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Sample records for hos vaegar anlagda

  1. 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

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

    PubMed

    Wang, Mengqiao; Collins, Ruth N

    2014-09-15

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

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

    PubMed

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

    2012-10-01

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

  4. 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

    ... Pyrotechnics Association (APA) Exemption From the 14-Hour Rule During Independence Day Celebrations AGENCY... 2011 and 2012 Independence Day periods because it argues that compliance with the current 14-hour rule... (APA) Exemption From the 14-Hour HOS Rule During 2011 and 2012 Independence Day Celebrations...

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

    PubMed

    Lee, Kyounghee; Seo, Pil Joon

    2015-01-01

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

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

    PubMed Central

    Wang, Mengqiao; Collins, Ruth N.

    2014-01-01

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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

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

    PubMed Central

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

    2006-01-01

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

  13. 78 FR 26690 - Hours of Service (HOS) of Drivers; Application for Renewal and Expansion of American Pyrotechnics...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-07

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

  14. 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.

  15. Density functional theory and the correlation consistent basis sets: the tight d effect on HSO and HOS.

    PubMed

    Wang, Nick X; Wilson, Angela K

    2005-08-18

    The HSO and HOS isomers have been revisited using the DFT functionals, B3LYP, B3PW91, and PBE, in combination with tight d-augmented correlation consistent basis sets, cc-pV(x+d)Z and aug-cc-pV(x+d)Z for second-row atoms. Structures, vibrationally averaged structures, relative energies, harmonic and anharmonic frequencies, enthalpies of formation of HSO and HOS, and the barrier for the HSO/HOS isomerization have been determined. These results were compared with results from previous DFT and ab initio studies in which the standard correlation consistent basis sets were used. The relative energies of the two isomers converge more rapidly and smoothly with respect to increasing basis set size for the tight d-augmented sets than for the standard basis sets. Our best calculations, B3PW91/aug-cc-pV(5+d)Z, for the relative energy of the isomers are in excellent agreement with previous CCSD(T) results given by Wilson and Dunning.

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

    NASA Astrophysics Data System (ADS)

    Fortenberry, Ryan C.; Francisco, Joseph S.

    2017-02-01

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

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

    PubMed

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

    2013-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

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

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

    PubMed

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

    2003-03-27

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

  20. 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.

  1. Capillarisin Exhibits Anticancer Effects by Inducing Apoptosis, Cell Cycle Arrest and Mitochondrial Membrane Potential Loss in Osteosarcoma Cancer Cells (HOS).

    PubMed

    Chen, N-J; Hao, F-Y; Liu, H; Zhao, H; Li, J-M

    2015-08-01

    The aim of the present study was to assess the anticancer activity of capillarisin against human osteosarcoma (HOS) cancer cells in vitro. Cell viability after capillarisin drug treatment and evaluated by MTT assay. The extent of cell death induced by capillarisin was estimated by using lactate dehydrogenase (LDH) assay. The effect of capillarisin on cell cycle phase distribution and mitochondrial membrane potential (ΛΨm) was demonstrated via flow cytometry using propidium iodide (PI) and rhodamine-123 (Rh-123) DNA-binding fluorescent dyes respectively. Fluorescence microscopy was employed to examine the morphological changes in osteosarcoma cancer cells and presence of apoptotic bodies following capillarisin treatment. The results of this study revealed that capillarisin induced dose-dependent growth inhibition of these cancer cells after 12-h of incubation. Further, capillarisin induced significant release of LDH from these cell cultures and this LDH release was much more noticeable at higher concentrations of capillarisin. Hoechst 33258 staining revealed characteristic morphological features of apoptosis triggered by capillarisin treatment. Cell cycle analysis revealed that capillarisin induced dose-dependent G0/G1-phase cell cycle arrest. Capillarisin also trigerred a progressive and dose-dependent reduction in the mitochondrial membrane potential. In conclusion, capillarisin inhibits cancer cell growth of osteosarcoma cells by inducing apoptosis accompanied with G0/G1-phase cell cycle arrest and loss in mitochondrial membrane potential.

  2. 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.

  3. 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

  4. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1982-11-01

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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 77 FR 38378 - Hours of Service (HOS) of Drivers; Revision of Exemption; American Pyrotechnics Association (APA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

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

  13. 76 FR 37880 - Hours of Service (HOS) of Drivers; Granting of Exemption; American Pyrotechnics Association (APA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

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

  14. 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

    ... Pyrotechnics Association (APA) for Exemption From the 14-Hour Rule During Independence Day Celebrations AGENCY... Register notice. The initial APA exemption application for relief from the 14-hour rule was submitted in... carriers. APA is seeking this exemption because compliance with the current 14-hour rule by its...

  15. 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.

  16. 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

    ... of the Exemption From the 14-Hour Provision of the Hours of Service Rule for Certain Pyrotechnics... 2003 final rule, driving after the 14th hour from the beginning of the work day was prohibited; rest... allowed to exclude off-duty and sleeper berth time of any length in the calculation of the 14-hour...

  17. 77 FR 40142 - Applications for Exemption: Commercial Driver's License (CDL) and Hours-of-Service (HOS) of Drivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

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

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

    ERIC Educational Resources Information Center

    Jonsson, Arne

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

  19. 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.

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

    NASA Astrophysics Data System (ADS)

    Solinsky, James C.; Feeney, John J.

    1994-03-01

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

  1. 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.

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

    PubMed

    Bowen, Sonya E

    2012-01-01

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

  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

    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…

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

    ERIC Educational Resources Information Center

    Hacieminoglu, Esme

    2014-01-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    ERIC Educational Resources Information Center

    Mohsen, Mohammed Ali

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. 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

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

    PubMed

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

    2008-05-01

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

  10. 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

  11. 77 FR 64093 - Hours of Service of Drivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-18

    .... Watson, Senior Advisor for Policy, FMCSA, (202) 385-2395. If you need sign language assistance to participate in this HOS listening session, contact Ms. Watson by Thursday, October 18, 2012, to allow us...

  12. 75 FR 49494 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ... outcomes measures, the HOS is used to collect the Management of Urinary Incontinence in Older Adults, Physical Activity in Older Adults, Fall Risk Management, and Osteoporosis Testing in Older Women...

  13. 77 FR 47850 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ... outcomes measures, the HOS is used to collect the Management of Urinary Incontinence in ] Older Adults, Physical Activity in Older Adults, Fall Risk Management, and Osteoporosis Testing in Older Women...

  14. 75 FR 31790 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-04

    ... outcomes measures, the HOS is used to collect the Management of Urinary Incontinence in Older Adults, Physical Activity in Older Adults, Fall Risk Management, and Osteoporosis Testing in Older Women...

  15. 77 FR 25181 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... Organizations (MAOs), is through the development of standardized, uniform performance measures to enable CMS to... Medicare HOS as part of the Effectiveness of Care component of the former Health Plan Employer Data...

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

    PubMed

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

    2015-07-01

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

  17. 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.

  18. 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.

  19. 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.

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

    PubMed Central

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

    2010-01-01

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

  1. 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

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

    PubMed

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

    2012-05-01

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

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

    PubMed

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

    2015-09-04

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

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

    PubMed

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

    2016-08-08

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

  5. 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.

  6. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2014-01-01

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

  10. 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.

  11. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

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

    PubMed

    D'Alonzo, Karen T

    2004-11-01

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

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

    PubMed

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

    2016-08-31

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

  15. 76 FR 5324 - Hours of Service of Drivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-31

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

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-14

    ... 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 the Federal Motor Carrier Safety Regulations. The exemption request is for RockTenn's shipping...

  18. 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...

  19. 75 FR 17207 - Electronic On-Board Recorders for Hours-of-Service Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-05

    ...The Federal Motor Carrier Safety Administration (FMCSA) amends the Federal Motor Carrier Safety Regulations (FMCSRs) to incorporate new performance standards for electronic on-board recorders (EOBRs) installed in commercial motor vehicles (CMVs) manufactured on or after June 4, 2012. On-board hours-of-service (HOS) recording devices meeting FMCSA's current requirements and installed in CMVs......

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

    PubMed

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

    2010-09-01

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

  1. 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...

  2. Burn Care in Iraq

    DTIC Science & Technology

    2007-01-01

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

  3. 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...

  4. 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...

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

    DTIC Science & Technology

    2008-03-01

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

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

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2014-08-01

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

  8. 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...

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

    PubMed

    Jensen, Anker; Dahl, Søren

    2009-01-01

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

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

    DTIC Science & Technology

    2006-06-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    DTIC Science & Technology

    1981-09-01

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

  14. 78 FR 39057 - Hours of Service of Drivers; Renewal and Expansion of American Pyrotechnics Association Exemption...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-28

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

  15. 76 FR 26681 - Hours of Service of Drivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-09

    ... Service of Drivers AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice... service (HOS) for commercial motor vehicle drivers. The Agency is reopening the comment period on the NPRM....gov/2008/pdf/E8-785.pdf . FOR FURTHER INFORMATION CONTACT: Mr. Thomas Yager, Chief, Driver and...

  16. 42 CFR 422.252 - Terminology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... PROGRAM (CONTINUED) MEDICARE ADVANTAGE PROGRAM Submission of Bids, Premiums, and Related Information and... undertake Healthcare Effectiveness Data and Information Set (HEDIS) and Health Outcome Survey (HOS) data... at section 1860D-13(a)(2) of the Act, as adjusted to reflect the difference between the plan's...

  17. 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…

  18. 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

    ... Property-Carrier Hours-of-Service Rules to the Driveaway Operation of Vehicles Designed to Transport... guidance. SUMMARY: 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...

  19. 75 FR 13441 - Hours of Service; Limited 90-Day Waiver for the Distribution of Anhydrous Ammonia in Agricultural...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-22

    ... the Distribution of Anhydrous Ammonia in Agricultural Operations AGENCY: Federal Motor Carrier Safety... Federal hours- of-service (HOS) regulations for the transportation of anhydrous ammonia from any...-LU) to certain motor carriers engaged in the distribution of anhydrous ammonia during the 2010...

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

    PubMed

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

    2014-10-01

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

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

    DTIC Science & Technology

    1994-01-01

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

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

    PubMed

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

    2016-11-01

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

  3. 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...

  4. 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.

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

    PubMed

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

    2004-02-01

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

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

    PubMed Central

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

    2017-01-01

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

  7. 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.

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

    PubMed

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

    2017-02-06

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

  9. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. 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.

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. 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.

  19. 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

  20. JPRS Report, East Europe.

    DTIC Science & Technology

    2007-11-02

    VONS, HOS, DI, CSHV, CD, and the editorial board of LN [LIDOVE NOVINY] have come out in favor of awarding him the Nobel Prize. These letters and...anyone who agrees with its thinking, participates in its work, and supports it. Since 1978, an independent editorial group of Charter 77...when they sent 50 letters by Czechoslovak citizens to Federal Assembly delegates in September 1987. DI also participated in preparation for the

  1. Lipid Bilayer-Integrated Optoelectronic Tweezers for Nanoparticle Manipulations

    DTIC Science & Technology

    2013-01-01

    hydrogenated amorphous silicon (a-Si) layer deposited on top of 100 nm of an indium tin oxide (ITO) layer, and the other side is only the 100 nm of ITO layer...aqueous solution was sandwiched between a transparent ITO electrode and a photoconductive ( hydrogenated amorphous silicon) electrode. By simultaneously...in the following experiments consisted of 96 mol % of DOPC and 4 mol % of thiol-ended lipids, PTE-SH (1,2-dipalmitoyl-sn-glycero-3- hos - phothioethanol

  2. Neoplastic transformation of human cells in vitro.

    PubMed

    Rhim, J S

    1993-01-01

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

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

    DTIC Science & Technology

    2005-01-01

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

  4. PEO Soldier Simulation Roadmap: Initial Steps in Implementation

    DTIC Science & Technology

    2005-07-01

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

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

    DTIC Science & Technology

    2014-05-09

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

  6. Manning the Force.

    DTIC Science & Technology

    1979-12-31

    Potential feed to ROTC program - Overfill TPU in some college comunities 1-2 k _ ..... a. CONCEPT: Stripes for hard-to-fill HOS FEATURES: - Enters service...in USAREUR - Limit to CMF 11, 13, 19 q. CONCEPT: Duty position incentive program FEATURES: - Geared to selected problem 3 digit MOS’s - Control by...focus for new ideas and early rejection of some concepts. e. Personal interviews. Members of the academic comunity and Reserve Components, selected

  7. Job Language Performance Requirements for MOS 16P. Short Range Air Defense Artillery Missile Crewman.

    DTIC Science & Technology

    1982-10-01

    AD MARMM FOF DONTAMINATD AREAS. CE .BASI TECiI:ICAL allo. commander average radiation 6xposure ballpoint pen entire unit charging end capable...everyday English. 3. Technical’vocabulary. Technical vocabulary is defined as those words, terms, and acronyms that are specific to the HOS training...course. Also. u. be included as part of the language performance requirements is the 14OS specific vocabulary. (Appendix 6) 2-5-16P /3 CONCLUSION

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

    DTIC Science & Technology

    1989-06-01

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

  9. The Military Casualty with Combat Related Acute Post Traumatic Stress Disorder

    DTIC Science & Technology

    1984-05-01

    would cause stress in most people 2. characterological deficits 3. unconscious id drives that are in conflict with the superego 4. a compromised...neurosis the conflict is between the ego and the hos- tile forces of the external world. Kardiner, spurred on by Freud’s work, did a study of veterans...because they already had a weakened ego structure (Glass, 1969). Since the mid 1920s a controversy has existed over the preexistence of neurotic disorders

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

    PubMed

    Moffett, Alexander; Ross, Lainie Friedman

    2011-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

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

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

    PubMed

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

    2009-03-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Starý, Tomás; Biktashev, Vadim N

    2015-04-01

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

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

    PubMed

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

    2017-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2009-01-01

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

  18. 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

  19. 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

  20. 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.

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

    PubMed

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

    2007-11-01

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

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

    PubMed

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

    2007-01-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. 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

  6. 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

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

    PubMed

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

    2014-01-01

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

  8. A Review of Models of the Fluidic Generator.

    DTIC Science & Technology

    1980-11-01

    ATTN l)ELA SAS-T INI. R ’ C’S N VANRIF ’ PORN )LC.iS C ENTER W HITE SANDS MISSILE RANGE, NIM HOS02 mMANDICE 1.PA IFD)LOS’ 1CS ARPMY "SH " STO G CPOR...8217 2POT TFIlEDYNE RP’)IN ENGI1NEERING ATTN PRR-.C-F 1,CNNR NTN ’)E 1243, ’A. ANIPS’ CIEM MINOR RESEARCH PARE ATTN MIC’HAEL 13CAE-LIEHI BE’NT HOG

  9. Gulf Security and the Gulf Arab Contribution

    DTIC Science & Technology

    1991-06-01

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

  10. 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

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

    DTIC Science & Technology

    2014-09-01

    network LED light emitting diode LHD landing helicopter dock amphibious ship LVL level MCM mine countermeasure ship MCS machinery control systems...valve is still closed. Observe: FLSD: the red “Low Tank LVL ” LED is lit. Observe: HOS: the green “PUMP ON” LED is lit 110 Step 5. FLSD...FLSD: the red “High Tank LVL ” LED is lit and the red “Low Tank LVL ” LED is extinguished. 112 Step 6. FLSD: adjust the dial to “50”% Observe

  12. 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

  13. ‘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

  14. Foundation of a Knowledge Representation System for Image Understanding.

    DTIC Science & Technology

    1980-10-01

    FOUNDATION OF A KNOWLEDGE REPRESENTATION SYSTEM FOR IMAGE UNDER-ETC(U) OCT GO L VAINA, S CUSHING N00039-79-C-0457 UNCLASSIFIED HOS-TR-27 NL...Understanding W a l ~i gI 8, _ ..... ... G. _VA RF"RMINGii)RG. -REPORT NUM6 -7.𔃾 UTHOR(,,-.- 8. CONTRACT OR GRANT NUMBERfs) Lucia Vainai Steven/Cushing 4...821739-79-C-� . 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT, PROJECT TASK Higher Order Software, Inc./ AREA & WORK UNIT NUMBERS

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

    DTIC Science & Technology

    2009-10-01

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

  16. United States Military Posture for FY 1979. Statement by General George S. Brown, USAF Chairman, Joint Chiefs of Staff, to the Congress.

    DTIC Science & Technology

    1978-01-20

    irredentist claims CURRENT SITUA TION have led to open warfare with Ethiopia over con- ol of the Somali-inhabited areas in the Ogaden. Long-standing...PACIFIC) KOREA 0 EIGHTH U.S. ARMY I CORPS HoS 20 INF DIV 0 WENGRGRP CONS’/ 4TH MSL COMO 38TH AD ODE EASTPAC i ST SIG OlE 1 MAF I ST MAR DIV 30 MAW...approved by OVERVIEW the Congress for FY 1978, and the CGN-42 nuclear A comparison of US, USSR and PRC general powered cruiser. A mix ol nuclear and

  17. 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.

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

    DTIC Science & Technology

    1981-02-01

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

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

    DTIC Science & Technology

    1986-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-05-01

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

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

    DTIC Science & Technology

    1981-10-01

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

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

    PubMed

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

    2002-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

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

    PubMed

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

    2014-03-01

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

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

    PubMed

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

    2007-01-01

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

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

    PubMed

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

    2008-12-01

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

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

    PubMed

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

    2015-09-01

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

  8. 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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2009-08-01

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

  12. 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.

  13. 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

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

    PubMed

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

    2014-04-14

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

  15. Response of cyanobacteria to low atmosphere pressure

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

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

    PubMed

    Hodgson, Derek J; Aubin, Yves

    2017-05-10

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

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

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

    PubMed

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

    1998-01-01

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

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

    PubMed Central

    Huttunen, P; Heino, J; Hyypiä, T

    1997-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  2. 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.

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

  5. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2005-06-01

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

  8. Pile Transfer Function,

    DTIC Science & Technology

    2007-11-02

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  10. Genetic Algorithms for solving SVM-ICA

    NASA Astrophysics Data System (ADS)

    Górriz, J. M.; Puntonet, C. G.

    2004-11-01

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

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

    PubMed

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

    2015-03-01

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

  12. 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.

  13. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1982-11-01

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

  15. 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.

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

    PubMed

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

    2017-04-01

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

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

    PubMed

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

    2009-07-01

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

  18. 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.

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

    PubMed

    Knight, K H; Elfenbein, M H

    1996-01-01

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

  20. Wnt/β-catenin Signaling Activates Expression of the Bone-related Transcription Factor RUNX2 in Select Human Osteosarcoma Cell Types.

    PubMed

    Vega, Oscar A; Lucero, Claudia M J; Araya, Hector F; Jerez, Sofia; Tapia, Julio C; Antonelli, Marcelo; Salazar-Onfray, Flavio; Las Heras, Facundo; Thaler, Roman; Riester, Scott M; Stein, Gary S; van Wijnen, Andre J; Galindo, Mario A

    2017-03-28

    Osteosarcoma is the most common malignant bone tumor in children and adolescents. Metastasis and poor responsiveness to chemotherapy in osteosarcoma correlates with over-expression of the runt-related transcription factor RUNX2, which normally plays a key role in osteogenic lineage commitment, osteoblast differentiation and bone formation. Furthermore, WNT/β-catenin signaling is over-activated in osteosarcoma and promotes tumor progression. Importantly, the WNT/β-catenin pathway normally activates RUNX2 gene expression during osteogenic lineage commitment. Therefore, we examined whether the WNT/β-catenin pathway controls the tumor-related elevation of RUNX2 expression in osteosarcoma. We analyzed protein levels and nuclear localization of β-catenin and RUNX2 in a panel of human osteosarcoma cell lines (SAOS, MG63, U2OS, HOS, G292 and 143B). In all six cell lines, β-catenin and RUNX2 are expressed to different degrees and localized in the nucleus and/or cytoplasm. SAOS cells have the highest levels of RUNX2 protein that is localized in the nucleus, while MG63 cells have the lowest RUNX2 levels which is mostly localized in the cytoplasm. Levels of β-catenin and RUNX2 protein are enhanced in HOS, G292 and 143B cells after treatment with the GSK3β inhibitor SB216763. Furthermore, small interfering RNA (siRNA)-mediated depletion of β-catenin inhibits RUNX2 expression in G292 cells. Thus, WNT/β-catenin activation is required for RUNX2 expression in at least some osteosarcoma cell types, where RUNX2 is known to promote expression of metastasis related genes. This article is protected by copyright. All rights reserved.

  1. T-box family of transcription factor-TBX5, insights in development and disease.

    PubMed

    Zhu, Ting; Qiao, Longwei; Wang, Qian; Mi, Rui; Chen, Jinnan; Lu, Yaojuan; Gu, Junxia; Zheng, Qiping

    2017-01-01

    The T-box gene family refers to a group of transcription factors that share a highly conserved, sequence-specific DNA-binding domain (T-box) containing around 180-amino acids. According to HUGO gene nomenclature committee (HGNC), there are 18 T-box family members. These T-box genes have been implicated essential roles during embryogenesis and cardiac development, given their specific expression pattern in developing mammalian heart for several T-box genes, including TBX5. TBX5 is consisted of three transcriptional variants which cover 9 exons and encode two distinct isoforms that differ in N-terminus. TBX5 is probably the most frequently studied T-box gene over the past decade due to the typical cardiac defects observed in Holt-Oram syndrome (HOS), which is caused by TBX5 mutation. Most of the mutations are within exons 3-7 where locate sequence coding for the T-box domain. Notably, a variety of cardiac defects, as well as abnormalities in limb and other organs have been seen in HOS syndrome with different kinds of TBX5 mutations, suggesting a heterogeneous disease mechanism. We have performed a meta-analysis of TBX5 and found a significant correlation between its single nucleotide polymorphism (SNP) rs3825214 (A to G), and risk of atrial fibrillation and its subtypes, supporting TBX5 as a master transcription factor for cardiac development. In addition, bioinformatics analysis of this SNP identified several TFs that may be affected for their binding affinity with TBX5. Identification and characterization of more TBX5 mutations and SNPs hold promise for therapeutic strategy targeting TBX5 associated developmental abnormalities and diseases.

  2. HIV-1 Vpu Promotes Release and Prevents Endocytosis of Nascent Retrovirus Particles from the Plasma Membrane

    PubMed Central

    Neil, Stuart J. D; Eastman, Scott W; Jouvenet, Nolwenn; Bieniasz, Paul D

    2006-01-01

    The human immunodeficiency virus (HIV) type-1 viral protein U (Vpu) protein enhances the release of diverse retroviruses from human, but not monkey, cells and is thought to do so by ablating a dominant restriction to particle release. Here, we determined how Vpu expression affects the subcellular distribution of HIV-1 and murine leukemia virus (MLV) Gag proteins in human cells where Vpu is, or is not, required for efficient particle release. In HeLa cells, where Vpu enhances HIV-1 and MLV release approximately 10-fold, concentrations of HIV-1 Gag and MLV Gag fused to cyan fluorescent protein (CFP) were initially detected at the plasma membrane, but then accumulated over time in early and late endosomes. Endosomal accumulation of Gag-CFP was prevented by Vpu expression and, importantly, inhibition of plasma membrane to early endosome transport by dominant negative mutants of Rab5a, dynamin, and EPS-15. Additionally, accumulation of both HIV and MLV Gag in endosomes required a functional late-budding domain. In human HOS cells, where HIV-1 and MLV release was efficient even in the absence of Vpu, Gag proteins were localized predominantly at the plasma membrane, irrespective of Vpu expression or manipulation of endocytic transport. While these data indicated that Vpu inhibits nascent virion endocytosis, Vpu did not affect transferrin endocytosis. Moreover, inhibition of endocytosis did not restore Vpu-defective HIV-1 release in HeLa cells, but instead resulted in accumulation of mature virions that could be released from the cell surface by protease treatment. Thus, these findings suggest that a specific activity that is present in HeLa cells, but not in HOS cells, and is counteracted by Vpu, traps assembled retrovirus particles at the cell surface. This entrapment leads to subsequent endocytosis by a Rab5a- and clathrin-dependent mechanism and intracellular sequestration of virions in endosomes. PMID:16699598

  3. 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.

  4. 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.

  5. 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

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

    PubMed Central

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

    2017-01-01

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

  7. 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.

  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. The Semen pH Affects Sperm Motility and Capacitation.

