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Sample records for hos vaegar anlagda

  1. MEDICARE HEALTH OUTCOMES SURVEY (HOS)

    EPA Science Inventory

    The Medicare Health Outcomes Survey (HOS) is the first Medicare managed care outcomes measure. CMS, in collaboration with NCQA, launched the Medicare HOS in the 1998 Health Plan Employer Data and Information Set (HEDIS?). The measure includes the most recent advances in summarizi...

  2. Beyond ubiquitination: proteolytic and nonproteolytic roles of HOS1.

    PubMed

    Jung, Jae-Hoon; Lee, Hyo-Jun; Park, Mi-Jeong; Park, Chung-Mo

    2014-08-01

    The E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) functions as a cold signaling attenuator by degrading the INDUCER OF CBF EXPRESSION 1 transcription factor, which is a key regulator of the cold-induced transcriptome and freezing tolerance in plants. Recent studies demonstrate that HOS1 also plays nonproteolytic roles in gene expression regulation. HOS1 acts as a chromatin remodeling factor that modulates FLOWERING LOCUS C chromatin in cold regulation of flowering time. It associates with the nuclear pore complex to facilitate nucleocytoplasmic mRNA export to maintain circadian periodicity over a range of light and temperature conditions. In this review, we summarize recent advances in molecular mechanisms underlying HOS1 function during plant development in response to fluctuating environmental conditions. PMID:24768209

  3. Alternative splicing and expression analysis of High expression of osmotically responsive genes1 (HOS1) in Arabidopsis.

    PubMed

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

    2012-09-01

    High expression of osmotically responsive genes1 (HOS1), a key regulator of low temperature response and flowering time, encodes an E3 ubiquitin ligase in Arabidopsis. Here, we report characterization of a newly identified splice variant (HOS1-L) of HOS1. Comparative analyses revealed that HOS1-L has a longer 5' nucleotide sequence than that of the previously identified HOS1 (HOS1-S) and that its protein sequence was more conserved than that of HOS1-S in plants. HOS1-L transcripts were spatio-temporally more abundant than those of HOS1-S. The recovery rate of HOS1-S expression was faster than that of HOS1-L after cold treatment. Diurnal oscillation patterns of HOS1-L revealed that HOS1-L expression was affected by photoperiod. An in vitro pull-down assay revealed that the HOS1-L protein interacted with the ICE1 protein. HOS1-L overexpression caused delayed flowering in wild-type plants. Collectively, these results suggest regulation of HOS1 expression at the post-transcriptional level. PMID:23010172

  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. Objective Pathological Voice Quality Assessment Based on HOS Features

    NASA Astrophysics Data System (ADS)

    Lee, Ji-Yeoun; Jeong, Sangbae; Choi, Hong-Shik; Hahn, Minsoo

    This work proposes new features to improve the pathological voice quality classification performance. They are the means, the variances, and the perturbations of the higher-order statistics (HOS) such as the skewness and the kurtosis. The HOS-based features show meaningful differences among normal, grade 1, grade 2, and grade 3 voices classified in the GRBAS scale. The jitter, the shimmer, the harmonic-to-noise ratio (HNR), and the variance of the short-time energy are utilized as the conventional features. The performances are measured by the classification and regression tree (CART) method. Specifically, the CART-based method by utilizing both the conventional features and the HOS-based ones shows its effectiveness in the pathological voice quality measurement, with the classification accuracy of 87.8%.

  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. HOS1-mediated activation of FLC via chromatin remodeling under cold stress.

    PubMed

    Jung, Jae-Hoon; Park, Chung-Mo

    2013-01-01

    The Arabidopsis E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 1 (HOS1) has been shown to act as a negative regulator of cold responses by degrading the INDUCER OF CBF EXPRESSION 1 (ICE1) transcription factor through the ubiquitin/proteasome pathway. Notably, loss-of-function hos1 mutants exhibit early flowering, and the transcript level of the floral repressor FLOWERING LOCUS C (FLC) is downregulated in the mutants. However, it is largely unknown how HOS1 regulates FLC transcription. We found that HOS1 activates FLC transcription by inhibiting the activity of histone deacetylase 6 (HDA6) under cold stress. Cold temperatures induce the binding of HOS1 to FLC chromatin in an FVE-dependent manner. Cold-activated HOS1 promotes the dissociation of HDA6 from FLC chromatin, and the cold effects disappear in both hos1 and fve mutants. It is therefore clear that HOS1 regulates FLC transcription via chromatin remodeling, providing new insights into the signaling crosstalks between cold response and flowering time control. PMID:24390058

  8. HOS1, a genetic locus involved in cold-responsive gene expression in arabidopsis.

    PubMed Central

    Ishitani, M; Xiong, L; Lee, H; Stevenson, B; Zhu, J K

    1998-01-01

    Low-temperature stress induces the expression of a variety of genes in plants. However, the signal transduction pathway(s) that activates gene expression under cold stress is poorly understood. Mutants defective in cold signaling should facilitate molecular analysis of plant responses to low temperature and eventually lead to the identification and cloning of a cold stress receptor(s) and intracellular signaling components. In this study, we characterize a plant mutant affected in its response to low temperatures. The Arabidopsis hos1-1 mutation identified by luciferase imaging causes superinduction of cold-responsive genes, such as RD29A, COR47, COR15A, KIN1, and ADH. Although these genes are also induced by abscisic acid, high salt, or polyethylene glycol in addition to cold, the hos1-1 mutation only enhances their expression under cold stress. Genetic analysis revealed that hos1-1 is a single recessive mutation in a nuclear gene. Our studies using the firefly luciferase reporter gene under the control of the cold-responsive RD29A promoter have indicated that cold-responsive genes can be induced by temperatures as high as 19 degrees C in hos1-1 plants. In contrast, wild-type plants do not express the luciferase reporter at 10 degrees C or higher. Compared with the wild type, hos1-1 plants are l ess cold hardy. Nonetheless, after 2 days of cold acclimation, hos1-1 plants acquired the same degree of freezing tolerance as did the wild type. The hos1-1 plants flowered earlier than did the wild-type plants and appeared constitutively vernalized. Taken together, our findings show that the HOS1 locus is an important negative regulator of cold signal transduction in plant cells and that it plays critical roles in controlling gene expression under cold stress, freezing tolerance, and flowering time. PMID:9668134

  9. HOS1 Regulates Argonaute1 by Promoting the Transcription of the MicroRNA Gene MIR168b in Arabidopsis

    PubMed Central

    Wang, Bangshing; Duan, Cheng-Guo; Wang, Xingang; Hou, Yueh-Ju; Yan, Jun; Gao, Caiqiu; Kim, Jin-Hong; Zhang, Huiming; Zhu, Jian-Kang

    2015-01-01

    Summary Proper accumulation and function of miRNAs is essential for plant growth and development. While core components of the miRNA biogenesis pathway and miRNA-induced silencing complex have been well characterized, cellular regulators of miRNAs remain to be fully explored. Here we report that HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 (HOS1) is a regulator of an important miRNA, mi168a/b, that targets the ARGONAUTE 1 (AGO1) gene in Arabidopsis. HOS1 functions to regulate plant cold stress responses as an ubiquitin E3 ligase, associate with the nuclear pores to regulate mRNA export and circadian clock and flowering time by binding to chromatin of the flowering regulator FLC. We isolated a loss-of-function Arabidopsis mutant of HOS1 in a genetic screen for enhancers of sic-1, which is defective in miRNA biogenesis. Like other hos1 mutant alleles, the new hos1-7 mutant allele flowered early and was smaller in stature than the wild type. Dysfunction in HOS1 reduced the abundance of miR168a/b but not of other miRNAs. In hos1 mutants, pri-MIR168b and pre-MIR168b levels were decreased, and RNA polymerase II occupancy was reduced at the promoter of MIR168b but not MIR168a. Chromatin immunoprecipitation assays revealed HOS1 protein is enriched at the chromatin of the MIR168b promoter. The reduced miR168a/b level in hos1 mutants results in an increase in the mRNA and protein levels of its target gene, AGO1. Our results reveal that HOS1 regulates miR168a/b and AGO1 levels in Arabidopsis by maintaining proper transcription of MIR168b. PMID:25619693

  10. HOS-ocean: Open-source solver for nonlinear waves in open ocean based on High-Order Spectral method

    NASA Astrophysics Data System (ADS)

    Ducrozet, Guillaume; Bonnefoy, Félicien; Le Touzé, David; Ferrant, Pierre

    2016-06-01

    HOS-ocean is an efficient High-Order Spectral code developed to solve the deterministic propagation of nonlinear wavefields in open ocean. HOS-ocean is released as open-source, developed and distributed under the terms of GNU General Public License (GPLv3). Along with the source code, a documentation under wiki format is available which makes easy the compilation and execution of the source files. The code has been shown to be accurate and efficient.

  11. 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.

  12. 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.

  13. Anticancer Activity Studies of Ruthenium(II) Complex Toward Human Osteosarcoma HOS Cells.

    PubMed

    Zhu, Jian-Wei; Liu, Si-Hong; Zhang, Gui-Qiang; Xu, Hui-Hua; Wang, Yu-Xuan; Wu, Yong; Liu, Ya-Min; Wang, Yan; Liang, Jun-Bo; Guo, Qi-Feng

    2016-08-01

    A new Ru(II) complex [Ru(dmp)2(NMIP)](ClO4)2 (dmp = 2,9-dimethyl-1,10-phenanthroline, NMIP = 2'-(2″-nitro-3″,4″-methylenedioxyphenyl)imidazo[4',5'-f][1,10]-phenanthroline) was synthesized and characterized by elemental analysis, ESI-MS and (1)H NMR. The cytotoxic activity of the complex against MG-63, U2OS, HOS, and MC3T3-e1 cell lines was investigated by MTT method. The complex shows moderate cytotoxicity toward HOS (IC50 = 35.6 ± 2.6 µM) and MC3T3-e1 (IC50 = 41.6 ± 2.8 µM) cell lines. The morphological studies show that the complex can induce apoptosis in HOS cells and cause an increase of reactive oxygen species levels and a decrease in the mitochondrial membrane potential. The cell cycle distribution demonstrates that the complex inhibits the cell growth at S phase. Additionally, the antitumor activity in vivo reveals that the complex can induce a decrease in tumor weight. PMID:27007877

  14. 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

  15. Higher Order Suppressor (HOS) for the PolLux Microspectroscope Beamline at the Swiss Light Source SLS

    NASA Astrophysics Data System (ADS)

    Frommherz, U.; Raabe, J.; Watts, B.; Stefani, R.; Ellenberger, U.

    2010-06-01

    The mechanical design and performance of a device to suppress higher orders of a spherical grating monochromator at a constant deviation angle is described. The higher order suppressor (HOS) is used for a scanning transmission x-ray microspectroscope beamline (PolLux) at a bending magnet of the Swiss Light Source (SLS). The instruments allow microspectroscopy in polymer science, of biological samples in the water window as well as the study of magnetic materials with circular or linear polarized light in a photon energy range of 200 eV to 1400 eV. The HOS uses three mirrors acting as a low pass filter for soft x-rays to improve the absorption spectroscopy of carbon, oxygen and nitrogen 1s core levels. The successful installation and operation of the HOS located after the monochromator is reported. First results obtained using samples from materials research and environmental sciences exemplify the improved spectroscopy capabilities of the instrument.

  16. Higher Order Suppressor (HOS) for the PolLux Microspectroscope Beamline at the Swiss Light Source SLS

    SciTech Connect

    Frommherz, U.; Stefani, R.; Ellenberger, U.; Raabe, J.; Watts, B.

    2010-06-23

    The mechanical design and performance of a device to suppress higher orders of a spherical grating monochromator at a constant deviation angle is described. The higher order suppressor (HOS) is used for a scanning transmission x-ray microspectroscope beamline (PolLux) at a bending magnet of the Swiss Light Source (SLS). The instruments allow microspectroscopy in polymer science, of biological samples in the water window as well as the study of magnetic materials with circular or linear polarized light in a photon energy range of 200 eV to 1400 eV. The HOS uses three mirrors acting as a low pass filter for soft x-rays to improve the absorption spectroscopy of carbon, oxygen and nitrogen 1s core levels. The successful installation and operation of the HOS located after the monochromator is reported. First results obtained using samples from materials research and environmental sciences exemplify the improved spectroscopy capabilities of the instrument.

  17. 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. PMID:26818787

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

    PubMed

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

    2006-05-23

    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. 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.

  20. 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

  1. 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

    ... motor carriers on behalf of their commercial motor vehicle (CMV) drivers. The Agency reviewed each... maintain a record of duty status (RODS) on board the CMV they are operating (49 CFR 395.8). However, operators of ``utility service vehicles'' (USVs) are exempt from all the HOS rules , including the...

  2. 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. PMID:27325406

  3. HOS3, an ELO-Like Gene, Inhibits Effects of ABA and Implicates a S-1-P/Ceramide Control System for Abiotic Stress Responses in Arabidopsis thaliana

    PubMed Central

    Quist, Tanya M.; Sokolchik, Irina; Shi, Huazhong; Joly, Robert J.; Bressan, Ray A.; Maggio, Albino; Narsimhan, Meena; Li, Xia

    2009-01-01

    A hyper-osmotically sensitive mutant of Arabidopsis thaliana, designated hos3-1 (high expression of osmotically responsive genes), was identified based on its hyper-luminescence of RD29A:LUC promoter fusion plants upon treatment with NaCl and ABA. These responses implicate the disrupted gene as a direct or indirect negative regulator of the RD29A stress-responsive pathway. By sequencing the flanking regions of the T-DNA borders, it was determined that the disrupted gene is at locus At4g36830, annotated as encoding a putative protein with high homology to CIG30 (ELO2/FEN1). CIG30 has been implicated in synthesis of very long chain fatty acids (VLCFA), which are essential precursors for sphingolipids and ceramides. Altered stress responses characteristic of ABA-hypersensitivity, including reduced root growth inhibition and reduced germination with ABA treatment and reduced water loss from leaves, were exhibited by allelic hos3-1 and hos3-2 mutants. The hos3-2 mutant is partially suppressed in its transcript abundance and is inherited as a recessive trait. Further, the HOS3 ORF under the control of the 35SCaMV promoter restored wild-type NaCl- and ABA-root growth sensitivity as well as RD29A:LUC luminescence in mutant plants. We also show here that the HOS3 wild-type gene functionally complements the sensitivity of elo2 and elo3 yeast mutants to monensin. Furthermore, both hos3-1 and hos3-2 alleles shared increased sensitivity to the herbicide Metolachlor, which inhibits acyl chain elongation in synthesis of VLCFA, and HOS3 functionally complemented both elo2 and elo3 and restored levels of VLCFA. Together, these data establish that HOS3 inhibits ABA-mediated stress responses and implicate the VLCFA pathway and products as control points for several aspects of abiotic stress signaling and responses. The results also provide support for a role of ceramide in the control of stomatal behavior. PMID:19529829

  4. 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. PMID:27373061

  5. Rice root curling, a response to mechanosensing, is modulated by the rice E3-ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 (OsHOS1).

    PubMed

    Lourenço, T F; Serra, T S; Cordeiro, A M; Swanson, S J; Gilroy, S; Saibo, N J M; Oliveira, M M

    2016-08-01

    Plant development depends on the perception of external cues, such as light, gravity, touch, wind or nutrients, among others. Nevertheless, little is known regarding signal transduction pathways integrating these stimuli. Recently, we have reported the involvement of a rice E3-ubiquitin ligase (OsHOS1, HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1), previously associated with abiotic stress response, in root responses to mechanical stimuli. We showed that OsHOS1 is involved in the regulation of root curling after mechanosensing and that RNAi::OsHOS1 plants failed to exhibit the root curling phenotype observed in WT. Interestingly, the straight root phenotype of these transgenics correlated with the up-regulation of rice ROOT MEANDER CURLING (OsRMC, a negative regulator of rice root curling) and was reverted by the exogenous application of jasmonic acid. Altogether, our results highlight the role of the proteasome modulating plant responses to mechanical stimuli and suggest that OsHOS1 is a hub integrating environmental and hormonal signaling into plant growth and development. PMID:27467198

  6. 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. PMID:25912990

  7. 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

  8. 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. PMID:26830378

  9. 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

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

    PubMed Central

    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

  11. 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.

  12. 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

    2000-12-01

    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. PMID:11112449

  13. The Set3/Hos2 Histone Deacetylase Complex Attenuates cAMP/PKA Signaling to Regulate Morphogenesis and Virulence of Candida albicans

    PubMed Central

    Hnisz, Denes; Majer, Olivia; Frohner, Ingrid E.; Komnenovic, Vukoslav; Kuchler, Karl

    2010-01-01

    Candida albicans, like other pleiomorphic fungal pathogens, is able to undergo a reversible transition between single yeast-like cells and multicellular filaments. This morphogenetic process has long been considered as a key fungal virulence factor. Here, we identify the evolutionarily conserved Set3/Hos2 histone deacetylase complex (Set3C) as a crucial repressor of the yeast-to-filament transition. Cells lacking core components of the Set3C are able to maintain all developmental phases, but are hypersusceptible to filamentation-inducing signals, because of a hyperactive cAMP/Protein Kinase A signaling pathway. Strikingly, Set3C-mediated control of filamentation is required for virulence in vivo, since set3Δ/Δ cells display strongly attenuated virulence in a mouse model of systemic infection. Importantly, the inhibition of histone deacetylase activity by trichostatin A exclusively phenocopies the absence of a functional Set3C, but not of any other histone deacetylase gene. Hence, our work supports a paradigm for manipulating morphogenesis in C. albicans through alternative antifungal therapeutic strategies. PMID:20485517

  14. 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.

  15. 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.

  16. 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.

  17. 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

    ... published in the Federal Register on January 17, 2008 (73 FR 3316) or you may visit http://edocket.access..., FMCSA granted a limited exemption to 14 new APA-member motor carriers (74 FR 29266, June 19, 2009) and renewed 61exemptions of APA-member motor carriers (74 FR 29264, June 19, 2009) for their...

  18. 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

    ... review DOT's complete Privacy Act Statement in the Federal Register published on January, 17, 2008 (73 FR... FR 29264, June 19, 2009). The renewal would cover 54 of the 61 member motor carriers listed in the... 14 new APA- member motor carriers (74 FR 29266, June 10, 2009) and renewed 61 exemptions of...

  19. 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

  20. 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

    .... In 2009, FMCSA granted the same limited exemption to 14 new APA-member motor carriers (74 FR 29266, June 19, 2009) and renewed 61exemptions of APA-member motor carriers (74 FR 29264, June 19, 2009) for..., FMCSA published a notice in the Federal Register (76 FR 30232) announcing APA's application...

  1. 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

  2. Atheromatic™: symptomatic vs. asymptomatic classification of carotid ultrasound plaque using a combination of HOS, DWT & texture.

    PubMed

    Acharya, U Rajendra; Faust, Oliver; Sree, S Vinitha; Alvin, Ang Peng Chuan; Krishnamurthi, Ganapathy; Seabra, José C R; Sanches, João; Suri, Jasjit S

    2011-01-01

    Quantitative characterization of carotid atherosclerosis and classification into either symptomatic or asymptomatic is crucial in terms of diagnosis and treatment planning for a range of cardiovascular diseases. This paper presents a computer-aided diagnosis (CAD) system (Atheromatic™, patented technology from Biomedical Technologies, Inc., CA, USA) which analyzes ultrasound images and classifies them into symptomatic and asymptomatic. The classification result is based on a combination of discrete wavelet transform, higher order spectra and textural features. In this study, we compare support vector machine (SVM) classifiers with different kernels. The classifier with a radial basis function (RBF) kernel achieved an accuracy of 91.7% as well as a sensitivity of 97%, and specificity of 80%. Encouraged by this result, we feel that these features can be used to identify the plaque tissue type. Therefore, we propose an integrated index, a unique number called symptomatic asymptomatic carotid index (SACI) to discriminate symptomatic and asymptomatic carotid ultrasound images. We hope this SACI can be used as an adjunct tool by the vascular surgeons for daily screening. PMID:22255336

  3. Materials Data on HoS (SG:225) 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

  4. 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

    ... carriers and added 9 new APA-member carriers (76 FR 37876 and 76 FR 37880, June 28, 2011) for their... published on June 28, 2011 (76 FR 37876-37882). Issued on: June 21, 2012. Larry W. Minor, Associate... Mandeville, LA 70471........ 548303 38. Rainbow Fireworks, Inc 76 Plum Ave Inman, KS 67546 1139643 39....

