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Sample records for 6c reveals determinants

  1. Genomic Profiling Reveals Unique Molecular Alterations in Hepatoblastomas and Adjacent Hepatocellular Carcinomas in B6C3F1 Mice.

    Bhusari, Sachin; Pandiri, Arun R; Nagai, Hiroaki; Wang, Yu; Foley, Julie; Hong, Hue-Hua L; Ton, Thai-Vu; DeVito, Michael; Shockley, Keith R; Peddada, Shyamal D; Gerrish, Kevin E; Malarkey, David E; Hooth, Michelle J; Sills, Robert C; Hoenerhoff, Mark J

    2015-12-01

    The cell of origin of hepatoblastoma (HB) in humans and mice is unknown; it is hypothesized to be a transformed hepatocyte, oval cell, or hepatic progenitor cell. In mice, current dogma is that HBs arise from preexisting hepatocellular neoplasms as a result of further neoplastic transformation. However, there is little evidence supporting this direct relationship. To better understand the relationship between hepatocellular carcinoma (HCC) and HB and determine molecular similarities between mouse and human HB, global gene expression analysis and targeted mutation analysis were performed using HB, HCC, and adjacent liver from the same animals in a recent National Toxicology Program bioassay. There were significant differences in Hras and Ctnnb1 mutation spectra, and by microarray, HBs showed dysregulation of embryonic development, stem cell pluripotency, and genomic imprinting compared to HCC. Meta-analysis showed similarities between HB, early mouse embryonic liver, and hepatocyte-derived stem/progenitor cells compared to HCC. Our data show that there are striking differences between HB and HCC and suggest that HB is a significantly different entity that may arise from a hepatic precursor cell. Furthermore, mouse HB is similar to the human disease at the pathway level and therefore is likely a relevant model for evaluating human cancer hazard. PMID:26289556

  2. 77 FR 34121 - Culturally Significant Objects Imported for Exhibition Determinations: “Revealing the African...

    2012-06-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Culturally Significant Objects Imported for Exhibition Determinations: ``Revealing the African Presence in..., 2003), I hereby determine that the objects to be included in the exhibition ``Revealing the...

  3. Ly6C(low and not Ly6C(high macrophages accumulate first in the heart in a model of murine pressure-overload.

    Christina Weisheit

    Full Text Available Cardiac tissue remodeling in the course of chronic left ventricular hypertrophy requires phagocytes which degrade cellular debris, initiate and maintain tissue inflammation and reorganization. The dynamics of phagocytes in left ventricular hypertrophy have not been systematically studied. Here, we characterized the temporal accumulation of leukocytes in the cardiac immune response by flow cytometry and fluorescence microscopy at day 3, 6 and 21 following transverse aortic constriction (TAC. Cardiac hypertrophy due to chronic pressure overload causes cardiac immune response and inflammation represented by an increase of immune cells at all three time points among which neutrophils reached their maximum at day 3 and macrophages at day 6. The cardiac macrophage population consisted of both Ly6C(low and Ly6C(high macrophages. Ly6C(low macrophages were more abundant peaking at day 6 in response to pressure overload. During the development of cardiac hypertrophy the expression pattern of adhesion molecules was investigated by qRT-PCR and flow cytometry. CD11b, CX3CR1 and ICAM-1 determined by qRT-PCR in whole cardiac tissue were up-regulated in response to pressure overload at day 3 and 6. CD11b and CX3CR1 were significantly increased by TAC on the surface of Ly6C(low but not on Ly6C(high macrophages. Furthermore, ICAM-1 was up-regulated on cardiac endothelial cells. In fluorescence microscopy Ly6C(low macrophages could be observed attached to the intra- and extra-vascular vessel-wall. Taken together, TAC induced the expression of adhesion molecules, which may explain the accumulation of Ly6C(low macrophages in the cardiac tissue, where these cells might contribute to cardiac inflammation and remodeling in response to pressure overload.