    PubMed

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

    2015-01-01

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

  10. Evaluation of the Spermicidal and Contraceptive Activity of Platycodin D, a Saponin from Platycodon grandiflorum

    PubMed Central

    Lu, Zongliang; Wang, Leiguang; Zhou, Rui; Qiu, Yi; Yang, Liuna; Zhang, Chanyu; Cai, Min; Mi, Mantian; Xu, Hongxia

    2013-01-01

    Background The extract of Platycodon grandiflorum has been reported to have effective spermicidal activity. This study was designed to evaluate the spermicidal and contraceptive activity, as well as the safety, of Platycodin D (PD), a major saponin in Platycodon grandiflorum. Methods Using the computer-aided sperm analysis (CASA) test criteria, the sperm-immobilizing activity of PD was studied using highly motile human sperm. The sperm viability was assessed by fluorescent staining using SYBR-14 (living sperm) and propidium iodide (dead sperm). The sperm membrane integrity was assessed by evaluating the hypo-osmotic swelling (HOS) and examinations by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The in vivo contraceptive efficacy was evaluated in rats using post-intrauterine PD application. The comet assay was employed to determine whether PD caused DNA damage in the sperm. Vaginal biopsies were also performed to determine whether the PD gel induced vaginal inflammation. Results A dose-dependent effect of PD on the sperm motility and viability was observed. The maximum spermicidal effect was observed with a 0.25 mM concentration of PD. More than 70% of the PD-treated sperm lost their HOS responsiveness at a concentration of 0.20 mM PD, indicating that PD caused injury to the sperm plasma membrane. TEM and SEM revealed significant damage to both the head and tail membranes of the sperm. PD decreased the fertility to zero in rats, was non-DNA damaging and was not harmful to the vaginal tissue in the rats. Conclusion PD has significant spermicidal activity that should be explored in further studies. PMID:24303079

  11. T-box family of transcription factor-TBX5, insights in development and disease

    PubMed Central

    Zhu, Ting; Qiao, Longwei; Wang, Qian; Mi, Rui; Chen, Jinnan; Lu, Yaojuan; Gu, Junxia; Zheng, Qiping

    2017-01-01

    The T-box gene family refers to a group of transcription factors that share a highly conserved, sequence-specific DNA-binding domain (T-box) containing around 180-amino acids. According to HUGO gene nomenclature committee (HGNC), there are 18 T-box family members. These T-box genes have been implicated essential roles during embryogenesis and cardiac development, given their specific expression pattern in developing mammalian heart for several T-box genes, including TBX5. TBX5 is consisted of three transcriptional variants which cover 9 exons and encode two distinct isoforms that differ in N-terminus. TBX5 is probably the most frequently studied T-box gene over the past decade due to the typical cardiac defects observed in Holt-Oram syndrome (HOS), which is caused by TBX5 mutation. Most of the mutations are within exons 3-7 where locate sequence coding for the T-box domain. Notably, a variety of cardiac defects, as well as abnormalities in limb and other organs have been seen in HOS syndrome with different kinds of TBX5 mutations, suggesting a heterogeneous disease mechanism. We have performed a meta-analysis of TBX5 and found a significant correlation between its single nucleotide polymorphism (SNP) rs3825214 (A to G), and risk of atrial fibrillation and its subtypes, supporting TBX5 as a master transcription factor for cardiac development. In addition, bioinformatics analysis of this SNP identified several TFs that may be affected for their binding affinity with TBX5. Identification and characterization of more TBX5 mutations and SNPs hold promise for therapeutic strategy targeting TBX5 associated developmental abnormalities and diseases. PMID:28337273

  12. Decay of sperm obtained from epididymes of wild ruminants depending on postmortem time.

    PubMed

    Martinez-Pastor, F; Guerra, C; Kaabi, M; Diaz, A R; Anel, E; Herraez, P; de Paz, P; Anel, L

    2005-01-01

    We have carried out a study on the effect of postmortem time (PT) in some characteristics of epididymal sperm salvaged from hunted Iberian red deer and roe deer. Testis were collected, identified, refrigerated down to 5 degrees C, and sent to our laboratory by the wardens of the hunting reserves. This way, samples were delivered at different times postmortem. Sperm were extracted from the cauda epididymis by means of cuts. Analyzed parameters were: osmolality, pH, motility-both subjectively and with CASA, HOS test reactivity, acrosomal status and viability (assessed with propidium iodide). Osmolality and pH rose with prolonged postmortem time, possibly due to tissue decomposition. Most sperm quality parameters negatively correlated with PT. Besides, when comparing PT classes (groups of 24 h for red deer and 30 h for roe deer), we could appreciate that motility was more affected by PT than other quality variables. Progressive motility was especially impaired. We also classified the samples in high, medium and low quality for each PT group (considering progressive motility, intact acrosomes and reactivity to the HOS test), and it was clear that after 2 days the number of high quality samples was testimonial, and after several days, we almost found only low quality samples. In conclusion, epididymal sperm from Iberian red deer and roe deer undergo a decrease of quality with PT, but it could stay acceptable within many hours postmortem. There are implications for wildlife conservation programs, as epididymal sperm is a good source of germplasm. If valuable animals die and it is not possible to process their sperm immediately, it may still be possible to obtain viable spermatozoa many hours later.

  13. 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

  14. 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

  15. The synergistic effect of SaOS-2 cell extract and other bone-inducing agents on human bone cell cultivation.

    PubMed

    Saif, Ashraf; Wende, Kristian; Lindequist, Ulrike

    2012-12-01

    Human osteosarcoma cell line SaOS-2 is an osteoblastic cell model that contains factors like bone morphogenetic proteins necessary for initiating bone formation. The cell line also expresses high levels of osteoinductive activity. In contrast to highly complicated and expensive ways to identify, purify, and separate specific bone-inducing agents from SaOS-2 cells, lysate can be used as an alternative to isolated bone-stimulating factors. Lysates of SaOS-2 stimulate the activity of the alkaline phosphatase of human osteoblastic cells HOS 58 in vitro. In other words, they probably possess osteoinductive activity. Different serial concentrations of substances like dexamethasone and insulin were tested with and without a lysate of SaOS-2 cells to assay their synergistic action. Results showed that a lysate of the SaOS-2 cell line acts as a synergistic agent and increases the osteoinductive activity of known bone-inducing agents. SaOS-2 cell lysate could be used in the future as a clinical agent to promote bone repair and possibly enhance osteointegration. Using SaOS-2 total cellular extract offers the possibility of lowering the effective dose of other bone-inducing agents.

  16. Protective Effect of Chitin Urocanate Nanofibers against Ultraviolet Radiation.

    PubMed

    Ito, Ikuko; Yoneda, Toshikazu; Omura, Yoshihiko; Osaki, Tomohiro; Ifuku, Shinsuke; Saimoto, Hiroyuki; Azuma, Kazuo; Imagawa, Tomohiro; Tsuka, Takeshi; Murahata, Yusuke; Ito, Norihiko; Okamoto, Yoshiharu; Minami, Saburo

    2015-12-19

    Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils (NFs). We typically obtain NFs by hydrolyzing chitin with acetic acid. However, in the present study, we used urocanic acid to prepare urocanic acid chitin NFs (UNFs) and examined its protective effect against UVB radiation. Hos: HR-1 mice coated with UNFs were UVB irradiated (302 nm, 150 mJ/cm²), and these mice showed markedly lower UVB radiation-induced cutaneous erythema than the control. Additionally, sunburn cells were rarely detected in the epidermis of UNFs-coated mice after UVB irradiation. Although the difference was not as significant as UNFs, the number of sunburn cells in mice treated with acetic acid chitin nanofibrils (ANFs) tended to be lower than in control mice. These results demonstrate that ANFs have a protective effect against UVB and suggest that the anti-inflammatory and antioxidant effects of NFs influence the protective effect of ANFs against UVB radiation. The combination of NFs with other substances that possess UV-protective effects, such as urocanic acid, may provide an enhanced protective effect against UVB radiation.

  17. Anti-Inflammatory Effect of Angelica gigas via Heme Oxygenase (HO)-1 Expression.

    PubMed

    Cho, Joon Hyeong; Kwon, Jung Eun; Cho, Youngmi; Kim, Inhye; Kang, Se Chan

    2015-06-15

    Angelica gigas (AG) is effective against various medical conditions such as bacterial infection, inflammation, and cancer. It contains a number of coumarin compounds and the group of interest is the pyranocoumarin, which comprises decursin and decursinol angelate. This group has an effect on controlling inflammation, which is caused by excessive nitric oxide (NO) production. Heme oxygenases (HOs), particularly HO-1, play a role in regulating the production of NO. Thus, this study aimed to investigate the anti-inflammatory effects of AG by measuring HO-1 expression. Treatments with CH2Cl2 layer and Angelica gigas extract (AGE) showed the highest NO inhibition effects. Decursin, decursinol angelate, and nodakenin were isolated from the CH2Cl2 layer of AGE. Decursin also demonstrated the highest anti-oxidative effect among the coumarins. Although decursin had the best NO inhibition and anti-oxidative effects, the effects of AGE treatment far surpassed that of decursin. This is owing to the combination effect of the coumarins present within AGE, which is a solvent extract of AG. The expression of HO-1 is an effective indicator of the anti-inflammatory effects of AG. Based on the results of the coumarin compounds, HO-1 expression was found to be dose dependent and specific to decursin.

  18. A liquid biopsy-based method for the detection and quantification of circulating tumor cells in surgical osteosarcoma patients

    PubMed Central

    Zhang, Haoqiang; Gao, Peng; Xiao, Xin; Heger, Michal; Geng, Lei; Fan, Bo; Yuan, Yulin; Huang, Chen; Chen, Guojing; Liu, Yao; Hu, Yongchen; Yu, Xiuchun; Wu, Sujia; Wang, Ling; Wang, Zhen

    2017-01-01

    A method for the enumeration and quantification of osteosarcoma (OS) circulating tumor cells (CTCs) is currently not available. A correlation between the number of CTCs and progression-free survival (PFS) has been established for other cancers, but not for OS CTCs. A method was therefore developed for CTC quantification in OS and validated in a prospective cohort of surgical patients with primary and recurrent/metastatic OS (N=23). Human OS cells, acting as CTCs, were enumerated from spiked human peripheral blood (PB) following erythrocyte and leukocyte depletion. The OS cells were quantified microscopically based on aneuploidy and a CK18−/CD45− phenotype. Aneuploidy was assayed by fluorescence in situ hybridization (FISH) using fluorescence-labeled alpha-satellite probes for the centromeres of chromosome (CEP 8). CK18 and CD45 phenotyping was performed with immunocytochemistry. HOS cells in spiked PB could be effectively retrieved with the FISH-based enumeration method, which was subsequently employed in an OS patient cohort. PB of recurrent/metastatic OS patients contained more CTCs than the PB of primary OS patients. OS patients with ≥2 CTCs per 7.5 ml of PB had worse PFS than patients whose PB contained <2 CTCs. In 2 cases, CTCs were present in PB of OS patients with negative X-ray and chest CT scans. In conclusion, our method was able to quantitate CTCs in liquid biopsies of OS patients. The number of CTCs has diagnostic and prognostic value. PMID:28350107

  19. A liquid biopsy-based method for the detection and quantification of circulating tumor cells in surgical osteosarcoma patients.

    PubMed

    Zhang, Haoqiang; Gao, Peng; Xiao, Xin; Heger, Michal; Geng, Lei; Fan, Bo; Yuan, Yulin; Huang, Chen; Chen, Guojing; Liu, Yao; Hu, Yongchen; Yu, Xiuchun; Wu, Sujia; Wang, Ling; Wang, Zhen

    2017-03-08

    A method for the enumeration and quantification of osteosarcoma (OS) circulating tumor cells (CTCs) is currently not available. A correlation between the number of CTCs and progression-free survival (PFS) has been established for other cancers, but not for OS CTCs. A method was therefore developed for CTC quantification in OS and validated in a prospective cohort of surgical patients with primary and recurrent/metastatic OS (N=23). Human OS cells, acting as CTCs, were enumerated from spiked human peripheral blood (PB) following erythrocyte and leukocyte depletion. The OS cells were quantified microscopically based on aneuploidy and a CK18-/CD45- phenotype. Aneuploidy was assayed by fluorescence in situ hybridization (FISH) using fluorescence-labeled alpha-satellite probes for the centromeres of chromosome (CEP 8). CK18 and CD45 phenotyping was performed with immunocytochemistry. HOS cells in spiked PB could be effectively retrieved with the FISH-based enumeration method, which was subsequently employed in an OS patient cohort. PB of recurrent/metastatic OS patients contained more CTCs than the PB of primary OS patients. OS patients with ≥2 CTCs per 7.5 ml of PB had worse PFS than patients whose PB contained <2 CTCs. In 2 cases, CTCs were present in PB of OS patients with negative X-ray and chest CT scans. In conclusion, our method was able to quantitate CTCs in liquid biopsies of OS patients. The number of CTCs has diagnostic and prognostic value.

  20. Ethylene glycol, but not DMSO, could replace glycerol inclusion in soybean lecithin-based extenders in ram sperm cryopreservation.

    PubMed

    Najafi, Abouzar; Daghigh-Kia, Hossein; Dodaran, Hossein Vaseghi; Mehdipour, Mahdieh; Alvarez-Rodriguez, Manuel

    2017-02-01

    The aim of this study was to evaluate the effects of glycerol, ethylene glycol or DMSO in a soybean lecithin extender for freezing ram semen. In this study, 20 ejaculates were collected from four Ghezel rams and diluted with soybean lecithin extender with glycerol (7%), ethylene glycol (3%, 5% and 7%) or DMSO (3%, 5% and 7%). Sperm motility (CASA), membrane integrity (HOS test), viability, total abnormality, mitochondrial activity (Rhodamine 123) and apoptotic features (Annexin V/Propidium iodide) were assessed after thawing. There was no significant difference between glycerol and ethylene glycol at different concentrations (3% and 5%) regarding sperm total and progressive motility, viability, and membrane integrity. The least percentages of mitochondrial functionality were observed in samples frozen with all different DMSO concentrations tested (P<0.05). Moreover, the percentage of post-thawed dead sperm was the greatest for all the DMSO concentrations compared with other groups (P<0.05). Thus, DMSO had an adverse effect on the post thaw ram sperm parameters. In contrast, ethylene glycol could be a desirable substitute of glycerol in the freezing extender, in view of similar results obtained in post-thaw quality of ram semen cryopreserved in a soybean lecithin extender. We propose that glycerol in a soybean lecithin based extender could be replaced by ethylene glycol at 3% or 5% concentrations.

  1. Tumor Suppressor WWOX inhibits osteosarcoma metastasis by modulating RUNX2 function.

    PubMed

    Del Mare, Sara; Aqeilan, Rami I

    2015-08-10

    Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. This malignant osteoid forming tumor is characterized by its metastatic potential, mainly to lungs. We recently demonstrated that WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human OS and that WWOX restoration in WWOX-negative OS cells suppresses tumorigenicity. Of note, WWOX levels are reduced in paired OS samples of post-treatment metastastectomies as compared to pre-treatment biopsies suggesting that decreased WWOX levels are associated with a more aggressive phenotype at the metastatic site. Nevertheless, little is known about WWOX function in OS metastasis. Here, we investigated the role of tumor suppressor WWOX in suppressing pulmonary OS metastasis both in vitro and in vivo. We demonstrated that ectopic expression of WWOX in OS cells, HOS and LM-7, inhibits OS invasion and cell migration in vitro. Furthermore, WWOX expression reduced tumor burden in vivo and inhibited metastases' seeding and colonization. Mechanistically, WWOX function is associated with reduced levels of RUNX2 metastatic target genes implicated in adhesion and motility. Our results suggest that WWOX plays a critical role in determining the aggressive phenotype of OS, and its expression could be an attractive therapeutic target to combat this devastating adolescent disease.

  2. Frequent Attenuation of the WWOX Tumor Suppressor in Osteosarcoma is Associated with Increased Tumorigenicity and Aberrant RUNX2 Expression

    PubMed Central

    Kurek, Kyle; Del Mare, Sara; Salah, Zaidoun; Abdeen, Suhaib; Sadiq, Hussain; Lee, Sukhee; Gaudio, Eugenio; Zanesi, Nicola; Jones, Kevin B.; DeYoung, Barry; Amir, Gail; Gebhardt, Mark; Warman, Matthew; Stein, Gary S.; Stein, Janet L.; Lian, Jane B.; Aqeilan, Rami I.

    2011-01-01

    The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is deleted or attenuated in most human tumors. Wwox-deficient mice develop osteosarcoma (OS), an aggressive bone tumor with poor prognosis that often metastasizes to lung. On the basis of these observations, we examined the status of WWOX in human OS specimens and cell lines. In human OS clinical samples, WWOX expression was absent or reduced in 58% of tumors examined (P< 0.0001). Compared to the primary tumors, WWOX levels frequently increased in tumors resected following chemotherapy. In contrast, tumor metastases to lung often exhibited reduced WWOX levels, relative to the primary tumor. In human OS cell lines having reduced WWOX expression, ectopic expression of WWOX inhibited proliferation and attenuated invasion in vitro, and suppressed tumorgenicity in nude mice. Expression of WWOX was associated with reduced RUNX2 expression in OS cell lines, whereas Runx2 levels were elevated in femurs of Wwox-deficient mice. Furthermore, WWOX reconstitution in HOS cells was associated with downregulation of RUNX2 levels and RUNX2 target genes, consistent with the ability of WWOX to suppress RUNX2 transactivation activity. In clinical samples, RUNX2 was expressed in the majority of primary tumors and undetectable in most tumors resected following chemotherapy, whereas most metastases were RUNX2 positive. Our results deepen the evidence of a tumor suppressor role for WWOX in OS, furthering its prognostic and therapeutic significance in this disease. PMID:20530675

  3. Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression.

    PubMed

    Kurek, Kyle C; Del Mare, Sara; Salah, Zaidoun; Abdeen, Suhaib; Sadiq, Hussain; Lee, Suk-Hee; Gaudio, Eugenio; Zanesi, Nicola; Jones, Kevin B; DeYoung, Barry; Amir, Gail; Gebhardt, Mark; Warman, Matthew; Stein, Gary S; Stein, Janet L; Lian, Jane B; Aqeilan, Rami I

    2010-07-01

    The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is deleted or attenuated in most human tumors. Wwox-deficient mice develop osteosarcoma (OS), an aggressive bone tumor with poor prognosis that often metastasizes to lung. On the basis of these observations, we examined the status of WWOX in human OS specimens and cell lines. In human OS clinical samples, WWOX expression was absent or reduced in 58% of tumors examined (P < 0.0001). Compared with the primary tumors, WWOX levels frequently increased in tumors resected following chemotherapy. In contrast, tumor metastases to lung often exhibited reduced WWOX levels relative to the primary tumor. In human OS cell lines having reduced WWOX expression, ectopic expression of WWOX inhibited proliferation and attenuated invasion in vitro, and suppressed tumorigenicity in nude mice. Expression of WWOX was associated with reduced RUNX2 expression in OS cell lines, whereas RUNX2 levels were elevated in femurs of Wwox-deficient mice. Furthermore, WWOX reconstitution in HOS cells was associated with downregulation of RUNX2 levels and RUNX2 target genes, consistent with the ability of WWOX to suppress RUNX2 transactivation activity. In clinical samples, RUNX2 was expressed in the majority of primary tumors and undetectable in most tumors resected following chemotherapy, whereas most metastases were RUNX2 positive. Our results deepen the evidence of a tumor suppressor role for WWOX in OS, furthering its prognostic and therapeutic significance in this disease.

  4. Tumor Suppressor WWOX inhibits osteosarcoma metastasis by modulating RUNX2 function

    PubMed Central

    Del Mare, Sara; Aqeilan, Rami I.

    2015-01-01

    Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. This malignant osteoid forming tumor is characterized by its metastatic potential, mainly to lungs. We recently demonstrated that WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human OS and that WWOX restoration in WWOX-negative OS cells suppresses tumorigenicity. Of note, WWOX levels are reduced in paired OS samples of post-treatment metastastectomies as compared to pre-treatment biopsies suggesting that decreased WWOX levels are associated with a more aggressive phenotype at the metastatic site. Nevertheless, little is known about WWOX function in OS metastasis. Here, we investigated the role of tumor suppressor WWOX in suppressing pulmonary OS metastasis both in vitro and in vivo. We demonstrated that ectopic expression of WWOX in OS cells, HOS and LM-7, inhibits OS invasion and cell migration in vitro. Furthermore, WWOX expression reduced tumor burden in vivo and inhibited metastases’ seeding and colonization. Mechanistically, WWOX function is associated with reduced levels of RUNX2 metastatic target genes implicated in adhesion and motility. Our results suggest that WWOX plays a critical role in determining the aggressive phenotype of OS, and its expression could be an attractive therapeutic target to combat this devastating adolescent disease. PMID:26256646

  5. Surveying the Impact of Work Hours and Schedules on Commercial Motor Vehicle Driver Sleep

    PubMed Central

    Hege, Adam; Perko, Michael; Johnson, Amber; Yu, Chong Ho; Sönmez, Sevil; Apostolopoulos, Yorghos

    2015-01-01

    Background Given the long hours on the road involving multiple and interacting work stressors (i.e., delivery pressures, irregular shifts, ergonomic hazards), commercial drivers face a plethora of health and safety risks. Researchers goal was to determine whether and to what extent long-haul trucker work schedules influence sleep duration and quality. Methods Survey and biometric data collected from male long-haul truck drivers at a major truckstop in central North Carolina over a six month period. Results Daily hours worked (mean = 11 hours, 55 minutes) and frequency of working over government-mandated daily HOS regulations (23.8% “frequently or always”) were statistically significant predictors of sleep duration. Miles driven per week (mean = 2,812.61), irregular daily hours worked (63.8%), and frequency of working over the daily hour limit (23.8% “frequently or always”) were statistically significant predictors of sleep quality. Conclusion Implications of findings suggest a comprehensive review of the regulations and operational conditions for commercial motor vehicle drivers be undertaken. PMID:26106509

  6. Mapping the Binding Interface of VEGF and a Monoclonal Antibody Fab-1 Fragment with Fast Photochemical Oxidation of Proteins (FPOP) and Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zhang, Ying; Wecksler, Aaron T.; Molina, Patricia; Deperalta, Galahad; Gross, Michael L.

    2017-03-01

    We previously analyzed the Fab-1:VEGF (vascular endothelial growth factor) system described in this work, with both native top-down mass spectrometry and bottom-up mass spectrometry (carboxyl-group or GEE footprinting) techniques. This work continues bottom-up mass spectrometry analysis using a fast photochemical oxidation of proteins (FPOP) platform to map the solution binding interface of VEGF and a fragment antigen binding region of an antibody (Fab-1). In this study, we use FPOP to compare the changes in solvent accessibility by quantitating the extent of oxidative modification in the unbound versus bound states. Determining the changes in solvent accessibility enables the inference of the protein binding sites (epitope and paratopes) and a comparison to the previously published Fab-1:VEGF crystal structure, adding to the top-down and bottom-up data. Using this method, we investigated peptide-level and residue-level changes in solvent accessibility between the unbound proteins and bound complex. Mapping these data onto the Fab-1:VEGF crystal structure enabled successful characterization of both the binding region and regions of remote conformation changes. These data, coupled with our previous higher order structure (HOS) studies, demonstrate the value of a comprehensive toolbox of methods for identifying the putative epitopes and paratopes for biotherapeutic antibodies.

  7. Synthesis, characterization, DNA interaction and cleavage, and in vitro cytotoxicity of copper(II) mixed-ligand complexes with 2-phenyl-3-hydroxy-4(1H)-quinolinone.

    PubMed

    Buchtík, Roman; Trávníček, Zdeněk; Vančo, Ján; Herchel, Radovan; Dvořák, Zdeněk

    2011-10-07

    A series of mixed-ligand complexes [Cu(qui)(L)]NO(3)·xH(2)O (1-6), where Hqui = 2-phenyl-3-hydroxy-4(1H)-quinolinone, L = 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), bis(2-pyridyl)amine (ambpy) (3), 5-methyl-1,10-phenanthroline (mphen) (4), 5-nitro-1,10-phenanthroline (nphen) (5) and bathophenanthroline (bphen) (6), have been synthesized and fully characterized. The X-ray structures of [Cu(qui)(phen)]NO(3)·H(2)O (2) and [Cu(qui)(ambpy)]NO(3) (3a) show a slightly distorted square-planar geometry in the vicinity of the central copper(II) atom. An in vitro cytotoxicity study of the complexes found significant activity against human osteosarcoma (HOS) and human breast adenocarcinoma (MCF7) cell lines, with the best results for complex 6, where IC(50) equals to 2.1 ± 0.2 μM, and 2.2 ± 0.4 μM, respectively. The strong interactions of the complexes with calf thymus DNA (CT-DNA) and high ability to cleave pUC19 DNA plasmid were found. A correlation has been found between the in vitro cytotoxicity and DNA cleavage studies of the complexes.

  8. Response of goat sperm to hypoosmotic steps modelled probit analysis.

    PubMed

    Leboeuf, B; Le Vern, Y; Furstoss, V; Kerboeuf, D; Guillouet, P; Magistrini, M

    2006-02-01

    Hypoosmotic swelling test (HOS) has been proposed by many authors to evaluate the functional integrity of the sperm membrane. Our approach in this experiment has consisted in exposing spermatozoa to a wide range of osmotic pressures then evaluating the reacted sperm cells by flow cytometry and finally modelling the sperm cell responses. Semen samples were diluted in skim milk or NPPC (native phosphocaseinate) extenders, and stored at 4 degrees C for 3 days. At D0 and D3 aliquots from each ejaculate (n=12) were submitted to seven hypoosmotic solutions varying from 230 to 10mOsm/kg. Sperm samples were analyzed using flow cytometry to determine two populations of spermatozoa identified by propidium iodide (PI): PI+ (including PI, red fluorescence) and PI- (excluding PI, no fluorescence). Spermatozoa PI+ were considered as spermatozoa with membrane damages. PI+ exhibited a high variation from 230 to 10mOsm/kg which was considered as a dose-response curve. Data were modelled using Mixed procedure and probit analysis to a sigmoid curve. Each model curve characterized the profile of response of the variable PI+ to the range of osmotic pressure from 230 to 10mOsm/kg. The estimated parameters modelling the sigmoid curves are discussed in order to evaluate the effect of extender (skim milk versus NPPC) and duration of preservation (D0 versus D3). Such modelling could help to differentiate storage method ejaculates within males or between male, contributing therefore to improve semen technology.

  9. Blind deconvolution and source separation in acoustics

    NASA Astrophysics Data System (ADS)

    Sibul, Leon H.; Roan, Michael J.; Coviello, Christian M.

    2005-09-01

    Blind deconvolution (BDC) and blind source separation (BSS) are active research topics with many important applications in acoustics. The goal of deconvolution is to recover original input signal from the output of a convolution filter. In blind deconvolution details of the convolution filter and input signals are not known. The fundamental assumption in BDC is that the input signal is a non-Gaussian stochastic process. A topic closely related to BDC is BSS. BSS is a process that is an inverse operation to a mixing process. In BSS it is assumed that inputs to the mixing systems are statistically independent stochastic processes, where only one input may be Gaussian, others must be non-Gaussian. Standard criterion functions for BDC and BSS are reviewed. Limitations of the second-order statistics and need for higher-order statistics (HOS) or information theoretic criteria that lead to nonlinear optimization algorithms are pointed out. Advantages of various information theoretic criteria for BDC and BSS are discussed. Because gradients of these criteria are nonlinear, resulting optimization algorithms are nonlinear. Linear and non-linear algorithms for BDC and BSS are examined. [Work supported by ONR Codes 321US and 333.