  5. 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

    ... Register on January 17, 2008 (73 FR 3316), or you may visit http:// ] edocket.access.gpo.gov/2008/pdfE8-794... Carriers, the predecessor to FMCSA, published an interim final rule implementing section 4007 (63 FR 67600). On August 20, 2004, FMCSA published a Final Rule (69 FR 51589) on this subject. Pursuant to that...

  6. 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

    ... published on January 17, 2008 (73 FR 3316). Public Participation: The www.regulations.gov Web site is.......... 1610728 115. 37. Rainbow Fireworks, Inc 76 Plum Ave Inman, KS 67546 1139643 38. RES Specialty...

  7. 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.

  8. 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[C][W

    PubMed Central

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

    2013-01-01

    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. PMID:24220632

  9. 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.

  10. High order software - A methodology for defining software

    NASA Technical Reports Server (NTRS)

    Hamilton, M.; Zeldin, S.

    1975-01-01

    Higher order software (HOS) is a formal methodology for reliable systems specification and development. HOS is concerned only with computable functions and their relationships for any given system. Questions of methodology are considered, taking into account aspects of formulation meta-language principles, and HOS analyzers. Details of system design are discussed, giving attention to aspects of immediate self-control and indirect self-control. A description is given of the approaches used for software management.

  11. 77 FR 47850 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ... notice published on April 27, 2012, (77 FR 25181). Subsequently, the HOS Questionnaire collection..., Physical Activity in Older Adults, Fall Risk Management, and Osteoporosis Testing in Older Women...

  12. 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

  13. 76 FR 81133 - Hours of Service of Drivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-27

    ... notice of proposed rulemaking (NPRM) to revise the HOS rules (75 FR 82170). The Agency sought comment on... period to accept comments on four studies related to the HOS proposal (76 FR 26681). C. Final Rule... history of the earlier provisions (65 FR 25540) and the December 29, 2010, NPRM of this final rule for...

  14. 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…

  15. 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…

  16. Bilateral Scapulohumeral Ankylosis after Prolonged Mechanical Ventilation.

    PubMed

    van Lotten, Manon L; Schreinemakers, J Rieneke; van Noort, Arthur; Rademakers, Maarten V

    2016-09-01

    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

  17. 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

  18. Heme oxygenases from Arabidopsis thaliana reveal different mechanisms of carbon monoxide binding

    NASA Astrophysics Data System (ADS)

    Gisk, Björn; Molitor, Bastian; Frankenberg-Dinkel, Nicole; Kötting, Carsten

    2012-03-01

    Heme oxygenases (HO) are widely distributed enzymes involved in the degradation of heme to biliverdin, carbon monoxide and Fe2+. The model plant Arabidopsis thaliana possesses three functional HOs (HY1, HO3 and HO4) which are thus far biochemically indistinguishable. Here, we investigate binding of the reaction product and putative inhibitor CO to these three HOs with various spectroscopic techniques: Nanosecond time-resolved absorption, millisecond time-resolved multi-wavelength absorption and Fourier-transform-infrared difference spectroscopy. Kinetics of CO rebinding were found to differ substantially among the HOs. At low CO concentrations a novel intermediate was identified for HO3 and HO4, substantially slowing down rebinding. All HOs show relatively slow geminate rebinding of CO indicating the existence of an additional transient binding niche for CO. The positions found for the IR absorptions of νCO and νFeC suggest a nonpolar distal binding site for all three HOs. The frequency of the νFeC vibration was calculated by a combination band on which we report here for the first time. Another band in the FTIR difference spectrum could be assigned to a histidine residue, probably the proximal ligand of the heme-iron. The observed different rebinding kinetics among the HOs could indicate adaptation of the HOs to different environments.

  19. Heme oxygenases from Arabidopsis thaliana reveal different mechanisms of carbon monoxide binding.

    PubMed

    Gisk, Björn; Molitor, Bastian; Frankenberg-Dinkel, Nicole; Kötting, Carsten

    2012-03-01

    Heme oxygenases (HO) are widely distributed enzymes involved in the degradation of heme to biliverdin, carbon monoxide and Fe(2+). The model plant Arabidopsis thaliana possesses three functional HOs (HY1, HO3 and HO4) which are thus far biochemically indistinguishable. Here, we investigate binding of the reaction product and putative inhibitor CO to these three HOs with various spectroscopic techniques: Nanosecond time-resolved absorption, millisecond time-resolved multi-wavelength absorption and Fourier-transform-infrared difference spectroscopy. Kinetics of CO rebinding were found to differ substantially among the HOs. At low CO concentrations a novel intermediate was identified for HO3 and HO4, substantially slowing down rebinding. All HOs show relatively slow geminate rebinding of CO indicating the existence of an additional transient binding niche for CO. The positions found for the IR absorptions of ν(CO) and ν(FeC) suggest a nonpolar distal binding site for all three HOs. The frequency of the ν(FeC) vibration was calculated by a combination band on which we report here for the first time. Another band in the FTIR difference spectrum could be assigned to a histidine residue, probably the proximal ligand of the heme-iron. The observed different rebinding kinetics among the HOs could indicate adaptation of the HOs to different environments. PMID:22204880

  20. A systematic review of studies performing the hypo-osmotic swelling test to evaluate the quality of canine spermatozoa.

    PubMed

    Karger, S; Arlt, S; Haimerl, P; Heuwieser, W

    2014-02-01

    The hypo-osmotic swelling test (HOS test) is a simple and inexpensive test to evaluate the functional integrity of sperm cell membranes. According to the existing literature, its simple applicability has turned it into a valuable additional parameter to standard canine semen analysis. In the recent years, much research has been conducted in this field. The aim of this systematic review was to evaluate the quality of published literature in canine reproduction concerning the HOS test. Using two distinguished databases, 38 articles were detected and analysed subsequently according to various aspects, for example study design, population, semen sampling and implementation concerning the HOS test. Although there are numerous articles available, the diagnostic value of the HOS test remains ambiguous. Until now, neither a recognized test protocol nor reliable reference values have been defined. Most of the trials evaluated show serious methodological flaws and therefore do not permit drawing reliable conclusions. According to our results, approximately half of the studies (n = 20) included a sample size of five or less animals. None of the studies examined the inter- or intraobserver agreement for the HOS test. Further research is warranted including appropriate statistical methods and a sufficient number of animals to establish a standardized test protocol as well as reliable reference values. Most importantly, it is required to clarify a correlation between the HOS test and the fertilizing capacity to determine the diagnostic value of the HOS test. PMID:23931704

  1. 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

  2. Antiproliferative effect of Tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines

    PubMed Central

    2010-01-01

    Background The treatment of oral squamous cell carcinomas (OSCC) and human osteosarcoma (HOS) includes surgery and/or radiotherapy which often lead to reduced quality of life. This study was aimed to study the antiproliferative activity of local honey (Tualang) on OSCC and HOS cell lines. Methods Several concentrations of Tualang honey (1% - 20%) were applied on OSCC and HOS cell lines for 3, 6, 12, 24, 48 and 72 hours. Morphological characteristics were observed under light and fluorescent microscope. Cell viability was assessed using MTT assay and the optical density for absorbance values in each experiment was measured at 570 nm by an ELISA reader. Detection of cellular apoptosis was done using the Annexin V-FITC Apoptosis Detection Kit. Results Morphological appearance showed apoptotic cellular changes like becoming rounded, reduction in cell number, blebbed membrane and apoptotic nuclear changes like nuclear shrinkage, chromatin condensation and fragmented nucleus on OSCC and HOS cell lines. Cell viability assay showed a time and dose-dependent inhibitory effect of honey on both cell lines. The 50% inhibitory concentration (IC50) for OSCC and HOS cell lines was found to be 4% and 3.5% respectively. The maximum inhibition of cell growth of ≥80% was obtained at 15% for both cell lines. Early apoptosis was evident by flow cytometry where percentage of early apoptotic cells increased in dose and time dependent manner. Conclusion Tualang honey showed antiproliferative effect on OSCC and HOS cell lines by inducing early apoptosis. PMID:20840769

  3. 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.

  4. 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.

  5. 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.

  6. Wave-breaking onset in a High-Order Spectral model

    NASA Astrophysics Data System (ADS)

    Seiffert, Betsy; Ducrozet, Guillaume

    2016-04-01

    We examine the implementation of a wave-breaking onset parameter into two numerical models, HOS-ocean and HOS-NWT, which are computationally efficient, open source codes that solve for highly nonlinear wave fields in the open ocean and a numerical wave tank, respectively, using the High-Order Spectral (HOS) method. Due to the assumptions of solving for potential flow, the HOS solvers assume a single-valued free surface and therefore cannot produce breaking waves. The goal of implementing a wave-breaking mechanism into the HOS models is to approximate the broken free surface as a single value. By doing this, we can increase the application range of the models including calculating more extreme sea states, which is important when predicting dynamics of offshore vessels, predicting loads on marine structures and the general physics of ocean waves, for example. In nature, a steep wave may grow to surpass some limiting threshold leading to a collapse of the water surface as a broken wave. Energy from the wave is transferred through the generation of currents and turbulence, and changes occur in the spectral distribution of energy before and after a wave breaks. To implement a wave-breaking mechanism into the HOS models, first a wave-breaking onset parameter needs to be identified, and second, a strategy for dissipating and distributing the energy after the wave has broken needs to be determined. To calculate wave breaking onset in the HOS solvers, a dynamic wave-breaking criteria is proposed, following the work of Barthelemy, et al. (submitted). The criteria assumes that if the ratio of local energy flux velocity to the local crest velocity surpasses a limiting threshold, the wave will break. Calculation of the local crest velocity is non-trivial, and therefore partial Hilbert transforms are used. When calculating this wave-breaking parameter in the HOS model, it successfully distinguishes between an "unbroken" wave and a "broken" wave, evidenced by the manifestation of

  7. A conserved histone deacetylase with a role in the regulation of cytokinesis in Schizosaccharomyces pombe

    PubMed Central

    2012-01-01

    Background In Schizosaccharomyces pombe the SET domain protein, Set3p - together with its interacting partners, Snt1p, and Hif2p - form a complex that aids in preventing cell division failure upon mild cytokinetic stress. Intriguingly, the human orthologs of these proteins (MLL5, NCOR2, and TBL1X) are also important for the faithful completion of cytokinesis in tissue culture cells. Since MLL5, NCOR2, and TBL1X form a complex with the histone deacetylase, HDAC3, we sought to determine if an orthologous counterpart played a regulatory role in fission yeast cytokinesis. Results In this report we identify the hos2 gene as the fission yeast HDAC3 ortholog. We show that Hos2p physically interacts with Set3p, Snt1p, and Hif2p, and that hos2∆ mutants are indeed compromised in their ability to reliably complete cell division in the presence of mild cytokinetic stresses. Furthermore, we demonstrate that over-expression of hos2 causes severe morphological and cytokinetic defects. Lastly, through recombinase mediated cassette exchange, we show that expression of human HDAC3 complements the cytokinetic defects exhibited by hos2∆ cells. Conclusions These data support a model in which Hos2p functions as an essential component of the Set3p-Snt1p-Hif2p complex with respect to the regulation of cytokinesis. The ability of human HDAC3 to complement the cytokinesis defects associated with the deletion of the hos2 gene suggests that further analysis of this system could provide insight into the role of HDAC3 in both the regulation of cell division, as well as other biological processes influenced by HDAC3 deacetylation. PMID:22559741

  8. 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

  9. Numerical Simulation of a Seaway with Breaking

    NASA Astrophysics Data System (ADS)

    Dommermuth, Douglas; O'Shea, Thomas; Brucker, Kyle; Wyatt, Donald

    2012-11-01

    The focus of this presentation is to describe the recent efforts to simulate a fully non-linear seaway with breaking by using a high-order spectral (HOS) solution of the free-surface boundary value problem to drive a three-dimensional Volume of Fluid (VOF) solution. Historically, the two main types of simulations to simulate free-surface flows are the boundary integral equations method (BIEM) and high-order spectral (HOS) methods. BIEM calculations fail at the point at which the surface impacts upon itself, if not sooner, and HOS methods can only simulate a single valued free-surface. Both also employ a single-phase approximation in which the effects of the air on the water are neglected. Due to these limitations they are unable to simulate breaking waves and air entrainment. The Volume of Fluid (VOF) method on the other hand is suitable for modeling breaking waves and air entrainment. However it is computationally intractable to generate a realistic non-linear sea-state. Here, we use the HOS solution to quickly drive, or nudge, the VOF solution into a non-linear state. The computational strategies, mathematical formulation, and numerical implementation will be discussed. The results of the VOF simulation of a seaway with breaking will also be presented, and compared to the single phase, single valued HOS results.

  10. A comparative prospective study using matched samples to determine the influence of subnormal hypo-osmotic test scores of spermatozoa on subsequent fertilization and pregnancy rates following in-vitro fertilization.

    PubMed

    Check, J H; Stumpo, L; Lurie, D; Benfer, K; Callan, C

    1995-05-01

    The achievement of pregnancies in vivo is rare in couples where the male partner has defective sperm membranes as shown by hypo-osmotic swelling (HOS) test scores of < 50%. However, there have been mixed reports on the value of the HOS test in predicting outcome following invitro fertilization; some studies suggest reduced fertilization rates and others find little, if any, predictability of decreased fertilization. The assumption has been made that fertilization rates are proportional to pregnancy rates; however, this may not necessarily be true since defective spermatozoa could lead to a less viable pre-embryo and therefore a decreased viable pregnancy rate. We performed a comparative prospective study using matched controls to evaluate fertilization rates and to determine subsequent pregnancy rates. The mean HOS scores were 70.0 and 36.7% respectively, with mean motile sperm concentrations of 35.7 and 34.0 x 10(6)/ml in 27 matched pairs. There was no difference in the mean number of oocytes retrieved, fertilization rates or number of embryos transferred between the two groups by HOS score. The clinical and viable pregnancy rates and implantation rates were 25.9, 18.5 and 9.9% for normal versus 3.7, 3.7 and 1.1% for subnormal groups. These data suggest that low HOS scores may be associated with the formation of defective embryos, leading to low pregnancy rates but normal fertilization rates. PMID:7657765

  11. MicroRNA 19a replacement partially rescues fin and cardiac defects in zebrafish model of Holt Oram syndrome.

    PubMed

    Chiavacci, Elena; D'Aurizio, Romina; Guzzolino, Elena; Russo, Francesco; Baumgart, Mario; Groth, Marco; Mariani, Laura; D'Onofrio, Mara; Arisi, Ivan; Pellegrini, Marco; Cellerino, Alessandro; Cremisi, Federico; Pitto, Letizia

    2015-01-01

    Holt-Oram Syndrome (HOS) is an autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene, a transcription factor capable of regulating hundreds of cardiac-specific genes through complex transcriptional networks. Here we show that, in zebrafish, modulation of a single miRNA is sufficient to rescue the morphogenetic defects generated by HOS. The analysis of miRNA-seq profiling revealed a decreased expression of miR-19a in Tbx5-depleted zebrafish embryos compared to the wild type. We revealed that the transcription of the miR-17-92 cluster, which harbors miR-19a, is induced by Tbx5 and that a defined dosage of miR-19a is essential for the correct development of the heart. Importantly, we highlighted that miR-19a replacement is able to rescue cardiac and pectoral fin defects and to increase the viability of HOS zebrafish embryos. We further observed that miR-19a replacement shifts the global gene expression profile of HOS-like zebrafish embryos towards the wild type condition, confirming the ability of miR-19a to rescue the Tbx5 phenotype. In conclusion our data demonstrate the importance of Tbx5/miR-19a regulatory circuit in heart development and provide a proof of principle that morphogenetic defects associated with HOS can be rescued by transient miRNA modulation. PMID:26657204

  12. MicroRNA 19a replacement partially rescues fin and cardiac defects in zebrafish model of Holt Oram syndrome

    PubMed Central

    Chiavacci, Elena; D’Aurizio, Romina; Guzzolino, Elena; Russo, Francesco; Baumgart, Mario; Groth, Marco; Mariani, Laura; D’Onofrio, Mara; Arisi, Ivan; Pellegrini, Marco; Cellerino, Alessandro; Cremisi, Federico; Pitto, Letizia

    2015-01-01

    Holt-Oram Syndrome (HOS) is an autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene, a transcription factor capable of regulating hundreds of cardiac-specific genes through complex transcriptional networks. Here we show that, in zebrafish, modulation of a single miRNA is sufficient to rescue the morphogenetic defects generated by HOS. The analysis of miRNA-seq profiling revealed a decreased expression of miR-19a in Tbx5-depleted zebrafish embryos compared to the wild type. We revealed that the transcription of the miR-17-92 cluster, which harbors miR-19a, is induced by Tbx5 and that a defined dosage of miR-19a is essential for the correct development of the heart. Importantly, we highlighted that miR-19a replacement is able to rescue cardiac and pectoral fin defects and to increase the viability of HOS zebrafish embryos. We further observed that miR-19a replacement shifts the global gene expression profile of HOS-like zebrafish embryos towards the wild type condition, confirming the ability of miR-19a to rescue the Tbx5 phenotype. In conclusion our data demonstrate the importance of Tbx5/miR-19a regulatory circuit in heart development and provide a proof of principle that morphogenetic defects associated with HOS can be rescued by transient miRNA modulation. PMID:26657204

  13. Isolation and Characterization of High-Osmolarity-Sensitive Mutants of Fission Yeast

    PubMed Central

    Aiba, Hirofumi; Kawaura, Ryosuke; Yamamoto, Eiji; Yamada, Hisami; Takegawa, Kaoru; Mizuno, Takeshi

    1998-01-01

    For the fission yeast Schizosaccharomyces pombe, adaptation to high-osmolarity medium is mediated by a mitogen-activated protein (MAP) kinase cascade, involving the Wis1 MAP kinase kinase and the Sty1 MAP kinase. The MAP kinase pathway transduces an osmotic signal and accordingly regulates the expression of the downstream target gene (gpd1+) that encodes NADH-dependent glycerol-3-phosphate dehydrogenase, in order to adaptively accumulate glycerol inside the cells as an osmoprotectant. We previously characterized a set of high-osmolarity-sensitive S. pombe mutants, including wis1, sty1, and gpd1. In this study, we attempted to further isolate novel osmolarity-sensitive mutants. For some of the mutants isolated, profiles of glycerol production in response to the osmolarity of the growth medium were indistinguishable from that of the wild-type cells, suggesting that they are novel types. They were classified into three distinct types genetically and, thus, were designated hos1, hos2, and hos3 (high osmolarity sensitive) mutants. One of them, the hos1 mutant, was characterized in detail. The hos1 mutant was demonstrated to have a mutational lesion in the known ryh1+ gene, which encodes a small GTP-binding protein. Disruption of the ryh1+ gene results not only in osmosensitivity but also in temperature sensitivity for growth. It was also found that the Δryh1 mutant is severely sterile. These results are discussed with special reference to the osmoadaptation of S. pombe. PMID:9748434

  14. 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

    2016-08-01

    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. PMID:27476747

  15. 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…

  16. 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. PMID:22992900

  17. 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.

  18. 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.

  19. Technical decision making with higher order structure data: higher order structure characterization during protein therapeutic candidate screening.

