first definition of oxidative stress was introduced by Helmut Sies, to date we have no accepted classification of oxidative stress. In order to fill up this gape here classification of oxidative stress based on its intensity is proposed. Due to that oxidative stress may be classified as basal oxidative stress (BOS), low intensity oxidative stress (LOS), intermediate intensity oxidative stress (IOS), and high intensity oxidative stress (HOS). Another classification of potential interest may differentiate three categories such as mild oxidative stress (MOS), temperate oxidative stress (TOS), and finally severe (strong) oxidative stress (SOS). Perspective directions of investigations in the field include development of sophisticated classification of oxidative stresses, accurate identification of cellular ROS targets and their arranged responses to ROS influence, real in situ functions and operation of so-called "antioxidants", intracellular spatiotemporal distribution and effects of ROS, deciphering of molecular mechanisms responsible for cellular response to ROS attacks, and ROS involvement in realization of normal cellular functions in cellular homeostasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Heme oxygenase-1 and neurodegeneration: expanding frontiers of engagement.

    PubMed

    Schipper, Hyman M; Song, Wei; Zukor, Hillel; Hascalovici, Jacob R; Zeligman, David

    2009-07-01

    The heme oxygenases (HOs), responsible for the degradation of heme to biliverdin/bilirubin, free iron and CO, have been heavily implicated in mammalian CNS aging and disease. In normal brain, the expression of HO-2 is constitutive, abundant and fairly ubiquitous, whereas HO-1 mRNA and protein are confined to small populations of scattered neurons and neuroglia. In contradistinction to HO-2, the ho-1 gene (Hmox1) is exquisitely sensitive to induction by a wide range of pro-oxidant and other stressors. In Alzheimer disease and mild cognitive impairment, immunoreactive HO-1 protein is over-expressed in neurons and astrocytes of the cerebral cortex and hippocampus relative to age-matched, cognitively intact controls and co-localizes to senile plaques, neurofibrillary tangles, and corpora amylacea. In Parkinson disease, HO-1 is markedly over-expressed in astrocytes of the substantia nigra and decorates Lewy bodies in affected dopaminergic neurons. HMOX1 is also up-regulated in glial cells surrounding human cerebral infarcts, hemorrhages and contusions, within multiple sclerosis plaques, and in other degenerative and inflammatory human CNS disorders. Heme-derived free ferrous iron, CO, and biliverdin/bilirubin are biologically active substances that have been shown to either ameliorate or exacerbate neural injury contingent upon specific disease models employed, the intensity and duration of HO-1 expression and the nature of the prevailing redox microenvironment. In 'stressed' astroglia, HO-1 hyperactivity promotes mitochondrial sequestration of non-transferrin iron and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure amply documented in Alzheimer disease, Parkinson disease and other aging-related neurodegenerative disorders. Glial HO-1 expression may also impact cell survival and neuroplasticity in these conditions by modulating brain sterol metabolism and proteosomal degradation of neurotoxic protein aggregates.

  10. The use of kernel local Fisher discriminant analysis for the channelization of the Hotelling model observer

    NASA Astrophysics Data System (ADS)

    Wen, Gezheng; Markey, Mia K.

    2015-03-01

    It is resource-intensive to conduct human studies for task-based assessment of medical image quality and system optimization. Thus, numerical model observers have been developed as a surrogate for human observers. The Hotelling observer (HO) is the optimal linear observer for signal-detection tasks, but the high dimensionality of imaging data results in a heavy computational burden. Channelization is often used to approximate the HO through a dimensionality reduction step, but how to produce channelized images without losing significant image information remains a key challenge. Kernel local Fisher discriminant analysis (KLFDA) uses kernel techniques to perform supervised dimensionality reduction, which finds an embedding transformation that maximizes betweenclass separability and preserves within-class local structure in the low-dimensional manifold. It is powerful for classification tasks, especially when the distribution of a class is multimodal. Such multimodality could be observed in many practical clinical tasks. For example, primary and metastatic lesions may both appear in medical imaging studies, but the distributions of their typical characteristics (e.g., size) may be very different. In this study, we propose to use KLFDA as a novel channelization method. The dimension of the embedded manifold (i.e., the result of KLFDA) is a counterpart to the number of channels in the state-of-art linear channelization. We present a simulation study to demonstrate the potential usefulness of KLFDA for building the channelized HOs (CHOs) and generating reliable decision statistics for clinical tasks. We show that the performance of the CHO with KLFDA channels is comparable to that of the benchmark CHOs.