  10. Hypocretin/Orexin Peptides Excite Rat Neuroendocrine Dopamine Neurons through Orexin 2 Receptor-Mediated Activation of a Mixed Cation Current

    PubMed Central

    Lyons, David J.; Hellysaz, Arash; Ammari, Rachida; Broberger, Christian

    2017-01-01

    Hypocretin/Orexin (H/O) neurons of the lateral hypothalamus are compelling modulator candidates for the chronobiology of neuroendocrine output and, as a consequence, hormone release from the anterior pituitary. Here we investigate the effects of H/O peptides upon tuberoinfundibular dopamine (TIDA) neurons – cells which control, via inhibition, the pituitary secretion of prolactin. In whole cell recordings performed in male rat hypothalamic slices, application of H/O-A, as well as H/O-B, excited oscillating TIDA neurons, inducing a reversible depolarising switch from phasic to tonic discharge. The H/O-induced inward current underpinning this effect was post-synaptic (as it endured in the presence of tetrodotoxin), appeared to be carried by a Na+-dependent transient receptor potential-like channel (as it was blocked by 2-APB and was diminished by removal of extracellular Na+), and was a consequence of OX2R receptor activation (as it was blocked by the OX2R receptor antagonist TCS OX2 29, but not the OX1R receptor antagonist SB 334867). Application of the hormone, melatonin, failed to alter TIDA membrane potential or oscillatory activity. This first description of the electrophysiological effects of H/Os upon the TIDA network identifies cellular mechanisms that may contribute to the circadian rhythmicity of prolactin secretion. PMID:28145492

  11. Mobile phones affect multiple sperm quality traits: a meta-analysis

    PubMed Central

    Dama, Madhukar Shivajirao

    2013-01-01

    As mobile phone usage is growing rapidly, there is a need for a comprehensive analysis of the literature to inform scientific debates about the adverse effects of mobile phone radiation on sperm quality traits. Therefore, we conducted a meta-analysis of the eligible published research studies on human males of reproductive age. Eleven studies were eligible for this analysis. Based on the meta-analysis, mobile phone use was significantly associated with deterioration in semen quality (Hedges’s g = -0.547; 95% CI: -0.713, -0.382; p < 0.001). The traits particularly affected adversely were sperm concentration, sperm morphology, sperm motility, proportion of non-progressive motile sperm (%), proportion of slow progressive motile sperm (%), and sperm viability. Direct exposure of spermatozoa to mobile phone radiation with in vitro study designs also significantly deteriorated the sperm quality (Hedges’s g = -2.233; 95% CI: -2.758, -1.708; p < 0.001), by reducing straight line velocity, fast progressive motility, Hypo-osmotic swelling (HOS) test score, major axis (µm), minor axis (µm), total sperm motility, perimeter (µm), area (µm 2), average path velocity, curvilinear velocity, motile spermatozoa, and  acrosome reacted spermatozoa (%). The strength of evidence for the different outcomes varied from very low to very high. The analysis shows that mobile phone use is possibly associated with a number of deleterious effects on the spermatozoa. PMID:24327874

  12. Anti-Inflammatory Effect of Angelica gigas via Heme Oxygenase (HO)-1 Expression

    PubMed Central

    Cho, Joon Hyeong; Kwon, Jung Eun; Cho, Youngmi; Kim, Inhye; Kang, Se Chan

    2015-01-01

    Angelica gigas (AG) is effective against various medical conditions such as bacterial infection, inflammation, and cancer. It contains a number of coumarin compounds and the group of interest is the pyranocoumarin, which comprises decursin and decursinol angelate. This group has an effect on controlling inflammation, which is caused by excessive nitric oxide (NO) production. Heme oxygenases (HOs), particularly HO-1, play a role in regulating the production of NO. Thus, this study aimed to investigate the anti-inflammatory effects of AG by measuring HO-1 expression. Treatments with CH2Cl2 layer and Angelica gigas extract (AGE) showed the highest NO inhibition effects. Decursin, decursinol angelate, and nodakenin were isolated from the CH2Cl2 layer of AGE. Decursin also demonstrated the highest anti-oxidative effect among the coumarins. Although decursin had the best NO inhibition and anti-oxidative effects, the effects of AGE treatment far surpassed that of decursin. This is owing to the combination effect of the coumarins present within AGE, which is a solvent extract of AG. The expression of HO-1 is an effective indicator of the anti-inflammatory effects of AG. Based on the results of the coumarin compounds, HO-1 expression was found to be dose dependent and specific to decursin. PMID:26083119

  13. Hydrophilic polymer drug from a derivative of salicylic acid: synthesis, controlled release studies and biological behavior.

    PubMed

    Rodríguez, Gema; Gallardo, Alberto; Fernández, Mar; Rebuelta, Mercedes; Buján, Julia; Bellón, Juan María; Honduvilla, Natalio G; Escudero, Cristina; San Román, Julio

    2004-06-25

    Hydrophilic polymeric drugs bearing "Triflusal" (4-trifluoromethylsalicylic acid), a drug widely used as antithrombogenic agent (Disgren), have been prepared by free radical copolymerization of methacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)] benzoate (HTRF) and N,N'-dimethylacrylamide (DMA). The reactivity ratios of both monomers have been determined by 1H NMR spectra by applying non-linear least square treatments to the copolymerization equation (terminal model), and the kinetic parameters obtained indicated that the microstructure of copolymer chains is homogeneous, with a random distribution of the active HTRF units along the copolymer chains. That means that for the copolymer system THDMA22 used in this work, HTRF units are mainly isolated in relatively long DMA sequences. Therefore, in this structure the intramolecular interactions between adjacent HTRF units are negligible. Release of Triflusal from THDMA22 has been studied in vitro using buffered solutions at pH = 2, 7.4 and 10 and 37 degrees C. The system showed an interesting pseudo-zero order release profile at pH = 7.4 during several months. It has been also evaluated the pharmacological activity and the behavior of the system in contact with biological media. In this sense, we have carried out some in vitro studies about the antiaggregant properties and biocompatibility of THDMA22. Results demonstrate that this copolymer inhibits platelet aggregation in its macromolecular form and presents a good biocompatibility with Human Osteoblastic Cells (HOS).

  14. Heme reversibly damps PERIOD2 rhythms in mouse suprachiasmatic nucleus explants.

    PubMed

    Guenthner, C J; Bickar, D; Harrington, M E

    2009-12-01

    The hypothalamic suprachiasmatic nucleus (SCN), which in mammals serves as the master circadian pacemaker by synchronizing autonomous clocks in peripheral tissues, is composed of coupled single-cell oscillators that are driven by interlocking positive/negative transcriptional/translational feedback loops. Several studies have suggested that heme, a common prosthetic group that is synthesized and degraded in a circadian manner in the SCN, may modulate the function of several feedback loop components, including the REV-ERB nuclear receptors and PERIOD2 (PER2). We found that ferric heme (hemin, 3-100 microM) dose-dependently and reversibly damped luminescence rhythms in SCN explants from mice expressing a PER2::LUCIFERASE (PER2::LUC) fusion protein. Inhibitors of heme oxygenases (HOs, which degrade heme to biliverdin, carbon monoxide, and iron) mimicked heme's effects on PER2 rhythms. In contrast, heme and HO inhibition did not damp luminescence rhythms in thymus and esophagus explants and had only a small effect on PER2::LUC damping in spleen explants, suggesting that heme's effects are tissue-specific. Analysis of the effects of heme's degradation products on SCN PER2::LUC rhythms indicated that they probably were not responsible for heme's effects on rhythms. The heme synthesis inhibitor N-methylprotoporphyrinIX (NMP) lengthened the circadian period of SCN PER2::LUC rhythms by about an hour. These data are consistent with an important role for heme in the circadian system.

  15. Wellness engineering for better quality of life of aging baby boomer

    NASA Astrophysics Data System (ADS)

    Szu, Harold

    2007-04-01

    Current health care system serving 78M aging baby-boomers is no longer sustainable, as the cost about 1/5 GDP will reach 1/4 GDT when all is retired in decades, unless the system is changed. We design a high-tech safe net to enhance the timeliness of early correct treatment execution (otherwise, causing 1/4 mortality associated with an escalating legal fee waste). We follow the common sense that "a stitch in time saves nine," and adopt the military surveillance know-how in designing early warning health management system, comprising of smart sensor pairs for point-care surveillance. However, the grand plan of affordable smart sensors hardware for households requires an ODM & OEM teaming to conduct parallel designing and sequential marketing strategy. The military software strategy combating a treacherous adversary enemy match well with point cares surveillance overcoming real world microorganism variability. Moreover, such smart military software provides self-reference change detection, not by traditional cohort ensemble average, but by individual own higher order statistics (HOS) independent component analysis (ICA), which take the advantage of known initial condition for each individual and desirable over-sampling daily dynamics. The triggering of warning follows the military algorithms comprising of Receiver Operation Characteristics (ROC) and Automatic Target Recognition (ATR). To further reduce the unwanted false negative rate, a benchmarked is made against the traditional cohort-ensemble baseline average & the upper & lower bounds of variance as adopted by the gatekeepers - Medical Doctors (MD) and Nurses.

  16. Inhibition of hyaluronan retention by 4-methylumbelliferone suppresses osteosarcoma cells in vitro and lung metastasis in vivo

    PubMed Central

    Arai, E; Nishida, Y; Wasa, J; Urakawa, H; Zhuo, L; Kimata, K; Kozawa, E; Futamura, N; Ishiguro, N

    2011-01-01

    Background: Hyaluronan (HA) plays crucial roles in the tumourigenicity of many types of malignant tumours. 4-Methylumbelliferone (MU) is an inhibitor of HA synthesis. Several studies have shown its inhibitory effects on malignant tumours; however, none have focused on its effects on osteosarcoma. Methods: We investigated the effects of MU on HA accumulation and tumourigenicity of highly metastatic murine osteosarcoma cells (LM8) that have HA-rich cell-associated matrix, and human osteosarcoma cell lines (MG-63 and HOS). Results: In vitro, MU inhibited HA retention, thereby reducing the formation of functional cell-associated matrices, and also inhibited cell proliferation, migration, and invasion. Akt phosphorylation was suppressed by MU (1.0 m). In vivo, although MU showed only a mild inhibitory effect on the growth of the primary tumour, it markedly inhibited (75% reduction) the development of lung metastasis. Hyaluronan retention in the periphery of the primary tumour was markedly suppressed by MU. Conclusion: These findings suggested that MU suppressed HA retention and cell-associated matrix formation in osteosarcoma cells, resulting in a reduction of tumourigenicity, including lung metastasis. 4-Methylumbelliferone is a promising therapeutic agent targeting both primary tumours and distant metastasis of osteosarcoma, possibly via suppression of HA retention. PMID:22045192

  17. Interferon but not MxB inhibits foamy retroviruses.

    PubMed

    Bähr, Ariane; Singer, Anna; Hain, Anika; Vasudevan, Ananda Ayyappan Jaguva; Schilling, Mirjam; Reh, Juliane; Riess, Maximilian; Panitz, Sylvia; Serrano, Vanessa; Schweizer, Matthias; König, Renate; Chanda, Sumit; Häussinger, Dieter; Kochs, Georg; Lindemann, Dirk; Münk, Carsten

    2016-01-15

    Foamy viruses (FV) are retroviruses that are widely distributed in primate and non-primate animal species. We tested here FV with capsids of simian and non-simian origin for sensitivity to interferon-β (IFN-β). Our data show significant inhibition of FV by IFN-β early in infection of human HOS and THP-1 but not of HEK293T cells. The post-entry restriction of FV was not mediated by the interferon-induced MxB protein that was recently identified as a capsid-interacting restriction factor targeting Human immunodeficiency virus (HIV) before integration. Neither the ectopic expression of MxA or MxB in HEK293T cells nor the lack of MxB expression in CRISPR/CAS MxB THP-1 knockout cells impacted the infection of the tested FV. IFN-β treated THP-1 and THP-1 KO MxB cells showed the same extend of restriction to FV. Together, the data demonstrate that IFN-β inhibits FV early in infection and that MxB is not a restriction factor of FV.

  18. Accessible solitons in complex Ginzburg-Landau media

    NASA Astrophysics Data System (ADS)

    He, Yingji; Malomed, Boris A.

    2013-10-01

    We construct dissipative spatial solitons in one- and two-dimensional (1D and 2D) complex Ginzburg-Landau (CGL) equations with spatially uniform linear gain; fully nonlocal complex nonlinearity, which is proportional to the integral power of the field times the harmonic-oscillator (HO) potential, similar to the model of “accessible solitons;” and a diffusion term. This CGL equation is a truly nonlinear one, unlike its actually linear counterpart for the accessible solitons. It supports dissipative spatial solitons, which are found in a semiexplicit analytical form, and their stability is studied semianalytically, too, by means of the Routh-Hurwitz criterion. The stability requires the presence of both the nonlocal nonlinear loss and diffusion. The results are verified by direct simulations of the nonlocal CGL equation. Unstable solitons spontaneously spread out into fuzzy modes, which remain loosely localized in the effective complex HO potential. In a narrow zone close to the instability boundary, both 1D and 2D solitons may split into robust fragmented structures, which correspond to excited modes of the 1D and 2D HOs in the complex potentials. The 1D solitons, if shifted off the center or kicked, feature persistent swinging motion.

  19. A new 2D monolayer BiXene, M2C (M = Mo, Tc, Os).

    PubMed

    Sun, Weiwei; Li, Yunguo; Wang, Baotian; Jiang, Xue; Katsnelson, Mikhail I; Korzhavyi, Pavel; Eriksson, Olle; Di Marco, Igor

    2016-08-25

    The existence of BiXenes, a new family of 2D monolayers, is hereby predicted. Theoretically, BiXenes have 1H symmetry (P6[combining macron]m2) and can be formed from the 4d/5d binary carbides. As the name suggests, they are close relatives of MXenes, which instead have 1T symmetry (P3[combining macron]m1). The newly found BiXenes, as well as some new MXenes, are shown to have formation energies close to that of germanene, which suggests that these materials should be possible to be synthesised. Among them, we illustrate that 1H-Tc2C and 1T-Mo2C are dynamically stable at 0 K, while 1H-Mo2C, 1T-Tc2C, 1H-Os2C, and 1T-Rh2C are likely to be stabilised via strain or temperature. In addition, the nature of the chemical bonding is analysed, emphasizing that the covalency between the transition metal ions and carbon is much stronger in BiXenes than in MXenes. The emergence of BiXenes can not only open up a new era of conducting 2D monolayers, but also provide good candidates for carrier materials aimed at energy storage and spintronic devices that have already been unveiled in MXenes.

  20. Metformin displays in vitro and in vivo antitumor effect against osteosarcoma

    PubMed Central

    Ko, Yunmi; Choi, Aery; Lee, Minyoung

    2016-01-01

    Purpose Patients with unresectable, relapsed, or refractory osteosarcoma need a novel therapeutic agent. Metformin is a biguanide derivative used in the treatment of type II diabetes, and is recently gaining attention in cancer research. Methods We evaluated the effect of metformin against human osteosarcoma. Four osteosarcoma cell lines (KHOS/NP, HOS, MG-63, U-2 OS) were treated with metformin and cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were evaluated using flow cytometric analysis, and migration and wound healing assay were performed. Fourteen female Balb/c-nude mice received KHOS/NP cell grafts in their thigh, and were allowed access to metformin containing water (2 mg/mL) ad libitum. Tumor volume was measured every 3–4 days for a period of 4 weeks. Results Metformin had a significant antiproliferative effect on human osteosarcoma cells. In particular, metformin inhibited the proliferation and migration of KHOS/NP cells by activation of AMP-activated protein kinase and consequent inhibition of the mammalian target of rapamycin pathway. It also inhibited the proliferation of cisplatin-resistant KHOS/NP clone cells. Analysis of KHOS/NP xenograft Balb/c-nude models indicated that metformin displayed potent in vivo antitumor effects. Conclusion Further studies are necessary to explore metformin's therapeutic potential and the possibilities for its use as an adjuvant agent for osteosarcoma. PMID:27721842

  1. Protective Effect of Chitin Urocanate Nanofibers against Ultraviolet Radiation

    PubMed Central

    Ito, Ikuko; Yoneda, Toshikazu; Omura, Yoshihiko; Osaki, Tomohiro; Ifuku, Shinsuke; Saimoto, Hiroyuki; Azuma, Kazuo; Imagawa, Tomohiro; Tsuka, Takeshi; Murahata, Yusuke; Ito, Norihiko; Okamoto, Yoshiharu; Minami, Saburo

    2015-01-01

    Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils (NFs). We typically obtain NFs by hydrolyzing chitin with acetic acid. However, in the present study, we used urocanic acid to prepare urocanic acid chitin NFs (UNFs) and examined its protective effect against UVB radiation. Hos: HR-1 mice coated with UNFs were UVB irradiated (302 nm, 150 mJ/cm2), and these mice showed markedly lower UVB radiation-induced cutaneous erythema than the control. Additionally, sunburn cells were rarely detected in the epidermis of UNFs-coated mice after UVB irradiation. Although the difference was not as significant as UNFs, the number of sunburn cells in mice treated with acetic acid chitin nanofibrils (ANFs) tended to be lower than in control mice. These results demonstrate that ANFs have a protective effect against UVB and suggest that the anti-inflammatory and antioxidant effects of NFs influence the protective effect of ANFs against UVB radiation. The combination of NFs with other substances that possess UV-protective effects, such as urocanic acid, may provide an enhanced protective effect against UVB radiation. PMID:26703629

  2. Synthesis and spectral characterization of silver/magnesium co-substituted hydroxyapatite for biomedical applications.

    PubMed

    Gopi, D; Shinyjoy, E; Kavitha, L

    2014-06-05

    The present work is aimed at the synthesis of antibacterial and bioactive silver/magnesium co-substituted hydroxyapatite (Ag/Mg-HAP) powders. For this purpose, firstly, different concentrations (0.5, 1.5, 2.5wt.%) of silver substituted HAP (Ag-HAP) powders were prepared by ultrasonic irradiation technique and were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDAX). Secondly, magnesium (Mg) is co-substituted as secondary material into Ag-HAP to offset the potential cytotoxicity of Ag, as higher concentration of Ag is toxic. The antibacterial activity of as-synthesized powders was evaluated by Escherichia coli (E. coli) and was found to be effectively high against bacterial colonization. Also, the in vitro cell-material interaction is evaluated with human osteosarcoma MG63 (HOS MG63) cells for cell proliferation. The results showed the evidence of cytotoxic effects of the higher concentration of Ag-HAP characterized by poor cellular viability whereas, Ag/Mg-HAP showed better cell viability indicating that co-substitution of Mg in Ag-HAP effectively offset the negative effects of Ag and improve performance compared with pure HAP. Thus, the as synthesized Ag/Mg-HAP will serve as a better candidate for biomedical applications with good antibacterial property and bone bonding ability.

  3. Sulfonated polyaniline-based organic electrodes for controlled electrical stimulation of human osteosarcoma cells.

    PubMed

    Min, Yong; Yang, Yanyin; Poojari, Yadagiri; Liu, Yidong; Wu, Jen-Chieh; Hansford, Derek J; Epstein, Arthur J

    2013-06-10

    Electrically conducting polymers (CPs) were found to stimulate various cell types such as neurons, osteoblasts, and fibroblasts in both in vitro and in vivo studies. However, to our knowledge, no studies have been reported on the utility of CPs in stimulation of cancer or tumor cells in the literature. Here we report a facile fabrication method of self-doped sulfonated polyaniline (SPAN)-based interdigitated electrodes (IDEs) for controlled electrical stimulation of human osteosarcoma (HOS) cells. Increased degree of sulfonation was found to increase the SPAN conductivity, which in turn improved the cell attachment and cell growth without electrical stimulation. However, an enhanced cell growth was observed under controlled electrical (AC) stimulation at low applied voltage and frequency (≤800 mV and ≤1 kHz). The cell growth reached a maximum threshold at an applied voltage or frequency and beyond which pronounced cell death was observed. We believe that these organic electrodes may find utility in electrical stimulation of cancer or tumor cells for therapy and research and may also provide an alternative to the conventional metal-based electrodes.

  4. Induction of a specific CD8+ T-cell response to cancer/testis antigens by demethylating pre-treatment against osteosarcoma.

    PubMed

    Li, Binghao; Zhu, Xiaobing; Sun, Lingling; Yuan, Li; Zhang, Jian; Li, Hengyuan; Ye, Zhaoming

    2014-11-15

    Conventional non-surgical therapeutic regimens against osteosarcoma are subject to chemoresistance and tumor relapse, and immunotherapy may be promising for this tumor. However, it's hard to find satisfactory epitopes for immunotherapy against osteosarcoma. Cancer/testis antigens (CTAs), such as MAGE-A family and NY-ESO-1, the potential antigens that almost exclusively express in tumor cells and immune-privileged sites, have been found expressed in osteosarcoma also. Nevertheless, the expression of CTAs is downregulated in many tumors, constraining the application of immunotherapy. In this article, we demonstrate that the expression of MAGE-A family and NY-ESO-1 in osteosarcoma cells can be upregulated following treatment with demethylating agent 5-aza-2'-deoxycytidine and consequently induces a CTA specific CD8+ T-cell response against osteosarcoma in vitro and in vivo. The in vivo imaging was realized by using luciferase-transfected HOS cells and DiR labeled T-cells in severely combined immunodeficiency mouse models. Cytotoxic T cells specifically recognizing MAGE-A family and NY-ESO-1 clustered at the tumor site in mice pre-treated with DAC and resulted in tumor growth suppression, while it was not observed in mice without DAC pre-treatment. This study is important for more targeted therapeutic approaches and suggests that adoptive immunotherapy, combined with demethylating treatment, has the potential for non-surgical therapeutic strategy against osteosarcoma.

  5. An Automatic Prediction of Epileptic Seizures Using Cloud Computing and Wireless Sensor Networks.

    PubMed

    Sareen, Sanjay; Sood, Sandeep K; Gupta, Sunil Kumar

    2016-11-01

    Epilepsy is one of the most common neurological disorders which is characterized by the spontaneous and unforeseeable occurrence of seizures. An automatic prediction of seizure can protect the patients from accidents and save their life. In this article, we proposed a mobile-based framework that automatically predict seizures using the information contained in electroencephalography (EEG) signals. The wireless sensor technology is used to capture the EEG signals of patients. The cloud-based services are used to collect and analyze the EEG data from the patient's mobile phone. The features from the EEG signal are extracted using the fast Walsh-Hadamard transform (FWHT). The Higher Order Spectral Analysis (HOSA) is applied to FWHT coefficients in order to select the features set relevant to normal, preictal and ictal states of seizure. We subsequently exploit the selected features as input to a k-means classifier to detect epileptic seizure states in a reasonable time. The performance of the proposed model is tested on Amazon EC2 cloud and compared in terms of execution time and accuracy. The findings show that with selected HOS based features, we were able to achieve a classification accuracy of 94.6 %.

  6. Dissecting DNA damage response pathways by analyzing protein localization and abundance changes during DNA replication stress

    PubMed Central

    Tkach, Johnny M.; Yimit, Askar; Lee, Anna Y.; Riffle, Michael; Costanzo, Michael; Jaschob, Daniel; Hendry, Jason A.; Ou, Jiongwen; Moffat, Jason; Boone, Charles; Davis, Trisha N.; Nislow, Corey; Brown, Grant W.

    2012-01-01

    Re-localization of proteins is a hallmark of the DNA damage response. We use high-throughput microscopic screening of the yeast GFP fusion collection to develop a systems-level view of protein re-organization following drug-induced DNA replication stress. Changes in protein localization and abundance reveal drug-specific patterns of functional enrichments. Classification of proteins by sub-cellular destination allows the identification of pathways that respond to replication stress. We analyzed pairwise combinations of GFP fusions and gene deletion mutants to define and order two novel DNA damage responses. In the first, Cmr1 forms subnuclear foci that are regulated by the histone deacetylase Hos2 and are distinct from the typical Rad52 repair foci. In a second example, we find that the checkpoint kinases Mec1/Tel1 and the translation regulator Asc1 regulate P-body formation. This method identifies response pathways that were not detected in genetic and protein interaction screens, and can be readily applied to any form of chemical or genetic stress to reveal cellular response pathways. PMID:22842922

  7. Reactions occurring during the sulfation of sodium chloride deposited on alumina substrates

    NASA Technical Reports Server (NTRS)

    Wu, C. S.; Birks, N.

    1986-01-01

    The reaction between solid NaCl and air containing 1 pct SO2 has been studied between 500 and 700 C. The reaction product, Na2SO4, forms not only on the surface of the NaCl but also on surrounding areas of the substrate due to the volatility of the NaCl at these temperatures. At the higher temperatures, the vapor pressure of NaCl is so high that the majority of the reaction product is distributed on the substrate. Above 625 C, the reaction product is a liquid solution of NaCl and Na2SO4 that exists only so long as NaCl is supplied from the original crystal source. Eventually, the liquid solidifies by constitutional solidification as the NaCl is converted to Na2SO4. While it exists, the liquid NaCl-Na2SO4 solution is shown to be highly corrosive to Al2O3 and, on a scale of Al2O3 growing on alloy HOS 875, particularly attacks the grain boundaries of the scale at preferred sites where chromium and iron oxides and sulfides rapidly develop. This is proposed as one mechanism by which NaCl deposition contributes to the initiation of low temperature hot corrosion.