    PubMed

    Jiang, Yijia; Li, Cynthia; Li, Jenny; Gabrielson, John P; Wen, Jie

    2015-04-01

    Protein therapeutics differ considerably from small molecule drugs because of the presence of higher order structure (HOS), post-translational modifications, inherent molecular heterogeneity, and unique stability profiles. At early stages of development, multiple molecular candidates are often produced for the same biological target. In order to select the most promising molecule for further development, studies are carried out to compare and rank order the candidates in terms of their manufacturability, purity, and stability profiles. This note reports a case study on the use of selected HOS characterization methods for candidate selection and the role of HOS data in identifying potential challenges that may be avoided by selecting the optimal molecular entity for continued development. PMID:25716705

  20. Psychometric Evaluation of the SF-36® Health Survey in Medicare Managed Care

    PubMed Central

    Gandek, Barbara; Sinclair, Samuel J.; Kosinski, Mark; Ware, John E.

    2004-01-01

    Data quality and scoring assumptions for the SF-36® Health Survey were evaluated among the elderly and disabled, using 1998 Cohort I baseline Medicare HOS data (n=177,714). Missing data rates were low, and scoring assumptions were met. Internal consistency reliability was 0.83 to 0.93 for the eight scales and 0.94 and 0.89, respectively, for the physical (PCS) and mental (MCS) component summary measures. Results declined with increased risk factors (e.g., older age, more chronic conditions), but were well above accepted standards for all subgroups. These findings support using standard algorithms for scoring the SF-36® in the HOS and subgroup analyses of HOS data. PMID:15493441

  1. Psychometric evaluation of the SF-36 health survey in Medicare managed care.

    PubMed

    Gandek, Barbara; Sinclair, Samuel J; Kosinski, Mark; Ware, John E

    2004-01-01

    Data quality and scoring assumptions for the SF-36 Health Survey were evaluated among the elderly and disabled, using 1998 Cohort I baseline Medicare HOS data (n=177,714). Missing data rates were low, and scoring assumptions were met. Internal consistency reliability was 0.83 to 0.93 for the eight scales and 0.94 and 0.89, respectively, for the physical (PCS) and mental (MCS) component summary measures. Results declined with increased risk factors (e.g., older age, more chronic conditions), but were well above accepted standards for all subgroups. These findings support using standard algorithms for scoring the SF-36 in the HOS and subgroup analyses of HOS data. PMID:15493441

  2. 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

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

    PubMed

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

    2016-07-01

    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

  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. 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

  6. Holt-Oram Syndrome Associated with Aortic Atresia: A Rare Association

    PubMed Central

    Rodagi, Sunil B.; Surana, Snehal S.; Potdar, Vijaykumar R.; Kirdi, Sharanbasav S.

    2016-01-01

    Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder that causes abnormalities of the upper limbs and heart. It is seen in 1:1, 00, 000 live births. It is linked to a single-gene TBX5 “protein-producing” mutation with gene map locus 12q24. Most commonly it is characterized by the cardiac septation defects and pre-axial radial ray abnormalities. We are reporting a case of HOS with aortic atresia which is a rare association. PMID:27293527

  7. On the measurement of human osteosarcoma cell elastic modulus using shear assay experiments.

    PubMed

    Cao, Yifang; Bly, Randy; Moore, Will; Gao, Zhan; Cuitino, Alberto M; Soboyejo, Wole

    2007-01-01

    This paper presents a method for determining the elastic modulus of human osteosarcoma (HOS) cells. The method involves a combination of shear assay experiments and finite element analysis. Following in-situ observations of cell deformation during shear assay experiments, a digital image correlation (DIC) technique was used to determine the local displacement and strain fields. Finite element analysis was then used to determine the Young's moduli of HOS cells. This involved a match of the maximum shear stresses estimated from the experimental shear assay measurements and those calculated from finite element simulations. PMID:17200819

  8. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. 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…

  11. The Hematopoietic Organ: A Cornerstone for Wolbachia Propagation Between and Within Hosts

    PubMed Central

    Braquart-Varnier, Christine; Raimond, Maryline; Mappa, Gaëtan; Chevalier, Frédéric D.; Le Clec’h, Winka; Sicard, Mathieu

    2015-01-01

    Wolbachia is an intracellular α-proteobacterium which is transmitted vertically from mother to offspring but also frequently switches horizontally from one host to another. Our hypothesis is based on the role of immune cells and the organs that produce them, the hematopoietic organs (HOs), as primordial niches for the propagation of Wolbachia via hemocytes both (i) within hosts: to initiate and maintain the systemic infection and (ii) between hosts: to promote both vertical and horizontal transmission of Wolbachia. Therefore, we review some fundamental ideas underlying this hypothesis and go further with new empirical data that lead to a first close-up analysis of the potential role of HOs in Wolbachia propagation. The monitoring of the first steps of Wolbachia infection in horizontally infected host organs by transmission electron microscopy and qPCR suggests that (i) HOs are colonized early and extensively as soon as they are in contact with Wolbachia which find in these cells a favorable niche to multiply and (ii) infected HOs which expel hemocytes all lifelong can generate and maintain a systemic infection that could contribute to increase both vertical and horizontal propagation of these symbionts. PMID:26733969

  12. Cytogenetic and Molecular Characterization of Durum Alien Disomic Addition Line with Enhanced Tolerance to Fusarium Head Blight Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium head blight (FHB), or scab, caused by the fungus Fusarium graminearum Schwabe, is a serious disease of durum wheat (Triticum turgidum L., 2n = 4x = 28; AABB genomes). Current durum cultivars have very little or no FHB resistance. A wild relative, diploid wheatgrass Lophopyrum elongatum (Hos...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    “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...

  14. ACTIVATION OF THE LAC GENES OF TN951 BY INSERTION SEQUENCES FROM PSUEDOMONAS CEPACIA

    EPA Science Inventory

    We have identified several transposable gene-activating elements from Psuedomonas cepacia on the basis of their ability to increase expression of the genes of the broad-hos-range plasmid pGC9l.14. hen introduced into auxotrophic derivatives of P. cepacia 249 (ATCC 17616), this pl...

  15. HYDROLOGIC-HYDROCHEMICAL CHARACTERIZATION OF TEXAS FRIO FORMATION USED FOR DEEP-WELL INJECTION OF CHEMICAL WASTES

    EPA Science Inventory

    Hydrologic hydrochemical investigations were conducted to determine the long-term fate of hazardous chemical waste disposed in the Texas Gulf Coast Tertiary formations by deep-well injection. The study focused on the hydrostatic section of the Frio Formation because it is the hos...

  16. 76 FR 32388 - Agency Information Collection Activities; Request for Comment; Extension of an Information...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-06

    ... Docket Management System published in the Federal Register on January 17, 2008 (73 FR 3316), or you may... duty status in a specified format and verify the accuracy of the HOS of each driver (47 FR 53383). The... public by reducing the number of tired CMV drivers on the highways. Most States receive grants from...

  17. 76 FR 50313 - Agency Information Collection Activities; Request for Comment; Extension of an Information...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-12

    ... the ICR (76 FR 32388). One comment was received. DATES: Please send your comments by September 12... their duty status in a specified format and verify the accuracy of the HOS of each driver (47 FR 53383... helps FMCSA protect the public by reducing the number of tired CMV drivers on the highways. Most...

  18. 78 FR 76392 - Hours of Service of Drivers: Application for Exemption; David Muresan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

    ... published on January 17, 2008 (73 FR 3316). Public Participation: The Federal eRulemaking Portal is... shifts required for drivers of property-carrying CMVs (68 FR 22456; April 28, 2003). However, drivers of... employ), including ``rest'' and ``sleep.'' Mr. Muresan believes that the Agency's HOS rules do...

  19. 77 FR 33331 - Regulatory Guidance on the Applicability of Property-Carrier Hours-of-Service Rules to the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-06

    ...The property-carrier hours-of-service (HOS) rules in 49 CFR 395.3 are applicable to drivers operating commercial motor vehicles designed or used to transport passengers on ``driveaway-towaway'' trips, as defined in 49 CFR 390.5. This notice provides Federal and State enforcement personnel, and the motor carrier industry, with uniform guidance concerning these...

  20. 78 FR 76757 - Regulatory Guidance on Hours of Service of Drivers Rest Break Requirement; Drivers Who Become...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-19

    ... December 27, 2011 (76 FR 81133), FMCSA published a final rule amending its HOS regulations for drivers of... Service of Drivers Rest Break Requirement; Drivers Who Become Ineligible for the ``Short-Haul'' Exception... why the rest break was not taken within the required 8 hours of the last off-duty break of at least...

  1. 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...

  2. "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…

  3. Dipsacus asperoides polysaccharide induces apoptosis in osteosarcoma cells by modulating the PI3K/Akt pathway.

    PubMed

    Chen, Jun; Yao, Dong; Yuan, Huixin; Zhang, Shaojun; Tian, Jinhong; Guo, Wenjing; Liang, Weizhi; Li, Huiyuan; Zhang, Yong

    2013-06-20

    An alkaline extractable and water-soluble polysaccharide (ADAPW), with an average molecular weight of 16kDa, was purified from the alkaline extraction of the roots of Dipsacus asperoides. Monosaccharide component analysis indicated that ADAPW was composed of glucose, rhamnose, arabinose and mannose in a molar ratio of 8.54:1.83:1.04:0.42. This study aimed to investigate the effect of ADAPW on the viability of human osteosarcoma cell line HOS cells, and explore the possible mechanisms. The results revealed that ADAPW inhibited the proliferation of HOS cells in a dose-dependent manner by inducing apoptosis. Furthermore, treatment with ADAPW caused a loss of mitochondrial membrane potential and accumulation of reactive oxygen species (ROS). In addition, Western blot analysis demonstrated that ADAPW down-regulated the protein expressions of PI3K and phosphorylated Akt (pAkt) in HOS cells. Taken together, induction of apoptosis on HOS cells by ADAPW was mainly associated with ROS production, mitochondrial dysfunction, and inhibition of PI3K/Akt signaling pathway. So this finding suggests that ADAPW may be potentially effective in cancer prevention against human osteosarcoma. PMID:23648042

  4. ACUTE METHANOL TOXICITY IN MINIPIGS

    EPA Science Inventory

    The pig hos been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its reported low liver tetrahydro folate levels and therefore, slower formate metabolism as compared to humans. o determine the validity of the animal model, min...

  5. 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…

  6. 75 FR 33664 - Hours of Service of Drivers: RockTenn, Application for Exemption

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-14

    ... the Federal Register published on April 11, 2000 (65 FR 19476) or you may visit http://DocketInfo.dot... Federal Motor Carrier Safety Administration Hours of Service of Drivers: RockTenn, Application for... RockTenn requesting an exemption from the driver hours-of-service (HOS) provisions in Part 395 of...

  7. 78 FR 64265 - Hours of Service of Drivers: U.S. Department of Defense (DOD); Application for Exemption

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-28

    ...FMCSA announces its decision to grant the U.S. Department of Defense (DOD) Military Surface Deployment and Distribution Command (SDDC) an exemption from the minimum 30-minute rest break provision of the Agency's hours-of-service (HOS) regulations for commercial motor vehicle (CMV) drivers. The exemption enables SDDC's contract motor carriers and their employee-drivers engaged in the......

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. 75 FR 9376 - Hours of Service

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-02

    ... the FDMS published in the Federal Register on January 17, 2008 (73 FR 3316), or you may visit http... listening sessions concerning the HOS rulemaking (75 FR 285). On January 15, 2010, FMCSA announced its plans to hold a fourth public listening session (75 FR 2467). FMCSA now announces a fifth public...

  10. 75 FR 2467 - Hours of Service

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... Federal Motor Carrier Safety Administration 49 CFR Part 395 RIN 2126-AB26 Hours of Service AGENCY: Federal...-service (HOS) regulations. Specifically, the Agency wants to know what factors, issues, and data it should... Act Statement for the FDMS published in the Federal Register on January 17, 2008 (73 FR 3316), or...

  11. The role of nitric oxide on the proliferation of a human osteoblast cell line stimulated with hydroxyapatite.

    PubMed

    Sosroseno, Wihaskoro; Sugiatno, Erwan; Samsudin, Abdul Rani; Ibrahim, Fikri

    2008-01-01

    The aim of the present study was to test the hypothesis that the proliferation of a human osteoblast cell line (HOS cells) stimulated with hydroxyapatite (HA) may be regulated by nitric oxide (NO). The cells were cultured on the surface of HA. Medium or cells alone were used as controls. L-arginine, D-arginine, 7-NI (an nNOS inhibitor), L-NIL (an iNOS inhibitor), L-NIO (an eNOS inhibitor) or carboxy PTIO, a NO scavenger, was added in the HA-exposed cell cultures. The cells were also precoated with anti-human integrin alphaV antibody. The levels of nitrite were determined spectrophotometrically. Cell proliferation was assessed by colorimetric assay. The results showed increased nitrite production and cell proliferation by HA-stimulated HOS cells up to day 3 of cultures. Anti-integrin alphaV antibody, L-NIO, or carboxy PTIO suppressed, but L-arginine enhanced, nitrite production and cell proliferation of HA-stimulated HOS cells. The results of the present study suggest, therefore, that interaction between HA and HOS cell surface integrin alphaV molecule may activate eNOS to catalyze NO production which, in turn, may regulate the cell proliferation in an autocrine fashion. PMID:18780564

  12. 78 FR 32001 - Agency Information Collection Activities; Approval of a New Information Collection Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-28

    ... electronic onboard recorders (EOBRs) installed in CMVs manufactured on or after June 4, 2012 (75 FR 17208... interstate commerce to use EOBRs to document their drivers' HOS (76 FR 5537, February 1, 2011). Based on... comment on the harassment issue on April 13, 2011 (76 FR 20611). The Agency sought and received...

  13. 77 FR 74267 - Agency Information Collection Activities; New Information Collection Request: Driver and Carrier...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-13

    ... Docket Management System published in the Federal Register on January 17, 2008 (73 FR 3316), or you may... operating CMVs in interstate commerce to use EOBRs to document their drivers' HOS (76 FR 5537, February 1... requesting public comment on the harassment issue on April 13, 2011 (76 FR 20612). The Agency sought...

  14. 78 FR 48927 - Hours of Service of Drivers: U.S. Department of Defense (DOD); Application for Exemption

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-12

    ...FMCSA announces that it has received an application from the U.S. Department of Defense (DOD) Military Surface Deployment and Distribution Command (SDDC) for an exemption from the minimum 30-minute rest break provision of the Agency's hours-of-service (HOS) regulations for commercial motor vehicle (CMV) drivers. The exemption would enable SDDC's contract motor carriers and their......

  15. 76 FR 8990 - Hours of Service of Drivers; Availability of Supplemental Documents and Corrections to Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-16

    ..., please see the preamble to the December 2010 HOS NPRM (75 FR 82170; December 29, 2010). The docket for... December 29, 2010 (75 FR 82170): ] 1. Page 82177. Correct footnote 17 to read as follows: \\17\\ Balkin, T..., J.A.M. & Wasserman, J.F., ``Improving Heavy-Duty Diesel Truck Ergonomics to Reduce Fatigue...

  16. 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,…

  17. Synthesis of Conformationally North-Locked Pyrimidine Nucleosides Built on an Oxa-bicyclo[3.1.0]hexane Scaffold

    PubMed Central

    Ludek, Olaf R.; Marquez, Victor E.

    2011-01-01

    Beginning with a known 3-oxabicyclo[3.1.0]hexane scaffold (I), the relocation of the fused cyclopropane ring bond and the shifting of the oxygen atom to an alternative location engendered a new 2-oxabicyclo[3.1.0]hexane template (II) that mimics more closely the tetrahydrofuran ring of conventional nucleosides. The synthesis of this new class of locked nucleosides involved a novel approach that required the isocyanate II (B = NCO) with a hydroxyl-protected scaffold as a pivotal intermediate that was obtained in eleven steps from a known dihydrofuran precursor. The completion of the nucleobases was successfully achieved by quenching the isocyanate with the lithium salts of the corresponding acrylic amides that led to the uracil and thymidine precursors in a single step. Ring closure of these intermediates led to the target, locked nucleosides. The anti-HIV activity of 29 (uridine analogue), 31 (thymidine analogue), and 34 (cytidine analogue) was explored in human osteosarcoma (HOS) cells or modified HOS cells (HOS-313) expressing the herpes simplex virus 1 thymidine kinase (HSV-1 TK). Only the cytidine analogue showed moderate activity in HOS-313 cells, which means that the compounds are not good substrates for the cellular kinases. PMID:22026578

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. Histone deacetylases in fungi: novel members, new facts.

    PubMed

    Trojer, Patrick; Brandtner, Eva M; Brosch, Gerald; Loidl, Peter; Galehr, Johannes; Linzmaier, Roland; Haas, Hubertus; Mair, Karin; Tribus, Martin; Graessle, Stefan

    2003-07-15

    Acetylation is the most prominent modification on core histones that strongly affects nuclear processes such as DNA replication, DNA repair and transcription. Enzymes responsible for the dynamic equilibrium of histone acetylation are histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this paper we describe the identification of novel HDACs from the filamentous fungi Aspergillus nidulans and the maize pathogen Cochliobolus carbonum. Two of the enzymes are homologs of Saccharomyces cerevisiae HOS3, an enzyme that has not been identified outside of the established yeast systems until now. One of these homologs, HosB, showed intrinsic HDAC activity and remarkable resistance against HDAC inhibitors like trichostatin A (TSA) when recombinant expressed in an Escherichia coli host system. Phylo genetic analysis revealed that HosB, together with other fungal HOS3 orthologs, is a member of a separate group within the classical HDACs. Immunological investigations with partially purified HDAC activities of Aspergillus showed that all classical enzymes are part of high molecular weight complexes and that a TSA sensitive class 2 HDAC constitutes the major part of total HDAC activity of the fungus. However, further biochemical analysis also revealed an NAD(+)-dependent activity that could be separated from the other activities by different types of chromatography and obviously represents an enzyme of the sirtuin class. PMID:12853613

  20. HYDRAULIC DISRUPTION AND PASSIVE MIGRATION BY A BACTERIAL PATHOGEN IN OAK TREE XYLEM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Xylella fastidiosa (Xf) is a xylem-limited bacterial pathogen that causes leaf scorch symptoms in numerous host plant species in urban, agricultural, and natural ecosystems worldwide. The exact mechanism of hydraulic disruption and systemic colonization of xylem by Xf remains elusive across all hos...

  1. 76 FR 5537 - Electronic On-Board Recorders and Hours of Service Supporting Documents

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-01

    ... complete Privacy Act Statement in the Federal Register notice published on April 11, 2000 (65 FR 19476). D... Motor Carrier Safety Regulations--FMCSRs Federal Register--FR Fleet Management System--FMS Global... carriers with significant HOS violations (75 FR 17208). That final rule required a motor carrier that...

  2. 77 FR 7544 - Hours of Service of Drivers: Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-13

    .... SUMMARY: FMCSA corrects the hours of service (HOS) final rule published on December 27, 2011 (76 FR 81143... the discussion of the Agency's intentions in the section- by-section analysis on 76 FR 81165 col. 3... December 27, 2011 rule. This notice does not change, in any manner, the regulatory text intended. In FR...

  3. 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. PMID:17892071

  4. Hyperglycemia is a risk factor for early death and morbidity in extremely low-birth weight infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVES. The objectives of this study were to determine the prevalence of hyperglycemia in extremely low birth-weight infants and to determine whether hyperglycemia increases the risk of early adverse outcomes (death or intraventricular hemorrhage of grade 3 or 4) and/or affects the length of hos...

  5. The fission yeast DASH complex is essential for satisfying the spindle assembly checkpoint induced by defects in the inner-kinetochore proteins.