  4. Main: 1Q6C [RPSD[Archive

    Full Text Available 1Q6C 大豆 Soybean Glycine max (L.) Merrill Beta-Amylase Glycine Max Molecule: Beta-Amylase; Chai...496 AA, Molecular weight: 56071 Da MATSDSNMLLNYVPVYVMLPLGVVNVDNVFEDPDGLKEQLLQLRAAGVDGVMVDVWWGIIELKGPKQYDWRAYRSLFQLVQECGLTLQAI...MSFHQCGGNVGDIVNIPIPQWVLDIGESNHDIFYTNRSGTRNKEYLTVGVDNEPIFHGRTAIEIYSDYMKSFRENMSDFLESGLIIDIEVG...FLTWYSNKLLNHGDQILDEANKAFLGCKVKLAIKVSGIHWWYKVENHAAELTAGYYNLNDRDGYRPIARMLSRHHAILNFTCLEMRDSEQPSDAKSGPQELVQQVLSG...GWREDIRVAGENALPRYDATAYNQIILNARPQGVNNNGPPKLSMFGVTYLRLSDDLLQKSNFNIFKKFVLKMHADQDYCANPQKYNHAITPLKPSAPKIPIEVLLEATKPTLPFPWLPETDMKVDG soybean_1Q6C.jpg ...

  5. Clonal expansion within pneumococcal serotype 6C after use of seven-valent vaccine.

    Nicholas J Loman

    Full Text Available Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7 is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n = 15 and disease (n = 4 states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST clonal complex 395 (CC395. A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design.

  6. Radiosynthesis of 6-[C-11]-D-glucose

    Availability of 6-[C-11]-D-glucose will permit positron emission tomography (PET) investigations of glucose utilization derived from the pentose shunt which supports biosynthesis in tissues. The first radiosynthesis of 6-[C-11]-D-glucose is described. As much as 1 mCi of 6-[C-11]-D-glucose, sufficient for animal studies, is obtained from [C-11]CO2 after 100 min with a 16% radiochemical yield (EOB). The radiosynthesis has many attractive features. The method uses [C-11]CH3I and combines a Wittig reaction and a stereoselective OsO4 catalyzed alkene hydroxylation. The OsO4 hydroxylation of the [C-11]-labeled alkene (9) is accomplished in less than 10 min with high stereoselectivity (94:6) in favor of the 6-[C-11]-D-gluco-isomer. HPLC purification (C-18) of the protected labeled sugar removes the undesired 6-[C-11]-L-ido-sugar at an early stage and avoids the use of an expensive low-capacity ion-exchange HPLC column. OsO4, a highly toxic reagent, is removed in the process by adsorption and inactivation on polymer-bound triphenylphosphine. (Author)

  7. Electronic Structure of Superconducting Ba6c60

    Erwin, Steven C.; Pederson, Mark R

    1993-01-01

    We report the results of first-principles electronic-structure calculations for superconducting Ba6C60. Unlike the A3C60 superconductors, this new compound shows strong Ba-C hybridization in the valence and conduction regions, mixed covalent/ionic bonding character, partial charge transfer, and insulating zero-gap band structure.

  8. Evaluation of EGM 2008 and EIGEN-6C3stat \

    Kostelecký, J.; Klokočník, Jaroslav; Bezděk, Aleš

    -, č. 5 (2015), s. 3-12. ISSN 1810-8555 R&D Projects: GA ČR GA13-36843S Grant ostatní: GA MŠk(CZ)(CZ) CZ.1.05/1.1.00/02.0090 Institutional support: RVO:67985815 Keywords : gravity field evaluation * EGM 2008 * EIGEN-6C3stat Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics

  9. Interleukin-6 c.-174G>C Polymorphism and Periodontitis in a Brazilian Population

    Fernanda Gabriela Teixeira

    2014-01-01

    Full Text Available Aim. Periodontitis is an inflammatory disease that affects the teeth supporting structures, triggered by periodontal pathogens, and is influenced by environmental and genetic factors. Genes encoding molecules related to the immune response, such as cytokine, are the main candidates for polymorphisms analysis and may be possibly associated with this pathology. A G/C promoter polymorphism on the IL6 gene has been shown to affect basal IL-6 levels. The aim of this study was to investigate the association between the IL6 c.-174G>C polymorphism and periodontitis in individuals from Vitória da Conquista, Bahia, Brazil. Material and Methods. Three hundred and thirty individuals (134 cases, 196 controls were genotyped for the IL6 c.-174G>C by MS-PCR technique. Concentrations of salivary IL-6 were determined by ELISA method. Results. The IL6 c.-174G>C polymorphism was associated with periodontitis when comparing the distribution of genotypes between patients with periodontitis and control subjects. The GC genotype appeared as a protective factor for periodontitis. Results showed increased levels of salivary IL-6 in periodontitis patients. Nevertheless, there was no relationship between the concentrations of IL-6 and genotypes when comparing the case and control groups. Conclusions. Our data indicate an association between IL6 c.-174G>C polymorphism and periodontitis and showed that IL-6 may be considered an important marker for periodontitis.

  10. Multilocus Sex Determination Revealed in Two Populations of Gynodioecious Wild Strawberry, Fragaria vesca subsp. bracteata.

    Ashman, Tia-Lynn; Tennessen, Jacob A; Dalton, Rebecca M; Govindarajulu, Rajanikanth; Koski, Matthew H; Liston, Aaron

    2015-12-01

    Gynodioecy, the coexistence of females and hermaphrodites, occurs in 20% of angiosperm families and often enables transitions between hermaphroditism and dioecy. Clarifying mechanisms of sex determination in gynodioecious species can thus illuminate sexual system evolution. Genetic determination of gynodioecy, however, can be complex and is not fully characterized in any wild species. We used targeted sequence capture to genetically map a novel nuclear contributor to male sterility in a self-pollinated hermaphrodite of Fragaria vesca subsp. bracteata from the southern portion of its range. To understand its interaction with another identified locus and possibly additional loci, we performed crosses within and between two populations separated by 2000 km, phenotyped the progeny and sequenced candidate markers at both sex-determining loci. The newly mapped locus contains a high density of pentatricopeptide repeat genes, a class commonly involved in restoration of fertility caused by cytoplasmic male sterility. Examination of all crosses revealed three unlinked epistatically interacting loci that determine sexual phenotype and vary in frequency between populations. Fragaria vesca subsp. bracteata represents the first wild gynodioecious species with genomic evidence of both cytoplasmic and nuclear genes in sex determination. We propose a model for the interactions between these loci and new hypotheses for the evolution of sex determining chromosomes in the subdioecious and dioecious Fragaria. PMID:26483011

  11. Multiperspective smFRET reveals rate-determining late intermediates of ribosomal translocation.

    Wasserman, Michael R; Alejo, Jose L; Altman, Roger B; Blanchard, Scott C

    2016-04-01

    Directional translocation of the ribosome through the mRNA open reading frame is a critical determinant of translational fidelity. This process entails a complex interplay of large-scale conformational changes within the actively translating particle, which together coordinate the movement of tRNA and mRNA substrates with respect to the large and small ribosomal subunits. Using pre-steady state, single-molecule fluorescence resonance energy transfer imaging, we tracked the nature and timing of these conformational events within the Escherichia coli ribosome from five structural perspectives. Our investigations revealed direct evidence of structurally and kinetically distinct late intermediates during substrate movement, whose resolution determines the rate of translocation. These steps involve intramolecular events within the EF-G-GDP-bound ribosome, including exaggerated, reversible fluctuations of the small-subunit head domain, which ultimately facilitate peptidyl-tRNA's movement into its final post-translocation position. PMID:26926435

  12. Structure determination of archaea-specific ribosomal protein L46a reveals a novel protein fold

    Highlights: • The archaea-specific ribosomal protein L46a has no homology to known proteins. • Three dimensional structure and backbone dynamics of L46a were determined by NMR. • The structure of L46a represents a novel protein fold. • A potential rRNA-binding surface on L46a was identified. • The potential position of L46a on the ribosome was proposed. - Abstract: Three archaea-specific ribosomal proteins recently identified show no sequence homology with other known proteins. Here we determined the structure of L46a, the most conserved one among the three proteins, from Sulfolobus solfataricus P2 using NMR spectroscopy. The structure presents a twisted β-sheet formed by the N-terminal part and two helices at the C-terminus. The L46a structure has a positively charged surface which is conserved in the L46a protein family and is the potential rRNA-binding site. Searching homologous structures in Protein Data Bank revealed that the structure of L46a represents a novel protein fold. The backbone dynamics identified by NMR relaxation experiments reveal significant flexibility at the rRNA binding surface. The potential position of L46a on the ribosome was proposed by fitting the structure into a previous electron microscopy map of the ribosomal 50S subunit, which indicated that L46a contacts to domain I of 23S rRNA near a multifunctional ribosomal protein L7ae