  8. Hybrid Collagenase Nanocapsules for Enhanced Nanocarrier Penetration in Tumoral Tissues.

    PubMed

    Villegas, María Rocío; Baeza, Alejandro; Vallet-Regí, María

    2015-11-04

    Poor penetration of drug delivery nanocarriers within dense extracellular matrices constitutes one of the main liabilities of current nanomedicines. The conjugation of proteolytic enzymes on the nanoparticle surface constitutes an attractive alternative. However, the scarce resistance of these enzymes against the action of proteases or other aggressive agents present in the bloodstream strongly limits their application. Herein, a novel nanodevice able to transport proteolytic enzymes coated with an engineered pH-responsive polymeric is presented. This degradable coat protects the housed enzymes against proteolytic attack at the same time that it triggers their release under mild acidic conditions, usually present in many tumoral tissues. These enzyme nanocapsules have been attached on the surface of mesoporous silica nanoparticles, as nanocarrier model, showing a significatively higher penetration of the nanoparticles within 3D collagen matrices which housed human osteosarcoma cells (HOS). This strategy can improve the therapeutic efficacy of the current nanomedicines, allowing a more homogeneous and deeper distribution of the therapeutic nanosystems in cancerous tissues.

  9. Propagation of 3D nonlinear waves over complex bathymetry using a High-Order Spectral method

    NASA Astrophysics Data System (ADS)

    Gouin, Maïté; Ducrozet, Guillaume; Ferrant, Pierre

    2016-04-01

    Scattering of regular and irregular surface gravity waves propagating over a region of arbitrary three-dimensional varying bathymetry is considered here. The three-dimensional High-Order Spectral method (HOS) with an extension to account for a variable bathymetry is used. The efficiency of the model has been proved to be conserved even with this extension. The method is first applied to a bathymetry consisting of an elliptical lens, as used in the Vincent and Briggs (1989) experiment. Incident waves passing across the lens are transformed and a strong convergence region is observed after the elliptical mound. The wave amplification depends on the incident wave. Numerical results for regular and irregular waves are analysed and compared with other methods and experimental data demonstrating the efficiency and practical applicability of the present approach. Then the method is used to model waves propagating over a real bathymetry: the canyons of Scripps/La Jolla in California. The implementation of this complex bathymetry in the model is presented, as well as the first results achieved. They will be compared to the ones obtained with another numerical model.

  10. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications.

    PubMed

    Ryter, Stefan W; Alam, Jawed; Choi, Augustine M K

    2006-04-01

    The heme oxygenases, which consist of constitutive and inducible isozymes (HO-1, HO-2), catalyze the rate-limiting step in the metabolic conversion of heme to the bile pigments (i.e., biliverdin and bilirubin) and thus constitute a major intracellular source of iron and carbon monoxide (CO). In recent years, endogenously produced CO has been shown to possess intriguing signaling properties affecting numerous critical cellular functions including but not limited to inflammation, cellular proliferation, and apoptotic cell death. The era of gaseous molecules in biomedical research and human diseases initiated with the discovery that the endothelial cell-derived relaxing factor was identical to the gaseous molecule nitric oxide (NO). The discovery that endogenously produced gaseous molecules such as NO and now CO can impart potent physiological and biological effector functions truly represented a paradigm shift and unraveled new avenues of intense investigations. This review covers the molecular and biochemical characterization of HOs, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by environmental stress. Furthermore, the current understanding of the functional significance of HO shall be discussed from the perspective of each of the metabolic by-products, with a special emphasis on CO. Finally, this presentation aspires to lay a foundation for potential future clinical applications of these systems.

  11. Small scale contact and adhesion of soft materials in nano- and bio-systems

    NASA Astrophysics Data System (ADS)

    Cao, Yifang

    This dissertation presents the results obtained from recent experimental, theoretical and computational studies of small scale contact and adhesion of soft materials in both the nano- and bio-systems. These include: stamped flexible/organic electronic devices, and polydimethylsiloxane (PDMS) and biological human osteoscarcoma (HOS) cells. Following a presentation of a method for determining the initial contact point and nanoindentation load-indentation depth characteristics for soft materials, adhesion and contact-induced phenomena are discussed for the processing of organic electronics structures. These include experiments and models that provide new insights into metallic electrode cold welding and organic material pattern transfer processes that are being explored for the fabrication of small organic structures that are relevant to flexible bioelectronics and bioMEMS. Subsequently, a shear assay technique and cell spreading study are presented for the characterization of cell viscoelastic properties and cell prestress. These then present new evidence of how contact guidance (alignment of cells) occurs along microgrooved PDMS structures that have the potential to reduce the overall levels of scar tissue formation. The implications of the results are also assessed for cell biophysics, and potential applications in flexible bioMEMS structures.

  12. Morphofunctional disturbances of human sperm after incubation with organophosphorate pesticides.

    PubMed

    Contreras, H R; Badilla, J; Bustos-Obregón, E

    1999-08-01

    The organophosphorate pesticides are highly toxic for insects and mammals, but their effects in the male reproductive tract are scarcely known. Many alterations induced by organophosphorate pesticides have been described, such as: cytogenetic alterations in germinal cells, oligozoospermia and teratozoospermia in the mouse. Parathion, the pesticide mostly utilized in Chilean agriculture, is rapidly metabolized to paraoxon, the active metabolite, in mammalian organisms. The purpose of this study is to evaluate the effect of Parathion and paraoxon on different morphological and functional parameters of the sperm. Human spermatozoa were incubated with Parathion and paraoxon at different concentrations (0.05, 0.1, 0.2, 0.4 and 0.8 mM). Vitality (tripan blue and eosin tests), acrosome reaction (triple stain test), plasma membrane integrity (HOS-test), and chromatin stability (sodium thioglycolate test) were determined. The observations were done by optical microscopy at 1000x of magnification and three hundred sperms were evaluated for each treatment. The results indicated that Parathion and paraoxon increase the percent of sperm with acrosome reaction and also increase the percentage of sperm with chromatin decondensation in a dose-dependent manner. The vitality and plasma membrane integrity decrease significantly in a dose-dependent manner. The results suggest a direct action of Parathion and paraoxon on the different parameters studied. The morphofunctionality of sperm is altered significatively, suggesting that Parathion and paraoxon, thanks to their alkylating and electrophylic properties, could act on DNA and proteins respectively, to elicit these changes.

  13. Intelligent Case Based Decision Support System for Online Diagnosis of Automated Production System

    NASA Astrophysics Data System (ADS)

    Ben Rabah, N.; Saddem, R.; Ben Hmida, F.; Carre-Menetrier, V.; Tagina, M.

    2017-01-01

    Diagnosis of Automated Production System (APS) is a decision-making process designed to detect, locate and identify a particular failure caused by the control law. In the literature, there are three major types of reasoning for industrial diagnosis: the first is model-based, the second is rule-based and the third is case-based. The common and major limitation of the first and the second reasonings is that they do not have automated learning ability. This paper presents an interactive and effective Case Based Decision Support System for online Diagnosis (CB-DSSD) of an APS. It offers a synergy between the Case Based Reasoning (CBR) and the Decision Support System (DSS) in order to support and assist Human Operator of Supervision (HOS) in his/her decision process. Indeed, the experimental evaluation performed on an Interactive Training System for PLC (ITS PLC) that allows the control of a Programmable Logic Controller (PLC), simulating sensors or/and actuators failures and validating the control algorithm through a real time interactive experience, showed the efficiency of our approach.

  14. Cell cycle arrest and apoptosis induced by aspidin PB through the p53/p21 and mitochondria-dependent pathways in human osteosarcoma cells.

    PubMed

    Wan, Daqian; Jiang, Chaoyin; Hua, Xin; Wang, Ting; Chai, Yimin

    2015-10-01

    Aspidin PB is a natural product extracted from Dryopteris fragrans (L.) Schott, which has been characterized for its various biological activities. We reported that aspidin PB induced cell cycle arrest and apoptosis through the p53/p21 and mitochondria-dependent pathways in human osteosarcoma cells. Aspidin PB inhibited the proliferation of Saos-2, U2OS, and HOS cells in a dose-dependent and time-dependent manner. Aspidin PB induced changes in the cell cycle regulators (cyclin A, pRb, CDK2, p53, and p21), which caused cell cycle arrest in the S phase. We also explored the role of siRNA targeted to p53; it led to a dose-dependent attenuation of aspidin PB-induced apoptosis signaling. Moreover, after treatment with aspidin PB, the p21-silenced cells decreased significantly at the S phase. Aspidin PB increased the percentage of cells with mitochondrial membrane potential disruption. Western blot analysis showed that aspidin PB inhibited Bcl-2 expression and induced Bax expression to disintegrate the outer mitochondrial membrane and caused cytochrome C release. Mitochondrial cytochrome C release was associated with the activation of caspase-9 and caspase-3 cascades. Furthermore, the double-stranded DNA breaks and reactive oxygen species signaling were both involved in aspidin PB-induced DNA damage. In addition, aspidin PB inhibited tumor growth significantly in U2OS xenografts. Above all, we conclude that aspidin PB represents a valuable natural source and may potentially be applicable in osteosarcoma therapy.

  15. Topical royal jelly alleviates symptoms of pruritus in a murine model of allergic contact dermatitis

    PubMed Central

    Yamaura, Katsunori; Tomono, Ayana; Suwa, Eriko; Ueno, Koichi

    2013-01-01

    Background: Royal jelly is widely used as a health tonic, especially in Asia. Royal jelly is commonly used in cosmetics as well as in dietary supplements and beverages. Little is known, however, about the pharmacologic efficacy of topical royal jelly. Therefore, we investigated the antipruritic activity of topical royal jelly on chronic pruritus in experimental allergic contact dermatitis in mice. Materials and Methods: Hairless mice (HOS: HR-1), with chronic allergic contact dermatitis induced by 5 weeks of repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the entire back skin were treated topically with royal jelly (0.01% or 1%) for 5 weeks after sensitization with TNCB. The effects of royal jelly on pruritus and inflammation were evaluated by measurement of scratching behavior and skin inflammation score, respectively. Results: Repeated application of TNCB to the back skin of mice elicited frequent scratching behavior immediately and 24h after challenge. Topical royal jelly (0.01% or 1%) and betamethasone (0.01%) significantly ameliorated this chronic pruritus throughout the experimental period. The level of nerve growth factor mRNA in back skin was increased in the mice with dermatitis and reduced by betamethasone, but not by royal jelly. Conclusion: The inhibitory effect of royal jelly on chronic pruritus may occur through different mechanisms from those of betamethasone. Topical application of royal jelly, as used in cosmetics, might be beneficial for the alleviation of chronic pruritus. PMID:23661987

  16. First report of ivermectin resistance in field populations of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) in Punjab districts of India.

    PubMed

    Singh, Nirbhay Kumar; Singh, Harkirat; Jyoti; Prerna, Mranalini; Rath, Shitanshu S

    2015-11-30

    The larval immersion test (LIT) was used on the progenies of Rhipicephalus (Boophilus) microplus collected from four districts of the Punjab state, India to test the resistance to ivermectin. The regression graphs of probit mortality of larval ticks plotted against log values of increasing concentrations of ivermectin were utilized for the determination of slope of mortality, lethal concentration for 50%(LC50), 95%(LC95), resistance ratios (RR50, RR95) and the resistance levels (RL). Values of the coefficient of determination (R(2)) for LIT ranged from 0.900 to 0.978, and the RR50 and RR95 values against ivermectin ranged from 2.97 to 8.85 and 2.42 to 8.47, respectively, indicating resistance status in all field isolates. On the basis of RR values, three field isolates (BAT, GUR, HOS) showed level II, whereas PTK isolate showed presence of level I resistance status against ivermectin. This appears to be the first report of ivermectin resistance in R. (B.) microplus from Punjab, India.

  17. Unraveling Site-Specific and Combinatorial Histone Modifications Using High-Resolution Mass Spectrometry in Histone Deacetylase Mutants of Fission Yeast.

    PubMed

    Abshiru, Nebiyu; Rajan, Roshan Elizabeth; Verreault, Alain; Thibault, Pierre

    2016-07-01

    Histone deacetylases (HDACs) catalyze the removal of acetylation marks from lysine residues on histone and nonhistone substrates. Their activity is generally associated with essential cellular processes such as transcriptional repression and heterochromatin formation. Interestingly, abnormal activity of HDACs has been reported in various types of cancers, which makes them a promising therapeutic target for cancer treatment. In the current study, we aim to understand the mechanisms underlying the function of HDACs using an in-depth quantitative analysis of changes in histone acetylation levels in Schizosaccharomyces pombe (S. pombe) lacking major HDAC activities. We employed a targeted quantitative mass spectrometry approach to profile changes of acetylation and methylation at multiple lysine residues on the N-terminal tail of histones H3 and H4. Our analyses identified a number of histone acetylation sites that are significantly affected by S. pombe HDAC mutations. We discovered that mutation of the Class I HDAC known as Clr6 causes a major increase in the abundance of triacetylated H4 molecules at K5, K8, and K12. A clr6-1 hypomorphic mutation also increased the abundance of multiple acetyl-lysines in histone H3. In addition, our study uncovered a few crosstalks between histone acetylation and methylation upon deletion of HDACs Hos2 and Clr3. We anticipate that the results from this study will greatly improve our current understanding of the mechanisms involved in HDAC-mediated gene regulation and heterochromatin assembly.

  18. Protection of male reproductive toxicity in rats exposed to di-n-butyl phthalate during embryonic development by testosterone.

    PubMed

    Giribabu, Nelli; Reddy, Pamanji Sreenivasula

    2017-03-01

    Di-n-butyl phthalate (DBP) widely spread industrial chemical that made drastic alteration in male reproductive system. The present study elucidates the protective role of testosterone on reproductive toxicity in prenatal DBP exposed adult male rats. Pregnant rats were injected with corn oil or 100 and 500mg/kg body weight of DBP on gestation day (GD) 1, 7 and 14. F1 male rats were weaned, injected with either testosterone or vehicle. On postnatal day (PND) 100 F1 adult male rats were cohabited with untreated female rats. Then rats were sacrificed and analyzed for other reproductive end points. Prenatal DBP exposed male rat testes, seminal vesicle weight, sperm count, motility, viability and HOS tail coiled sperm were significantly decreased with increased sperm morphological abnormalities. The levels of testicular 3β, 17βHSD, serum testosterone were significantly decreased with increased FSH, LH levels in experimental rats. The fertility studies revealed that increased pre, post-implantation losses and resorptions in normal females cohabited with experimental rats. Higher testicular LPO with lower SOD, CAT and GPx activity levels in experimental rats. Administration of testosterone to prenatal DBP treated male rats showed significant protection in above all parameters. In conclusions, testosterone deteriorates prenatal DBP induced reproductive and fertility toxicity by decreased oxidative stress and increased testicular antioxidant enzymes.

  19. Ovarian tumor characterization and classification: a class of GyneScan™ systems.

    PubMed

    Acharya, U Rajendra; Sree, Vinitha S; Saba, Luca; Molinari, Filippo; Guerriero, Stefano; Suri, Jasjit S

    2012-01-01

    In this work, we have developed an adjunct Computer Aided Diagnostic (CAD) technique that uses 3D acquired ultrasound images of the ovary and data mining algorithms to accurately characterize and classify benign and malignant ovarian tumors. In this technique, we extracted image-texture based and Higher Order Spectra (HOS) based features from the images. The significant features were then selected and used to train and test the Decision Tree (DT) classifier. The proposed technique was validated using 1000 benign and 1000 malignant images, obtained from 10 patients with benign and 10 with malignant disease, respectively. On evaluating the classifier with 10-fold stratified cross validation, we observed that the DT classifier presented a high accuracy of 95.1%, sensitivity of 92.5% and specificity of 97.7%. Thus, the four significant features could adequately quantify the subtle changes and nonlinearities in the pixel intensities. The preliminary results presented in this paper indicate that the proposed technique can be reliably used as an adjunct tool for ovarian tumor classification since the system is accurate, completely automated, cost-effective, and can be easily written as a software application for use in any computer.

  20. Stb3 plays a role in the glucose-induced transition from quiescence to growth in Saccharomyces cerevisiae.

    PubMed

    Liko, Dritan; Conway, Michael K; Grunwald, Douglas S; Heideman, Warren

    2010-07-01

    Addition of glucose to quiescent Saccharomyces cerevisiae cells causes the immediate induction of approximately 1000 genes. These genes include ribosomal proteins (RP) and non-RP genes needed for ribosome production and other growth processes. RRPE sequence elements are commonly found 5' of non-RP growth gene ORFs, and Stb3 has recently been identified as an RRPE binding protein. Stb3 overexpression (Stb3OE) produces a slow growth phenotype that is associated with reduced expression of non-RP genes and a drop in the rate of amino acid incorporation. Genes affected by Stb3 are associated with a TGAAAAA motif. Stb3 is restricted to the nucleus in quiescent cells and is immediately released into the cytoplasm after glucose repletion. The Stb3OE slow growth phenotype is reversed by loss of Hos2 histone deactylase activity, consistent with the idea that repression involves histone deacetylation. SCH9 overexpression or PPH22 deletion, mutations that activate target of rapamycin (Tor) nutrient sensing pathways, also reverse the Stb3OE phenotype. Inhibition of Tor signaling makes the phenotype more severe and restricts Stb3 to the nucleus. The results support a model in which Stb3 is one of the components that repress a large set of growth genes as nutrients are depleted. This repression is ended by glucose.

  1. Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib

    PubMed Central

    Rimassa, Lorenza; Abbadessa, Giovanni; Personeni, Nicola; Porta, Camillo; Borbath, Ivan; Daniele, Bruno; Salvagni, Stefania; Van Laethem, Jean-Luc; Van Vlierberghe, Hans; Trojan, Jörg; De Toni, Enrico N.; Weiss, Alan; Miles, Steven; Gasbarrini, Antonio; Lencioni, Monica; Lamar, Maria E.; Wang, Yunxia; Shuster, Dale; Schwartz, Brian E.; Santoro, Armando

    2016-01-01

    ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82%) versus before (40%) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials. PMID:27579536

  2. The role of thermal shock in cyclic oxidation

    NASA Technical Reports Server (NTRS)

    Lowell, C. E.; Deadmore, D. L.

    1978-01-01

    The effect of thermal shock on the spalling of oxides from the surfaces of several commercial alloys was determined. The average cooling rate was varied from approximately 240 C per second to less than 1.0 C per second during cyclic oxidation tests in air. The tests consisted of one hundred cycles of one hour at the maximum temperature (1100 or 1200 C). The alloys were HOS-875, TD-Ni, TD-NiCrAl, IN-601, IN-702, and B-1900 plus Hf. All of these alloys exhibited partial spalling within the oxide rather than total oxide loss down to bare metal. Thermal shock resulted in deformation of the metal which in turn resulted, in most cases, in changing the oxide failure mode from compressive to tensile. Tensile failures were characterized by cracking of the oxide and little loss, while compressive failures were characterized by explosive loss of platelets of oxide. This behavior was confirmed by examination of mechanically stressed oxide scales. The thermally shocked oxides spalled less than the slow cooled samples with the exception of TD-NiCrAl. This material failed in a brittle manner rather than by plastic deformation.

  3. Set3 contributes to heterochromatin integrity by promoting transcription of subunits of Clr4-Rik1-Cul4 histone methyltransferase complex in fission yeast

    PubMed Central

    Yu, Yao; Zhou, Huan; Deng, Xiaolong; Wang, Wenchao; Lu, Hong

    2016-01-01

    Heterochromatin formation in fission yeast depends on RNAi machinery and histone-modifying enzymes. One of the key histone-modifying complexes is Clr4-Rik1-Cul4 methyltransferase complex (CLRC), which mediates histone H3K9 methylation, a hallmark for heterochromatin. CLRC is composed of the Clr4 histone methyltransferase, Rik1, Raf1, Raf2 and Pcu4. However, transcriptional regulation of the CLRC subunits is not well understood. In this study, we identified Set3, a core subunit of the Set3/Hos2 histone deacetylase complex (Set3C), as a contributor to the integrity and silencing of heterochromatin at centromeres, telomeres and silent mating-type locus. This novel role of Set3 relies on its PHD finger, but is independent of deacetylase activity or structural integrity of Set3C. Set3 is not located to the centromeric region. Instead, Set3 is targeted to the promoters of clr4+ and rik1+, probably through its PHD finger. Set3 promotes transcription of clr4+ and rik1+. Consistently, the protein levels of Clr4 and Rik1 were reduced in the set3Δ mutant. The heterochromatin silencing defect in the set3Δ mutant could be rescued by overexpressing of clr4+ or rik1+. Our study suggests transcriptional activation of essential heterochromatin factors underlies the tight regulation of heterochromatin integrity. PMID:27538348

  4. Different concentrations of cysteamine and ergothioneine improve microscopic and oxidative parameters in ram semen frozen with a soybean lecithin extender.

    PubMed

    Najafi, Abozar; Kia, Hossein Daghigh; Mohammadi, Hossein; Najafi, Mir Hossein; Zanganeh, Zaynab; Sharafi, Mohsen; Martinez-Pastor, Felipe; Adeldust, Hamideh

    2014-08-01

    The aim of this study was to evaluate the effects of ergothioneine and cysteamine as antioxidant supplements in a soybean lecithin extender for freezing ram semen. Twenty-four ejaculates were collected from four rams and diluted with extenders (1.5% soybean lecithin, 7% glycerol) containing no supplements (control) and cysteamine or ergothioneine (2, 4, 6 or 8mM). Motility by CASA, viability, plasma membrane functionality (HOS test), total abnormality, lipid peroxidation, glutathione peroxidase (GPx) activity and capacitation status (CTC staining) were assessed after thawing. Using 6mM of either antioxidant improved total motility. Cysteamine at 6mM and ergothioneine at 4 and 6mM improved viability and reduced lipid peroxidation (malondialdehyde concentration). Both antioxidants improved membrane functionality significantly, except at 8mM. Progressive motility, kinematic parameters, GPx activity, capacitation status and sperm abnormalities were not influenced by the antioxidant supplements. In conclusion, cysteamine at 6mM and ergothioneine at 4 or 6mM seem to improve the post-thawing quality of ram semen cryopreserved in a soybean lecithin extender.

  5. The unified ICE-CBF pathway provides a transcriptional feedback control of freezing tolerance during cold acclimation in Arabidopsis.

    PubMed

    Kim, Ye Seul; Lee, Minyoung; Lee, Jae-Hyung; Lee, Hyo-Jun; Park, Chung-Mo

    2015-09-01

    During cold acclimation, C-repeat binding factors (CBFs) activate downstream targets, such as cold-regulated genes, leading to the acquisition of freezing tolerance in plants. Inducer of CBF expression 1 (ICE1) plays a key role by activating CBF3 expression in shaping the cold-induced transcriptome. While the ICE1-CBF3 regulon constitutes a major cold acclimation pathway, gene regulatory networks governing the CBF signaling are poorly understood. Here, we demonstrated that ICE1 and its paralog ICE2 induce CBF1, CBF2, and CBF3 by binding to the gene promoters. ICE2, like ICE1, was ubiquitinated by the high expression of osmotically responsive gene 1 (HOS1) E3 ubiquitin ligase. Whereas ICE2-defective ice2-2 mutant did not exhibit any discernible freezing-sensitive phenotypes, ice1-2 ice2-2/+ plant, which is defective in ICE1 and has a heterozygotic ice2 mutation, exhibited significantly reduced freezing tolerance. Accordingly, all three CBF genes were markedly down-regulated in the ice1-2 ice2-2/+ plant, indicating that ICE1 and ICE2 are functionally redundant with different implementations in inducing CBF genes. Together with the negative regulation of CBF3 by CBF2, we propose that the unified ICE-CBF pathway provides a transcriptional feedback of freezing tolerance to sustain plant development and survival during cold acclimation.

  6. Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes

    PubMed Central

    Govind, Chhabi K.; Qiu, Hongfang; Ginsburg, Daniel S.; Ruan, Chun; Hofmeyer, Kimberly; Hu, Cuihua; Swaminathan, Venkatesh; Workman, Jerry L.; Li, Bing; Hinnebusch, Alan G.

    2010-01-01

    Methylation of histone H3 by Set1 and Set2 is required for deacetylation of nucleosomes in coding regions by histone deacetylase complexes (HDACs) Set3C and Rpd3C(S), respectively. We report that Set3C and Rpd3C(S) are co-transcriptionally recruited in the absence of Set1 and Set2, but in a manner stimulated by Pol II CTD kinase Cdk7/Kin28. Consistently, Rpd3C(S) and Set3C interact with Ser5-phosphorylated Pol II and histones in extracts, but only the histone interactions require H3 methylation. Moreover, reconstituted Rpd3C(S) binds specifically to Ser5-phosphorylated CTD peptides in vitro. Hence, whereas interaction with methylated H3 residues is required for Rpd3C(S) and Set3C deacetylation activities, their co-transcriptional recruitment is stimulated by the phosphorylated CTD. We further demonstrate that Rpd3, Hos2, and Hda1 have overlapping functions in deacetylating histones and suppressing co-transcriptional histone eviction. A strong correlation between increased acetylation and lower histone occupancy in HDA mutants implies that histone acetylation is a key determinant of nucleosome eviction. PMID:20670892

  7. John Collins Warren and his act of conscience: a brief narrative of the trial and triumph of a great surgeon.

    PubMed Central

    Moore, F D

    1999-01-01

    On examination of the correspondence among the principals involved, as well as the original patent application being prepared by Morton, it has become possible to reconstruct some of the remarkable details attending the first use of ether anesthesia at the Massachusetts General Hos pital in the autumn of 1846. At the time that Warren invited Morton to demonstrate the use of his "ethereal vapor" for anesthesia in a minor operation on Oct. 16, 1846, the exact chemical composition of the agent used was being held secret by Morton; Warren was clearly disturbed by this unethical use of a secret "nostrum." When the time arrived 3 weeks later for its possible use for a serious "capital" operation, Warren employed a simple stratagem of public confrontation to discover from Morton the true nature of the substance to be used. On being informed that it was pure unadulterated sulfuric ether, not some mysterious new discovery labeled "Letheon," Warren gave approval for its first use in a "capital" operation (low thigh amputation) on Nov. 7, 1846. Despite this revelation to the immediate participants, a veil of secrecy continued to surround the substance for many months, an anomalous situation evidently traceable to Morton's desire for personal reward from the discovery. It was this matter of secrecy, rather than priority for its discovery, that surrounded the early use of ether anesthesia with controversy and recrimination both in this country and abroad. Images Figure 2. PMID:10024099

  8. Role of mesenchymal stem cells in osteosarcoma and metabolic reprogramming of tumor cells

    PubMed Central

    Bonuccelli, Gloria; Avnet, Sofia; Grisendi, Giulia; Salerno, Manuela; Granchi, Donatella; Dominici, Massimo; Kusuzaki, Katsuyuki; Baldini, Nicola

    2014-01-01

    The tumor microenvironment plays an important role in cancer progression. Here, we focused on the role of reactive mesenchymal stem cells (MSC) in osteosarcoma (OS), and used human adipose MSC and a panel of OS cell lines (Saos-2, HOS, and 143B) to investigate the mutual effect of normal-cancer cell metabolic programming. Our results showed that MSC are driven by oxidative stress induced by OS cells to undergo Warburg metabolism, with increased lactate production. Therefore, we analyzed the expression of lactate monocarboxylate transporters. By real time PCR and immunofluorescence, in MSC we detected the expression of MCT-4, the transporter for lactate efflux, whereas MCT-1, responsible for lactate uptake, was expressed in OS cells. In agreement, silencing of MCT-1 by siRNA significantly affected the ATP production in OS cancer cells. Thus, cancer cells directly increase their mitochondrial biogenesis using this energy-rich metabolite that is abundantly provided by MSC as an effect of the altered microenvironmental conditions induced by OS cells. We also showed that lactate produced by MSC promotes the migratory ability of OS cells. These data provide novel information to be exploited for cancer therapies targeting the mutual metabolic reprogramming of cancer cells and their stroma. PMID:25277190

  9. Molecular cloning, characterization, and expression of an alfalfa (Medicago sativa L.) heme oxygenase-1 gene, MsHO1, which is pro-oxidants-regulated.