  11. Recruitment of Saccharomyces cerevisiae Cmr1/Ydl156w to Coding Regions Promotes Transcription Genome Wide

    PubMed Central

    Govind, Chhabi K.

    2016-01-01

    Cmr1 (changed mutation rate 1) is a largely uncharacterized nuclear protein that has recently emerged in several global genetic interaction and protein localization studies. It clusters with proteins involved in DNA damage and replication stress response, suggesting a role in maintaining genome integrity. Under conditions of proteasome inhibition or replication stress, this protein localizes to distinct sub-nuclear foci termed as intranuclear quality control (INQ) compartments, which sequester proteins for their subsequent degradation. Interestingly, it also interacts with histones, chromatin remodelers and modifiers, as well as with proteins involved in transcription including subunits of RNA Pol I and Pol III, but not with those of Pol II. It is not known whether Cmr1 plays a role in regulating transcription of Pol II target genes. Here, we show that Cmr1 is recruited to the coding regions of transcribed genes of S. cerevisiae. Cmr1 occupancy correlates with the Pol II occupancy genome-wide, indicating that it is recruited to coding sequences in a transcription-dependent manner. Cmr1-enriched genes include Gcn4 targets and ribosomal protein genes. Furthermore, our results show that Cmr1 recruitment to coding sequences is stimulated by Pol II CTD kinase, Kin28, and the histone deacetylases, Rpd3 and Hos2. Finally, our genome-wide analyses implicate Cmr1 in regulating Pol II occupancy at transcribed coding sequences. However, it is dispensable for maintaining co-transcriptional histone occupancy and histone modification (acetylation and methylation). Collectively, our results show that Cmr1 facilitates transcription by directly engaging with transcribed coding regions. PMID:26848854

  12. Recruitment of Saccharomyces cerevisiae Cmr1/Ydl156w to Coding Regions Promotes Transcription Genome Wide.

    PubMed

    Jones, Jeffery W; Singh, Priyanka; Govind, Chhabi K

    2016-01-01

    Cmr1 (changed mutation rate 1) is a largely uncharacterized nuclear protein that has recently emerged in several global genetic interaction and protein localization studies. It clusters with proteins involved in DNA damage and replication stress response, suggesting a role in maintaining genome integrity. Under conditions of proteasome inhibition or replication stress, this protein localizes to distinct sub-nuclear foci termed as intranuclear quality control (INQ) compartments, which sequester proteins for their subsequent degradation. Interestingly, it also interacts with histones, chromatin remodelers and modifiers, as well as with proteins involved in transcription including subunits of RNA Pol I and Pol III, but not with those of Pol II. It is not known whether Cmr1 plays a role in regulating transcription of Pol II target genes. Here, we show that Cmr1 is recruited to the coding regions of transcribed genes of S. cerevisiae. Cmr1 occupancy correlates with the Pol II occupancy genome-wide, indicating that it is recruited to coding sequences in a transcription-dependent manner. Cmr1-enriched genes include Gcn4 targets and ribosomal protein genes. Furthermore, our results show that Cmr1 recruitment to coding sequences is stimulated by Pol II CTD kinase, Kin28, and the histone deacetylases, Rpd3 and Hos2. Finally, our genome-wide analyses implicate Cmr1 in regulating Pol II occupancy at transcribed coding sequences. However, it is dispensable for maintaining co-transcriptional histone occupancy and histone modification (acetylation and methylation). Collectively, our results show that Cmr1 facilitates transcription by directly engaging with transcribed coding regions.

  13. MicroRNA 218 mediates the effects of Tbx5a over-expression on zebrafish heart development.