    PubMed

    Kobayashi, Yasuyo; Saitoh, Shigeaki; Ogiyama, Yuki; Soejima, Saeko; Takahashi, Kohta

    2007-03-01

    Spindle assembly checkpoint (SAC) is an evolutionarily conserved surveillance system for chromosome missegregation. We isolated fission yeast Hos2, a component of the Dam1/DASH complex, as a multicopy suppressor of temperature-sensitive (ts) growth of nnf1-495 mutant that exhibits the minichromosome instability (mis) phenotype, producing lethal aneuploids without prominent mitotic delay. It remains elusive why SAC is satisfied in mis mutants despite the occurrence of missegregation. We found that Hos2 binds to the inner-kinetochore regions in both prometaphase and metaphase. Hos2 is essential for kinetochore localization of Dis1, a microtubule (MT) associated Dis1/XMAP215/TOG family protein that is required for proper MT dynamics. Cells lacking DASH exhibit cold-sensitive (cs) growth with the defective in sister-chromatid disjoining (dis) phenotype, which is characterized by hyper-condensed sister-chromatid pairs and elongated spindle MTs. Although DASH-deficient cells are viable at high temperatures, DASH-deletion transforms all the inner-kinetochore mis mutants so far tested into a constitutively active state of SAC, leading to the dis phenotype. We also discovered that Hos2 over-expression commonly suppresses growth retardation in a variety of inner-kinetochore mutants. These genetic interactions highlight the DASH-action(s) in satisfying SAC when aneuploids are formed during mitosis in the inner-kinetochore-defective mis mutants. PMID:17352737

  6. 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. PMID:25545760

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. Polydnaviruses: Roles in insect pathology and applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the more unusual groups of insect pathogens consists of members of the family Polydnaviridae, DNA insect viruses that live in mutual symbioses with their associated parasitoid wasp (Hymentoptera) carriers until they are injected into specific Lepidopteran hosts. Once inside this secondary hos...

  9. 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. PMID:27131958

  10. Anemone altaica Induces Apoptosis in Human Osteosarcoma Cells.

    PubMed

    Chang, I-Chang; Chiang, Tsay-I; Lo, Chun; Lai, Yi-Hua; Yue, Chia-Herng; Liu, Jer-Yuh; Hsu, Li-Sung; Lee, Chia-Jen

    2015-01-01

    In the past decade, no significant improvement has been made in chemotherapy for osteosarcoma (OS). To develop improved agents against OS, we screened 70 species of medicinal plants and treated two human OS cell lines with different agent concentrations. We then examined cell viability using the MTT assay. Results showed that a candidate plant, particularly the rhizomes of Anemone altaica Fisch. ex C. A. Mey aqueous extract (AAE), suppressed the viability of HOS and U2OS cells in a concentration-dependent manner. Flow cytometry analysis revealed that AAE significantly increased the amount of cell shrinkage (Sub-G1 fragments) in HOS and U2OS cells. Moreover, AAE increased cytosolic cytochrome c and Bax, but decreased Bcl-2. The amount of cleaved caspase-3 and poly-(ADP-ribose) polymerase-1 (PARP-1) were significantly increased. AAE suppressed the growth of HOS and U2OS through the intrinsic apoptotic pathway. Data suggest that AAE is cytotoxic to HOS and U2OS cells and has no significant influence on human osteoblast hFOB cells. The high mRNA levels of apoptosis-related factors (PPP1R15A, SQSTM1, HSPA1B, and DDIT4) and cellular proliferation markers (SKA2 and BUB1B) were significantly altered by the AAE treatment of HOS and U2OS cells. Results show that the anticancer activity of AAE could up-regulate the expression of a cluster of genes, especially those in the apoptosis-related factor family and caspase family. Thus, AAE has great potential as a useful therapeutic drug for human OS. PMID:26224029

  11. 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

  12. 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. PMID:27342664

  13. 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. PMID:26753116

  14. A two-stage approach using Gaussian mixture models and higher-order statistics for a classification of normal and pathological voices

    NASA Astrophysics Data System (ADS)

    Lee, Ji Yeoun

    2012-12-01

    A two-stage classifier is used to improve the classification performance between normal and pathological voices. A primary classification between normal and pathological voices is achieved by the Gaussian mixture model (GMM) log-likelihood scores. For samples that do not meet the thresholds for normal or disordered voice in the GMM, the final decision is made by a higher-order statistics (HOS)-based parameter. The normalized skewness and kurtosis, and means of the normalized skewness and kurtosis were estimated using a sustained vowel /a/ from 53 normal and 173 pathological voices taken from the Disordered Voice Database. Mel-frequency cepstral coefficients (MFCC)-based GMM, the HOS methods, and a two-stage classifier based on the GMM-HOS were performed for each voice signal. A Mann-Whitney rank sum test was used to detect differences in the means of the HOS-based parameters. A fivefold cross-validation scheme was performed to test the classification method. When 16 Gaussian mixtures were used, the MFCC-based GMM algorithm is performed with 92.0% accuracy. When means of the normalized skewness and kurtosis were used, performances of 82.31 and 83.67% were obtained, respectively. The two-stage classifier with 16 Gaussian mixtures and the mean of the normalized kurtosis classified samples with a 96.96% accuracy were obtained. The proposed two-stage classifier is more accurate than the MFCC-based GMM and HOS methods alone and shows potential for the classification of voices in the clinic.

  15. 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.

  16. Knowledge Regarding Basic Facts of Stroke Among Final Year MBBS Students and House Officers: A Cross-Sectional Survey of 708 Respondents from Pakistan

    PubMed Central

    Khubaib, Mohammad U; Waqas, Ahmed; Jan, Mohsin M; Sohail, Sana

    2016-01-01

    Introduction: Stroke is the leading cause of neurological disability in the world. In Pakistan, house officers (HOs) are usually the first contact for a stroke patient in the emergency department. Sometimes they need to make quick decisions regarding diagnosis and management without specialist supervision. Thousands of current final year MBBS (Bachelor of Medicine, Bachelor of Surgery) students will be performing the duties of HOs soon. This study documents the knowledge and confidence levels of final year students and HOs in Pakistan regarding basic facts related to initial diagnosis and management of stroke. Materials and Methods: A questionnaire was developed using two standard textbooks of medicine and current stroke guidelines of the American Heart Association. The pre-tested self-administered questionnaire was distributed among 800 final year MBBS students and HOs in 14 medical colleges and hospitals in four different cities. The response rate was 88.5%. Data analysis was done using SPSS V.21. The CMH Lahore Medical College Ethics Review Committee approved this project. Results: Respondents included medical students (n=496) and HOs (N= 212); most were female (n = 452, 63.9%). Of these, 31.4% had managed or assisted in the management of a patient with a stroke and had a higher confidence level in its diagnosis (p< 0.001) and management (p <0.001). Having a family member with stroke was associated with higher confidence in the diagnosis of stroke (p < 0.05) but not with confidence in its management (p = 0.41). Most correctly defined stroke (60.6%), identified the CT scan as the initial diagnostic modality (88.1%), knew the dosage of aspirin (64.9%), knew the time limit for thrombolysis (67.4%), and were familiar with the risk of deep vein thrombosis in immobilized stroke patients (85.4%). Less than half (44.5%) chose tissue plasminogen activator (t-PA) as the preferred initial intervention for acute ischemic stroke. Conclusion: This multicenter survey shows

  17. Application of Omics Technologies in Occupational and Environmental Health Research; Current Status and Projections

    PubMed Central

    Vlaanderen, Jelle; Moore, Lee E.; Smith, Martyn T.; Lan, Qing; Zhang, Luoping; Skibola, Christine F.; Rothman, Nathaniel; Vermeulen, Roel

    2010-01-01

    OMICS technologies are relatively new biomarker discovery tools that can be applied to study large sets of biological molecules. Their application in human observational studies (HOS) has become feasible in recent years due to a spectacular increase in the sensitivity, resolution and throughput of OMICS based assays. Although, the number of OMIC techniques is ever expanding, the five most developed OMICS technologies are genotyping, transcriptomics, epigenomics, proteomics and metabolomics. These techniques have been applied in HOS to various extents. However, their application in Occupational Environmental Health (OEH) research has been limited. Here, we will discuss the opportunities these new techniques provide for OEH research. In addition we will address difficulties and limitations to the interpretation of the data that is generated by OMICS technologies. To illustrate the current status of the application of OMICS in OEH research, we will provide examples of studies that used OMICS technologies to investigate human health effects of two well known toxicants, benzene and arsenic. PMID:19933307

  18. Electron heating due to microwave photoexcitation in the high mobility GaAs/AlGaAs two dimensional electron system

    NASA Astrophysics Data System (ADS)

    Ramanayaka, A. N.; Mani, R. G.; Wegscheider, W.

    2013-12-01

    We extract the electron temperature in the microwave photo-excited high mobility GaAs/AlGaAs two dimensional electron system (2DES) by studying the influence of microwave radiation on the amplitude of Shubnikov-de Haas oscillations (SdHOs) in a regime where the cyclotron frequency, ωc, and the microwave angular frequency, ω, satisfy 2ω ≤ ωc ≤ 3.5ω The results indicate that increasing the incident microwave power has a weak effect on the amplitude of the SdHOs and therefore the electron temperature, in comparison to the influence of modest temperature changes on the dark-specimen SdH effect. The results indicate negligible electron heating under modest microwave photo-excitation, in good agreement with theoretical predictions.

  19. Electron heating due to microwave photoexcitation in the high mobility GaAs/AlGaAs two dimensional electron system

    SciTech Connect

    Ramanayaka, A. N.; Mani, R. G.; Wegscheider, W.

    2013-12-04

    We extract the electron temperature in the microwave photo-excited high mobility GaAs/AlGaAs two dimensional electron system (2DES) by studying the influence of microwave radiation on the amplitude of Shubnikov-de Haas oscillations (SdHOs) in a regime where the cyclotron frequency, ω{sub c}, and the microwave angular frequency, ω, satisfy 2ω ≤ ω{sub c} ≤ 3.5ω The results indicate that increasing the incident microwave power has a weak effect on the amplitude of the SdHOs and therefore the electron temperature, in comparison to the influence of modest temperature changes on the dark-specimen SdH effect. The results indicate negligible electron heating under modest microwave photo-excitation, in good agreement with theoretical predictions.

  20. 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.

  1. 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

  2. Overexpression of urokinase receptor increases matrix invasion without altering cell migration in a human osteosarcoma cell line.

    PubMed

    Karikó, K; Kuo, A; Boyd, D; Okada, S S; Cines, D B; Barnathan, E S

    1993-07-01

    Proteolysis triggered by receptor-bound urokinase-type plasminogen activator (uPA) involves a cascade of species-specific molecular interactions. To study the role of the uPA receptor (uPAR) in such interactions, a human osteosarcoma cell line (HOS), which normally expresses low levels of uPAR, was transfected with human uPAR complementary DNA. One of several stably transformed clonal cells lines, designated 2A2, was characterized and compared to the parental HOS, revealing the following: (a) stable incorporation of uPAR complementary DNA into the genome demonstrated by Southern blot analysis; (b) a 10-fold increase in steady state mRNA levels of uPAR assessed by Northern blot analysis; (c) a 2-fold increase in the surface expression of glycosylphosphatidylinositol anchored uPAR protein determined by enzyme-linked immunosorbent assay and by the specific binding of radiolabeled single chain uPA; (d) a 2-fold increase in internalization and degradation of radiolabeled uPA/PAI-1 complexes; and (e) a 2-fold increase in receptor-bound uPA-mediated plasmin generation measured by the cleavage of a chromogenic substrate and degradation of 125I-labeled laminin. The involvement of uPAR in cellular processes was determined by comparing 2A2 and HOS cells in in vitro migration and invasion assays. The migration of 2A2 cells were slower on fibronectin-coated surfaces in a linear under-agarose assay, but both cell lines migrated at the same rate on uncoated polycarbonate filters in Boyden chamber assays. In the invasion experiments, 4 times more 2A2 than HOS cells penetrated through the barrier of reconstituted basement membrane Matrigel. These data suggest that uPAR does not potentiate random cell migration but facilitates matrix degradation and subsequent cell invasion. PMID:8391387

  3. Oncogenic roles of carbonic anhydrase 8 in human osteosarcoma cells.

    PubMed

    Wang, Tze-Kai; Lin, Yu-Ming; Lo, Che-Min; Tang, Chih-Hsin; Teng, Chieh-Lin Jerry; Chao, Wei-Ting; Wu, Min Huan; Liu, Chin-San; Hsieh, Mingli

    2016-06-01

    Carbonic anhydrase 8 (CA8), a member of the carbonic anhydrase family, is one of the three isozymes that do not catalyze the reversible hydration of carbon dioxide due to the lack of one important histidine. In the present study, we observed increased expression of CA8 in more aggressive types of human osteosarcoma (OS) cells and found that CA8 expression is correlated with disease stages, such that more intense expression occurs in the disease late stage. We also demonstrated that overexpression of CA8 in human OS (HOS) cells significantly increased cell proliferation both in vitro and in vivo. Downregulated CA8 sensitized cells to apoptotic stress induced by staurosporine and cisplatin, suggesting a specific role of CA8 to protect cells from stresses. In addition, downregulation of CA8 in HOS cells reduced cell invasion and colony formation ability in soft agar and further decreased matrix metalloproteinase 9 and focal adhesion kinase expression, indicating that CA8 might facilitate cancer cell invasion via the activation of FAK-MMP9 signaling. Interestingly, HOS cells with CA8 knockdown showed a significant decrease in glycolytic activity and cell death under glucose withdrawal, further indicating that CA8 may be involved in regulating aerobic glycolysis and enhancing cell viability. Knockdown of CA8 significantly decreased phosphorylated Akt expression suggesting that the oncogenic role of CA8 may be mediated by the regulation of Akt activation through p-Akt induction. Importantly, the inhibition of glycolysis by 2-deoxyglucose sensitized CA8 HOS-CA8-myc cells to cisplatin treatment under low glucose condition, highlighting a new therapeutic option for OS cancer. PMID:26711783

  4. 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.

  5. The role of propionates in substrate binding to heme oxygenase from Neisseria meningitidis; A NMR study†

    PubMed Central

    Peng, Dungeng; Ma, Li-Hua; Smith, Kevin M.; Zhang, Xuhong; Sato, Michihiko; La Mar, Gerd N.

    2012-01-01

    Heme oxygenase, HO, cleaves hemin into biliverdin, iron and CO. For mammalian HOs, both native hemin propionates are required for substrate binding and activity. The HO from the pathogenic bacterium Neisseria meningitidis, NmHO, possesses a crystallographically undetected C-terminal fragment that by solution 1H NMR is found to fold and interact with the active site. One of the substrate propionates has been proposed to form a salt bridge to the C-terminus rather than to the conventional buried cationic side chain in other HOs. Moreover, the C-terminal dipeptide Arg208His209 cleaves spontaneously over ~24 hours at a rate dependent on substituent size. 2D 1H NMR of NmHO azide complexes with hemins with selectively deleted or rearranged propionates all bind to NmHO with a structurally conserved active site as reflected in optical spectra and NMR NOESY cross peak and hyperfine shift patterns. In contrast to mammalian HOs, NmHO requires only a single propionate interacting with the buried terminus of Lys16 to exhibit full activity and tolerates the existence of a propionate at the exposed 8-position. The structure of the C-terminus is qualitatively retained upon deletion of the 7-propionate but a dramatic change in the 7-propionate carboxylate 13C chemical shift upon C-terminal cleavage confirms its role in the interaction with the C-terminus. The stronger hydrophobic contacts between pyrroles A and B with NmHO contribute more substantially to the substrate binding free energy than in mammalian HOs, “liberating” one propionate to stabilize the C-terminus. The functional implications of the C-terminus in product release are discussed. PMID:22913621

  6. 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. PMID:19246083

  7. Comparability of higher order structure in proteins: chemometric analysis of second-derivative amide I Fourier transform infrared spectra.

    PubMed

    Stockdale, Gregory; Murphy, Brian M; D'Antonio, Jennifer; Manning, Mark Cornell; Al-Azzam, Wasfi

    2015-01-01

    Comparing higher order structure (HOS) in therapeutic proteins is a significant challenge. Previously, we showed that changes in solution conditions produced detectable changes in the second-derivative amide I Fourier transform infrared (FTIR) spectra for a variety of model proteins. Those comparisons utilized vector-based approaches, such as spectral overlap and spectral correlation coefficients to quantify differences between spectra. In this study, chemometric analyses of the same data were performed, to classify samples into different groups based on the solution conditions received. The solution conditions were composed of various combinations of temperature, pH, and salt types. At first, principal component analysis (PCA) was used to visually demonstrate that FTIR spectra respond to changes in solution conditions, which, presumably indicates variations in HOS. This observed when samples from the same solution condition form clusters within a PCA score plot. The second approach, called soft independent modeling of class analogy (SIMCA), was conducted to account for the within-class experimental error for the lysozyme spectra. The DModX values, indicative of the distance of each spectra to their respective class models, was found to be a more sensitive quantitative indicator of changes in HOS, when compared with the modified area of overlap algorithm. The SIMCA approach provides a metric to determine whether new observations do, or do not belong to a particular class or group. Thus, SIMCA is the recommended approach when multiple samples from each condition are available. PMID:25382804

  8. Higher-Order Statistics for the Detection of Small Objects in a Noisy Background Application on Sonar Imaging

    NASA Astrophysics Data System (ADS)

    Maussang, F.; Chanussot, J.; Hétet, A.; Amate, M.

    2007-12-01

    An original algorithm for the detection of small objects in a noisy background is proposed. Its application to underwater objects detection by sonar imaging is addressed. This new method is based on the use of higher-order statistics (HOS) that are locally estimated on the images. The proposed algorithm is divided into two steps. In a first step, HOS (skewness and kurtosis) are estimated locally using a square sliding computation window. Small deterministic objects have different statistical properties from the background they are thus highlighted. The influence of the signal-to-noise ratio (SNR) on the results is studied in the case of Gaussian noise. Mathematical expressions of the estimators and of the expected performances are derived and are experimentally confirmed. In a second step, the results are focused by a matched filter using a theoretical model. This enables the precise localization of the regions of interest. The proposed method generalizes to other statistical distributions and we derive the theoretical expressions of the HOS estimators in the case of a Weibull distribution (both when only noise is present or when a small deterministic object is present within the filtering window). This enables the application of the proposed technique to the processing of synthetic aperture sonar data containing underwater mines whose echoes have to be detected and located. Results on real data sets are presented and quantitatively evaluated using receiver operating characteristic (ROC) curves.

  9. Quantifying wave-breaking dissipation using nonlinear phase-resolved wave-field simulations with a phenomenological-based wave breaking model

    NASA Astrophysics Data System (ADS)

    Qi, Yusheng; Yue, Dick

    2015-11-01

    We use direct nonlinear phase-resolved simulations based on a High-Order Spectral (HOS) method (Dommermuth & Yue 1987) to understand and quantify wave-breaking dissipation in the evolution of general irregular short-crested wave-fields. We achieve this by incorporating a robust phenomenological-based wave breaking model in HOS simulations to account for energy dissipation. This model can automatically simulate the onset of wave breaking, and the simulated wave-breaking dissipation strength differentiates corresponding to different wave breaking type (such as spilling or plunging breaking waves). 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, which provides the times, locations and intensity of wave breaking events. From the dissipation field we further calculate the distribution of total length of breaking wave front per unit surface area per unit increment of breaking velocity (Phillips 1985), and obtain qualitative agreement with Phillips theoretical power-law.