    PubMed

    Fu, Guang-Qing; Xu, Sheng; Xie, Yan-Jie; Han, Bin; Nie, Li; Shen, Wen-Biao; Wang, Ren

    2011-07-01

    It has been documented that plant heme oxygenase-1 (HO-1; EC 1.14.99.3) is both development- and stress-regulated, thus it plays a vital role in light signalling and stress responses. In this study, an alfalfa (Medica sativa L.) HO-1 gene MsHO1 was isolated and sequenced. It contains four exons and three introns within genomic DNA sequence and encodes a polypeptide with 283 amino acids. MsHO1 had a conserved HO signature sequence and showed high similarity to other HOs in plants, especially HO-1 isoform. The MsHO1:GFP fusion protein was localized in the chloroplast. Further biochemical activity analysis of mature MsHO1, which was expressed in Escherichia coli, showed that the Vmax was 48.78 nmol biliverdin-IXα (BV) h⁻¹ nmol⁻¹ protein with an apparent Km value for hemin of 2.33 μM, and the optimum Tm and pH were 37 °C and 7.2, respectively. Results of semi-quantitative RT-PCR and western blot showed that the expressions of MsHO1 were higher in alfalfa stems and leaves than those in germinating seeds and roots. Importantly, MsHO1 gene expression and protein level were induced significantly by some pro-oxidant compounds, including hemin and nitric oxide (NO) donor sodium nitroprusside (SNP). In conclusion, MsHO1 may play an important role in oxidative responses.

  10. Mechanosensitivity of human osteosarcoma cells and phospholipase C {beta}2 expression

    SciTech Connect

    Hoberg, M. . E-mail: Maik.Hoberg@med.uni-tuebingen.de; Gratz, H.-H.; Noll, M.; Jones, D.B.

    2005-07-22

    Bone adapts to mechanical load by osteosynthesis, suggesting that osteoblasts might respond to mechanical stimuli. We therefore investigated cell proliferation and phospholipase C (PLC) expression in osteoblasts. One Hertz uniaxial stretching at 4000 {mu}strains significantly increased the proliferation rates of human osteoblast-like osteosarcoma cell line MG-63 and primary human osteoblasts. However, U-2/OS, SaOS-2, OST, and MNNG/HOS cells showed no significant changes in proliferation rate. We investigated the expression pattern of different isoforms of PLC in these cell lines. We were able to detect PLC {beta}1, {beta}3, {gamma}1, {gamma}2, and {delta}1 in all cells, but PLC {beta}2 was only detectable in the mechanosensitive cells. We therefore investigated the possible role of PLC {beta}2 in mechanotransduction. Inducible antisense expression for 24 h inhibited the translation of PLC {beta}1 in U-2/OS cells by 35% and PLC {beta}2 in MG-63 by 29%. Fluid shear flow experiments with MG-63 lacking PLC {beta}2 revealed a significantly higher level of cells losing attachment to coverslips and a significantly lower number of cells increasing intracellular free calcium.

  11. Triggering of apoptosis in osteosarcoma cells by graphene/single-walled carbon nanotube hybrids via the ROS-mediated mitochondrial pathway.

    PubMed

    Yan, Xinxin; Yang, Wen; Shao, Zengwu; Yang, Shuhua; Liu, Xianzhe

    2017-02-01

    Carbon nanomaterials are increasingly significant in the biological and medical fields, especially becoming promising candidates in treating difficult and complicated disease. Graphene/single-walled carbon nanotubes (G/SWCNT) hybrids is 3D structure which has been constructed by combining 1D single-walled carbon nanotubes (SWCNTs) and 2D graphene. However, the effects of the nanomaterial on biological systems are limited. In this study, we report a systematic investigation of the cytotoxicity and in vivo biodistribution of G/SWCNT hybrids on osteosarcoma cells (HOS and U2OS). The CCK-8, neutral red, and lactic dehydrogenase assays demonstrated that the cytotoxicity of G/SWCNT hybrids exhibits a dose-dependent behavior on osteosarcoma cells. In our conditions, the hybrids were less cytotoxic than graphene and single-walled carbon nanotubes. The results also showed the apoptosis of osteosarcoma cells induced by G/SWCNT hybrids was through the increase of intracellular reactive oxygen species, the decrease of mitochondrial membrane potential, the alternation of apoptosis-related proteins, and then triggered the ROS-mediated mitochondrial pathway. Moreover, the in vivo biodistribution of G/SWCNT hybrids was observed by histological analysis of major organs in mice, and showed that organs were neither damaged nor inflammatory. This study demonstrated that G/SWCNT hybrids could serve as a potential platform in anticancer therapy. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 443-453, 2017.

  12. Anticancer Activity, Antioxidant Activity, and Phenolic and Flavonoids Content of Wild Tragopogon porrifolius Plant Extracts

    PubMed Central

    Rishmawi, Suzi; Ariqat, Sharehan H.; Khalid, Mahmoud F.; Warad, Ismail; Salah, Zaidoun

    2016-01-01

    Tragopogon porrifolius, commonly referred to as white salsify, is an edible herb used in folk medicine to treat cancer. Samples of Tragopogon porrifolius plant grown wild in Palestine were extracted with different solvents: water, 80% ethanol, and 100% ethanol. The extracts were analyzed for their total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity (AA). Four different antioxidant assays were used to evaluate AA of the extracts: two measures the reducing power of the extracts (ferric reducing antioxidant power (FRAP) and cupric reducing antioxidant power (CUPRAC)), while two other assays measure the scavenging ability of the extracts (2,2-azino-di-(3-ethylbenzothialozine-sulphonic acid (ABTS)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH)). Anticancer activity of the plant extracts were also tested on HOS and KHOS osteosarcoma cell lines. The results revealed that the polarity of the extraction solvent affects the TPC, TFC, and AA. It was found that both TPC and AA are highest for plant extracted with 80% ethanol, followed by water, and finally with 100% ethanol. TFC however was the highest in the following order: 80% ethanol > 100% ethanol > water. The plant extracts showed anticancer activities against KHOS cancer cell lines; they reduced total cell count and induced cell death in a drastic manner. PMID:27999608

  13. Growth modulation of human cells in vitro by mild oxidative stress and 1,4-dihydropyridine derivative antioxidants.

    PubMed

    Lovaković, Tomislava; Poljak-Blazi, Marija; Duburs, Gunars; Cipak, Ana; Cindrić, Marina; Vigante, Brigita; Bisenieks, Egils; Jaganjac, Morana; Mrakovcić, Lidija; Dedić, Azra; Zarković, Neven

    2011-03-01

    Reactive oxygen species and lipid peroxidation products are not only cytotoxic but may also modulate signal transduction in cells. Accordingly, antioxidants may be considered as modifiers of cellular redox signaling. Therefore, the effects of two novel synthetic antioxidants, analogues of 1,4-dihydropyridine derivatives, cerebrocrast and Z41-74 were analysed in vitro on human osteosarcoma cell line HOS, the growth of which can be modulated by lipid peroxidation. The cells were pretreated with either cerebrocrast or Z41-74 and afterwards exposed to mild, copper induced lipid peroxidation or to 4-hydroxynonenal (HNE), the end product of lipid peroxidation. The results obtained have shown that both antioxidants exert growth modulating effects interfering with the lipid peroxidation. Namely, cells treated with antioxidants showed increased metabolic rate and cell growth, thereby attenuating the effects of lipid peroxidation. Such biomodulating effects of cerebrocrast and Z41-74 resembled growth modulating effects of HNE, suggesting that the antioxidants could eventually promote cellular adaptation to oxidative stress interacting with redox signaling and hydroxynonenal HNE-signal transduction pathways. This may be of particular relevance for better understanding the beneficial role of hydroxynonenal HNE in cell growth control. Therefore, cerebrocrast and Z41-74 could be convenient to study further oxidative homeostasis involving lipid peroxidation.

  14. 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.

  15. Effect of antioxidant supplementation in semen extenders on semen quality and reactive oxygen species of chilled canine spermatozoa.

    PubMed

    Michael, A J; Alexopoulos, C; Pontiki, E A; Hadjipavlou-Litina, D J; Saratsis, P; Ververidis, H N; Boscos, C M

    2009-05-01

    The objective of this study was to evaluate quality of chilled dog semen processed with extenders containing various antioxidants. Single ejaculates from five dogs were always pooled and evaluated for concentration, sperm motility, progressive motility (RSF-movement), viability, acrosomal integrity and by the hypo-osmotic swelling (HOS)-test. Also, superoxide (O(2)(-)) production, hydroxyl radicals (OH) and total reactive oxygen species (tROS) were determined. Pooled semen was divided in seven aliquots (for control and test conditions), which were diluted to a final concentration of 67x10(6)spermatozoa/ml with TRIS-glucose-egg yolk extender with or without the following supplements: control (without antioxidants), vitamin C (0.5mM), N-acetyl-l-cysteine (NAC; 0.5mM), taurine (0.2mM), catalase (100u/ml), vitamin E (0.1mM) and 5-(4-dimethylamino-phenyl)-2-phenyl-penta-2,4-dienoic acid (B16; 0.1mM). The semen aliquots were chilled and preserved at 4 degrees C. Portions of chilled semen were removed at 24 and 72h, and semen quality was evaluated after rewarming. At 24h the mean (+/-S.E.M.) sperm motility was higher (p<0.001) when vitamin E, taurine and B16 were added in the extender, whereas more spermatozoa with RSF-movement were observed (p<0.001) in the vitamin E, catalase, B16 and taurine groups. Sperm viability was higher (p=0.040) in B16 and vitamin E groups and the percentage of swollen spermatozoa was higher (p=0.002) only in the B16 group. Acrosomal integrity and OH were not significantly influenced by any of the antioxidants tested. Superoxide production was significantly lower when vitamin C, B16 and vitamin E were added in semen extenders compared with the control (p=0.017). All antioxidant groups, except vitamin C and NAC, contained less tROS compared to the control group, but only the B16 group value differed significantly (p=0.05). At 72h sperm motility was higher (p<0.001) when vitamin E, catalase, B16, taurine and NAC were added in the extender. More

  16. First row transition metal complexes of (E)-2-(2-(2-hydroxybenzylidene) hydrazinyl)-2-oxo-N-phenylacetamide complexes

    NASA Astrophysics Data System (ADS)

    Yousef, T. A.; Abu El-Reash, G. M.; Rakha, T. H.; El-Ayaan, Usama

    2011-12-01

    Manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and chromium(III) complexes of (E)-2-(2-(2-hydroxybenzylidene)hydrazinyl)-2-oxo-N-phenylacetamide were synthesized and characterized by elemental and thermal (TG and DTA) analyses, IR, UV-vis and 1H NMR spectra as well as magnetic moment. Mononuclear complexes are obtained with 1:1 molar ratio except [Mn(HOS) 2(H 2O) 2] and [Co(OS) 2](H 2O) 2 complexes which are obtained with 1:2 molar ratios. The IR spectra of ligand and metal complexes reveal various modes of chelation. The ligand behaves as a monobasic bidentate one and coordination occurs via the enolic oxygen atom and azomethine nitrogen atom. The ligand behaves also as a monobasic tridentate one and coordination occurs through the carbonyl oxygen atom, azomethine nitrogen atom and the hydroxyl oxygen. Moreover, the ligand behaves as a dibasic tridentate and coordination occurs via the enolic oxygen, azomethine nitrogen and the hydroxyl oxygen atoms. The electronic spectra and magnetic moment measurements reveal that all complexes possess octahedral geometry except the copper complexes possesses a square planar geometry. From the modeling studies, the bond length, bond angle, HOMO, LUMO and dipole moment had been calculated to confirm the geometry of the ligands and their investigated complexes. The thermal studies showed the type of water molecules involved in metal complexes as well as the thermal decomposition of some metal complexes. The protonation constant of the ligand and the stability constant of metal complexes were determined pH-metrically in 50% (v/v) dioxane-water mixture at 298 K and found to be consistent with Irving-Williams order. Moreover, the minimal inhibitory concentration (MIC) of these compounds against Staphylococcus aureus, Escherechia coli and Candida albicans were determined.

  17. MicroRNA 218 mediates the effects of Tbx5a over-expression on zebrafish heart development.

    PubMed

    Chiavacci, Elena; Dolfi, Luca; Verduci, Lorena; Meghini, Francesco; Gestri, Gaia; Evangelista, Alberto Mercatanti Monica; Wilson, Stephen W; Cremisi, Federico; Pitto, Letizia

    2012-01-01

    tbx5, a member of the T-box gene family, encodes one of the key transcription factors mediating vertebrate heart development. Tbx5 function in heart development appears to be exquisitely sensitive to gene dosage, since both haploinsufficiency and gene duplication generate the cardiac abnormalities associated with Holt-Oram syndrome (HOS), a highly penetrant autosomal dominant disease characterized by congenital heart defects of varying severity and upper limb malformation. It is suggested that tight integration of microRNAs and transcription factors into the cardiac genetic circuitry provides a rich and robust array of regulatory interactions to control cardiac gene expression. Based on these considerations, we performed an in silico screening to identify microRNAs embedded in genes highly sensitive to Tbx5 dosage. Among the identified microRNAs, we focused our attention on miR-218-1 that, together with its host gene, slit2, is involved in heart development. We found correlated expression of tbx5 and miR-218 during cardiomyocyte differentiation of mouse P19CL6 cells. In zebrafish embryos, we show that both Tbx5 and miR-218 dysregulation have a severe impact on heart development, affecting early heart morphogenesis. Interestingly, down-regulation of miR-218 is able to rescue the heart defects generated by tbx5 over-expression supporting the notion that miR-218 is a crucial mediator of Tbx5 in heart development and suggesting its possible involvement in the onset of heart malformations.

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

    SciTech Connect

    Vekariya, Kiritkumar K.; Kaur, Jasmine; Tikoo, Kulbhushan

    2013-04-15

    Aromatase inhibitors like anastrozole play an undisputed key role in the treatment of breast cancer, but on the other hand, various side effects like osteoporosis and increased risk of bone fracture accompany the chronic administration of these drugs. Here we show for the first time that selenium nanoparticles, when given in conjugation to anastrozole, lower the bone toxicity caused by anastrozole and thus reduce the probable damage to the bone. Selenium nanoparticles at a dose of 5 μg/ml significantly reduced the cell death caused by anastrozole (1 μM) in HOS (human osteoblast) cells. In addition, our results also highlighted that in female SD rat model, SeNPs (0.25, 0.5, 1 mg/kg/day) significantly prevented the decrease in bone density and increase in biochemical markers of bone resorption induced by anastrozole (0.2 mg/kg/day) treatment. Histopathological examination of the femurs of SeNP treated group revealed ossification, mineralization, calcified cartilaginous deposits and a marginal osteoclastic activity, all of which indicate a marked restorative action, suggesting the protective action of the SeNPs. Interestingly, SeNPs (1 mg/kg/day) also exhibited protective effect in ovariectomized rat model, by preventing osteoporosis, which signifies that bone loss due to estrogen deficiency can be effectively overcome by using SeNPs. - Highlights: ► SeNPs significantly reduce bone toxicity in anastrozole treated rats. ► SeNPs successfully prevented osteoporosis in ovariectomized rats. ► SeNP treatment lowered the levels of TRAP and increased the levels of ALKP.

  19. A Comprehensive TALEN-Based Knockout Library for Generating Human Induced Pluripotent Stem Cell-Based Models for Cardiovascular Diseases.

    PubMed

    Karakikes, Ioannis; Termglinchan, Vittavat; Cepeda, Diana A; Lee, Jaecheol; Diecke, Sebastian; Hendel, Ayal; Itzhaki, Ilanit; Ameen, Mohamed; Shrestha, Rajani; Wu, Haodi; Ma, Ning; Shao, Ning-Yi; Seeger, Timon; Woo, Nicole A; Wilson, Kitchener D; Matsa, Elena; Porteus, Matthew H; Sebastiano, Vittorio; Wu, Joseph C

    2017-02-28

    Rationale: Targeted genetic engineering using programmable nucleases such as transcription activator-like effector nucleases (TALENs) is a valuable tool for precise, site-specific genetic modification in the human genome. Objective: The emergence of novel technologies such as human induced pluripotent stem cells (iPSCs) and nuclease-mediated genome editing represent a unique opportunity for studying cardiovascular diseases in vitro. Methods and Results: By incorporating extensive literature and database searches, we designed a collection of TALEN constructs to knockout (KO) eighty-eight human genes that are associated with cardiomyopathies and congenital heart diseases. The TALEN pairs were designed to induce double-strand DNA break near the starting codon of each gene that either disrupted the start codon or introduced a frameshift mutation in the early coding region, ensuring faithful gene KO. We observed that all the constructs were active and disrupted the target locus at high frequencies. To illustrate the general utility of the TALEN-mediated KO technique, six individual genes (TNNT2, LMNA/C, TBX5, MYH7, ANKRD1, and NKX2.5) were knocked out with high efficiency and specificity in human iPSCs. By selectively targeting a dilated cardiomyopathy (DCM)-causing mutation (TNNT2 p.R173W) in patient-specific iPSC-derived cardiac myocytes (iPSC-CMs), we demonstrated that the KO strategy ameliorates the DCM phenotype in vitro. In addition, we modeled the Holt-Oram syndrome (HOS) in iPSC-CMs in vitro and uncovered novel pathways regulated by TBX5 in human cardiac myocyte development. Conclusions: Collectively, our study illustrates the powerful combination of iPSCs and genome editing technology for understanding the biological function of genes and the pathological significance of genetic variants in human cardiovascular diseases. The methods, strategies, constructs and iPSC lines developed in this study provide a validated, readily available resource for cardiovascular

  20. Basic cardiopulmonary resuscitation knowledge of house-officers in a tertiary institution: factors determining accuracy

    PubMed Central

    Okonta, Kelechi Emmanuel; Okoh, Boma Alali Ngozi

    2014-01-01

    Background To assess the level of knowledge of CPR among House-Officers (HO) and some factors determining accuracy of knowledge. Methods A total of 50 structured questionnaires were administered to HO with 35 (70%) questionnaires duly filled and returned. Data on the participants’ brief biodata and the understanding of basic skills of BLS were collected and analyzed using International Business Machine SPSS Statistics version 21 for Windows. The t-test for independent samples was applied for the grouped data with P < 0.05 taken as level of significance. Results The age of the respondents ranged from 20-37 years with the mean age of 25.4 + SD2.7 years and the male/female ratio was 1:1.3. Eleven (31.4%) out of the 35 HO had no prior CPR training while 68.6% had prior training; Eighteen (51.4%) had training within the last 2 years. Twenty (57.1%) had performed CPR in a real situation, while 42.9% had not. Six (17.1%) HO scored above 50% while 82.9% scored below 50%. The female HO got more correct answers than the males (25% versus 6.7%, p = 0.167). The number of respondents who had prior CPR training had more correct answers than those who did not (25% versus 0%, p = 0.083) while those who had previously performed CPR had more correct answers than those who had not (33.3% versus 5%, P <0.05). Conclusion There was a general poor knowledge of the performance of basic CPR amongst HOs. However, previous experience of having performed CPR in real setting, or the use of mannequins, improved their theoretical knowledge of CPR. PMID:25419335

  1. Invariant NKT cells increase drug-induced osteosarcoma cell death

    PubMed Central

    Fallarini, S; Paoletti, T; Orsi Battaglini, N; Lombardi, G

    2012-01-01

    BACKGROUND AND PURPOSE In osteosarcoma (OS) patients, only a limited number of drugs are active and the regimens currently in use include a combination of at least two of these drugs: doxorubicin, cisplatin, methotrexate and ifosfamide. Today, 30–40% of patients still die of OS highlighting the urgent need for new treatments. Invariant NKT (iNKT) cells are a lymphocyte lineage with features of both T and NK cells, playing important roles in tumour suppression. Our aim was to test whether the cytoxicity induced by cisplatin, doxorubicin and methotrexate against OS cells can be enhanced by iNKT cell treatment. EXPERIMENTAL APPROACH iNKT cells were purified from human peripheral blood mononuclear cells by cell sorting (Vα24Vβ11+ cells) and used as effector cells against OS cells (U2-OS, HOS, MG-63). Cell death (calcein-AM method), perforin/granzyme B and Fas/FasL expressions were determined by flow cytometry. CD1d expression was analysed at both the gene and protein level. KEY RESULTS iNKT cells were cytotoxic against OS cells through a CD1d-dependent mechanism. This activity was specific for tumour cells, because human CD1d+ mesenchymal stem cells and CD1d- osteoblasts were not affected. iNKT cell treatment enhanced drug-induced OS cell death in a concentration-dependent manner and this effect was reduced in CD1d-silenced OS cells. CONCLUSION AND IMPLICATIONS iNKT cells kill malignant, but not non-malignant, cells. iNKT cell treatment enhances the cytotoxicity of anti-neoplastic drugs against OS cells in a CD1d-dependent manner. The present data encourage further studies on the use of iNKT cells in OS therapy. PMID:22817659

  2. A zinc(II) quinolinone complex (Et3NH)[Zn(qui)Cl2]: Synthesis, X-ray structure, spectral properties and in vitro cytotoxicity

    NASA Astrophysics Data System (ADS)

    Buchtík, Roman; Nemec, Ivan; Trávníček, Zdeněk

    2014-02-01

    A new zinc(II) complex with 2-phenyl-3-hydroxy-4(1H)-quinolinone (Hqui) of the composition (Et3NH)[Zn(qui)Cl2] was prepared and characterized by elemental analysis, FT IR, 1D and 2D NMR, and fluorescence spectroscopy, mass spectrometry and single crystal X-ray analysis. The molecular structure is composed of the triethylammonium (Et3NH+) cations and tetrahedral [ZnII(qui)Cl2]- complex anions, in which the Zn(II) atoms are bidentate coordinated by one qui ligand through keto (OK) and phenolate (OP) oxygen atoms and by two chlorido ligands, thus forming the {O2Cl2} donor set, with Zn-OK = 1.9860(14) Å, Zn-OP 1.9961(14) Å and Zn-Cl = 2.2509(6) Å and 2.2266(6) Å. The complex cations are aligned into 1D supramolecular chains through the NH⋯Cl hydrogen bonding between the amine group of the quinolinone ligand and the chlorido ligand of the adjacent complex anion. The amine group from the Et3NH+ cations provides the NH⋯OP hydrogen bond with the phenolate oxygen atoms from the complex anion. Screening of in vitro cytotoxicity of the compound was studied on human osteosarcoma (HOS) and human breast adenocarcinoma (MCF7) cell lines, with IC50 > 50 μM. The fluorescence study showed that the complex exhibits a relatively high integral intensity (29%) as compared to the standard quinine sulfate, and 1.6-fold enhancement of emission with respect to free Hqui.

  3. Preparation of bone-implants by coating hydroxyapatite nanoparticles on self-formed titanium dioxide thin-layers on titanium metal surfaces.

    PubMed

    Wijesinghe, W P S L; Mantilaka, M M M G P G; Chathuranga Senarathna, K G; Herath, H M T U; Premachandra, T N; Ranasinghe, C S K; Rajapakse, R P V J; Rajapakse, R M G; Edirisinghe, Mohan; Mahalingam, S; Bandara, I M C C D; Singh, Sanjleena

    2016-06-01

    Preparation of hydroxyapatite coated custom-made metallic bone-implants is very important for the replacement of injured bones of the body. Furthermore, these bone-implants are more stable under the corrosive environment of the body and biocompatible than bone-implants made up of pure metals and metal alloys. Herein, we describe a novel, simple and low-cost technique to prepare biocompatible hydroxyapatite coated titanium metal (TiM) implants through growth of self-formed TiO2 thin-layer (SFTL) on TiM via a heat treatment process. SFTL acts as a surface binder of HA nanoparticles in order to produce HA coated implants. Colloidal HA nanorods prepared by a novel surfactant-assisted synthesis method, have been coated on SFTL via atomized spray pyrolysis (ASP) technique. The corrosion behavior of the bare and surface-modified TiM (SMTiM) in a simulated body fluid (SBF) medium is also studied. The highest corrosion rate is found to be for the bare TiM plate, but the corrosion rate has been reduced with the heat-treatment of TiM due to the formation of SFTL. The lowest corrosion rate is recorded for the implant prepared by heat treatment of TiM at 700 °C. The HA-coating further assists in the passivation of the TiM in the SBF medium. Both SMTiM and HA coated SMTiM are noncytotoxic against osteoblast-like (HOS) cells and are in high-bioactivity. The overall production process of bone-implant described in this paper is in high economic value.