  13. Structure determination of archaea-specific ribosomal protein L46a reveals a novel protein fold

    Feng, Yingang, E-mail: fengyg@qibebt.ac.cn [Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong 266101 (China); Song, Xiaxia [Department of Biological Science and Engineering, School of Chemical and Biological Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Lin, Jinzhong [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Xuan, Jinsong [Department of Biological Science and Engineering, School of Chemical and Biological Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Cui, Qiu [Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong 266101 (China); Wang, Jinfeng [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

    2014-07-18

    Highlights: • The archaea-specific ribosomal protein L46a has no homology to known proteins. • Three dimensional structure and backbone dynamics of L46a were determined by NMR. • The structure of L46a represents a novel protein fold. • A potential rRNA-binding surface on L46a was identified. • The potential position of L46a on the ribosome was proposed. - Abstract: Three archaea-specific ribosomal proteins recently identified show no sequence homology with other known proteins. Here we determined the structure of L46a, the most conserved one among the three proteins, from Sulfolobus solfataricus P2 using NMR spectroscopy. The structure presents a twisted β-sheet formed by the N-terminal part and two helices at the C-terminus. The L46a structure has a positively charged surface which is conserved in the L46a protein family and is the potential rRNA-binding site. Searching homologous structures in Protein Data Bank revealed that the structure of L46a represents a novel protein fold. The backbone dynamics identified by NMR relaxation experiments reveal significant flexibility at the rRNA binding surface. The potential position of L46a on the ribosome was proposed by fitting the structure into a previous electron microscopy map of the ribosomal 50S subunit, which indicated that L46a contacts to domain I of 23S rRNA near a multifunctional ribosomal protein L7ae.

  14. Genome sequencing and analysis reveals possible determinants of Staphylococcus aureus nasal carriage

    Cole Alexander M

    2008-09-01

    Full Text Available Abstract Background Nasal carriage of Staphylococcus aureus is a major risk factor in clinical and community settings due to the range of etiologies caused by the organism. We have identified unique immunological and ultrastructural properties associated with nasal carriage isolates denoting a role for bacterial factors in nasal carriage. However, despite extensive molecular level characterizations by several groups suggesting factors necessary for colonization on nasal epithelium, genetic determinants of nasal carriage are unknown. Herein, we have set a genomic foundation for unraveling the bacterial determinants of nasal carriage in S. aureus. Results MLST analysis revealed no lineage specific differences between carrier and non-carrier strains suggesting a role for mobile genetic elements. We completely sequenced a model carrier isolate (D30 and a model non-carrier strain (930918-3 to identify differential gene content. Comparison revealed the presence of 84 genes unique to the carrier strain and strongly suggests a role for Type VII secretion systems in nasal carriage. These genes, along with a putative pathogenicity island (SaPIBov present uniquely in the carrier strains are likely important in affecting carriage. Further, PCR-based genotyping of other clinical isolates for a specific subset of these 84 genes raise the possibility of nasal carriage being caused by multiple gene sets. Conclusion Our data suggest that carriage is likely a heterogeneic phenotypic trait and implies a role for nucleotide level polymorphism in carriage. Complete genome level analyses of multiple carriage strains of S. aureus will be important in clarifying molecular determinants of S. aureus nasal carriage.