  10. OST1 kinase modulates freezing tolerance by enhancing ICE1 stability in Arabidopsis.

    PubMed

    Ding, Yanglin; Li, Hui; Zhang, Xiaoyan; Xie, Qi; Gong, Zhizhong; Yang, Shuhua

    2015-02-01

    Cold stress is a major environmental factor that limits plant growth and development. The C-repeat-binding factor (CBF)-dependent cold signaling pathway is extensively studied in Arabidopsis; however, the specific protein kinases involved in this pathway remain elusive. Here we report that OST1 (open stomata 1), a well-known Ser/Thr protein kinase in ABA signaling, acts upstream of CBFs to positively regulate freezing tolerance. The ost1 mutants show freezing hypersensitivity, whereas transgenic plants overexpressing OST1 exhibit enhanced freezing tolerance. The OST1 kinase is activated by cold stress. Moreover, OST1 interacts with both the transcription factor ICE1 and the E3 ligase HOS1 in the CBF pathway. Cold-activated OST1 phosphorylates ICE1 and enhances its stability and transcriptional activity. Meanwhile, OST1 interferes with the interaction between HOS1 and ICE1, thus suppressing HOS1-mediated ICE1 degradation under cold stress. Our results thus uncover the unexpected roles of OST1 in modulating CBF-dependent cold signaling in Arabidopsis. PMID:25669882

  11. 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

    2016-04-01

    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. PMID:26327572

  12. 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

  13. Pre-operative Thresholds for Achieving Meaningful Clinical Improvement after Arthroscopic Treatment of Femoroacetabular Impingement

    PubMed Central

    Nwachukwu, Benedict U.; Fields, Kara G.; Nawabi, Danyal H.; Kelly, Bryan T.; Ranawat, Anil S.

    2016-01-01

    Objectives: Knowledge of the thresholds and determinants for successful femoroacetabular impingement (FAI) treatment is evolving. The primary purpose of this study was to define pre-operative outcome score thresholds that can be used to predict patients most likely to achieve meaningful clinically important difference (MCID) after arthroscopic FAI treatment. Secondarily determinants of achieving MCID were evaluated. Methods: A prospective institutional hip arthroscopy registry was reviewed to identify patients with FAI treated with arthroscopic labral surgery, acetabular rim trimming, and femoral osteochondroplasty. The modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS) and the international Hip Outcome Tool (iHOT-33) tools were administered at baseline and at one year post-operatively. MCID was calculated using a distribution-based method. A receiver operating characteristic (ROC) analysis was used to calculate cohort-based threshold values predictive of achieving MCID. Area under the curve (AUC) was used to define predictive ability (strength of association) with AUC >0.7 considered acceptably predictive. Univariate and multivariable analyses were used to analyze demographic, radiographic and intra-operative factors associated with achieving MCID. Results: There were 374 patients (mean + SD age, 32.9 + 10.5) and 56.4% were female. The MCID for mHHS, HOS activities of daily living (HOS-ADL), HOS Sports, and iHOT-33 was 8.2, 8.4,14.5, and 12.0 respectively. ROC analysis (threshold, % achieving MCID, strength of association) for these tools in our population was: mHHS (61.6, 78%, 0.68), HOS-ADL (83.8, 68%, 0.84), HOS-Sports (63.9, 64%, 0.74), and iHOT-33 (54.3, 82%, 0.65). Likelihood for achieving MCID declined above and increased below these thresholds. In univariate analysis female sex, femoral version, lower acetabular outerbridge score and increasing CT sagittal center edge angle (CEA) were predictive of achieving MCID. In multivariable analysis

  14. 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. PMID:23301169

  15. Piperine inhibits proliferation of human osteosarcoma cells via G2/M phase arrest and metastasis by suppressing MMP-2/-9 expression.

    PubMed

    Zhang, Jian; Zhu, Xiaobing; Li, Hengyuan; Li, Binghao; Sun, Lingling; Xie, Tao; Zhu, Ting; Zhou, Hong; Ye, Zhaoming

    2015-01-01

    The piperidine alkaloid piperine, a major ingredient in black pepper, inhibits the growth and metastasis of cancer cells both in vivo and in vitro, although its mechanism of action is unclear. Furthermore, its anticancer activity against osteosarcoma cells has not been reported. In this study, we show that piperine inhibited the growth of HOS and U2OS cells in dose- and time-dependent manners but had a weaker effect on the growth of normal hFOB cells. Piperine inhibited osteosarcoma cell proliferation by causing G2/M phase cell cycle arrest associated with decreased expression of cyclin B1 and increased phosphorylation of Cyclin-dependent kinase-1(CDK1) and checkpoint kinase 2 (Chk2). In addition, piperine treatment inhibited phosphorylation of Akt and activated phosphorylation of c-Jun N-terminal kinase (c-JNK) and p38 mitogen-activated protein kinase (MAPK) in HOS and U2OS cells. Piperine induced colony formation in these two cell types. We proved that piperine could suppress the metastasis of osteosarcoma cells using scratch migration assays and Transwell chamber tests. Moreover, gelatin zymography showed that piperine inhibited the activity of matrix metalloproteinase (MMP)-2/-9 and increased the expression of tissue inhibitor of metalloproteinase (TIMP)-1/-2. Taken together, our results indicate that piperine inhibits proliferation, by inducing G2/M cell cycle arrest, and the migration and invasion of HOS and U2OS cells, via increased expression of TIMP-1/-2 and down-regulation of MMP-2/-9. These findings support further study of piperine as a promising therapeutic agent in the treatment of osteosarcoma. PMID:25479727

  16. 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

  17. Shubnikov-de Haas Effect measured on single crystals of CeOs4 Sb 12 and NdOs4 Sb 12 along the high symmetry directions

    NASA Astrophysics Data System (ADS)

    Ho, P.-C.; Singleton, J.; Maple, M. B.; Shrekenhamer, D. B.; X., Lee; Thale, A.; Yanagisawa, T.

    2011-03-01

    The filled skutterudite compounds CeOs 4 Sb 12 , PrOs 4 Sb 12 , and NdOs 4 Sb 12 are respectively a 1~K antiferromagnetic (AFM) Kondo insulator, a 1.85~K unconventional superconductor, and a 1~K mean-field type ferromagnet (FM), suggesting that superconductivity in PrOs 4 Sb 12 may result from proximity to AFM and FM quantum-critical points. Fermi-surface measurements of NdOs 4 Sb 12 and CeOs 4 Sb 12 could therefore give insights into the pairing mechanism. We have used a MHz skin-depth technique to observe Shubnikov-de Haas oscillations (SdHos) in single crystals of these materials at fields of up to 60~T. In CeOs 4 Sb 12 for H [001], a previously-unobserved semimetal-to-metal transition was detected at ~ 25 ~T; above this, a series of SdHos with a frequency of 1700~T and mCR ~ 3.6me emerge. For H [011] in NdOs 4 Sb 12 , a single series of SdHos, frequency ~ 874 ~T, was found. These may correspond to the β band in PrOs 4 Sb 12 , but with a much smaller mCR ~ 1.5me . Research at CSU-Fresno is supported by RC CCSA # 7669 and the start-up fund; at NHMFL by DOE, NSF, and FL.; at UCSD by NSF # 0802478 and US DOE DE FG02-04ER46105; at Hokkaido U by MEXT, Japan.

  18. 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

  19. Strength and pain are related to different measures of functional ability in patients with end-stage hip osteoarthritis

    PubMed Central

    Zeni, Joseph; Abujaber, Sumayah; Pozzi, Federico; Raisis, Leo

    2014-01-01

    Objective Performance tests and self-reported questionnaires capture different domains of function in patients with lower extremity osteoarthritis, but the impairments related to each of these domains have not been elucidated. The purpose of this study was to determine how strength and joint pain influence performance-based tests and self-reported questionnaires of functional ability of individuals with end-stage hip osteoarthritis. Methods Fifty-six patients scheduled to undergo unilateral total hip arthroplasty were included in this cross sectional analysis. Subjects completed the Hip Outcome Survey (HOS) and pain in the affected hip was quantified on a scale from 0–10. Performance-based tests included the Six Minute Walk (6MW), Timed Up and Go (TUG), and Stair Climbing Test (SCT). Isometric strength of the hip abductors and knee extensors was collected. Hierarchical linear regressions were created to determine the contributions of pain, knee extensor strength, and hip strength for each outcome measure (TUG, 6MW, SCT, HOS). Height and BMI were entered first, followed by pain, then knee extensor strength, then hip abduction strength. Results Greater pain significantly predicted lower HOS scores, but hip strength did not significantly improve the model. Hip pain was also significantly related to TUG, SCT and 6MW values, but hip and knee strength explained additional variance for these performance-based measures. Conclusions Self-report and performance-based measures capture different aspects of disability and are influenced by different underlying impairments. Both types of outcome measures should be used in studies that evaluate functional changes in patients with hip osteoarthritis. PMID:24664893

  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. Effect of incubation on freezability of cholesterol-loaded cyclodextrin treated buffalo (Bubalus bubalis) spermatozoa

    PubMed Central

    Lone, S. A.; Prasad, J. K.; Ghosh, S. K.; Das, G. K.; Balamurugan, B.; Katiyar, R.; Verma, M. R.

    2016-01-01

    Aim: The aim of this study was to investigate the effect of incubation on freezability of cholesterol loaded cyclodextrin (CLC) treated buffalo spermatozoa. Materials and Methods: Semen samples with mass motility of 3+ and greater, collected from Murrah buffalo bulls were utilized. Immediately after collection, four equal groups of semen sample were made. Group I was kept as control and diluted with Tris upto concentration of 60×106 sperm/ml, where as Groups II, III, and IV were treated with CLC at 3 mg/120× 106 spermatozoa, incubated at 37°C for action of CLC for 10, 15 and 20 min, respectively, and diluted with tris upto concentration of 60×106 sperm/ml. All groups were subjected to equilibration and freezing. The evaluation of semen samples from all groups was carried out at fresh, pre-freeze and post-thaw stage for progressive motility, viability and hypo-osmotic swelling response (HOS response). Results: At the pre-freeze stage, significantly (p<0.05) higher percentage of progressive motility and viability was observed in treatment groups as compared to control with no significant difference among treatment groups. HOS response was significantly (p<0.05) higher in treatment groups as compared to control at pre-freeze stage. At post-thaw stage, significantly (p<0.05) higher percentage of progressive motility, viability and HOS response was recorded in Group II as compared to control and other treatment groups (III and IV). Group II retained significant post-thaw motility and viability at various post-thaw incubation periods. Conclusion: Incubation period of 10 min for CLC treated buffalo spermatozoa yielded significantly higher results in terms of freezability as compared to incubation for 15 and 20 min. PMID:27051205

  2. Effects of the crude extract of Polygala tenuifolia Willd on human sperm in vitro.

    PubMed

    Qiu, Yi; Wang, Lei-guang; Jia, Yi-fang; Yang, Dan-tong; Zhang, Mei-hua; Zhang, Yan-ping; Zhang, Li-hong; Gai, Ling

    2011-06-01

    The aim of the present study is to analyze sperm membrane changes and the spermicidal effect in treatment with the crude extract from Polygala tenuifolia Willd (PTW) in vitro. The root of PTW was extracted in distilled water. Normal human spermatozoa were used to assess the spermicidal activity (Sander-Cramer assay) of the extract from the PTW root. The hypo-osmotic swelling (HOS) test and the eosin Y (EY) staining were used to detect the integrity of sperm membrane and vitality. The sperm chromatin dispersion (SCD) test was performed to determine sperm DNA integrity. N-9 was used as a reference standard and semen added to physiological saline was used as the control. Semen samples were donated by 42 healthy fertile men. The crude extract from the root of PTW could immobilize and kill 100% spermatozoa within 20 s in vitro at the concentrations of 20.0 and 10.0 mg/ml; at the concentration of 5.0 mg/ml, spermatozoa were immobilized in (39.5±3.2) s. In the groups of the crude extract from the root of PTW and N-9 solution, the rate of the normal HOS (tails swollen) and the white head (unstained) was 0%, and the rate of the abnormal HOS (tails unswollen) and red head (stained) was 100%. Sperm DNA fragmentation showed no change in exposure to the crude extract from the root of PTW and N-9 solution. The sperm revival test did not show any spermatozoa that recovered their motilities. The rapid spermicidal activity of the crude extract from the root of PTW in vitro may occur by the disruption of the sperm membrane integrity. PMID:21634037

  3. Microfracture in the hip: a matched-control study with average 3-year follow-up

    PubMed Central

    Lodhia, Parth; Gui, Chengcheng; Chandrasekaran, Sivashankar; Suarez-Ahedo, Carlos; Vemula, S. Pavan; Domb, Benjamin G.

    2015-01-01

    There is a paucity of literature regarding microfracture surgery in the hip. The purpose of this study was to compare outcomes in patients undergoing hip arthroscopy predominantly for labral tears with focal full thickness chondral damage on the acetabulum or femoral head treated with microfracture and a matched control group that did not have focal full thickness chondral damage. A prospective matched-control study was performed examining four patient-reported outcome (PRO) scores: modified Harris Hip Score (mHHS), non-arthritic hip score, Hip Outcome Score—Activities of Daily Living (HOS-ADL), and Hip Outcome Score—Sports Specific Subscale (HOS-SSS) at minimum 2 years post-operatively between 35 patients undergoing microfracture for chondral defects during hip arthroscopy and 70 patients in a control group that did not have chondral defects. The patients were matched based on gender, age within 7 years, Workman’s compensation claim, labral treatment and acetabular crossover percentage less than or greater than 20. There was no significant difference (P > 0.05) in PRO scores preoperatively between the groups. Both groups demonstrated significant improvement (P < 0.05) in all post-operative PRO scores at all time points. There was no statistically significant difference (P > 0.05) in post-operative PRO scores between the microfracture and control groups, except for HOS-ADL and the visual analog scale (VAS) score, both of which were superior in the control group (P < 0.05). Patient satisfaction was 6.9 for the microfracture group and 7.7 for the control group (P > 0.05). Arthroscopic microfracture of the hip during treatment of labral tears results in favorable outcomes that are similar to the results arthroscopic treatment of labral tears in patients without full thickness chondral damage. PMID:27011867

  4. Evaluation of muscle force classification using shape analysis of the sEMG probability density function: a simulation study.

    PubMed

    Ayachi, F S; Boudaoud, S; Marque, C

    2014-08-01

    In this work, we propose to classify, by simulation, the shape variability (or non-Gaussianity) of the surface electromyogram (sEMG) amplitude probability density function (PDF), according to contraction level, using high-order statistics (HOS) and a recent functional formalism, the core shape modeling (CSM). According to recent studies, based on simulated and/or experimental conditions, the sEMG PDF shape seems to be modified by many factors as: contraction level, fatigue state, muscle anatomy, used instrumentation, and also motor control parameters. For sensitivity evaluation against these several sources (physiological, instrumental, and neural control) of variability, a large-scale simulation (25 muscle anatomies, ten parameter configurations, three electrode arrangements) is performed, by using a recent sEMG-force model and parallel computing, to classify sEMG data from three contraction levels (20, 50, and 80% MVC). A shape clustering algorithm is then launched using five combinations of HOS parameters, the CSM method and compared to amplitude clustering with classical indicators [average rectified value (ARV) and root mean square (RMS)]. From the results screening, it appears that the CSM method obtains, using Laplacian electrode arrangement, the highest classification scores, after ARV and RMS approaches, and followed by one HOS combination. However, when some critical confounding parameters are changed, these scores decrease. These simulation results demonstrate that the shape screening of the sEMG amplitude PDF is a complex task which needs both efficient shape analysis methods and specific signal recording protocol to be properly used for tracking neural drive and muscle activation strategies with varying force contraction in complement to classical amplitude estimators. PMID:24961179

  5. 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

  6. 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

  7. Cathepsin H indirectly regulates morphogenetic protein-4 (BMP-4) in various human cell lines

    PubMed Central

    Rojnik, Matija; Jevnikar, Zala; Mirkovic, Bojana; Janes, Damjan; Zidar, Nace; Kikelj, Danijel; Kos, Janko

    2011-01-01

    Background Cathepsin H is a cysteine protease considered to play a major role in tumor progression, however, its precise function in tumorigenesis is unclear. Cathepsin H was recently proposed to be involved in processing of bone morphogenetic protein 4 (BMP-4) in mice. In order to clarify whether cathepsin H also regulates BMP-4 in humans, its impact on BMP-4 expression, processing and degradation was investigated in prostate cancer (PC-3), osteosarcoma (HOS) and pro-monocytic (U937) human cell lines. Materials and methods BMP-4 expression was founded to be regulated by cathepsin H using PCR array technology and confirmed by real time PCR. Immunoassays including Western blot and confocal microscopy were used to evaluate the influence of cathepsin H on BMP-4 processing. Results In contrast to HOS, the expression of BMP-4 mRNA in U937 and PC3 cells was significantly decreased by cathepsin H. The different regulation of BMP-4 synthesis could be associated with the absence of the mature 28 kDa cathepsin H form in HOS cells, where only the intermediate 30 kDa form was observed. No co-localization of BMP-4 and cathepsin H was observed in human cell lines and the multistep processing of BMP-4 was not altered in the presence of specific cathepsin H inhibitor. Isolated cathepsin H does not cleave mature recombinant BMP-4, neither with its amino- nor its endopeptidase activity. Conclusions Our results exclude direct proteolytic processing of BMP-4 by cathepsin H, however, they provide support for its involvement in the regulation of BMP-4 expression. PMID:22933963

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

    PubMed

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

    2013-04-01

    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 α-Ca(2+)/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca(2+)-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 (OS) cell lines [MG-63, N-methyl-N'-nitro-N-nitrosoguanidine (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 short hairpin RNA (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%), whereas α-CaMKII overexpression resulted in tumor formation in a previously nontumor 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. 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

  10. Hypoosmotic swelling test for quality control of sperm prepared for assisted reproduction.

    PubMed

    Mladenović, I; Mićić, S; Genbaćev, O; Papić, N

    1995-01-01

    This study evaluates the clinical usefulness of one additional parameter for assessment of human sperm cell function in vitro--the hypoosmotic swelling test. The hypoosmotic swelling test evaluated the functional integrity of the sperm plasma membrane. The investigation included a comparison of the hypoosmotic swelling test in samples containing motile and immotile spermatozoa and their correlation with the intrauterine insemination outcome. Motile spermatozoa expressed better membrane characteristics, without any importance of the hypoosmotic conditions. Positive correlation exists between HOS results and the outcome of IUI. This test can be a useful addition to the standard battery of semen analyzing tests. PMID:7625880

  11. 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

  12. 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.

  13. Recreational Athletes Return to Sport at a Comparable Rate to Elite Athletes Following Hip Arthroscopy for Femoroacetabular Impingement

    PubMed Central

    Weber, Alexander E.; Kuhns, Benjamin; Cvetanovich, Gregory; Levy, David; Nho, Shane Jay

    2016-01-01

    Objectives: The objective of the current study was to evaluate patient reported outcomes and return to sport in a cohort of distinctly recreational and amateur level athletes following hip arthroscopy for femoroacetabular impingement (FAI). Methods: Following IRB approval, clinical data was retrospectively retrieved for 66 consecutive FAI patients (26 men, 40 women) who had undergone hip arthroscopy and identified themselves as recreational or amateur athletes on intake forms. Two-year patient-reported outcomes (PRO) included 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 analyzed. Results: The mean age and BMI of all subjects was 26.8 ± 7.6 years and 23.9 ± 3.2 kg/m2, respectively. Athletes had withdrawn from sport for an average of 9.5 ± 6.7 months prior to surgery and on average required 9.7 ± 5.1 months to return to sport. After two years, all mean PRO scores had improved significantly (Figure 1), and 57 patients (92%) had returned to play and continued participation. Patients who had withdrawn from sport for greater than 8 months before surgery returned to sport significantly more slowly than those who had withdrawn for less than 8 months (p=0.01). Greater withdrawal from sport prior to surgery also correlated with lower postoperative improvements in HOS-ADL and HOS-SS scores. Bivariate analysis revealed that increasing body-mass index (BMI) was associated with lower improvements in PROs. Conclusion: Recreational athletes, following hip arthroscopy for FAI, return to play at a high rate. Increasing BMI and preoperative withdrawal from sport both significantly prolong return to play and diminish two-year PROs. Most return-to-play studies following hip arthroscopy for FAI have focused on professional athletes, with limited generalizability to the average sports medicine surgeon practice. This is the first study of its kind to focus

  14. 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.