  4. Development of an Adaptive Multi-Method Algorithm for Automatic Picking of First Arrival Times: Application to Near Surface Seismic Data

    NASA Astrophysics Data System (ADS)

    Khalaf, A.; Camerlynck, C. M.; Schneider, A. C.; Florsch, N.

    2015-12-01

    Accurate picking of first arrival times plays an important role in many seismic studies, particularly in seismic tomography and reservoirs or aquifers monitoring. Many techniques have been developed for picking first arrivals automatically or semi-automatically, but most of them were developed for seismological purposes which does not attain the accuracy objectives due to the complexity of near surface structures, and to usual low signal-to-noise ratio. We propose a new adaptive algorithm for near surface data based on three picking methods, combining multi-nested windows (MNW), Higher Order Statistics (HOS), and Akaike Information Criterion (AIC). They exploit the benefits of integrating many properties, which reveal the presence of first arrivals, to provide an efficient and robust first arrivals picking. This strategy mimics the human first-break picking, where at the beginning the global trend is defined. Then the exact first-breaks are searched in the vicinity of the now defined trend. In a multistage algorithm, three successive phases are launched, where each of them characterize a specific signal property. Within each phase, the potential picks and their error range are automatically estimated, and then used sequentially as leader in the following phase picking. The accuracy and robustness of the implemented algorithm are successfully validated on synthetic and real data which have special challenges for automatic pickers. The comparison of resulting P-wave arrival times with those picked manually, and other algorithms of automatic picking, demonstrated the reliable performance of the new scheme under different noisy conditions. All parameters of our multi-method algorithm are auto-adaptive thanks to the integration in series of each sub-algorithm results in the flow. Hence, it is nearly a parameter-free algorithm, which is straightforward to implement and demands low computational resources.

  5. Effects of SOST Gene Silencing on Proliferation, Apoptosis, Invasion, and Migration of Human Osteosarcoma Cells Through the Wnt/β-Catenin Signaling Pathway.

    PubMed

    Zou, Jian; Zhang, Wei; Li, Xiao-Lin

    2017-02-28

    Our study explored the effects of SOST gene silencing on the proliferation, apoptosis, invasion, and migration of human osteosarcoma cells through Wnt/β-catenin signaling pathway. Fresh tissues were obtained from 108 patients with osteosarcoma and 46 patients with osteochondroma. Human osteosarcoma cells (MG-63, U2-OS, HOS, and Saos-2) and normal osteoblast (hFoB1.19) were selected and cultured. Osteosarcoma cells were grouped randomly into the blank group, the scrambled control group, and the SOST-siRNA group. Cell proliferation was determined by MTT assay. Cell cycle and apoptosis were tested by flow cytometry. Transwell and scratch test were performed to determine cell invasion and migration. The qRT-PCR and Western blotting were used to detect mRNA and protein expression level of sclerostin, Wnt1, β-catenin, C-Myc, Cyclin D1, and MMP-7. The activity of caspase-3 was assessed by immunocytochemistry. Alkaline phosphatase (ALP) activity was measured using P-nitrophenylphosphate as a substrate. Low SOST mRNA and sclerostin protein expression levels were observed in osteosarcoma tissues and cells. Compared with the blank and scrambled control groups, sclerostin expression, apoptotic cells, ALP activity, and caspase-3 activity were down-regulated, while the proliferation, invasion, and migration abilities of osteosarcoma cells were evidently enhanced in the SOST-siRNA group. After SOST gene silencing, the mRNA and protein expression levels of Wnt1, β-catenin, C-Myc, Cyclin D1, and MMP-7 in osteosarcoma cells and β-catenin protein expression levels in the nucleus and cytoplasm were significantly elevated. SOST gene silencing promotes the proliferation, invasion, and migration, and inhibits apoptosis of osteosarcoma cells by activating Wnt/β-catenin signaling pathway.

  6. Heme Reversibly Damps PERIOD2 Rhythms in Mouse Suprachiasmatic Nucleus Explants

    PubMed Central

    Guenthner, Casey J.; Bickar, David; Harrington, Mary E.

    2009-01-01

    The hypothalamic suprachiasmatic nucleus (SCN), which in mammals serves as the master circadian pacemaker by synchronizing autonomous clocks in peripheral tissues, is composed of coupled single-cell oscillators that are driven by interlocking positive/negative transcriptional/translational feedback loops. Several studies have suggested that heme, a common prosthetic group that is synthesized and degraded in a circadian manner in the SCN, may modulate the function of several feedback loop components, including the REV-ERB nuclear receptors and PERIOD2 (PER2). We found that ferric heme (hemin, 3-100 μM) dose-dependently and reversibly damped luminescence rhythms in SCN explants from mice expressing a PER2∷LUCIFERASE (PER2∷LUC) fusion protein. Inhibitors of heme oxygenases (HOs, which degrade heme to biliverdin, carbon monoxide, and iron) mimicked heme’s effects on PER2 rhythms. In contrast, heme and HO inhibition did not damp luminescence rhythms in thymus and esophagus explants and had only a small effect on PER2∷LUC damping in spleen explants, suggesting that heme’s effects are tissue-specific. Analysis of the effects of heme’s degradation products on SCN PER2∷LUC rhythms indicated that they probably were not responsible for heme’s effects on rhythms. The heme synthesis inhibitor N-methylprotoporphyrin IX (NMP) lengthened the circadian period of SCN PER2∷LUC rhythms by about an hour. These data are consistent with an important role for heme in the circadian system. PMID:19698763

  7. The post-thaw irradiation of avian spermatozoa with He-Ne laser differently affects chicken, pheasant and turkey sperm quality.

    PubMed

    Iaffaldano, N; Paventi, G; Pizzuto, R; Passarella, S; Cerolini, S; Zaniboni, L; Marzoni, M; Castillo, A; Rosato, M P

    2013-11-30

    The effects of post-thaw Helium-Neon (He-Ne) laser irradiation on mobility and functional integrity of frozen/thawed chicken, pheasant and turkey spermatozoa were investigated. Cytochrome C oxidase (COX) activity was also determined as a measure of the effect of irradiation on mitochondrial bioenergetics. Semen samples from each species were collected, processed and frozen according to the pellet procedure. After thawing, each semen sample was divided into two subsamples: the first one was the control; the second one was irradiated with a single mode continuous He-Ne laser wave (wavelength 632.8 nm; 6 mW; 3.96 J/cm(2)). Then the samples were assessed for sperm mobility (Accudenz(®) swim-down test), viability (SYBR-14/PI staining), osmotic-resistance (HOS test) and COX activity. The irradiation was effective P<0.05 increasing sperm motility in the turkey semen (0.228 ± 0.01 compared with 0.294 ± 0.02). The irradiation also caused an increase (P<0.05) of the COX activity in pheasant (+135 ± 4%) and turkey (+116 ± 4%) sperm, without affecting viability and osmotic-resistance. The COX was positively correlated (P<0.05) with the viability of chicken sperm, however no significant interactions were found between mobility and COX activity in the three avian species. Due to the difference in energetic metabolism among avian species used in this study, the He-Ne laser irradiation has a differential action on bio-stimulation of turkey, chicken and pheasant spermatozoa. The present results are the first to elucidate the possibility for restoration of motility of cryopreserved avian spermatozoa by bio-stimulation provided via He-Ne laser irradiation.

  8. NuA4 links methylation of histone H3 lysines 4 and 36 to acetylation of histones H4 and H3.

    PubMed

    Ginsburg, Daniel S; Anlembom, Timi Elvuchio; Wang, Jianing; Patel, Sanket R; Li, Bing; Hinnebusch, Alan G

    2014-11-21

    Cotranscriptional methylation of histone H3 lysines 4 and 36 by Set1 and Set2, respectively, stimulates interaction between nucleosomes and histone deacetylase complexes to block cryptic transcription in budding yeast. We previously showed that loss of all H3K4 and H3K36 methylation in a set1Δset2Δ mutant reduces interaction between native nucleosomes and the NuA4 lysine acetyltransferase (KAT) complex. We now provide evidence that NuA4 preferentially binds H3 tails mono- and dimethylated on H3K4 and di- and trimethylated on H3K36, an H3 methylation pattern distinct from that recognized by the RPD3C(S) and Hos2/Set3 histone deacetylase complexes (HDACs). Loss of H3K4 or H3K36 methylation in set1Δ or set2Δ mutants reduces NuA4 interaction with bulk nucleosomes in vitro and in vivo, and reduces NuA4 occupancy of transcribed coding sequences at particular genes. We also provide evidence that NuA4 acetylation of lysine residues in the histone H4 tail stimulates SAGA interaction with nucleosomes and its recruitment to coding sequences and attendant acetylation of histone H3 in vivo. Thus, H3 methylation exerts opposing effects of enhancing nucleosome acetylation by both NuA4 and SAGA as well as stimulating nucleosome deacetylation by multiple HDACs to maintain the proper level of histone acetylation in transcribed coding sequences.

  9. Triboluminescent Materials for Smart Optical Damage Sensors for Space Applications

    NASA Technical Reports Server (NTRS)

    Aggarwal, Mohan D.; Penn, Benjamin G.; Miller, Jim

    2007-01-01

    Triboluminescence is light that is produced by pressure, friction or mechanical shock. New composite materials are constantly being reengi neered in an effort to make lightweight spacecrafts for various NASA missions. For these materials there is interest in monitoring the con dition of the composite in real time to detect any delamination or cr acking due to damage, fatigue or external forces. Methods of periodic inspection of composite structures for mechanical damage such as ult rasonic testing are rather mature. However, there is a need to develop a new technique of damage detection for composites, which could dete ct cracking or delamination from any desired location within a materi al structure in real time. This could provide a valuable tool in the confident use of composite materials for various space applications. Recently, triboluminnescent materials have been proposed as smart sen sors of structural damage. To sense the damage, these materials can b e epoxy bonded or coated in a polymer matrix or embedded in a composi te host structure. When the damage or fracture takes place in the hos t structure, it will lead to the fracture of triboluminescent crystal s resulting in a light emission. This will warn, in real time, that a structural damage has occurred. The triboluminescent emission of the candidate phosphor has to be sufficiently bright, so that the light signal reaching from the point of fracture to the detector through a fiber optic cable is sufficiently strong to be detected. There are a large number of triboluminescent materials, but few satisfy the above criterion. Authors have synthesized a Eu based organic material know n as Europium tetrakis (dibenzoylmethide) triethylammonium .(EuD(sub 4)TEA), one of the bright triboluminescent materials, which is a pote ntial candidate for application as a damage sensor and could be made into a wireless sensor with the addition of microchip, antenna and el ectronics. Preliminary results on the synthesis and

  10. Spectroscopic insights into axial ligation and active-site H-bonding in substrate-bound human heme oxygenase-2.

    PubMed

    Gardner, Jessica D; Yi, Li; Ragsdale, Stephen W; Brunold, Thomas C

    2010-09-01

    Heme oxygenases (HOs) are monooxygenases that catalyze the first step in heme degradation, converting heme to biliverdin with concomitant release of Fe(II) and CO from the porphyrin macrocycle. Two heme oxygenase isoforms, HO-1 and HO-2, exist that differ in several ways, including a complete lack of Cys residues in HO-1 and the presence of three Cys residues as part of heme-regulatory motifs (HRMs) in HO-2. HRMs in other heme proteins are thought to directly bind heme, or to otherwise regulate protein stability or activity; however, it is not currently known how the HRMs exert these effects on HO-2 function. To better understand the properties of this vital enzyme and to elucidate possible roles of its HRMs, various forms of HO-2 possessing distinct alterations to the HRMs were prepared. In this study, variants with Cys265 in a thiol form are compared with those with this residue in an oxidized (part of a disulfide bond or existing as a sulfenate moiety) form. Absorption and magnetic circular dichroism spectroscopic data of these HO-2 variants clearly demonstrate that a new low-spin Fe(III) heme species characteristic of thiolate ligation is formed when Cys265 is reduced. Additionally, absorption, magnetic circular dichroism, and resonance Raman data collected at different temperatures reveal an intriguing temperature dependence of the iron spin state in the heme-HO-2 complex. These findings are consistent with the presence of a hydrogen-bonding network at the heme's distal side within the active site of HO-2 with potentially significant differences from that observed in HO-1.

  11. An analysis of driving and working hour on commercial motor vehicle driver safety using naturalistic data collection.

    PubMed

    Soccolich, Susan A; Blanco, Myra; Hanowski, Richard J; Olson, Rebecca L; Morgan, Justin F; Guo, Feng; Wu, Shih-Ching

    2013-09-01

    Current hours-of-service (HOS) regulations prescribe limits to commercial motor vehicle (CMV) drivers' operating hours. By using naturalistic-data-collection, researchers were able to assess activities performed in the 14-h workday and the relationship between safety-critical events (SCEs) and driving hours, work hours, and breaks. The data used in the analyses were collected in the Naturalistic Truck Driving Study and included 97 drivers and about 735,000 miles of continuous driving data. An assessment of the drivers' workday determined that, on average, drivers spent 66% of their shift driving, 23% in non-driving work, and 11% resting. Analyses evaluating the relationship between driving hours (i.e., driving only) and SCE risk found a time-on-task effect across hours, with no significant difference in safety outcomes between 11th driving hour and driving hours 8, 9 or 10. Analyses on work hours (i.e., driving in addition to non-driving work) found that risk of being involved in an SCE generally increased as work hours increased. This suggests that time-on-task effects may not be related to driving hours alone, but implies an interaction between driving hours and work hours: if a driver begins the day with several hours of non-driving work, followed by driving that goes deep into the 14-h workday, SCE risk was found to increase. Breaks from driving were found to be beneficial in reducing SCEs (during 1-h window after a break) and were effective in counteracting the negative effects of time-on-task.

  12. BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma.

    PubMed

    Gobin, Bérengère; Huin, Marc Baud'; Lamoureux, François; Ory, Benjamin; Charrier, Céline; Lanel, Rachel; Battaglia, Séverine; Redini, Françoise; Lezot, Frédéric; Blanchard, Frédéric; Heymann, Dominique

    2015-02-15

    It has been established that disturbances in intracellular signaling pathways play a considerable part in the oncologic process. Phosphatidylinositol-3-kinase (PI3K) has become of key interest in cancer therapy because of its high mutation frequency and/or gain in function of its catalytic subunits in cancer cells. We investigated the therapeutic value of BYL719, a new specific PI3Kα inhibitor that blocks the ATP site, on osteosarcoma and bone cells. The in vitro effects of BYL719 on proliferation, apoptosis, and cell cycle were assessed in human and murine osteosarcoma cell. Its impact on bone cells was determined using human mesenchymal stem cells (hMSC) and human CD14+ osteoclast precursors. Two different murine preclinical models of osteosarcoma were used to analyze the in vivo biological activities of BYL719. BYL719 decreased cell proliferation by blocking cell cycle in G0/G1 phase with no outstanding effects on apoptosis cell death in HOS and MOS-J tumor cells. BYL719 inhibited cell migration and can thus be considered as a cytostatic drug for osteosarcoma. In murine preclinical models of osteosarcoma, BYL719 significantly decreased tumor progression and tumor ectopic bone formation as shown by a decrease of Ki67+ cells and tumor vascularization. To explore the maximum therapeutic potential of BYL719, the drug was studied in combination with conventional chemotherapeutic drugs, revealing promising efficacy with ifosfamide. BYL719 also exhibited dual activities on osteoblast and osteoclast differentiation. Overall, the present work shows that BYL719 is a promising drug in either a single or multidrug approach to curing bone sarcoma.

  13. Age- and Parkinson's disease-related evaluation of gait by General Tau Theory.

    PubMed

    Zhang, Shutao; Qian, Jinwu; Zhang, Zhen; Shen, Linyong; Wu, Xi; Hu, Xiaowu

    2016-10-01

    The degeneration of postural control in the elderly and patients with Parkinson's disease (PD) can be debilitating and may lead to increased fall risk. This study evaluated the changes in postural control during gait affected by PD and aging using a new method based on the General Tau Theory. Fifteen patients with PD, 11 healthy old adults (HOs), and 15 healthy young adults (HYs) were recruited. Foot trajectories of each participant were monitored during walking by a three-camera Optotrak Certus(®) motion capture system. The anteroposterior direction of foot movement during stepping was analyzed by tau-G and tau-J guidance strategies. Two linear regression analyses suggested that the tau of the step-gap was strongly coupled onto the tau-J guidance during walking. The regression slope K could estimate the coupling ratio in the tau-coupling equation which reflects the performance of postural control during gait. The mean K value for the PD group, which was highest among the three groups, was approximately 0.5. Therefore, participants in the PD group walked with the poorest postural control and exhibited a relatively hard contact with the endpoint during stepping when compared with those in the HO and HY groups. The HY and HO groups obtained mean K values significantly lower than 0.5, which indicated that the gait was well controlled and ended at low speed with low deceleration. However, the HO group showed a decreased tendency for postural control, in which the mean K value was significantly higher than that of the HY group. The K value was moderately positively correlated with the double support time and negatively correlated with the stride length and walking speed. The tau-J coupling ratio can provide additional insight into gait disturbances and may serve as a reliable, objective, and quantitative tool to evaluate dynamic postural control during walking.

  14. Genetic differentiation of Mexican Holstein cattle and its relationship with Canadian and U.S. Holsteins.

    PubMed

    García-Ruiz, Adriana; Ruiz-López, Felipe de J; Van Tassell, Curtis P; Montaldo, Hugo H; Huson, Heather J

    2015-01-01

    The Mexican Holstein (HO) industry has imported Canadian and US (CAN + USA) HO germplasm for use in two different production systems, the conventional (Conv) and the low income (Lowi) system. The objective of this work was to study the genetic composition and differentiation of the Mexican HO cattle, considering the production system in which they perform and their relationship with the Canadian and US HO populations. The analysis included information from 149, 303, and 173 unrelated or with unknown pedigree HO animals from the Conv, Lowi, and CAN + USA populations, respectively. Canadian and US Jersey (JE) and Brown Swiss (BS) genotypes (162 and 86, respectively) were used to determine if Mexican HOs were hybridized with either of these breeds. After quality control filtering, a total of 6,617 out of 6,836 single nucleotide polymorphism markers were used. To describe the genetic diversity across the populations, principal component (PC), admixture composition, and linkage disequilibrium (LD; r(2) ) analyses were performed. Through the PC analysis, HO × JE and HO × BS crossbreeding was detected in the Lowi system. The Conv system appeared to be in between Lowi and CAN + USA populations. Admixture analysis differentiated between the genetic composition of the Conv and Lowi systems, and five ancestry groups associated to sire's country of origin were identified. The minimum distance between markers to estimate a useful LD was found to be 54.5 kb for the Mexican HO populations. At this average distance, the persistence of phase across autosomes of Conv and Lowi systems was 0.94, for Conv and CAN + USA was 0.92 and for the Lowi and CAN + USA was 0.91. Results supported the flow of germplasm among populations being Conv a source for Lowi, and dependent on migration from CAN + USA. Mexican HO cattle in Conv and Lowi populations share common ancestry with CAN + USA but have different genetic signatures.

  15. Genetic differentiation of Mexican Holstein cattle and its relationship with Canadian and U.S. Holsteins

    PubMed Central

    García-Ruiz, Adriana; Ruiz-López, Felipe de J.; Van Tassell, Curtis P.; Montaldo, Hugo H.; Huson, Heather J.

    2015-01-01

    The Mexican Holstein (HO) industry has imported Canadian and US (CAN + USA) HO germplasm for use in two different production systems, the conventional (Conv) and the low income (Lowi) system. The objective of this work was to study the genetic composition and differentiation of the Mexican HO cattle, considering the production system in which they perform and their relationship with the Canadian and US HO populations. The analysis included information from 149, 303, and 173 unrelated or with unknown pedigree HO animals from the Conv, Lowi, and CAN + USA populations, respectively. Canadian and US Jersey (JE) and Brown Swiss (BS) genotypes (162 and 86, respectively) were used to determine if Mexican HOs were hybridized with either of these breeds. After quality control filtering, a total of 6,617 out of 6,836 single nucleotide polymorphism markers were used. To describe the genetic diversity across the populations, principal component (PC), admixture composition, and linkage disequilibrium (LD; r2) analyses were performed. Through the PC analysis, HO × JE and HO × BS crossbreeding was detected in the Lowi system. The Conv system appeared to be in between Lowi and CAN + USA populations. Admixture analysis differentiated between the genetic composition of the Conv and Lowi systems, and five ancestry groups associated to sire’s country of origin were identified. The minimum distance between markers to estimate a useful LD was found to be 54.5 kb for the Mexican HO populations. At this average distance, the persistence of phase across autosomes of Conv and Lowi systems was 0.94, for Conv and CAN + USA was 0.92 and for the Lowi and CAN + USA was 0.91. Results supported the flow of germplasm among populations being Conv a source for Lowi, and dependent on migration from CAN + USA. Mexican HO cattle in Conv and Lowi populations share common ancestry with CAN + USA but have different genetic signatures. PMID:25709615

  16. Further evidence against a direct genotoxic mode of action for arsenic-induced cancer

    SciTech Connect

    Klein, Catherine B.; Leszczynska, Joanna; Hickey, Christina; Rossman, Toby G.

    2007-08-01

    Arsenic in drinking water, a mixture of arsenite and arsenate, is associated with increased skin and other cancers in Asia and Latin America, but not the United States. Arsenite alone in drinking water does not cause skin cancers in experimental animals; therefore, it is not a complete carcinogen in skin. We recently showed that low concentrations of arsenite enhanced the tumorigenicity of solar UV irradiation in hairless mice, suggesting arsenic cocarcinogenesis with sunlight in skin cancer and perhaps with different carcinogenic partners for lung and bladder tumors. Cocarcinogenic mechanisms could include blocking DNA repair, stimulating angiogenesis, altering DNA methylation patterns, dysregulating cell cycle control, induction of aneuploidy and blocking apoptosis. Arsenicals are documented clastogens but not strong mutagens, with weak mutagenic activity reported at highly toxic concentrations of inorganic arsenic. Previously, we showed that arsenite, but not monomethylarsonous acid (MMA[III]), induced delayed mutagenesis in HOS cells. Here, we report new data on the mutagenicity of the trivalent methylated arsenic metabolites MMA(III) and dimethylarsinous acid [DMA(III)] at the gpt locus in Chinese hamster G12 cells. Both methylated arsenicals seemed mutagenic with apparent sublinear dose responses. However, significant mutagenesis occurred only at highly toxic concentrations of MMA(III). Most mutants induced by MMA(III) and DMA(III) exhibited transgene deletions. Some non-deletion mutants exhibited altered DNA methylation. A critical discussion of cell survival leads us to conclude that clastogenesis occurs primarily at highly cytotoxic arsenic concentrations, casting further doubt as to whether a genotoxic mode of action (MOA) for arsenicals is supportable.

  17. Variation of the oxidation state of verdoheme in the heme oxygenase reaction

    SciTech Connect

    Gohya, Tomohiko; Sato, Michihiko; Zhang Xuhong; Migita, Catharina T.

    2008-11-14

    Heme oxygenase (HO) converts hemin to biliverdin, CO, and iron applying molecular oxygen and electrons. During successive HO reactions, two intermediates, {alpha}-hydroxyhemin and verdoheme, have been generated. Here, oxidation state of the verdoheme-HO complexes is controversial. To clarify this, the heme conversion by soybean and rat HO isoform-1 (GmHO-1 and rHO-1, respectively) was compared both under physiological conditions, with oxygen and NADPH coupled with ferredoxin reductase/ferredoxin for GmHO-1 or with cytochrome P450 reductase for rHO-1, and under a non-physiological condition with hydrogen peroxide. EPR measurements on the hemin-GmHO-1 reaction with oxygen detected a low-spin ferric intermediate, which was undetectable in the rHO-1 reaction, suggesting the verdoheme in the six-coordinate ferric state in GmHO-1. Optical absorption measurements on this reaction indicated that the heme degradation was extremely retarded at verdoheme though this reaction was not inhibited under high-CO concentrations, unlike the rHO-1 reaction. On the contrary, the Gm and rHO-1 reactions with hydrogen peroxide both provided ferric low-spin intermediates though their yields were different. The optical absorption spectra suggested that the ferric and ferrous verdoheme coexisted in reaction mixtures and were slowly converted to the ferric biliverdin complex. Consequently, in the physiological oxygen reactions, the verdoheme is found to be stabilized in the ferric state in GmHO-1 probably guided by protein distal residues and in the ferrous state in rHO-1, whereas in the hydrogen peroxide reactions, hydrogen peroxide or hydroxide coordination stabilizes the ferric state of verdoheme in both HOs.

  18. An integrated index for automated detection of infarcted myocardium from cross-sectional echocardiograms using texton-based features (Part 1).

    PubMed

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

    2016-04-01

    Cross-sectional view echocardiography is an efficient non-invasive diagnostic tool for characterizing Myocardial Infarction (MI) and stages of expansion leading to heart failure. An automated computer-aided technique of cross-sectional echocardiography feature assessment can aid clinicians in early and more reliable detection of MI patients before subsequent catastrophic post-MI medical conditions. Therefore, this paper proposes a novel Myocardial Infarction Index (MII) to discriminate infarcted and normal myocardium using features extracted from apical cross-sectional views of echocardiograms. The cross-sectional view of normal and MI echocardiography images are represented as textons using Maximum Responses (MR8) filter banks. Fractal Dimension (FD), Higher-Order Statistics (HOS), Hu's moments, Gabor Transform features, Fuzzy Entropy (FEnt), Energy, Local binary Pattern (LBP), Renyi's Entropy (REnt), Shannon's Entropy (ShEnt), and Kapur's Entropy (KEnt) features are extracted from textons. These features are ranked using t-test and fuzzy Max-Relevancy and Min-Redundancy (mRMR) ranking methods. Then, combinations of highly ranked features are used in the formulation and development of an integrated MII. This calculated novel MII is used to accurately and quickly detect infarcted myocardium by using one numerical value. Also, the highly ranked features are subjected to classification using different classifiers for the characterization of normal and MI LV ultrasound images using a minimum number of features. Our current technique is able to characterize MI with an average accuracy of 94.37%, sensitivity of 91.25% and specificity of 97.50% with 8 apical four chambers view features extracted from only single frame per patient making this a more reliable and accurate classification.