  15. Identification of Sex-Specific Markers Reveals Male Heterogametic Sex Determination in Pseudobagrus ussuriensis.

    Pan, Zheng-Jun; Li, Xi-Yin; Zhou, Feng-Jian; Qiang, Xiao-Gang; Gui, Jian-Fang

    2015-08-01

    Comprehending sex determination mechanism is a first step for developing sex control breeding biotechnologies in fish. Pseudobagrus ussuriensis, one of bagrid catfishes in Bagridae, had been observed to have about threefold size dimorphism between males and females, but its sex determination mechanism had been unknown. In this study, we firstly used the amplified fragment length polymorphism (AFLP)-based screening approach to isolate a male-specific DNA fragment and thereby identified a 10,569 bp of male-specific sequence and a 10,365 bp of female-related sequence by genome walking in the bagrid catfish, in which a substantial genetic differentiation with 96.35 % nucleotide identity was revealed between them. Subsequently, a high differentiating region of 650 bp with only 70.26 % nucleotide identity was found from the corresponding two sequences, and three primer pairs of male-specific marker, male and female-shared marker with different length products in male and female genomes, and female-related marker were designed. Significantly, when these markers were used to identify genetic sex of the bagrid catfish, only male individuals was detected to amplify the male-specific marker fragment, and female-related marker was discovered to produce dosage association in females and in males. Our current data provide significant genetic evidence that P. ussuriensis has heterogametic XY sex chromosomes in males and homogametic XX sex chromosomes in females. Therefore, sex determination mechanism of P. ussuriensis is male heterogametic XX/XY system. PMID:25981673

  16. Transcription closed and open complex dynamics studies reveal balance between genetic determinants and co-factors

    Sala, Adrien; Shoaib, Muhammad; Anufrieva, Olga; Mutharasu, Gnanavel; Jahan Hoque, Rawnak; Yli-Harja, Olli; Kandhavelu, Meenakshisundaram

    2015-05-01

    In E. coli, promoter closed and open complexes are key steps in transcription initiation, where magnesium-dependent RNA polymerase catalyzes RNA synthesis. However, the exact mechanism of initiation remains to be fully elucidated. Here, using single mRNA detection and dual reporter studies, we show that increased intracellular magnesium concentration affects Plac initiation complex formation resulting in a highly dynamic process over the cell growth phases. Mg2+ regulates transcription transition, which modulates bimodality of mRNA distribution in the exponential phase. We reveal that Mg2+ regulates the size and frequency of the mRNA burst by changing the open complex duration. Moreover, increasing magnesium concentration leads to higher intrinsic and extrinsic noise in the exponential phase. RNAP-Mg2+ interaction simulation reveals critical movements creating a shorter contact distance between aspartic acid residues and Nucleotide Triphosphate residues and increasing electrostatic charges in the active site. Our findings provide unique biophysical insights into the balanced mechanism of genetic determinants and magnesium ion in transcription initiation regulation during cell growth.

  17. Ly6C- Monocytes Regulate Parasite-Induced Liver Inflammation by Inducing the Differentiation of Pathogenic Ly6C+ Monocytes into Macrophages.

    Yannick Morias

    2015-05-01

    Full Text Available Monocytes consist of two well-defined subsets, the Ly6C+ and Ly6C- monocytes. Both CD11b+ myeloid cells populations have been proposed to infiltrate tissues during inflammation. While infiltration of Ly6C+ monocytes is an established pathogenic factor during hepatic inflammation, the role of Ly6C- monocytes remains elusive. Mice suffering experimental African trypanosome infection die from systemic inflammatory response syndrome (SIRS that is initiated by phagocytosis of parasites by liver myeloid cells and culminates in apoptosis/necrosis of liver myeloid and parenchymal cells that reduces host survival. C57BL/6 mice are considered as trypanotolerant to Trypanosoma congolense infection. We have reported that in these animals, IL-10, produced among others by myeloid cells, limits the liver damage caused by pathogenic TNF-producing Ly6C+ monocytes, ensuring prolonged survival. Here, the heterogeneity and dynamics of liver myeloid cells in T. congolense-infected C57/BL6 mice was further dissected. Moreover, the contribution of Ly6C- monocytes to trypanotolerance was investigated. By using FACS analysis and adoptive transfer experiments, we found that the accumulation of Ly6C- monocytes and macrophages in the liver of infected mice coincided with a drop in the pool of Ly6C+ monocytes. Pathogenic TNF mainly originated from Ly6C+ monocytes while Ly6C- monocytes and macrophages were major and equipotent sources of IL-10 within myeloid cells. Moreover, Nr4a1 (Nur77 transcription factor-dependent Ly6C- monocytes exhibited IL-10-dependent and cell contact-dependent regulatory properties contributing to trypanotolerance by suppressing the production of TNF by Ly6C+ monocytes and by promoting the differentiation of the latter cells into macrophages. Thus, Ly6C- monocytes can dampen liver damage caused by an extensive Ly6C+ monocyte-associated inflammatory immune response in T. congolense trypanotolerant animals. In a more general context, Ly6C- or Ly6C