  15. Shubnikov-de Haas oscillations in a two-dimensional electron gas under subterahertz radiation

    NASA Astrophysics Data System (ADS)

    Shi, Q.; Martin, P. D.; Hatke, A. T.; Zudov, M. A.; Watson, J. D.; Gardner, G. C.; Manfra, M. J.; Pfeiffer, L. N.; West, K. W.

    2015-08-01

    We report on magnetotransport measurements in a two-dimensional (2D) electron gas subject to subterahertz radiation in the regime where Shubnikov-de Haas oscillations (SdHOs) and microwave-induced resistance oscillations (MIROs) coexist over a wide magnetic field range, spanning several harmonics of the cyclotron resonance. Surprisingly, we find that the SdHO amplitude is modified by the radiation in a nontrivial way, owing to the oscillatory correction which has the same period and phase as MIROs. This finding challenges our current understanding of microwave photoresistance in 2D electron gas, calling for future investigations.

  16. High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F2α concentrations relative to a control high–oleic acid meal: a randomized controlled trial1234

    PubMed Central

    Purcell, Robert; Latham, Sally H; Botham, Kathleen M; Hall, Wendy L; Wheeler-Jones, Caroline PD

    2014-01-01

    Background: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear. Objectives: The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high–oleic acid meals; the secondary objective was to characterize the effects of linoleic acid–enriched high-fat meals relative to the control meal. Design: We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high–oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high–linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35–70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.9 ± 0.5 mmol/L). Results: Elevations in triacylglycerol concentration relative to baseline were slightly reduced after FO and HLS compared with the HOS control (P < 0.05). The characteristic decrease from baseline in plasma nonesterified fatty acids after a mixed meal was inhibited after AO (Δ 0–3 h, P < 0.05). HLS increased the augmentation index compared with the other test meals (P < 0.05), although the digital volume pulse–reflection index was not significantly different. Plasma 8-isoprostane F2α analysis revealed opposing effects of FO (increased) and AO (reduced) compared with the control (P < 0.05). No differences in nitric oxide metabolites were observed. Conclusions: These data show differential postprandial 8-isoprostane F2α responses to high-fat meals containing EPA + DHA–rich fish oil compared with DHA-rich AO, but these differences were not associated with consistent effects on postprandial vascular function or lipemia. More detailed analyses of polyunsaturated fatty acid–derived lipid mediators are required to determine possible

  17. ‘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

  18. 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

  19. Effects of dietary n-3 fatty acids and vitamin C on semen characteristics, lipid composition of sperm and blood metabolites in fat-tailed Moghani rams.

    PubMed

    Jafaroghli, M; Abdi-Benemar, H; Zamiri, M J; Khalili, B; Farshad, A; Shadparvar, A A

    2014-06-10

    Sixteen fertile rams were randomly allotted to four groups and fed either of the four diets for 14 weeks: (1) control diet (COD) without fish oil (FO) and vitamin C (VC), (2) diet containing 2.5% FO (FOD), (3) diet containing 300 mg/kg DM VC (VCD), and (4) diet containing 2.5% FO and 300 mg/kg DM VC (FCD). Semen was collected at 14-d intervals from 1 April to 10 July (out of the physiologic breeding season in Iran). Semen volume and percentages of motile and progressively motile sperm were increased by FO and VC feeding. A significant interaction was also found between FOD and VCD on motility and progressive motility percentage (P<0.05). HOS-test and percentage of sperm with normal acrosome improved significantly by FO and VC. Rams fed FCD had better HOS-test and higher proportion of sperm with normal acrosome than rams in other groups (82.4 and 93.6%, respectively). Diets containing FO and FO and VC increased the proportion of docosahexaenoic acid in sperm (P<0.05). The activity of lactate dehydrogenase in the seminal fluid was significantly affected by VC and the interaction between FO and VC (P<0.05). Blood metabolites, except glucose, were affected positively by FO. The results showed that dietary supplementation with FO and VC improved seminal quality and may have beneficial effects on fertility in Moghani rams. PMID:24745668

  20. Proliferation and harvest of human mesenchymal stem cells using new thermoresponsive nanocomposite gels.

    PubMed

    Kotobuki, Noriko; Murata, Kazutaka; Haraguchi, Kazutoshi

    2013-02-01

    For tissue engineering and regenerative medicine, stem cells should be effectively cultured in vitro. New thermoresponsive nanocomposite gels (MD-NC gels), consisting of inorganic clay (hectorite) and copolymers composed of hydrophobic 2-methoxyethyl acrylate (MEA) and hydrophilic N,N-dimethylacrylamide (DMAA) units, could be applied in cell culture and cell harvesting without trypsinization, specifically using mesenchymal stem cells (MSCs). The composition of the MD-NC gel (the ratio of the two monomer types and the clay content) was found to determine its swelling properties in the culture medium, thermosensitivity, protein adsorption, and cell attachment and proliferation. Various kinds of human cells, including MSCs, osteoblast (HOS) cells, fibroblast (NHDF) cells, and epithelial cells could be effectively cultured on MD-NC gels. In particular, on an MD10-NC2 gel with relatively low DMAA and clay content, the cells could be harvested by decreasing the temperature, either as a cell sheet (MSCs or NHDF cells) or as a population of suspension cells (HOS cells). Further, it was found that the MD10-NC2 gel is suitable for stem cell differentiation. Because of their thermosensitivity, controllable modulus, and surface properties, MD-NC gels are promising cell culture substrates useful for tissue engineering and regenerative medicine. PMID:22926940

  1. 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. PMID:24411382

  2. 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. PMID:26679163

  3. 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/sec to less than 1.0 C/sec 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. 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. 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. The HOS-875 and the TD-Ni did not spall during either type of cooling. Thus, the effect of thermal shock on spalling is determined, in large part, by the mechanical properties of the metal.

  4. 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. PMID:22928866

  5. Wettability and cellular response of UV light irradiated anodized titanium surface

    PubMed Central

    Park, Kyou-Hwa; Koak, Jai-Young; Kim, Seong-Kyun

    2011-01-01

    PURPOSE The object of this study was to investigate the effect of UV irradiation (by a general commercial UV sterilizer) on anodized titanium surface. Surface characteristics and cellular responses were compared between anodized titanium discs and UV irradiated anodized titanium discs. MATERIALS AND METHODS Titanium discs were anodized and divided into the following groups: Group 1, anodized (control), and Group 2, anodized and UV irradiated for 24 hours. The surface characteristics including contact angle, roughness, phase of oxide layer, and chemical elemental composition were inspected. The osteoblast-like human osteogenic sarcoma (HOS) cells were cultured on control and test group discs. Initial cellular attachment, MTS-based cell proliferation assay, and ALP synthesis level were compared between the two groups for the evaluation of cellular response. RESULTS After UV irradiation, the contact angle decreased significantly (P<.001). The surface roughness and phase of oxide layer did not show definite changes, but carbon showed a considerable decrease after UV irradiation. Initial cell attachment was increased in test group (P=.004). Cells cultured on test group samples proliferated more actively (P=.009 at day 2, 5, and 7) and the ALP synthesis also increased in cells cultured on the test group (P=.016 at day 3, P=.009 at day 7 and 14). CONCLUSION UV irradiation induced enhanced wettability, and increased initial cellular responses of HOS cells on anodized titanium surface. PMID:21814613

  6. Swarm intelligence for detecting interesting events in crowded environments.

    PubMed

    Kaltsa, Vagia; Briassouli, Alexia; Kompatsiaris, Ioannis; Hadjileontiadis, Leontios J; Strintzis, Michael Gerasimos

    2015-07-01

    This paper focuses on detecting and localizing anomalous events in videos of crowded scenes, i.e., divergences from a dominant pattern. Both motion and appearance information are considered, so as to robustly distinguish different kinds of anomalies, for a wide range of scenarios. A newly introduced concept based on swarm theory, histograms of oriented swarms (HOS), is applied to capture the dynamics of crowded environments. HOS, together with the well-known histograms of oriented gradients, are combined to build a descriptor that effectively characterizes each scene. These appearance and motion features are only extracted within spatiotemporal volumes of moving pixels to ensure robustness to local noise, increase accuracy in the detection of local, nondominant anomalies, and achieve a lower computational cost. Experiments on benchmark data sets containing various situations with human crowds, as well as on traffic data, led to results that surpassed the current state of the art (SoA), confirming the method's efficacy and generality. Finally, the experiments show that our approach achieves significantly higher accuracy, especially for pixel-level event detection compared to SoA methods, at a low computational cost. PMID:25769154

  7. Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis

    PubMed Central

    Takagi, Satoshi; Takemoto, Ai; Takami, Miho; Oh-hara, Tomoko; Fujita, Naoya

    2014-01-01

    The interactions of tumor cells with platelets contribute to the progression of tumor malignancy, and the expression levels of platelet aggregation-inducing factors positively correlate with the metastatic potential of osteosarcoma cells. However, it is unclear how tumor-platelet interaction contributes to the proliferation of osteosarcomas. We report here that osteosarcoma-platelet interactions induce the release of platelet-derived growth factor (PDGF) from platelets, which promotes the proliferation of osteosarcomas. Co-culture of platelets with MG63 or HOS osteosarcoma cells, which could induce platelet aggregation, enhanced the proliferation of each cell line in vitro. Analysis of phospho-antibody arrays revealed that co-culture of MG63 cells with platelets induced the phosphorylation of platelet derived growth factor receptor (PDGFR) and Akt. The addition of supernatants of osteosarcoma-platelet reactants also increased the growth of MG63 and HOS cells as well as the level of phosphorylated-PDGFR and -Akt. Sunitinib or LY294002, but not erlotinib, significantly inhibited the platelet-induced proliferation of osteosarcoma cells, indicating that PDGF released from platelets plays an important role in the proliferation of osteosarcomas by activating the PDGFR and then Akt. Our results suggest that inhibitors that specifically target osteosarcoma-platelet interactions may eradicate osteosarcomas. PMID:24974736

  8. Holt-Oram syndrome: a clinical genetic study.

    PubMed Central

    Newbury-Ecob, R A; Leanage, R; Raeburn, J A; Young, I D

    1996-01-01

    A clinical and genetic study of the Holt-Oram syndrome (HOS) has been carried out in the United Kingdom involving 55 cases designated Holt-Oram syndrome, together with their parents and sibs. Data from the clinical assessment of both familial and isolated cases were used to define the HOS phenotype and to outline the spectrum of abnormalities, especially factors affecting severity. Skeletal defects affected the upper limbs exclusively and were bilateral and asymmetrical. They ranged from minor signs such as clinodactyly, limited supination, and sloping shoulders to severe reduction deformities of the upper arm (4.5%). The radial ray was predominantly affected than the right. All affected cases showed evidence of upper limb involvement. Cardiac defects were seen in 95% of familial cases and included both atrial septal defect (ASD, 34%) and ventricular septal defect (VSD, 25%); 39% had only ECG changes. Cardiac involvement ranged from asymptomatic conduction disturbances to multiple structural defects requiring surgery in infancy. Sudden death could be caused by heart block. Inheritance was autosomal dominant with 100% penetrance and no evidence of reduced fitness. Increasing severity occurred in succeeding generations consistent with anticipation. Images PMID:8730285

  9. Diallyl trisulfide induces osteosarcoma cell apoptosis through reactive oxygen species-mediated downregulation of the PI3K/Akt pathway.

    PubMed

    Wang, Hongliang; Sun, Na; Li, Xin; Li, Ka; Tian, Jiguang; Li, Jianmin

    2016-06-01

    Diallyl trisulfide (DATS) is a natural organosulfur compound isolated from garlic, and has been reported to possess anticancer activities. However, the cancer growth inhibitory effects and molecular mechanisms in human osteosarcoma cells have not been well studied. The present study demonstrated that DATS significantly reduced cell viability in a dose- and time-dependent manner in MG63 and MNNG/HOS cells. DATS-induced G0/G1 phase arrest was found to correlate with a decrease in cyclin D1 in concomitance with an increase in p21 and p27. DATS induced a marked increase in reactive oxygen species (ROS) levels and collapse of mitochondrial membrane potential (Δψm) in the osteosarcoma cells. DATS induced apoptosis in the MG63 and MNNG/HOS cells via inhibition of the PI3K/Akt signaling pathway and through the mitochondrial apoptotic pathway. The efficiency of DATS basically approached the efficacy of LY294002, a specific PI3K inhibitor. However, N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the DATS-induced ROS increase, inhibition of the PI3K/Akt pathway and cell apoptosis. Overall, DATS has the potential to be developed as a new anticancer drug. The mechanisms of action involve the ROS-mediated downregulation of the PI3K/Akt pathway. PMID:27035545

  10. 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

  11. 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.

  12. 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

  13. Application of higher-order spectra for automated grading of diabetic maculopathy.

    PubMed

    Mookiah, Muthu Rama Krishnan; Acharya, U Rajendra; Chandran, Vinod; Martis, Roshan Joy; Tan, Jen Hong; Koh, Joel E W; Chua, Chua Kuang; Tong, Louis; Laude, Augustinus

    2015-12-01

    Diabetic macular edema (DME) is one of the most common causes of visual loss among diabetes mellitus patients. Early detection and successive treatment may improve the visual acuity. DME is mainly graded into non-clinically significant macular edema (NCSME) and clinically significant macular edema according to the location of hard exudates in the macula region. DME can be identified by manual examination of fundus images. It is laborious and resource intensive. Hence, in this work, automated grading of DME is proposed using higher-order spectra (HOS) of Radon transform projections of the fundus images. We have used third-order cumulants and bispectrum magnitude, in this work, as features, and compared their performance. They can capture subtle changes in the fundus image. Spectral regression discriminant analysis (SRDA) reduces feature dimension, and minimum redundancy maximum relevance method is used to rank the significant SRDA components. Ranked features are fed to various supervised classifiers, viz. Naive Bayes, AdaBoost and support vector machine, to discriminate No DME, NCSME and clinically significant macular edema classes. The performance of our system is evaluated using the publicly available MESSIDOR dataset (300 images) and also verified with a local dataset (300 images). Our results show that HOS cumulants and bispectrum magnitude obtained an average accuracy of 95.56 and 94.39% for MESSIDOR dataset and 95.93 and 93.33% for local dataset, respectively. PMID:25894464

  14. 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.

  15. 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.

  16. PRE- AND POST-OPERATIVE SELF-REPORTED FUNCTION AND QUALITY OF LIFE IN WOMEN WITH AND WITHOUT GENERALIZED JOINT LAXITY UNDERGOING HIP ARTHROSCOPY FOR FEMOROACETABULAR IMPINGEMENT

    PubMed Central

    Pontiff, Mattie; Ithurburn, Matthew P.; Ellis, Thomas; Cenkus, Kathleen

    2016-01-01

    ABSTRACT Background Generalized joint laxity is more prevalent in women than men and may lead to poorer post-operative outcomes in select orthopedic populations. There are no studies examining peri-operative function in patients with generalized joint laxity (GJL) and femoroacetabular impingement (FAI). Purpose The purpose of this study was to determine the difference in perceived function and quality of life as measured by the Hip Outcome Score ADL subscale (HOS-ADL), International Hip Outcomes Tool (iHOT-33) and the Short Form 12-Item Health Survey (SF-12) in women with and without GJL prior to and six months after undergoing hip arthroscopy for FAI. Study Design Cohort Study Methods Peri-operative data were collected from women with FAI from November 2011-September 2014. Lax subjects were women with laxity scores ≥4/9 on the Beighton and Horan Joint Mobility Index; Nonlax subjects were women with laxity scores <4/9. Functional outcomes were evaluated using the HOS-ADL, iHOT-33, PCS-12, and the MCS-12 pre-operatively and at 6 months post-operatively. Change scores (post-score – pre-score) were calculated for each outcome measure and compared between groups, along with pre-operative and post-operative means, using Mann-Whitney U tests. Results 166 women met the inclusion criteria: Nonlax (n = 131), Lax (n = 35). There were no statistically significant differences between groups in pre-operative functional outcomes (all p > .05). Additionally, there were no statistically significant differences between groups in post-operative means or change scores, respectively, for HOS-ADL (p = .696, .358), iHOT-33 (p = .550, .705), PCS-12 (p = .713, .191), and MCS-12 (p = .751, .082). Laxity score was not associated with any post-operative functional outcome score or change score (all p > .05). Conclusion Women with and without generalized joint laxity do not appear to report differences in hip function in the 6-month peri-operative period before and after hip

  17. 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

  18. Human T-cell leukemia virus type 1 infection leads to arrest in the G1 phase of the cell cycle.

    PubMed

    Liu, Meihong; Yang, Liangpeng; Zhang, Ling; Liu, Baoying; Merling, Randall; Xia, Zheng; Giam, Chou-Zen

    2008-09-01

    Infection by the human T-cell leukemia virus type 1 (HTLV-1) is thought to cause dysregulated T-cell proliferation, which in turn leads to adult T-cell leukemia/lymphoma. Early cellular changes after HTLV-1 infection have been difficult to study due to the poorly infectious nature of HTLV-1 and the need for cell-to-cell contact for HTLV-1 transmission. Using a series of reporter systems, we show that HeLa cells cease proliferation within one or two division cycles after infection by HTLV-1 or transduction of the HTLV-1 tax gene. HTLV-1-infected HeLa cells, like their tax-transduced counterparts, expressed high levels of p21(CIP1/WAF1) and p27(KIP1), developed mitotic abnormalities, and became arrested in G(1) in senescence. In contrast, cells of a human osteosarcoma lineage (HOS) continued to divide after HTLV-1 infection or Tax expression, albeit at a reduced growth rate and with mitotic aberrations. Unique to HOS cells is the dramatic reduction of p21(CIP1/WAF1) and p27(KIP1) expression, which is in part associated with the constitutive activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) pathway. The loss of p21(CIP1/WAF1) and p27(KIP1) in HOS cells apparently allows HTLV-1- and Tax-induced G(1) arrest to be bypassed. Finally, HTLV-1 infection and Tax expression also cause human SupT1 T cells to arrest in the G(1) phase of the cell cycle. These results suggest that productive HTLV-1 infection ordinarily leads to Tax-mediated G(1) arrest. However, T cells containing somatic mutations that inactivate p21(CIP1/WAF1) and p27(KIP1) may continue to proliferate after HTLV-1 infection and Tax expression. These infected cells can expand clonally, accumulate additional chromosomal abnormalities, and progress to cancer. PMID:18596104

  19. Gold(I) complexes of 9-deazahypoxanthine as selective antitumor and anti-inflammatory agents.

    PubMed

    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

  20. 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

  1. Crystallographic and Spectroscopic Insights into Heme Degradation by Mycobacterium tuberculosis MhuD

    PubMed Central

    2015-01-01

    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 1H 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 1H NMR spectrum of MhuD–heme–CN is consistent with population of both a 2Eg electronic state with a (dxy)2(dxz,dyz)3 electron configuration, similar to the ground state of canonical HOs, and a 2B2g 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 2B2g electronic ground state with a low-lying 2Eg 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. PMID

  2. Inhibition of Plastocyanin to P700+ Electron Transfer in Chlamydomonas reinhardtii by Hyperosmotic Stress1

    PubMed Central

    Cruz, Jeffrey A.; Salbilla, Brian A.; Kanazawa, Atsuko; Kramer, David M.