  19. Spermicidal and Contraceptive Potential of Desgalactotigonin: A Prospective Alternative of Nonoxynol-9

    PubMed Central

    Chakraborty, Debanjana; Maity, Arindam; Jha, Tarun; Mondal, Nirup Bikash

    2014-01-01

    Crude decoction of Chenopodium album seed showed spermicidal effect at MIC 2 mg/ml in earlier studies. Systematic isolation, characterization and evaluation revealed that the major metabolite Desgalactotigonin (DGT) is the most effective principle in both in vitro and in vivo studies. The in vitro studies comprises (a) rat and human sperm motility and immobilizing activity by Sander-Cramer assay; (b) sperm membrane integrity was observed by HOS test and electron microscopy; (c) microbial potential was examined in Lactobacillus broth culture, and (d) the hemolytic index was determined by using rat RBCs. The in vivo contraceptive efficacy was evaluated by intra uterine application of DGT in rat. Lipid peroxidation and induction of apoptosis by DGT on human spermatozoa were also studied. The minimum effective concentration (MEC) of DGT that induced instantaneous immobilization in vitro was 24.18 µM for rat and 58.03 µM for human spermatozoa. Microbial study indicated DGT to be friendly to Lactobacillus acidophilus. Implantation was prevented in DGT treated uterine horn while no hindrance occurred in the untreated contra lateral side. At the level of EC50, DGT induced apoptosis in human spermatozoa as determined by increased labeling with Annexin-V and decreased polarization of sperm mitochondria. Desgalactotigonin emerged 80 and 2×104 times more potent than the decoction and Nonoxynol-9 respectively. It possesses mechanism based detrimental action on both human and rat spermatozoa and spares lactobacilli and HeLa cells at MEC which proves its potential as a superior ingredient for the formulation of a contraceptive safer/compatible to vaginal microflora. PMID:25243914

  20. Study on the description method of upper limb's muscle force levels during simulated in-orbit operations

    NASA Astrophysics Data System (ADS)

    Zhao, Yan; Li, DongXu; Liu, ZhiZhen; Liu, Liang

    2013-03-01

    The dexterous upper limb serves as the most important tool for astronauts to implement in-orbit experiments and operations. This study developed a simulated weightlessness experiment and invented new measuring equipment to quantitatively evaluate the muscle ability of the upper limb. Isometric maximum voluntary contractions (MVCs) and surface electromyography (sEMG) signals of right-handed pushing at the three positions were measured for eleven subjects. In order to enhance the comprehensiveness and accuracy of muscle force assessment, the study focused on signal processing techniques. We applied a combination method, which consists of time-, frequency-, and bi-frequency-domain analyses. Time- and frequency-domain analyses estimated the root mean square (RMS) and median frequency (MDF) of sEMG signals, respectively. Higher order spectra (HOS) of bi-frequency domain evaluated the maximum bispectrum amplitude ( B max), Gaussianity level (Sg) and linearity level (S l ) of sEMG signals. Results showed that B max, S l , and RMS values all increased as force increased. MDF and Sg values both declined as force increased. The research demonstrated that the combination method is superior to the conventional time- and frequency-domain analyses. The method not only described sEMG signal amplitude and power spectrum, but also deeper characterized phase coupling information and non-Gaussianity and non-linearity levels of sEMG, compared to two conventional analyses. The finding from the study can aid ergonomist to estimate astronaut muscle performance, so as to optimize in-orbit operation efficacy and minimize musculoskeletal injuries.

  1. Crystal structure of dimeric heme oxygenase-2 from Synechocystis sp. PCC 6803 in complex with heme.

    PubMed

    Sugishima, Masakazu; Hagiwara, Yoshinori; Zhang, Xuhong; Yoshida, Tadashi; Migita, Catharina T; Fukuyama, Keiichi

    2005-03-22

    Phycobiliproteins, light-harvesting proteins in cyanobacteria, red algae, and cryptophytes, contain phycobilin pigments. Phycobilins are synthesized from biliverdin, which is produced by the oxidative cleavage of the heme porphyrin ring catalyzed by heme oxygenase (HO). Two paralogs of ho (ho1 and ho2) have been identified in the genome of the cyanobacterium, Synechocystis sp. PCC 6803. The recombinant proteins of both paralogs (Syn HO-1 and Syn HO-2) possess in vitro heme degradation activity. We have determined the crystal structures of Syn HO-2 in complex with heme (heme-Syn HO-2) and its reduced and NO bound forms. The heme-Syn HO-2 crystal was a nonmerohedral twin, and detwinned diffraction data were used to refine the structure. Although heme-Syn HO-2 shares common folding with other HOs, the C-terminal segment is ordered and turns back to the heme-binding side. Gel-filtration chromatography analysis and molecular packing in the crystal indicate that heme-Syn HO-2 forms a homodimer, in which the C-terminal ordered segments interact with each other. Because Syn HO-2 is a monomer in the apo state, the dimeric interaction may aid in the selection of the reducing partner but likely does not interfere with heme binding. The heme iron is coordinated by a water molecule in the ferric form, but the distal water is absent in the ferrous form. In all of the Syn HO-2 structures, several water molecules form a hydrogen-bond network at the distal hemepocket, which is involved in HO activity. Upon NO binding, the side-chain conformation of Tyr 156 changes. Tyr 156 is located at the hydrophobic cluster, which interrupts the possible H(+) pathway from the molecular surface to the hemepocket. Thus, Tyr 156 may function as a H(+) shuttle by changing conformation.

  2. A Bulk Segregant Gene Expression Analysis of a Peach Population Reveals Components of the Underlying Mechanism of the Fruit Cold Response

    PubMed Central

    Pons, Clara; Martí, Cristina; Forment, Javier; Crisosto, Carlos H.; Dandekar, Abhaya M.; Granell, Antonio

    2014-01-01

    Peach fruits subjected for long periods of cold storage are primed to develop chilling injury once fruits are shelf ripened at room temperature. Very little is known about the molecular changes occurring in fruits during cold exposure. To get some insight into this process a transcript profiling analyses was performed on fruits from a PopDG population segregating for chilling injury CI responses. A bulked segregant gene expression analysis based on groups of fruits showing extreme CI responses indicated that the transcriptome of peach fruits was modified already during cold storage consistently with eventual CI development. Most peach cold-responsive genes have orthologs in Arabidopsis that participate in cold acclimation and other stresses responses, while some of them showed expression patterns that differs in fruits according to their susceptibility to develop mealiness. Members of ICE1, CBF1/3 and HOS9 regulons seem to have a prominent role in differential cold responses between low and high sensitive fruits. In high sensitive fruits, an alternative cold response program is detected. This program is probably associated with dehydration/osmotic stress and regulated by ABA, auxins and ethylene. In addition, the observation that tolerant siblings showed a series of genes encoding for stress protective activities with higher expression both at harvest and during cold treatment, suggests that preprogrammed mechanisms could shape fruit ability to tolerate postharvest cold-induced stress. A number of genes differentially expressed were validated and extended to individual genotypes by medium-throughput RT-qPCR. Analyses presented here provide a global view of the responses of peach fruits to cold storage and highlights new peach genes that probably play important roles in the tolerance/sensitivity to cold storage. Our results provide a roadmap for further experiments and would help to develop new postharvest protocols and gene directed breeding strategies to better

  3. The use of kernel local Fisher discriminant analysis for the channelization of the Hotelling model observer

    NASA Astrophysics Data System (ADS)

    Wen, Gezheng; Markey, Mia K.

    2015-03-01

    It is resource-intensive to conduct human studies for task-based assessment of medical image quality and system optimization. Thus, numerical model observers have been developed as a surrogate for human observers. The Hotelling observer (HO) is the optimal linear observer for signal-detection tasks, but the high dimensionality of imaging data results in a heavy computational burden. Channelization is often used to approximate the HO through a dimensionality reduction step, but how to produce channelized images without losing significant image information remains a key challenge. Kernel local Fisher discriminant analysis (KLFDA) uses kernel techniques to perform supervised dimensionality reduction, which finds an embedding transformation that maximizes betweenclass separability and preserves within-class local structure in the low-dimensional manifold. It is powerful for classification tasks, especially when the distribution of a class is multimodal. Such multimodality could be observed in many practical clinical tasks. For example, primary and metastatic lesions may both appear in medical imaging studies, but the distributions of their typical characteristics (e.g., size) may be very different. In this study, we propose to use KLFDA as a novel channelization method. The dimension of the embedded manifold (i.e., the result of KLFDA) is a counterpart to the number of channels in the state-of-art linear channelization. We present a simulation study to demonstrate the potential usefulness of KLFDA for building the channelized HOs (CHOs) and generating reliable decision statistics for clinical tasks. We show that the performance of the CHO with KLFDA channels is comparable to that of the benchmark CHOs.

  4. STAT3 inhibitor, cucurbitacin I, is a novel therapeutic agent for osteosarcoma

    PubMed Central

    Oi, Toru; Asanuma, Kunihiro; Matsumine, Akihiko; Matsubara, Takao; Nakamura, Tomoki; Iino, Takahiro; Asanuma, Yumiko; Goto, Mikinobu; Okuno, Kazuma; Kakimoto, Takuya; Yada, Yuki; Sudo, Akihiro

    2016-01-01

    The development of clinical agents remains a costly and time-consuming process. Although identification of new uses of existing drugs has been recognized as a more efficient approach for drug discovery than development of novel drugs, little screening of drugs that might be used for a rare malignant tumor such as osteosarcoma (OS) has been performed. In this study, we attempted to identify new molecular targeted agents for OS by employing Screening Committee of Anticancer Drugs (SCADS) kits. To screen compounds for OS treatment, their effect on cell viability of the OS cell lines 143B, MG63, HOS, SAOS-2, and HUO9 were evaluated. Candidate drugs were narrowed down based on a global anti-proliferative effect against these five OS cell lines. After excluding cytotoxic compounds and compounds unsuitable for in vivo administration, cucurbitacin I was extracted. Cucurbitacin I has been found to have cytotoxic and anti-proliferative properties against several tumors through inhibition of signal transducer and activator of transcription 3 (STAT3) activation. Cucurbitacin I dose- and time-dependently inhibited the proliferation of all five OS cell lines. Following cucurbitacin I treatment, STAT3 was inactivated and analysis of Mcl-1, cleaved PARP and caspase-3 indicated apoptosis induction. Expression of cell cycle regulator proteins, such as phospho-cyclin D1, c-Myc and survivin, were suppressed. Finally, cucurbitacin I potently inhibited the tumor growth of human OS 143B cells in nude mice. Our in vitro and in vivo results suggest that STAT3 inhibition by cucurbitacin I will be an effective and new approach for the treatment of OS. PMID:27840900

  5. Carbon Nanofiber/Polycaprolactone/Mineralized Hydroxyapatite Nanofibrous Scaffolds for Potential Orthopedic Applications.

    PubMed

    Elangomannan, Shinyjoy; Louis, Kavitha; Dharmaraj, Bhagya Mathi; Kandasamy, Venkata Saravanan; Soundarapandian, Kannan; Gopi, Dhanaraj

    2017-02-22

    Hydroxyapatite (Ca10 (PO4)6(OH)2, HAP), a multimineral substituted calcium phosphate is one of the most substantial bone mineral component that has been widely used as bone replacement materials because of its bioactive and biocompatible properties. However, the use of HAP as bone implants is restricted due to its brittle nature and poor mechanical properties. To overcome this defect and to generate suitable bone implant material, HAP is combined with biodegradable polymer (polycaprolactone, PCL). To enhance the mechanical property of the composite, carbon nanofibers (CNF) is incorporated to the composite, which has long been considered for hard and soft tissue implant due to its exceptional mechanical and structural properties. It is well-known that nanofibrous scaffold are the most-prominent material for the bone reconstruction. We have developed a new remarkable CNF/PCL/mineralized hydroxyapatite (M-HAP) nanofibrous scaffolds on titanium (Ti). The as-developed coatings were characterized by various techniques. The results indicate the formation and homogeneous distribution of components in the nanofibrous scaffolds. Incorporation of CNF into the PCL/M-HAP composite significantly improves the adhesion strength and elastic modulus of the scaffolds. Furthermore, the responses of human osteosarcoma (HOS MG63) cells cultured onto the scaffolds demonstrate that the viability of cells were considerably high for CNF-incorporated PCL/M-HAP than for PCL/M-HAP. In vivo analysis show the presence of soft fibrous tissue growth without any significant inflammatory signs, which suggests that incorporated CNF did not counteract the favorable biological roles of HAP. For load-bearing applications, research in various bone models is needed to substantiate the clinical availability. Thus, from the obtained results, we suggest that CNF/PCL/M-HAP nanofibrous scaffolds can be considered as potential candidates for orthopedic applications.

  6. Tbx5 and Osr1 interact to regulate posterior second heart field cell cycle progression for cardiac septation

    PubMed Central

    Zhou, Lun; Liu, Jielin; Olson, Patrick; Zhang, Ke; Wynne, Joshua; Xie, Linglin

    2015-01-01

    Rationale Mutations of TBX5 cause Holt–Oram syndrome (HOS) in humans, a disease characterized by atrial or occasionally ventricular septal defects in the heart and skeletal abnormalities of the upper extremity. Previous studies have demonstrated that Tbx5 regulates Osr1 expression in the second heart field (SHF) of E9.5 mouse embryos. However, it is unknown whether and how Tbx5 and Osr1 interact in atrial septation. Objective To determine if and how Tbx5 and Osr1 interact in the posterior SHF for cardiac septation. Methods and Results In the present study, genetic inducible fate mapping showed that Osr1-expressing cells contribute to atrial septum progenitors between E8.0 and E11.0. Osr1 expression in the pSHF was dependent on the level of Tbx5 at E8.5 and E9.5 but not E10.5, suggesting that the embryo stage before E10.5 is critical for Tbx5 interacting with Osr1 in atrial septation. Significantly more atrioventricular septal defects (AVSDs) were observed in embryos with compound haploinsufficiency for Tbx5 and Osr1. Conditional compound haploinsufficiency for Tbx5 and Osr1 resulted in a significant cell proliferation defect in the SHF, which was associated with fewer cells in the G2 and M phases and a decreased level of Cdk6 expression. Remarkably, genetically targeted disruption of Pten expression in atrial septum progenitors rescued AVSDs caused by Tbx5 and Osr1 compound haploinsufficiency. There was a significant decrease in Smo expression, which is a Hedgehog (Hh) signaling pathway modulator, in the pSHF of Osr1 knockout embryos at E9.5, implying a role for Osr1 in regulating Hh signaling. Conclusions Tbx5 and Osr1 interact to regulate posterior SHF cell cycle progression for cardiac septation. PMID:25986147

  7. Fetal liver-derived mesenchymal stromal cells augment engraftment of transplanted hepatocytes

    PubMed Central

    Joshi, Meghnad; Patil, Pradeep B.; He, Zhong; Holgersson, Jan; Olausson, Michael; Sumitran-Holgersson, Suchitra

    2012-01-01

    Background aims One important problem commonly encountered after hepatocyte transplantation is the low numbers of transplanted cells found in the graft. If hepatocyte transplantation is to be a viable therapeutic approach, significant liver parenchyma repopulation is required. Mesenchymal stromal cells (MSC) produce high levels of various growth factors, cytokines and metalloproteinases, and have immunomodulatory effects. We therefore hypothesized that co-transplantation of MSC with human fetal hepatocytes (hFH) could augment in vivo expansion after transplantation. We investigated the ability of human fetal liver MSC (hFLMSC) to augment expansion of phenotypically and functionally well-characterized hFH. Methods Two million hFH (passage 6) were either transplanted alone or together (1:1 ratio) with green fluorescence protein-expressing hFLMSC into the spleen of C57BL/6 nude mice with retrorsine-induced liver injury. Results After 4 weeks, engraftment of cells was detected by fluorescence in situ hybridization using a human-specific DNA probe. Significantly higher numbers of cells expressing human cytokeratin (CK)8, CK18, CK19, Cysteine-rich MNNG HOS Transforming gene (c-Met), alpha-fetoprotein (AFP), human nuclear antigen, mitochondrial antigen, hepatocyte-specific antigen and albumin (ALB) were present in the livers of recipient animals co-transplanted with hFLMSC compared with those without. Furthermore, expression of human hepatocyte nuclear factor (HNF)-4α and HNF-1β, and cytochrome P450 (CYP) 3A7 mRNA was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) in these animals. In addition, significantly increased amounts of human ALB were detected. Importantly, hFLMSC did not transdifferentiate into hepatocytes. Conclusions Our study reports the use of a novel strategy for enhanced liver repopulation and thereby advances this experimental procedure closer to clinical liver cell therapy. PMID:22424216

  8. Induction of G2/M phase cell cycle arrest and apoptosis by ginsenoside Rf in human osteosarcoma MG‑63 cells through the mitochondrial pathway.

    PubMed

    Shangguan, Wen-Ji; Li, He; Zhang, Yue-Hui

    2014-01-01

    Ginsenosides, extracted from the traditional Chinese herb ginseng, are a series of novel natural anticancer products known for their favorable safety and efficacy profiles. The present study aimed to investigate the cytotoxicity of ginsenoside Rf to human osteosarcoma cells and to explore the anticancer molecular mechanisms of ginsenoside Rf. Five human osteosarcoma cell lines (MG-63, OS732, U-2OS, HOS and SAOS-2) were employed to investigate the cytotoxicity of ginsenoside Rf by MTT and colony forming assays. After treatment with ginsenoside Rf, MG-63 cells which were the most sensitive to ginsenoside Rf, were subjected to flow cytometry to detect cell cycle distribution and apoptosis, and nuclear morphological changes were visualized by Hoechst 33258 staining. Caspase-3, -8 and -9 activities were also evaluated. The expression of cell cycle markers including cyclin B1 and Cdk1 was detected by RT-PCR and western blotting. The expression of apoptotic genes Bcl-2 and Bax and the release of cytochrome c were also examined by western blotting. Change in the mitochondrial membrane potential was observed by JC-1 staining in situ. Our results demonstrated that the cytotoxicity of ginsenoside Rf to these human osteosarcoma cell lines was dose-dependent, and the MG-63 cells were the most sensitive to exposure to ginsenoside Rf. Additionally, ginsenoside Rf induced G2/M phase cell cycle arrest and apoptosis in MG-63 cells. Furthermore, we observed upregulation of Bax and downregulation of Bcl-2, Cdk1 and cyclin B1, the activation of caspase-3 and -9 and the release of cytochrome c in MG-63 cells following treatment with ginsenoside Rf. Our findings demonstrated that ginsenoside Rf induces G2/M phase cell cycle arrest and apoptosis in human osteosarcoma MG-63 cells through the mitochondrial pathway, suggesting that ginsenoside Rf, as an effective natural product, may have a therapeutic effect on human osteosarcoma.

  9. Disproportionate growth between the spine and pelvis in patients with thoracic adolescent scoliosis: a new look into the pattern's growth.

    PubMed

    Bao, H; Liu, Z; Yan, P; Qiu, Y; Zhu, F

    2015-12-01

    A self-control ratio, the spine-pelvis index (SPI), was proposed for the assessment of patients with adolescent idiopathic scoliosis (AIS) in this study. The aim was to evaluate the disproportionate growth between the spine and pelvis in these patients using SPI. A total of 64 female patients with thoracic AIS were randomly enrolled between December 2010 and October 2012 (mean age 13 years, standard deviation (sd) 2.17; 9 to 18) and a further 73 healthy female patients with a mean age of 12.4 years (mean age 12.4 years, sd 2.24; 9 to 18), were randomly selected from a normal control database at our centre. The radiographic parameters measured included length of spine (LOS), height of spine (HOS), length of thoracic vertebrae (LOT), height of thoracic vertebrae (HOT), width of pelvis (WOP), height of pelvis (HOP) and width of thorax (WOT). SPI was defined as the ratio LOS/HOP. The SPI and LOT/HOP in patients with AIS showed a significant increase when compared with normal girls (p < 0.001 and p < 0.001 respectively), implying an abnormal pattern of growth of the spine relative to the pelvis in patients with AIS. No significant difference in SPI was found in different age groups in the control group, making the SPI an age-independent parameter with a mean value of 2.219 (2.164 to 2.239). We also found that the SPI was not related to maturity in the control group. This study, for the first time, used a self-control ratio to confirm the disproportionate patterns of growth of the spine and pelvis in patients with thoracic AIS, highlighting that the SPI is not affected by age or maturity.

  10. Classification of oxidative stress based on its intensity

    PubMed Central

    Lushchak, Volodymyr I.

    2014-01-01

    In living organisms production of reactive oxygen species (ROS) is counterbalanced by their elimination and/or prevention of formation which in concert can typically maintain a steady-state (stationary) ROS level. However, this balance may be disturbed and lead to elevated ROS levels called oxidative stress. To our best knowledge, there is no broadly acceptable system of classification of oxidative stress based on its intensity due to which proposed here system may be helpful for interpretation of experimental data. Oxidative stress field is the hot topic in biology and, to date, many details related to ROS-induced damage to cellular components, ROS-based signaling, cellular responses and adaptation have been disclosed. However, it is common situation when researchers experience substantial difficulties in the correct interpretation of oxidative stress development especially when there is a need to characterize its intensity. Careful selection of specific biomarkers (ROS-modified targets) and some system may be helpful here. A classification of oxidative stress based on its intensity is proposed here. According to this classification there are four zones of function in the relationship between “Dose/concentration of inducer” and the measured “Endpoint”: I – basal oxidative stress (BOS); II – low intensity oxidative stress (LOS); III – intermediate intensity oxidative stress (IOS); IV – high intensity oxidative stress (HOS). The proposed classification will be helpful to describe experimental data where oxidative stress is induced and systematize it based on its intensity, but further studies will be in need to clear discriminate between stress of different intensity. PMID:26417312

  11. Effects of water quality on the vector competence of Culex tarsalis (Diptera: Culicidae) for western equine encephalomyelitis (Togaviridae) and St. Louis encephalitis (Flaviviridae) viruses.

    PubMed

    Reisen, W K; Hardy, J L; Presser, S B

    1997-11-01

    The effects of water quality during immature development on the vector competence of adult female Culex tarsalis Coquillett for western equine encephalomyelitis (WEE) and St. Louis encephalitis (SLE) viruses was evaluated during 6 field and 4 laboratory experiments. Immatures of the Bakersfield Field Station laboratory strain and the F1 progeny of field-collected females were reared in the field or laboratory and then infected by feeding on pledgets, after which remnants (head, thorax, abdomen), legs, and salivary secretions were tested for WEE or SLE virus to estimate infection, dissemination, and transmission rates, respectively. Although the salt content of the 6 larval habitats varied markedly (range, alkalinity 160-1,310 ppm CaCO3, conductivity 460-7,600 microns hos/cm, chlorides 22-1,560 ppm) and significantly altered immature survival, development time, and female body size (wing length), consistent changes in infection, dissemination, or transmission rates were not observed. Susceptibility (ID50) to WEE virus in field strains decreased as a linear function of developmental time, with populations from a dry alkali lake bed (Goose Lake) least susceptible. Three subsequent laboratory experiments that tested the effects of rearing immatures in dilution series of water from Goose Lake failed to produce consistent within or among experiment patterns in vector competence. A 4th laboratory experiment tested changes in NaCl concentration with negative results. Changes in female size was not related to vector competence. These and previous temperature studies indicated that temporal changes in vector competence observed within and among field populations probably were related to intrinsic genetic factors and were not related directly to extrinsic factors in the immature aquatic environment.

  12. Transformation of human osteoblast cells to the tumorigenic phenotype by depleted uranium-uranyl chloride.

    PubMed Central

    Miller, A C; Blakely, W F; Livengood, D; Whittaker, T; Xu, J; Ejnik, J W; Hamilton, M M; Parlette, E; John, T S; Gerstenberg, H M; Hsu, H

    1998-01-01

    Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Although the health effects of occupational uranium exposure are well known, limited data exist regarding the long-term health effects of internalized DU in humans. We established an in vitro cellular model to study DU exposure. Microdosimetric assessment, determined using a Monte Carlo computer simulation based on measured intracellular and extracellular uranium levels, showed that few (0.0014%) cell nuclei were hit by alpha particles. We report the ability of DU-uranyl chloride to transform immortalized human osteoblastic cells (HOS) to the tumorigenic phenotype. DU-uranyl chloride-transformants are characterized by anchorage-independent growth, tumor formation in nude mice, expression of high levels of the k-ras oncogene, reduced production of the Rb tumor-suppressor protein, and elevated levels of sister chromatid exchanges per cell. DU-uranyl chloride treatment resulted in a 9.6 (+/- 2.8)-fold increase in transformation frequency compared to untreated cells. In comparison, nickel sulfate resulted in a 7.1 (+/- 2.1)-fold increase in transformation frequency. This is the first report showing that a DU compound caused human cell transformation to the neoplastic phenotype. Although additional studies are needed to determine if protracted DU exposure produces tumors in vivo, the implication from these in vitro results is that the risk of cancer induction from internalized DU exposure may be comparable to other biologically reactive and carcinogenic heavy-metal compounds (e.g., nickel). Images Figure 1 Figure 2 Figure 3 PMID:9681973

  13. Recent progresses of neural network unsupervised learning: I. Independent component analyses generalizing PCA

    NASA Astrophysics Data System (ADS)

    Szu, Harold H.