  18. Phylodynamic reconstruction reveals norovirus GII.4 epidemic expansions and their molecular determinants.

    J Joukje Siebenga

    2010-05-01

    Full Text Available Noroviruses are the most common cause of viral gastroenteritis. An increase in the number of globally reported norovirus outbreaks was seen the past decade, especially for outbreaks caused by successive genogroup II genotype 4 (GII.4 variants. Whether this observed increase was due to an upswing in the number of infections, or to a surveillance artifact caused by heightened awareness and concomitant improved reporting, remained unclear. Therefore, we set out to study the population structure and changes thereof of GII.4 strains detected through systematic outbreak surveillance since the early 1990s. We collected 1383 partial polymerase and 194 full capsid GII.4 sequences. A Bayesian MCMC coalescent analysis revealed an increase in the number of GII.4 infections during the last decade. The GII.4 strains included in our analyses evolved at a rate of 4.3-9.0x10(-3 mutations per site per year, and share a most recent common ancestor in the early 1980s. Determinants of adaptation in the capsid protein were studied using different maximum likelihood approaches to identify sites subject to diversifying or directional selection and sites that co-evolved. While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication. We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant. While norovirus infections are generally mild and self-limiting, more severe outcomes of infection frequently occur in elderly and immunocompromized people, and no treatment is available. The observed pattern of continually emerging novel variants of GII.4, causing elevated numbers of infections, is therefore a

  19. Determinants of National Fire Plan Fuels Treatment Expenditures: A Revealed Preference Analysis for Northern New Mexico

    Shepherd, Curt; Grimsrud, Kristine; Berrens, Robert P.

    2009-10-01

    The accumulation of fire fuels in forests throughout the world contributes significantly to the severity of wildfires. To combat the threat of wildfire, especially in the wildland-urban interface (WUI), US federal land management agencies have implemented a number of forest restoration and wildfire risk reduction programs. In the spirit of revealed preference analyses, the objective of this study is to investigate the pattern and determinants of National Fire Plan (NFP) expenditures for fuel reduction treatments in northern New Mexico (USA). Estimation results from a set of Generalized Estimating Equations models are mixed with respect to risk reduction hypotheses, and also raise issues regarding how risk reduction should be defined for a region characterized by both pockets of urban sprawl into the WUI and large areas of chronic rural poverty. Program preferences for project funding under the federal Collaborative Forest Restoration Program in New Mexico are shown to be distinctly different (e.g., exhibiting greater concern for social equity) than for other NFP-funded projects.

  20. 78 FR 55772 - Culturally Significant Object Imported for Exhibition Determinations: “Beauty Revealed: Images of...

    2013-09-11

    ... Qing Dynasty Chinese Painting'' SUMMARY: Notice is hereby given of the following determinations...: Images of Women in Qing Dynasty Chinese Painting,'' imported from abroad for temporary exhibition...

  1. The small 6C RNA of Corynebacterium glutamicum is involved in the SOS response.

    Pahlke, Jennifer; Dostálová, Hana; Holátko, Jiří; Degner, Ursula; Bott, Michael; Pátek, Miroslav; Polen, Tino

    2016-09-01

    The 6C RNA family is a class of small RNAs highly conserved in Actinobacteria, including the genera Mycobacterium, Streptomyces and Corynebacterium whose physiological function has not yet been elucidated. We found that strong transcription of the cgb_03605 gene, which encodes 6C RNA in C. glutamicum, was driven by the SigA- and SigB-dependent promoter Pcgb_03605. 6C RNA was detected at high level during exponential growth phase (180 to 240 molcules per cell) which even increased at the entry of the stationary phase. 6C RNA level did not decrease within 240 min after transcription had been stopped with rifampicin, which suggests high 6C RNA stability. The expression of cgb_03605 further increased approximately twofold in the presence of DNA-damaging mitomycin C (MMC) and nearly threefold in the absence of LexA. Deletion of the 6C RNA gene cgb_03605 resulted in a higher sensitivity of C. glutamicum toward MMC and UV radiation. These results indicate that 6C RNA is involved in the DNA damage response. Both 6C RNA level-dependent pausing of cell growth and branched cell morphology in response to MMC suggest that 6C RNA may also be involved in a control of cell division. PMID:27362471