    2001-01-01

    Oxygen electrode and fluorescence studies demonstrate that linear electron transport in the freshwater alga Chlamydomonas reinhardtii can be completely abolished by abrupt hyperosmotic shock. We show that the most likely primary site of inhibition of electron transfer by hyperosmotic shock is a blockage of electron transfer between plastocyanin (PC) or cytochrome c6 and P700. The effects on this reaction were reversible upon dilution of the osmolytes and the stability of plastocyanin or photosystem (PS) I was unaffected. Electron micrographs of osmotically shocked cells showed a significant decrease in the thylakoid lumen volume. Comparison of estimated lumenal width with the x-ray structures of plastocyanin and PS I suggest that lumenal space contracts during HOS so as to hinder the movement of docking to PS I of plastocyanin or cytochrome c6. PMID:11706196

  3. Establishment of a cell line producing bone morphogenetic protein from a human osteosarcoma.

    PubMed

    Takaoka, K; Yoshikawa, H; Masuhara, K; Sugamoto, K; Tsuda, T; Aoki, Y; Ono, K; Sakamoto, Y

    1989-07-01

    A human osteosarcoma cell line was established from a biopsy specimen from a 13-year-old girl. The osteosarcoma tissue was maintained in athymic nude mice (Balb C nu/nu) by serial transplantation for three years. The tumor was excised from a host mouse and digested with collagenase. The isolated cells were cultured by 98 passages in 14 months, and clones of osteosarcoma cells were obtained by limiting dilution. A clone named human osteosarcoma cell 6 (H-OS-6) that showed the osteoblastic phenotypes of productions of bone morphogenetic protein (BMP) and alkaline phosphatase and a response to human parathyroid hormone (h-PTH 1-34) was selected. The morphology of its chromosomes indicated its human origin. This human osteosarcoma cell line is unique in producing BMP under in vitro conditions. PMID:2545399

  4. The rovibrational nature of closed-shell third-row triatomics: HOX and HXO, X = Si+, P, S+, and Cl

    NASA Astrophysics Data System (ADS)

    Kitchens, Mason J. R.; Fortenberry, Ryan C.

    2016-06-01

    Atmospheric and even interstellar chemistry are dominated by the presence of small molecules. This work examines closed-shell, triatomic, hydroxide molecules containing a single third-row atom: HOSi+, HSiO+, HPO, HOS+, HSO+, HOCl, and HClO as well as their deuterated isotopologues and those with 37Cl. The use of proven composite energy-defined quartic force fields is further benchmarked where experimental data is known in order to provide an estimate for the accuracy of other previously unknown values for these and even previously unexamined species. Rotational constants within 1 MHz and vibrational frequencies within 1 cm-1 of experiment are produced in some cases with typical comparison around 50 MHz and 10 cm-1, respectively. As such the remaining previously unreported geometries, spectroscopic constants, vibrational frequencies, and dipole moments will enhance the spectroscopic analysis of any environment, terrestrially or astronomically, where the properties of these molecules may serve better to inform the chemistry of these regions.

  5. Biology of MET: a double life between normal tissue repair and tumor progression

    PubMed Central

    2015-01-01

    MNNG HOS transforming gene (MET) is a class IV receptor tyrosine kinase, expressed on the surface of epithelial cells. The interaction with the hepatocyte grow factor (HGF) induces MET dimerization and the activation of multiple intracellular pathways leading to cell proliferation, anti-apoptosis, morphogenic differentiation, motility, invasion, and angiogenesis. Knock out mice have demonstrated that MET is necessary for normal embryogenesis including the formation of striate muscles, liver and trophoblastic structures. The overexpression of MET and HGF are common in solid tumors and contribute to determine their growth. Indeed, MET has been cloned as a transforming gene from a chemically induced human osteosarcoma cell line and therefore is considered a proto-oncogene. Germline MET mutations are characteristic of hereditary papillary kidney cancers and MET amplification is observed in tumors including lung and gastric adenocarcinomas. The inhibition of MET signaling is the target for specific drugs that are raising exciting expectation for medical treatment of cancer. PMID:25992381

  6. Diabetes and alcohol: Double jeopardy with regard to oxidative toxicity and sexual dysfunction in adult male Wistar rats.

    PubMed

    Himabindu, B; Madhu, P; Reddy, P Sreenivasula

    2015-01-01

    The aim of this study was to test whether diabetic rats exposed to alcohol demonstrate a higher degree of reproductive toxicity and suffer with elevated oxidative toxicity when compared with alcohol exposed control rats. Diabetes was induced by injecting single dose of streptozotocin and alcohol was administered through orogastric tube once daily for a period of 55 days. Daily sperm production, epididymal sperm count, motile, viable and HOS-tail coiled sperms, serum testosterone levels and testicular 3β- and 17β-hydroxysteroid dehydrogenase activity levels were significantly decreased in diabetic rats. Significant reduction in testicular and epididymal superoxide dismutase and catalase activity levels, and elevation in lipid peroxidation products were observed in diabetic rats. Similar reproductive and oxidative toxicity was observed in alcohol treated control rats. Further, alcohol exposed diabetic rats showed additional deterioration in reproductive endpoints and noteworthy elevation in oxidative toxicity suggesting that treatment with alcohol further deteriorates sexual dysfunction in STZ-induced diabetic rats. PMID:25541261

  7. Fine-structure map of the histidine transport genes in Salmonella typhimurium.

    PubMed Central

    Ames, G F; Noel, K D; Taber, H; Spudich, E N; Nikaido, K; Afong, J

    1977-01-01

    Afine-structure genetic map of the histidine transport region of the Salmonella typhimurium chromosome was constructed. Twenty-five deletion mutants were isolated and used for dividing the hisJ and hisP genes into 8 and 13 regions respectively. A total of 308 mutations, spontaneous and mutagen induced, have been placed in these regions by deletion mapping. The histidine transport operon is presumed to be constituted of genes dhuA, hisJ, and hisP, and the regulation of the hosP and hisJ genes by dhuA is discussed. The orientation of this operon relative to purF has been established by three-point crosses as being: purF duhA hisJ hisP. PMID:321422

  8. Fine-structure map of the histidine transport genes in Salmonella typhimurium.

    PubMed

    Ames, G F; Noel, K D; Taber, H; Spudich, E N; Nikaido, K; Afong, J

    1977-03-01

    Afine-structure genetic map of the histidine transport region of the Salmonella typhimurium chromosome was constructed. Twenty-five deletion mutants were isolated and used for dividing the hisJ and hisP genes into 8 and 13 regions respectively. A total of 308 mutations, spontaneous and mutagen induced, have been placed in these regions by deletion mapping. The histidine transport operon is presumed to be constituted of genes dhuA, hisJ, and hisP, and the regulation of the hosP and hisJ genes by dhuA is discussed. The orientation of this operon relative to purF has been established by three-point crosses as being: purF duhA hisJ hisP. PMID:321422

  9. Design of biomaterials for intracellular delivery of carbon monoxide.

    PubMed

    Inaba, Hiroshi; Fujita, Kenta; Ueno, Takafumi

    2015-11-01

    Carbon monoxide (CO) is recognized as one of the most important gas signaling molecules involved in governing various therapeutic responses. Intracellular generation of CO is spatiotemporally controlled by catalytic reactions of heme oxygenases (HOs). Thus, the ability to control intracellular CO delivery with modulation of the CO-release rate in specific amounts and locations is expected to improve our fundamental understanding of the functions of CO and the development of clinical applications. For this purpose, CO-releasing molecules (CORMs) have been developed and investigated in vitro and in vivo. Most CORMs are based on transition metal carbonyl complexes. Recently, various biomaterials consisting of metal carbonyls with biomacromolecular scaffolds have been reported to improve the properties of bare metal carbonyls. In this mini-review, current progress in CO delivery, recent strategies for the development of CORMs, and future directions in this field are discussed. PMID:26252321

  10. Hospital planning for weapons of mass destruction incidents.

    PubMed

    Perry, Ronald W; Lindell, Michael K

    2007-01-01

    As terrorist attacks increase in fre-quency, hospital disaster plans need to be scrutinized to ensure that they take into account issues unique to weapons of mass destruction. This paper reports a review of the literature addressing hospital experiences with such incidents and the planning lessons thus learned. Construction of hos-pital disaster plans is examined as an ongoing process guided by the disaster planning committee. A review is completed of six special elements of weapons of mass destruction incidents that should be addressed in hospital disaster plans. The paper closes with a dis-cussion of the importance of train-ing and exercises in maintaining and improving the disaster plan. PMID:17970447

  11. 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.

  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. PMID:20433058

  13. 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.

  14. 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.

  15. Entropy analysis of muscular near-infrared spectroscopy (NIRS) signals during exercise programme of type 2 diabetic patients: quantitative assessment of muscle metabolic pattern.

    PubMed

    Molinari, Filippo; Acharya, U Rajendra; Martis, Roshan Joy; De Luca, Riccardo; Petraroli, Giuliana; Liboni, William

    2013-12-01

    Diabetes mellitus (DM) is a metabolic disorder that is widely rampant throughout the world population these days. The uncontrolled DM may lead to complications of eye, heart, kidney and nerves. The most common type of diabetes is the type 2 diabetes or insulin-resistant DM. Near-infrared spectroscopy (NIRS) technology is widely used in non-invasive monitoring of physiological signals. Three types of NIRS signals are used in this work: (i) variation in the oxygenated haemoglobin (O2Hb) concentration, (ii) deoxygenated haemoglobin (HHb), and (iii) ratio of oxygenated over the sum of the oxygenated and deoxygenated haemoglobin which is defined as: tissue oxygenation index (TOI) to analyze the effect of exercise on diabetes subjects. The NIRS signal has the characteristics of non-linearity and non-stationarity. Hence, the very small changes in this time series can be efficiently extracted using higher order statistics (HOS) method. Hence, in this work, we have used sample and HOS entropies to analyze these NIRS signals. These computer aided techniques will assist the clinicians to diagnose and monitor the health accurately and easily without any inter or intra observer variability. Results showed that after a one-year of physical exercise programme, all diabetic subjects increased the sample entropy of the NIRS signals, thus revealing a better muscle performance and an improved recruitment by the central nervous system. Moreover, after one year of physical therapy, diabetic subjects showed a NIRS muscular metabolic pattern that was not distinguished from that of controls. We believe that sample and bispectral entropy analysis is need when the aim is to compare the inner structure of the NIRS signals during muscle contraction, particularly when dealing with neuromuscular impairments. PMID:24075080

  16. 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

  17. 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. PMID:15925576

  18. Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma

    PubMed Central

    Lamoureux, Francois; Baud'huin, Marc; Ory, Benjamin; Guiho, Romain; Zoubeidi, Amina; Gleave, Martin; Heymann, Dominique; Rédini, Françoise

    2014-01-01

    Purpose Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid (ZOL) represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, ZOL triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), which could enhance tumor cell survival and treatment resistance. We hypothesized that targeting CLU using siRNA or the antisense drug, OGX-011, will suppress treatment-induced CLU induction and enhance ZOL-induced cell death in osteosarcoma (OS) cells. Methods The combined effects of OGX-011 and ZOL were investigated in vitro on cell growth, viability, apoptosis and cell cycle repartition of ZOL-sensitive or -resistant human OS cell lines (SaOS2, U2OS, MG63 and MNNG/HOS). Results In OS cell lines, ZOL increased levels of HSPs, especially CLU, in a dose- and time-dependent manner by mechanism including increased HSF1 transcription activity. The OS resistant cells to ZOL exhibited higher CLU expression level than the sensitive cells. Moreover, CLU overexpression protects OS sensitive cells to ZOL-induced cell death by modulating the MDR1 and farnesyl diphosphate synthase expression. OGX-011 suppressed treatment-induced increases in CLU and synergistically enhanced the activity of ZOL on cell growth and apoptosis. These biologic events were accompanied by decreased expression of HSPs, MDR1 and HSF1 transcriptional activity. In vivo, OGX-011, administered 3 times a week (IP, 20mg/kg), potentiated the effect of ZOL (s.c; 50μg/kg), significantly inhibiting tumor growth by 50% and prolonging survival in MNNG/HOS xenograft model compared to ZOL alone. Conclusion These results indicate that ZOL-mediated induction of CLU can be attenuated by OGX-011, with synergistic effects on delaying progression of

  19. 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. PMID:26750098

  20. 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.

  1. 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

  2. Molecular perspective of antibody aggregates and their adsorption on Protein A resin.

    PubMed

    Yu, Deqiang; Song, Yuanli; Huang, Richard Y-C; Swanson, Ryan K; Tan, Zhijun; Schutsky, Elizabeth; Lewandowski, Angela; Chen, Guodong; Li, Zheng Jian

    2016-07-29

    Antibody aggregate is a common issue in therapeutic antibodies, which may compromise product efficacy and cause adverse effects. Antibody aggregate level is normally controlled in bioprocessing by polishing steps after Protein A capture. This paper studied the Higher Order Structures (HOS) of antibody aggregates (dimer H1 and H2) and their adsorption on Protein A resin and thus elucidated the mechanism using Protein A capture for enhanced aggregate removal. The HOS of antibody aggregates and their complex with Protein A were characterized using HDX-MS combined with SEC-MALS, Protein Conformational Array (PCA), and molecular modeling. The aggregate size and Protein A binding ratio suggested that H2 has much more compact structure than H1. HDX-MS and PCA further revealed that H1 was formed by single Fab-Fab interaction while H2 formed by Fab-Fab and likely Fc-Fc interaction. On Protein A resin, both the molar binding ratio and the correlation between protein size and ligand distance support that each monomer can only bind one Protein A ligand, while each dimer can bind two ligands, thus resulting in stronger resin binding. Furthermore, dimer H2 binds stronger than dimer H1 due to its compact structure. By integrating biophysical analysis and molecular modeling with process development, this study revealed the antibody aggregate structures and the mechanism of aggregate removal using Protein A chromatography. It also provided a general strategy for in-depth product and process understanding in antibody and other biologics development. PMID:27344283

  3. A high-fat meal enriched with eicosapentaenoic acid reduces postprandial arterial stiffness measured by digital volume pulse analysis in healthy men.

    PubMed

    Hall, Wendy L; Sanders, Katie A; Sanders, Thomas A B; Chowienczyk, Philip J

    2008-02-01

    Diets rich in eicosapentaenoic acid [EPA; 20:5(n-3)] are associated with decreased arterial stiffness, but postprandial effects on vascular function are unknown. We investigated whether an EPA-enriched high-fat meal could improve postprandial vascular function. Seventeen healthy men ingested 2 test meals (51 g fat), 1 wk apart, in random order: 5 g EPA plus high-oleic sunflower oil (HOS) vs. HOS only. A second high-fat meal (44 g fat), the same on both study days, was provided 4 h later. Blood pressure and arterial function were measured using digital volume pulse (DVP) to derive a stiffness index (DVP-SI) and reflection index in fasting subjects at 3 and 6 h following the test meal. Blood samples were taken following the test meal for plasma 8-isoprostane F2alpha, nitric oxide (NO) metabolites (NOx), glucose, insulin, triacylglycerol, and fatty acid analysis. The plasma EPA concentration (mean +/- SD) reached a peak of 2.10 +/- 0.99 mmol/L following the EPA meal (5 h) and did not rise above 0.27 +/- 0.16 mmol/L 1 h following the placebo meal. DeltaDVP-SI did not differ between the 2 test meals at 3 h but was greater at 6 h following EPA (6 h -0.65 +/- 0.65 m/s) compared with placebo (6 h -0.33 +/- 1.26 m/s). Plasma 8-isoprostane F2alpha concentrations increased by 48% at 6 h compared with baseline following the EPA meal and plasma NOx decreased following both meals, with no differences between the meals in the changes. Changes in other variables measured also did not differ after subjects consumed the 2 meals. In conclusion, adding EPA to a high-fat meal results in acute changes in vascular tone, independent of changes in oxidative stress. PMID:18203893

  4. 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. PMID:27111123

  5. The Semen pH Affects Sperm Motility and Capacitation

    PubMed Central

    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. PMID:26173069

  6. 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

  7. Prostate tissue characterization/classification in 144 patient population using wavelet and higher order spectra features from transrectal ultrasound images.

    PubMed

    Pareek, Gyan; Acharya, U Rajendra; Sree, S Vinitha; Swapna, G; Yantri, Ratna; Martis, Roshan Joy; Saba, Luca; Krishnamurthi, Ganapathy; Mallarini, Giorgio; El-Baz, Ayman; Al Ekish, Shadi; Beland, Michael; Suri, Jasjit S

    2013-12-01

    In this work, we have proposed an on-line computer-aided diagnostic system called "UroImage" that classifies a Transrectal Ultrasound (TRUS) image into cancerous or non-cancerous with the help of non-linear Higher Order Spectra (HOS) features and Discrete Wavelet Transform (DWT) coefficients. The UroImage system consists of an on-line system where five significant features (one DWT-based feature and four HOS-based features) are extracted from the test image. These on-line features are transformed by the classifier parameters obtained using the training dataset to determine the class. We trained and tested six classifiers. The dataset used for evaluation had 144 TRUS images which were split into training and testing sets. Three-fold and ten-fold cross-validation protocols were adopted for training and estimating the accuracy of the classifiers. The ground truth used for training was obtained using the biopsy results. Among the six classifiers, using 10-fold cross-validation technique, Support Vector Machine and Fuzzy Sugeno classifiers presented the best classification accuracy of 97.9% with equally high values for sensitivity, specificity and positive predictive value. Our proposed automated system, which achieved more than 95% values for all the performance measures, can be an adjunct tool to provide an initial diagnosis for the identification of patients with prostate cancer. The technique, however, is limited by the limitations of 2D ultrasound guided biopsy, and we intend to improve our technique by using 3D TRUS images in the future. PMID:23745787

  8. 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.

  9. Simple NMR methods for evaluating higher order structures of monoclonal antibody therapeutics with quinary structure.

    PubMed

    Chen, Kang; Long, Dianna S; Lute, Scott C; Levy, Michaella J; Brorson, Kurt A; Keire, David A

    2016-09-01

    Monoclonal antibody (mAb) drugs constitute the largest class of protein therapeutics currently on the market. Correctly folded protein higher order structure (HOS), including quinary structure, is crucial for mAb drug quality. The quinary structure is defined as the association of quaternary structures (e.g., oligomerized mAb). Here, several commonly available analytical methods, i.e., size-exclusion-chromatography (SEC) FPLC, multi-angle light scattering (MALS), circular dichroism (CD), NMR and multivariate analysis, were combined and modified to yield a complete profile of HOS and comparable metrics. Rituximab and infliximab were chosen for method evaluation because both IgG1 molecules are known to be homologous in sequence, superimposable in Fab crystal structure and identical in Fc structure. However, herein the two are identified to be significantly different in quinary structure in addition to minor secondary structure differences. All data collectively showed rituximab was mostly monomeric while infliximab was in mono-oligomer equilibrium driven by its Fab fragment. The quinary structure differences were qualitatively inferred from the less used but more reproducible dilution-injection-SEC-FPLC curve method. Quantitative principal component analysis (PCA) was performed on NMR spectra of either the intact or the in-situ enzymatic-digested mAb samples. The cleavage reactions happened directly in NMR tubes without further separation, which greatly enhanced NMR spectra quality and resulted in larger inter- and intra-lot variations based on PCA. The new in-situ enzymatic digestion method holds potential in identifying structural differences on larger therapeutic molecules using NMR. PMID:27344629

  10. 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

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

    PubMed

    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

  12. In vitro cytotoxicity, DNA cleavage and SOD-mimic activity of copper(II) mixed-ligand quinolinonato complexes.

    PubMed

    Buchtík, Roman; Trávníček, Zdeněk; Vančo, Ján

    2012-11-01

    Six mixed-ligand copper(II) complexes with the composition [Cu(qui)(L)]BF(4)·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), were prepared, fully characterized and studied for their in vitro cytotoxicity on human osteosarcoma (HOS) and human breast adenocarcinoma (MCF7) cancer cell lines. The overall promising results of the cytotoxicity were found for all the complexes, while the best results were achieved for complex 6, with IC(50)=2.6 ± 0.8 μM (HOS), and 1.3 ± 0.5 μM (MCF7). The interactions of the Cu(II) complexes 1-6 with calf thymus DNA were investigated by the UV-visible spectral titration. An agarose-gel electrophoretic method of oxidative damage determination to circular plasmid pUC19 was used to assess the ability of the complexes to act as chemical nucleases. A high effectiveness of DNA cleavage was observed for 2, 4 and 5. In vitro antioxidative activity of the complexes was studied by the superoxide dismutase-mimic (SOD-mimic) method. The best result was afforded by complex 1 with IC(50)=4.7 ± 1.0 μM, which corresponds to 10.2% of the native Cu,Zn-SOD enzyme activity. The ability of the tested complexes to interact with sulfur-containing biomolecules (cysteine and reduced glutathione) at physiological levels was proved by electrospray-ionization mass spectrometry (ESI-MS). PMID:23022693

  13. How to modify 7-azaindole to form cytotoxic Pt(II) complexes: highly in vitro anticancer effective cisplatin derivatives involving halogeno-substituted 7-azaindole.