    1999-03-01

    The early vision principle of redundancy reduction of 108 sensor excitations is understandable from computer vision viewpoint toward sparse edge maps. It is only recently derived using a truly unsupervised learning paradigm of artificial neural networks (ANN). In fact, the biological vision, Hubel- Wiesel edge maps, is reproduced seeking the underlying independent components analyses (ICA) among 102 image samples by maximizing the ANN output entropy (partial)H(V)/(partial)[W] equals (partial)[W]/(partial)t. When a pair of newborn eyes or ears meet the bustling and hustling world without supervision, they seek ICA by comparing 2 sensory measurements (x1(t), x2(t))T equalsV X(t). Assuming a linear and instantaneous mixture model of the external world X(t) equals [A] S(t), where both the mixing matrix ([A] equalsV [a1, a2] of ICA vectors and the source percentages (s1(t), s2(t))T equalsV S(t) are unknown, we seek the independent sources approximately equals [I] where the approximated sign indicates that higher order statistics (HOS) may not be trivial. Without a teacher, the ANN weight matrix [W] equalsV [w1, w2] adjusts the outputs V(t) equals tanh([W]X(t)) approximately equals [W]X(t) until no desired outputs except the (Gaussian) 'garbage' (neither YES '1' nor NO '-1' but at linear may-be range 'origin 0') defined by Gaussian covariance G equals [I] equals [W][A] HOS theories since 1991 (advanced by Jutten & Herault, Comon, Oja, Bell-Sejnowski, Amari-Cichocki, Cardoso), the LYAPONOV function L(v1,...,vn, w1,...wn,) equals E(v1,...,vn) - H(w1,...wn) is constructed as the HELMHOTZ free energy to prove both convergences of supervised energy E and unsupervised entropy H learning. Consequently, rather

  14. How Do Maternal Subclinical Symptoms Influence Infant Motor Development during the First Year of Life?

    PubMed Central

    Piallini, Giulia; Brunoro, Stefania; Fenocchio, Chiara; Marini, Costanza; Simonelli, Alessandra; Biancotto, Marina; Zoia, Stefania

    2016-01-01

    An unavoidable reciprocal influence characterizes the mother-child dyad. Within this relationship, the presence of depression, somatization, hostility, paranoid ideation, and interpersonal sensitivity symptoms at a subclinical level and their possible input on infant motor competences has not been yet considered. Bearing in mind that motor abilities represent not only an indicator of the infant's health-status, but also the principal field to infer his/her needs, feelings and intentions, in this study the quality of infants' movements were assessed and analyzed in relationship with the maternal attitudes. The aim of this research was to investigate if/how maternal symptomatology may pilot infant's motor development during his/her first year of life by observing the characteristics of motor development in infants aged 0–11 months. Participants included 123 mothers and their infants (0–11 months-old). Mothers' symptomatology was screened with the Symptom Checklist-90-Revised (SCL-90-R), while infants were tested with the Peabody Developmental Motor Scale-Second Edition. All dyads belonged to a non-clinical population, however, on the basis of SCL-90-R scores, the mothers' sample was divided into two groups: normative and subclinical. Descriptive, t-test, correlational analysis between PDMS-2 scores and SCL-90-R results are reported, as well as regression models results. Both positive and negative correlations were found between maternal perceived symptomatology, Somatization (SOM), Interpersonal Sensitivity (IS), Depression (DEP), Hostility (HOS), and Paranoid Ideation (PAR) and infants' motor abilities. These results were further verified by applying regression models to predict the infant's motor outcomes on the basis of babies' age and maternal status. The presence of positive symptoms in the SCL-90-R questionnaire (subclinical group) predicted good visual-motor integration and stationary competences in the babies. In particular, depressive and hostility

  15. A Qualitative Assessment of Return to Sport After Hip Arthroscopy for Femoroacetabular Impingement

    PubMed Central

    Tjong, Vehniah K.; Cogan, Charles J.; Riederman, Brett D.; Terry, Michael A.

    2016-01-01

    Background: Hip arthroscopy for femoroacetabular impingement (FAI) is known to produce excellent outcomes, yet some patients do not return to their preinjury level of sport participation. Much literature on return to sport has revolved around anterior cruciate ligament reconstruction and even shoulder instability, but none to date have used qualitative, semistructured patient interviews on patients with hip labral tears. Purpose: To understand the factors influencing the decision to return to sport after arthroscopic hip surgery for FAI. Study Design: Case series; Level of evidence, 4. Methods: An experienced interviewer conducted qualitative, semistructured interviews of patients aged 18 to 60 years who had arthroscopic hip surgery for FAI. All had preinjury participation in sport and a minimum 2-year follow-up with no revision surgery. Qualitative analysis was then performed to derive codes, categories, and themes. An assessment of preinjury and current sports participation by type, level of competition, and frequency along with patient-reported hip function was also obtained. In addition, current modified Harris Hip Score (mHHS), international Hip Outcome Tool (iHOT-12), Hip Outcome Score–sports-specific subscale (HOS-SSS), and a coping mechanism evaluation (Brief COPE) were also recorded. Results: A total of 23 patients were interviewed to reveal the overarching themes of internal motivation, external encouragement, and resetting expectations as the predominant factors influencing a patient’s decision to return to preinjury sport. Subjective outcome measurements (mHHS, iHOT-12, patient satisfaction) showed significant differences between patients who did and did not return to sport. Interestingly, the adaptive and maladaptive coping mechanisms matched and supported our themes in those patients who described fear and self-motivation as defining features influencing their cessation of or return to play, respectively. Conclusion: Self-motivation, aging, pain

  16. N6-benzyladenosine derivatives as novel N-donor ligands of platinum(II) dichlorido complexes.

    PubMed

    Starha, Pavel; Popa, Igor; Trávníček, Zdeněk; Vančo, Ján

    2013-06-14

    The platinum(II) complexes trans-[PtCl₂(Ln)₂]∙xSolv 1-13 (Solv = H₂O or CH3OH), involving N6-benzyladenosine-based N-donor ligands, were synthesized; L(n) stands for N6-(2-methoxybenzyl)adenosine (L₁, involved in complex 1), N6-(4-methoxy-benzyl)adenosine (L₂, 2), N6-(2-chlorobenzyl)adenosine (L₃, 3), N6-(4-chlorobenzyl)-adenosine (L₄, 4), N6-(2-hydroxybenzyl)adenosine (L₅, 5), N6-(3-hydroxybenzyl)-adenosine (L₆, 6), N6-(2-hydroxy-3-methoxybenzyl)adenosine (L₇, 7), N6-(4-fluoro-benzyl)adenosine (L₈, 8), N6-(4-methylbenzyl)adenosine (L₉, 9), 2-chloro-N6-(3-hydroxy-benzyl)adenosine (L₁₀, 10), 2-chloro-N6-(4-hydroxybenzyl)adenosine (L₁₁, 11), 2-chloro-N6-(2-hydroxy-3-methoxybenzyl)adenosine (L₁₂, 12) and 2-chloro-N6-(2-hydroxy-5-methylbenzyl)adenosine (L₁₃, 13). The compounds were characterized by elemental analysis, mass spectrometry, IR and multinuclear (¹H-, ¹³C-, ¹⁹⁵Pt- and ¹⁵N-) and two-dimensional NMR spectroscopy, which proved the N7-coordination mode of the appropriate N6-benzyladenosine derivative and trans-geometry of the title complexes. The complexes 1-13 were found to be non-toxic in vitro against two selected human cancer cell lines (HOS and MCF7; with IC₅₀ > 50.0 µM). However, they were found (by ESI-MS study) to be able to interact with the physiological levels of the sulfur-containing biogenic biomolecule L-methionine by a relatively simple 1:1 exchange mechanism (one L(n) molecule was replaced by one L-methionine molecule), thus forming a mixed-nitrogen/sulfur-ligand dichlorido-platinum(II) coordination species.

  17. Early Paleozoic magmatism and metallogeny in Northeast China: a record from the Tongshan porphyry Cu deposit

    NASA Astrophysics Data System (ADS)

    Hu, Xinlu; Yao, Shuzhen; Ding, Zhenju; He, Mouchun

    2017-01-01

    The Tongshan Cu deposit is located in the northern segment of the Great Xing'an Range and represents one of the few early Paleozoic porphyry Cu deposits in northeastern China. The granitic rocks in the Tongshan Cu deposit include concealed granodiorite and exposed tonalite, which yield LA-ICP-MS zircon U-Pb ages of 478 ± 3 Ma and 214 ± 3 Ma, respectively. The granodiorite has relatively high SiO2 (60.5-63.5 wt%) and Sr (596-786 ppm) contents, low Yb (1.21-1.53 ppm) and Y (9.81-13.0 ppm) contents, and initial 87Sr/86Sr ratios (0.7038-0.7040), suggesting adakitic affinity. Combined with its positive ɛNd( t) values (3.5-5.4), low Mg# values (41-50), and low contents of Cr (18.6-29.0 ppm) and Ni (7.3-9.1 ppm), we propose an origin by partial melting of a juvenile mafic lower crust in a post-collisional setting after the amalgamation of the Erguna and Xing'an Blocks. The tonalite is characterized by high SiO2 (63.1-65.9 wt%) and Al2O3 (16.0-16.3 wt%) contents, low (87Sr/86Sr) i ratios (0.7041-0.7042), positive ɛNd( t) values (2.6-3.0), along with LILE and LREE enrichments and Nb-Ta-Ti depletions, suggesting an origin by partial melting of juvenile mafic lower crust, coupled with fractional crystallization, in a post-orogenic setting after the collision between the Xing'an and Songnen Blocks. The δD values of ore-forming fluids range from -100 to -93 ‰, and the δ18O values calculated from hydrothermal quartz are between -3 and 10 ‰. The δ34S values of sulfides vary from -2.6 to -1.1 ‰. Field observations, as well as the geochronological and H-O-S isotopic data, suggest that the Cu mineralization at Tongshan was genetically linked with the granodiorite.

  18. Hydroxyapatite and fluor-hydroxyapatite layered film on titanium processed by a sol-gel route for hard-tissue implants.

    PubMed

    Kim, Hae-Won; Knowles, Jonathan C; Salih, Vehid; Kim, Hyoun-Ee

    2004-10-15

    A double-layered coating, consisting of a hydroxyapatite (HA) outer film and a fluor-hydroxyapatite (FHA) inner film, was produced on a Ti substrate by a sol-gel route to improve the biocompatibility and functionality of the system. Dissolution behavior of and in vitro cellular responses to the layered film were investigated. Calcium nitrate and triethyl phosphite were used for calcium and phosphate precursors, respectively, and ammonium fluoride was added as a fluorine-ion source for FHA. The FHA layer was deposited on Ti by spin coating and subsequent heat treatment at 550 degrees C for 30 min in air, and then the HA layer was laid down over the FHA-coated Ti under the same conditions. After heat treatment, characteristic apatite structures and phases were developed on both FHA and HA films. The cross-section view of the HA/FHA film clearly showed a double-layered structure on Ti with each layer approximately 0.6-0.8-microm thickness. The coating layer was highly uniform and dense, and adhered to Ti substrate strongly with an adhesion strength of about 40 MPa. The in vitro solubility of the HA/FHA layered film in a physiological solution was between that of HA and FHA pure film, and the dissolution profile was quite biphasic, that is, an initial rapid period and a slowdown with increasing time, reflecting the gradient solubility of the fast HA outer structure/slow FHA inner structure. The human osteoblast-like HOS TE85 cells cultured on the HA/FHA layered film attached, spread, and grew favorably. The proliferation rate of the cells on the layered film was significantly higher (considered at p < 0.05 for n = 6) than that on Ti substrate and was similar to that on pure HA film. The alkaline phosphatase (ALP) activity and osteocalcin (OC) produced by the cells on the layered film were significantly higher (considered at p < 0.05 for n = 6) than those on Ti substrate. Moreover, the ALP and OC levels of cells on the layered film showed the trends of HA outer

  19. Application of non-linear and wavelet based features for the automated identification of epileptic EEG signals.

    PubMed

    Acharya, U Rajendra; Sree, S Vinitha; Alvin, Ang Peng Chuan; Yanti, Ratna; Suri, Jasjit S

    2012-04-01

    Epilepsy, a neurological disorder, is characterized by the recurrence of seizures. Electroencephalogram (EEG) signals, which are used to detect the presence of seizures, are non-linear and dynamic in nature. Visual inspection of the EEG signals for detection of normal, interictal, and ictal activities is a strenuous and time-consuming task due to the huge volumes of EEG segments that have to be studied. Therefore, non-linear methods are being widely used to study EEG signals for the automatic monitoring of epileptic activities. The aim of our work is to develop a Computer Aided Diagnostic (CAD) technique with minimal pre-processing steps that can classify all the three classes of EEG segments, namely normal, interictal, and ictal, using a small number of highly discriminating non-linear features in simple classifiers. To evaluate the technique, segments of normal, interictal, and ictal EEG segments (100 segments in each class) were used. Non-linear features based on the Higher Order Spectra (HOS), two entropies, namely the Approximation Entropy (ApEn) and the Sample Entropy (SampEn), and Fractal Dimension and Hurst Exponent were extracted from the segments. Significant features were selected using the ANOVA test. After evaluating the performance of six classifiers (Decision Tree, Fuzzy Sugeno Classifier, Gaussian Mixture Model, K-Nearest Neighbor, Support Vector Machine, and Radial Basis Probabilistic Neural Network) using a combination of the selected features, we found that using a set of all the selected six features in the Fuzzy classifier resulted in 99.7% classification accuracy. We have demonstrated that our technique is capable of achieving high accuracy using a small number of features that accurately capture the subtle differences in the three different types of EEG (normal, interictal, and ictal) segments. The technique can be easily written as a software application and used by medical professionals without any extensive training and cost. Such software

  20. Partial characterization of cell-type X collagen interactions.

    PubMed Central

    Luckman, Steven P; Rees, Elaine; Kwan, Alvin P L

    2003-01-01

    Type X collagen is a short-chain non-fibrillar collagen that is deposited exclusively at sites of new bone formation. Although this collagen has been implicated in chondrocyte hypertrophy and endochondral ossification, its precise function remains unclear. One possible function could be to regulate the processes of chondrocyte hypertrophy through direct cell-type X collagen interactions. Adhesions of embryonic chick chondrocytes, and cell lines with known expression of collagen-binding integrins (MG63 and HOS), were assayed on chick type X collagen substrates, including the native, heat-denatured and pepsin-digested collagen, and the isolated C-terminal non-collagenous (NC1) domain. Type X collagen supported the greatest level of adhesion for all cell types tested. The involvement of the alpha2beta1 integrin in type X collagen-cell interaction was demonstrated by adhesion studies in the presence of Mg(2+) and Ca(2+) ions and integrin-function-blocking antibodies. Cells expressing alpha2beta1 integrin (chick chondrocytes and MG63 cells) also adhered to heat-denatured type X collagen and the isolated NC1 domain; however, removal of the non-collagenous domains by limited pepsinization of type X collagen resulted in very low levels of adhesion. Both focal contacts and actin stress-fibre formation were apparent in cells plated on type X collagen. The presence of alpha2 and beta1 integrin subunits in isolated chondrocytes and epiphyseal cartilage was also confirmed by immunolocalization. Our results demonstrate, for the first time, that type X collagen is capable of interacting directly with chondrocytes and other cells, primarily via alpha2beta1 integrin. These findings are atypical from the fibrillar collagen-cell interactions via collagen binding integrins in that: (1) the triple-helical conformation is not strictly required for cell adhesion; (2) the NC1 domain is also involved in the adhesion of alpha2beta1-expressing cells. These data form the basis for further

  1. Multi-scale cell/surface interaction on modified titanium aluminum vanadium surfaces

    NASA Astrophysics Data System (ADS)

    Chen, Jianbo

    This dissertation presents a series of experimental studies of the effects of multi-scale cell/surface interactions on modified Ti-6Al-4V surfaces. These include laser-grooved surfaces; porous structures and RGD-coated laser-grooved surfaces. A nano-second DPSS UV lasers with a Gaussian pulse energy profile was used to introduce the desired micro-groove geometries onto Ti-6Al-4V surfaces. This was done without inducing micro-cracks or significant changes in surface chemistry within the heat affected zones. The desired 8-12 mum groove depths and widths were achieved by the control of pulse frequency, scan speed, and the lens focal length that controls spot size. The interactions between human osteosarcoma (HOS) cells and laser-grooved Ti-6Al-4V surfaces were investigated after 48 hours of cell culture. The cell behavior, including cell spreading, alignment and adhesion, was elucidated using scanning electronic microscopy (SEM), immuno-fluorescence staining and enzymatic detachment. Contact guidance was shown to increase as grooved spacing decreased. For the range of micro-groove geometries studied, micro-grooves with groove spacings of 20 mum provided the best combination of cell orientation and adhesion. Short-term adhesion experiments (15 mins to 1 day) also revealed that there is a positive correlation between cell orientation and cell adhesion. Contact guidance on the micro-grooved surfaces is shown to be enhanced by nano- and micro-scale asperities that provide sites for the attachment of lamellopodia during cell locomotion and spreading. Contact guidance is also promoted by the geometrical confinement provided by laser grooves. An experimental study of initial cell spreading and ingrowth into Ti-6Al-4V porous structures was also carried out on porous structures with different pore sizes and geometries. A combination of SEM, the tetrazolium salt (MTT) colorimetric assay and enzymatic detachment were used to study cell spreading and adhesion. The extent of cell

  2. Carbon monoxide in biology and microbiology: surprising roles for the "Detroit perfume".

    PubMed

    Davidge, Kelly S; Motterlini, Roberto; Mann, Brian E; Wilson, Jayne Louise; Poole, Robert K

    2009-01-01

    Carbon monoxide (CO) is a colorless, odorless gas with a reputation for being an anthropogenic poison; there is extensive documentation of the modes of human exposure, toxicokinetics, and health effects. However, CO is also generated endogenously by heme oxygenases (HOs) in mammals and microbes, and its extraordinary biological activities are now recognized and increasingly utilized in medicine and physiology. This review introduces recent advances in CO biology and chemistry and illustrates the exciting possibilities that exist for a deeper understanding of its biological consequences. However, the microbiological literature is scant and is currently restricted to: 1) CO-metabolizing bacteria, CO oxidation by CO dehydrogenase (CODH) and the CO-sensing mechanisms that enable CO oxidation; 2) the use of CO as a heme ligand in microbial biochemistry; and 3) very limited information on how microbes respond to CO toxicity. We demonstrate how our horizons in CO biology have been extended by intense research activity in recent years in mammalian and human physiology and biochemistry. CO is one of several "new" small gas molecules that are increasingly recognized for their profound and often beneficial biological activities, the others being nitric oxide (NO) and hydrogen sulfide (H2S). The chemistry of CO and other heme ligands (oxygen, NO, H2S and cyanide) and the implications for biological interactions are briefly presented. An important advance in recent years has been the development of CO-releasing molecules (CO-RMs) for aiding experimental administration of CO as an alternative to the use of CO gas. The chemical principles of CO-RM design and mechanisms of CO release from CO-RMs (dissociation, association, reduction and oxidation, photolysis, and acidification) are reviewed and we present a survey of the most commonly used CO-RMs. Amongst the most important new applications of CO in mammalian physiology and medicine are its vasoactive properties and the

  3. Season effect on genitalia and epididymal sperm from Iberian red deer, roe deer and Cantabrian chamois.

    PubMed

    Martinez-Pastor, Felipe; Guerra, Camino; Kaabi, Mohammed; Garcia-Macias, Vanesa; de Paz, Paulino; Alvarez, M; Herraez, Paz; Anel, Luis

    2005-04-15

    Seasonality deeply affects the physiology and behavior of many species, and must be taken into account when biological resource banks (BRBs) are established. We have studied the effect of seasonality on many reproductive parameters of free-ranging Iberian red deer, roe deer and Cantabrian chamois, living in Spain. Testicles from hunted animals were collected and sent to our laboratory at different times during the year. We recorded the weight and volume of testis, the weight of the epididymis and its separate parts (caput, corpus, and cauda), the weight of the sperm sample collected from the cauda epididymis, and several sperm parameters (sperm concentration, spermatozoa recovered, motility, HOS test reactivity, acrosomal status, and viability). We studied the data according to several periods, defined accordingly to each species. For red deer, we defined rut (mid-September to mid-October), post-rut (mid-October to mid-December), and non-breeding season (February). For roe deer, they were pre-rut (June), rut (July), post-rut (first fortnight of August), and non-breeding season (September). For chamois: non-breeding season (June to mid-September) and breeding season (October-November). The rut/breeding season yielded significantly higher numbers for almost all parameters. However, in the case of red deer, sperm quality was higher in the post-rut. For roe deer, testicular weight was similar in the pre-rut and in the rut, and sperm quality did not differ significantly between these two periods, although we noticed higher values in the rut. In the case of chamois, sperm quality did not differ significantly from the breeding season, but data distribution suggested that in the non-breeding season there are less males with sperm of good quality. On the whole, we find these results of interest for BRB planning. The best season to collect sperm in this species would be the breeding season. However, post-rut in red deer, pre-rut in roe deer, and non-breeding season in

  4. Influence of Wind and Dissipation on the Modulational Instability

    NASA Astrophysics Data System (ADS)

    Touboul, Julien; Kharif, Christian

    2010-05-01

    numerically by means of a High Order Spectral Method (HOS). The effect of wind is introduced in the model through the Miles mechanism (Touboul et al. (2008)), whereas dissipation is introduced in accordance with Wu, Liu & Yue (2006). The stable/unstable behavior of the wave train in these conditions is observed, and compared to the marginal stability criterium derived by Kharif et al. (2010). References [1] C. Kharif & E. Pelinovsky, "Physical mechanisms of the rogue wave phenomenon", Euro. J. Mech., B/Fluids, 22, 603-634, (2003). [2] H. Segur, D. Henderson, J. Carter, J. Hammack, C.-M. Li, D. Pheiff & K. Socha, "Stabilizing the Benjamin-Feir instability", J. Fluid Mech., 539, 229-271, (2005). [3] G. Wu, Y. Liu & D. K. Yue, "A note on stabilizing the Benjamin-Feir instability", J. Fluid Mech., 556, 45-54, (2006). [4] C. Kharif, R. A. Kraenkel, M. A. Manna & R. Thomas, "The modulational instability in deep water under the action of wind and dissipation", Submitted to J. Fluid Mech., (2010). [5] J. Touboul, C. Kharif, E. Pelinovsky & J. P. Giovanangeli, "On the interaction of wind and steep gravity wave groups using Miles and Jeffreys mechanisms", Nonlinear Proc. Geophys., 15 (6), 1023-1031, (2008).

  5. Nitric oxide and iron modulate heme oxygenase activity as a long distance signaling response to salt stress in sunflower seedling cotyledons.

    PubMed

    Singh, Neha; Bhatla, Satish C

    2016-02-29

    Nitric oxide is a significant component of iron signaling in plants. Heme is one of the iron sensors in plants. Free heme is highly toxic and can cause cell damage as it catalyzes the formation of reactive oxygen species (ROS). Its catabolism is carried out by heme oxygenase (HOs; EC 1.14.99.3) which uses heme both as a prosthetic group and as a substrate. Two significant events, which accompany adaptation to salt stress in sunflower seedlings, are accumulation of ROS and enhanced production of nitric oxide (NO) in roots and cotyledons. Present investigations on the immunolocalization of heme oxygenase distribution in sunflower seedling cotyledons by confocal laser scanning microscopic (CLSM) imaging provide new information on the differential spatial distribution of the inducible form of HO (HO-1) as a long distance in response to NaCl stress. The enzyme is abundantly distributed in the specialized cells around the secretory canals (SCs) in seedling cotyledons. Abundance of tyrosine nitrated proteins has also been observed in the specialized cells around the secretory canals in cotyledons derived from salt stressed seedlings. The spatial distribution of tyrosine nitrated proteins and HO-1 expression further correlates with the abundance of mitochondria in these cells. Present findings, thus, highlight a link among distribution of HO-1 expression, abundance of tyrosine nitrated proteins and mitochondria in specialized cells around the secretory canal as a long distance mechanism of salt stress tolerance in sunflower seedlings. Enhanced spatial distribution of HO-1 in response to NaCl stress in seedling cotyledons is in congruence with the observed increase in specific activity of HO-1 in NaCl stressed conditions. The enzyme activity is further enhanced by hemin (HO-1 inducer) both in the absence or presence of NaCl stress and inhibited by zinc protoporphyrin. Western blot analysis of cotyledon homogenates using anti-HO-1 polyclonal antibody shows one major band (29

  6. Atmospheric and land surface measurements in a prototype hydrologic observatory

    NASA Astrophysics Data System (ADS)

    Scanlon, B.; Krajewski, W.; Famiglietti, J.; Duffy, C.

    2003-12-01

    different microclimate, vegetation, land use, and soils regions to assess the relative importance of these parameters as controls on fluxes and to provide baseline data for predicting potential impacts of future climate and land use change on these fluxes. Critical parameters for hydrological modeling will be included in the measurement design. Although this prototype HO focuses on a porous media system in a humid environment, many of the design aspects are generic and should apply to HOs in other settings (fractured media, arid settings). Another goal of the program is to locate ground-based measurement stations to provide ground referencing for satellite systems. An example application is the use of satellite data (LandSat TM, AVHRR, and MODIS) to estimate ET with comparison to ground-based systems (Eddy Covariance/Bowen Ratio) and scintillometers. The use of Advanced Microwave Scanning Radiometer (AMSR-E) for monitoring soil moisture will also be evaluated using ground-based water content monitoring and field campaigns. Precipitation gauge clusters will be optimally located to evaluate NEXRAD and satellite precipitation data. Understanding the correlation between satellite and ground-based data is essential because spaceborne observations provide spatially and temporally distributed measurements and a framework for scaling local measurements to regional areas. The HO networks will provide valuable information on many aspects of the water cycle to advance our understanding on controls on spatial and temporal variability in fluxes across interfaces.