    PubMed

    Štarha, Pavel; Trávníček, Zdeněk; Popa, Alexandr; Popa, Igor; Muchová, Tereza; Brabec, Viktor

    2012-10-01

    The platinum(II) dichlorido and oxalato complexes of the general formula cis-[PtCl(2)(nHaza)(2)] (1-3) [Pt(ox)(nHaza)(2)] (4-6) involving 7-azaindole halogeno-derivatives (nHaza) were prepared and thoroughly characterized. A single-crystal X-ray analysis of cis-[PtCl(2)(3ClHaza)(2)]·DMF (1·DMF; 3ClHaza symbolizes 3-chloro-7-azaindole) revealed a distorted square-planar arrangement with both the 3ClHaza molecules coordinated through their N7 atoms in a cis fashion. In vitro cytotoxicity of the complexes was evaluated by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay against the HOS (osteosarcoma), MCF7 (breast adenocarcinoma) and LNCaP (prostate adenocarcinoma) human cancer cell lines. The dichlorido complexes 1-3 (IC(50)=3.8, 3.9, and 2.5 μM, respectively) showed significantly higher in vitro anticancer effect against HOS as compared with cisplatin, whose IC(50)=37.7 μM. The biological effect of cisplatin against MCF7 (IC(50)=24.5 μM) and LNCaP (IC(50)=3.8 μM) was also exceeded by 1-3 (except for 2 against LNCaP), but the difference can be classified as significant only in the case of 1 (IC(50)=3.4 μM) and 3 (IC(50)=2.0 μM) against MCF7. The molecular pharmacological studies (RNA synthesis by T7 RNA polymerase in vitro) proved that 1-3 bind to DNA in a similar manner as cisplatin, since the RNA synthesis products of 1-3 and cisplatin showed a similar sequence profile of major bands. PMID:22922312

  14. Investigating the role of a backbone to substrate hydrogen bond in OMP decarboxylase using a site-specific amide to ester substitution

    PubMed Central

    Desai, Bijoy J.; Goto, Yuki; Cembran, Alessandro; Fedorov, Alexander A.; Almo, Steven C.; Gao, Jiali; Suga, Hiroaki; Gerlt, John A.

    2014-01-01

    Hydrogen bonds between backbone amide groups of enzymes and their substrates are often observed, but their importance in substrate binding and/or catalysis is not easy to investigate experimentally. We describe the generation and kinetic characterization of a backbone amide to ester substitution in the orotidine 5′-monophosphate (OMP) decarboxylase from Methanobacter thermoautotrophicum (MtOMPDC) to determine the importance of a backbone amide–substrate hydrogen bond. The MtOMPDC-catalyzed reaction is characterized by a rate enhancement (∼1017) that is among the largest for enzyme-catalyzed reactions. The reaction proceeds through a vinyl anion intermediate that may be stabilized by hydrogen bonding interaction between the backbone amide of a conserved active site serine residue (Ser-127) and oxygen (O4) of the pyrimidine moiety and/or electrostatic interactions with the conserved general acidic lysine (Lys-72). In vitro translation in conjunction with amber suppression using an orthogonal amber tRNA charged with l-glycerate (HOS) was used to generate the ester backbone substitution (S127HOS). With 5-fluoro OMP (FOMP) as substrate, the amide to ester substitution increased the value of Km by ∼1.5-fold and decreased the value of kcat by ∼50-fold. We conclude that (i) the hydrogen bond between the backbone amide of Ser-127 and O4 of the pyrimidine moiety contributes a modest factor (∼102) to the 1017 rate enhancement and (ii) the stabilization of the anionic intermediate is accomplished by electrostatic interactions, including its proximity of Lys-72. These conclusions are in good agreement with predictions obtained from hybrid quantum mechanical/molecular mechanical calculations. PMID:25275007

  15. In vitro biocompatibility of 45S5 Bioglass-derived glass-ceramic scaffolds coated with poly(3-hydroxybutyrate).

    PubMed

    Bretcanu, Oana; Misra, Superb; Roy, Ipsita; Renghini, Chiara; Fiori, Fabrizio; Boccaccini, Aldo R; Salih, Vehid

    2009-02-01

    The aim of this work was to study the in vitro biocompatibility of glass-ceramic scaffolds based on 45S5 Bioglass, using a human osteosarcoma cell line (HOS-TE85). The highly porous scaffolds were produced by the foam replication technique. Two different types of scaffolds with different porosities were analysed. They were coated with a biodegradable polymer, poly(3-hydroxybutyrate) (P(3HB)). The scaffold bioactivity was evaluated by soaking in a simulated body fluid (SBF) for different durations. Compression strength tests were performed before and after immersion in SBF. These experiments showed that the scaffolds are highly bioactive, as after a few days of immersion in SBF a hydroxyapatite-like layer was formed on the scaffold's surface. It was also observed that P(3HB)-coated samples exhibited higher values of compression strength than uncoated samples. Biocompatibility assessment was carried out by qualitative evaluation of cell morphology after different culture periods, using scanning electron microscopy, while cell proliferation was determined by using the AlamarBlue assay. Alkaline phosphatase (ALP) and osteocalcin (OC) assays were used as quantitative in vitro indicators of osteoblast function. Two different types of medium were used for ALP and OC tests: normal supplemented medium and osteogenic medium. HOS cells were seeded and cultured onto the scaffolds for up to 2 weeks. The AlamarBlue assay showed that cells were able to proliferate and grow on the scaffold surface. After 7 days in culture, the P(3HB)-coated samples had a higher number of cells on their surfaces than the uncoated samples. Regarding ALP- and OC-specific activity, no significant differences were found between samples with different pore sizes. All scaffolds containing osteogenic medium seemed to have a slightly higher level of ALP and OC concentration. These experiments confirmed that Bioglass/P(3HB) scaffolds have potential as osteoconductive tissue engineering substrates for

  16. Heme oxygenase metabolites inhibit tubuloglomerular feedback (TGF).

    PubMed

    Ren, YiLin; D'Ambrosio, Martin A; Wang, Hong; Liu, Ruisheng; Garvin, Jeffrey L; Carretero, Oscar A

    2008-10-01

    Tubuloglomerular feedback (TGF) is the mechanism by which the macula densa (MD) senses increases in luminal NaCl concentration and sends a signal to constrict the afferent arteriole (Af-Art). The kidney expresses constitutively heme oxygenase-2 (HO-2) and low levels of HO-1. HOs release carbon monoxide (CO), biliverdin, and free iron. We hypothesized that renal HOs inhibit TGF via release of CO and biliverdin. Rabbit Af-Arts and attached MD were simultaneously microperfused in vitro. The TGF response was determined by measuring Af-Art diameter before and after increasing NaCl in the MD perfusate. When HO activity was inhibited by adding stannous mesoporphyrin (SnMP) to the MD perfusate, the TGF response increased from 2.1+/-0.2 to 4.1+/-0.4 microm (P=0.003, control vs. SnMP, n=7). When a CO-releasing molecule, (CORM-3; 50 microM), was added to the MD perfusate, the TGF response decreased by 41%, from 3.6+/-0.3 to 2.1+/-0.2 microm (P<0.001, control vs. CORM-3, n=12). When CORM-3 at 100 microM was added to the perfusate, it completely blocked the TGF response, from 4.2+/-0.4 to -0.2+/-0.3 microm (P<0.001, control vs. CORM-3, n=6). When biliverdin was added to the perfusate, the TGF response decreased by 79%, from 3.4+/-0.3 to 0.7+/-0.4 microm (P=0.001, control vs. biliverdin, n=6). The effects of SnMP and CORM-3 were not blocked by inhibition of nitric oxide synthase. We concluded that renal HO inhibits TGF probably via release of CO and biliverdin. HO regulation of TGF is a novel mechanism that could lead to a better understanding of the control of renal microcirculation and function. PMID:18715939

  17. 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

  18. 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

  19. Discovering miRNA Regulatory Networks in Holt-Oram Syndrome Using a Zebrafish Model.

    PubMed

    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 mi

  20. Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1 alpha,25-dihydroxyvitamin D3.

    PubMed

    Atkins, Gerald J; Anderson, Paul H; Findlay, David M; Welldon, Katie J; Vincent, Cristina; Zannettino, Andrew C W; O'Loughlin, Peter D; Morris, Howard A

    2007-06-01

    Circulating 1 alpha,25-dihydroxyvitamin D(3) (1,25D) derives from renal conversion of 25-hydroxyvitamin D(3) (25D), by the 25D 1 alpha-hydroxylase (CYP27B1). Blood 25D levels, but not 1,25D levels, are the best indicator of vitamin D status and predict fracture risk in the elderly. We examined the extent to which osteoblasts can metabolize 25D. Well-characterized human primary osteoblasts and osteosarcoma (OS) cell lines were examined for the expression and regulation of genes associated with vitamin D metabolism, using real-time PCR. Primary osteoblasts and OS cell lines were found to express CYP27B1 mRNA and secreted detectable 1,25D in response to 25D. Of the OS cell lines tested, HOS expressed the most CYP27B1 mRNA and secreted the highest levels of 1,25D. All osteoblastic cells examined up-regulated expression of the catabolic regulator of 1,25D, the 25-hydroxyvitamin D-24-hydroxylase (CYP24), when incubated with either 1,25D or 25D. Exposure to physiological levels of 25D resulted in up-regulated transcription of the 1,25D responsive genes, osteocalcin (OCN), osteopontin (OPN) and RANKL. Specific knockdown of CYP27B1 in HOS cells using siRNA resulted in up to 80% reduction in both 1,25D secretion and the transcription of OCN and CYP24, strongly implying that the 25D effect in osteoblasts is preceded by conversion to 1,25D. Incubation with 25D, like 1,25D, inhibited primary osteoblast proliferation and promoted in vitro mineralization. Finally, we detected expression by osteoblasts of receptors for vitamin D binding protein (DBP), cubilin and megalin, suggesting that osteoblasts are able to internalize DBP-25D complexes in vivo. Together, our results suggest that autocrine, and perhaps paracrine, pathways of vitamin D(3) metabolism may regulate key osteoblast functions independently of circulating, kidney derived 1,25D. Our results are therefore consistent with the reported benefits of maintaining a healthy vitamin D status in the elderly to reduce the risk of

  1. 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

  2. Oligocene-Early Miocene Planktonic Microbiostratigraphy and Paleoenvironments of the South Slovakian Basin (Lučenec Depression)

    NASA Astrophysics Data System (ADS)

    Ozdínová, Silvia; Soták, Ján

    2015-01-01

    Oligocene and Lower Miocene sediments of the Lučenec Depression were studied to demonstrate the planktonic bioevents and climatic proxies from the Číž Formation (Rupelian) and Lučenec Formation (Chattian-Aquitanian) on the basis of quantitative analyses of foraminifers and calcareous nannofossils. The oldest nannofossil assemblages of the Číž Formation belonged to the NP23 Zone and were dominated by Reticulofenestra ornata known for preference of temperate eutrophic water conditions. An increase in bioproductivity was documented by abundant large-sized planktonic foraminifers (e.g. Turborotalia ampliapertura, Paragloborotalia nana, Subbotina gortanii) and epifaunal to shal-low-infaunal benthic species. The middle part of the Číž Formation reveals a lowstand progradation of deltaic sediments of the Rapovce Member. There, the planktonic foraminifers are impoverished in both size and diversity, containing mostly tenuitellid and cassigerinellid species, probably as a result of decreased salinity and increased anoxia in the Tard Clay. Contrary of this, the benthic foraminifers are rich, mainly the infaunal forms of uvigerinid species. They probably proliferated due to a high organic flux from riverine input. Open marine conditions were restored in the upper part of the Číž Formation above the lowest occurrence (LO) of Cyclicargolithus abisectus on the NP23-NP24 zone boundary. The transitional interval between the Číž and Lučenec formations (O5/O6 - NP24/25) was approximated by the HOs of Paragloborotalia opima and Sphenolithus distentus and the LOs of Globigerinoides primordius and Pontosphaera enormis. Benthic foraminifera of the Lučenec Formation indicate a high productivity and oxygen-deplected environ-ments. The Oligocene-Miocene boundary in the Lučenec Formation was appointed by the HOs of Helicospahera recta and Dictyococcites bisectus. Foraminiferal markers of this boundary were established from the HO of Globigerina ciperoensis and the LO of

  3. A systems biology approach reveals common metastatic pathways in osteosarcoma

    PubMed Central

    2012-01-01

    Background Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest-path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models

  4. Automated determination of P-phase arrival times at regional and local distances using higher order statistics

    NASA Astrophysics Data System (ADS)

    Küperkoch, L.; Meier, T.; Lee, J.; Friederich, W.; Working Group, EGELADOS

    2010-05-01

    We present an algorithm for automatic P-phase arrival time determination for local and regional seismic events based on higher order statistics (HOS). Using skewness or kurtosis a characteristic function is determined to which a new iterative picking algorithm is applied. For P-phase identification we apply the Akaike Information Criterion to the characteristic function, while for a precise determination of the P-phase arrival time a pragmatic picking algorithm is applied to a recalculated characteristic function. In addition, an automatic quality estimate is obtained, based on the slope and the signal-to-noise ratio, both calculated from the characteristic function. To get rid of erroneous picks, a Jackknife procedure and an envelope function analysis is used. The algorithm is applied to a large data set with very heterogeneous qualities of P-onsets acquired by a temporary, regional seismic network of the EGELADOS-project in the southern Aegean. The reliability and robustness of the proposed algorithm is tested by comparing more than 3000 manually derived P readings, serving as reference picks, with the corresponding automatically estimated P-wave arrival times. We find an average deviation from the reference picks of 0.26 +/- 0.64s when using kurtosis and 0.38 +/- 0.75s when using skewness. If automatically as excellent classified picks are considered only, the average difference from the reference picks is 0.07 +/- 0.31s and 0.07 +/- 0.41s, respectively. However, substantially more P-arrival times are determined when using kurtosis, indicating that the characteristic function derived from kurtosis estimation is to be preferred. Since the characteristic function is calculated recursively, the algorithm is very fast and hence suited for earthquake early warning purposes. Furthermore, a comparative study with automatically derived P-readings using Allen's and Baer & Kradolfer's picking algorithms applied to the same data set demonstrates better quantitative and

  5. 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

  6. Acetabular Labral Tears in Patients with Sports Injury

    PubMed Central

    Kang, Chan; Cha, Soo-Min

    2009-01-01

    Background We wanted to investigate acetabular labral tears and their correlation with femoroacetabular impingement in patients with sports injury. Methods Among 111 patients who were diagnosed with the acetabular labral tears after arthroscopic treatment from January 2004 to December 2007, we selected 41 patients with sports injury. There were 12 cases of Taekwondo injury, 5 of golf injury, 4 of soccer injury, 3 of gymnastics injury, 2 of Hapkido injury, 2 of aerobics injury, 2 of rock-climbing injury, 2 of fitness training injury and 9 of other sports injuries. We checked the subtypes of acetabular labral tears and the accompanying femoroacetabular impingement. For the cases with accompanying femoroacetabular impingement, we investigated the subtypes according to the types of sports, gender and age. At last follow-up, we checked the Harris Hip Score (HHS), the Hip Outcome Score (HOS) sports scale and the percentage of patients who returned to their sports activity. Results The average age of symptomatic onset was 26 years (range, 12 to 65 years). The ratio of males to females was 29 : 12. An average duration of the hip pain was 17 months (range, 1 to 60 months). The degenerative type of acetabular labral tears was the most prevalent with 32 cases (78%), and there were 9 cases (22%) of the partial tear type. Thirty cases (73%) were accompanied by femoroacetabular impingement. The average age of the 23 cases (56%) of the cam-type was 23 years (range, 12 to 48 years), and it was more likely to occur in men (87%) and for people practicing martial arts such as Taekwondo or Hapkido. An average age of the 5 cases (12%) of the pincer-type was 26 (range, 16 to 43 years), it usually occurred in women (60%) and for non-martial arts such as golf and gymnastics. There were 2 cases of the mixed type (cam + pincer-type). At 27 months follow-up, the HHS was 61 to 92 points, the HOS sports scale increased 43 to 75%, and the rate of returning to sports was 71%. Conclusions In

  7. Application of higher order spectra for accurate delineation of atrial arrhythmia.

    PubMed

    Prasad, Hari; Martis, Roshan Joy; Acharya, U Rajendra; Min, Lim Choo; Suri, Jasjit S

    2013-01-01

    The electrocardiogram (ECG) is being commonly used as a diagnostic tool to distinguish different types of atrial tachyarrhythmias. The inherent complexity and mechanistic and clinical inter-relationships often brings about diagnostic difficulties to treating physicians and primary health care professionals creating frequent misdiagnoses and cross classifications using visual criteria. The current paper presents a methodology for ECG based pattern analysis for detection of atrial flutter, atrial fibrillation and normal sinus rhythm beats. ECG is an inherently non-linear and non-stationary signal; its variation may contain indicators of current disease, or warnings about impending cardiac diseases. Routinely used time domain and frequency domain methods will not be able to capture the hidden information present in the ECG beats. In the present study, we have used non-linear features of higher order spectra (HOS) to differentiate the normal, atrial fibrillation and atrial flutter ECG beats. The bispectrum features were subjected to independent component analysis (ICA) for data reduction. The ICA coefficients were subsequently subjected to K-nearest-neighbor (KNN), classification and regression tree (CART) and neural network (NN) classifiers to evaluate the best automated classifier. We have obtained an average accuracy of 97.65%, sensitivity and specificity of 98.75% and 99.53% respectively using ten-fold cross validation. Overall, the results show that application of higher order spectra statistics is useful for the classification of atrial tachyarrhythmias with reasonably high accuracies. Further validation of the proposed technique will yield acceptable results for clinical implementation. PMID:24109623

  8. Alleviating anastrozole induced bone toxicity by selenium nanoparticles in SD rats.

    PubMed

    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 5μg/ml significantly reduced the cell death caused by anastrozole (1μM) in HOS (human osteoblast) cells. In addition, our results also highlighted that in female SD rat model, SeNPs (0.25, 0.5, 1mg/kg/day) significantly prevented the decrease in bone density and increase in biochemical markers of bone resorption induced by anastrozole (0.2mg/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 (1mg/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. PMID:23415680

  9. Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cells metastasis by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways.

    PubMed

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

    2016-03-01

    Zoledronate is a standard treatment for preventing skeletal complications of osteoporosis and some types of cancer associated with bone metastases, but we little know whether the effect of zoledronate on metastasis of osteosarcoma. Here, we investigated the inhibitory effects of zoledronate on cell viability, motility, migration and invasion of 4 osteosarcoma cell lines (Saos2, MG-63, HOS and U2OS) by affecting cell morphology, epithelial-mesenchymal transition (EMT) and cytoskeletal organization as well as induction of E-cadherin and reduction of N-cadherin with activation of transcription factors Slug and Twist, especially in U2OS cells. Zoledronate decreased JNK and p38 phosphorylation and upper streams of focal adhesion kinase (FAK) and Src to suppress the motility, invasiveness and migration of U2OS cells. In addition to zoledronate-inhibited Rho A and Cdc42 membrane translocation and GTPγS activities, the anti-metastatic effects in U2OS cells including inhibition of adhesion were reversed by geranylgeraniol, but not farnesol. In conclusion, Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cell-matrix and cell-cell interactions, migration potential, the invasive activity, and the adhesive ability by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways. PMID:26848867

  10. 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.