  2. Multilocus Sex Determination Revealed in Two Populations of Gynodioecious Wild Strawberry, Fragaria vesca subsp. bracteata

    Ashman, Tia-Lynn; Tennessen, Jacob A.; Dalton, Rebecca M.; Govindarajulu, Rajanikanth; Koski, Matthew H.; Liston, Aaron

    2015-01-01

    Gynodioecy, the coexistence of females and hermaphrodites, occurs in 20% of angiosperm families and often enables transitions between hermaphroditism and dioecy. Clarifying mechanisms of sex determination in gynodioecious species can thus illuminate sexual system evolution. Genetic determination of gynodioecy, however, can be complex and is not fully characterized in any wild species. We used targeted sequence capture to genetically map a novel nuclear contributor to male sterility in a self-...

  3. Conformation and crystal structures of 1-aminocyclohexaneacetic acid (β3,3Ac6c in N-protected derivatives

    Naiem Ahmad Wani

    2014-11-01

    Full Text Available N-Protected derivatives of 1-aminocyclohexaneacetic acid (β3,3-Ac6c, namely Valeroyl-β3,3-Ac6c-OH [2-(1-pentanamidocyclohexylacetic acid, C13H23NO3], (I, Fmoc-β3,3-Ac6c-OH [2-(1-{[(9H-fluoren-9-yloxycarbonyl]amino}cyclohexylacetic acid, C23H25NO4], (II, and Pyr-β3,3-Ac6c-OH {2-[1-(pyrazine-2-amidocyclohexyl]acetic acid, C13H17N3O3}, (III, were synthesized and their conformational properties were determined by X-ray diffraction analysis. The backbone torsion angles (ϕ, θ for β3,3-Ac6c-OH are restricted to gauche conformations in all the derivatives, with a chair conformation of the cyclohexane ring. In the crystal structure of (I, the packing of molecules shows both carboxylic acid R22(8 O—H...O and centrosymmetric R22(14 N—H...O hydrogen-bonding interactions, giving rise to chains along the c-axis direction. In (II, centrosymmetric carboxylic acid R22(8 O—H...O dimers are extended through N—H...O hydrogen bonds and together with inter-ring π–π interactions between Fmoc groups [ring centroid distance = 3.786 (2 Å], generate a layered structure lying parallel to (010. In the case of compound (III, carboxylic acid O—H...Npyrazine hydrogen bonds give rise to zigzag ribbon structures extending along the c-axis direction.

  4. Intracellular biology and virulence determinants of Francisella tularensis revealed by transcriptional profiling inside macrophages

    Wehrly, Tara D.; Chong, Audrey; Virtaneva, Kimmo; Sturdevant, Dan E.; Child, Robert; Edwards, Jessica A.; Brouwer, Dedeke; Nair, Vinod; Fischer, Elizabeth R.; Wicke, Luke; Curda, Alissa J.; Kupko, John J.; Martens, Craig; Crane, Deborah D.; Bosio, Catharine M.

    2009-01-01

    The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. Here we have performed a global transcriptional profiling of the highly virulent F. tularensis subsp. tularensis Schu S4 strain during its intracellular cycle within primary murine macrophages, to characterize its intracellular biology and identify pathogenic determinants based on their intracellular expression profile...

  5. 40 CFR 721.2088 - Carboxylic acids, (C6-C9) branched and linear.

    2010-07-01

    ... linear. 721.2088 Section 721.2088 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.2088 Carboxylic acids, (C6-C9) branched and linear. (a) Chemical... as carboxylic acids, (C6-C9) branched and linear (PMNs P-93-313, 314, 315, and 316) are subject...

  6. Ly6C(+) monocyte efferocytosis and cross-presentation of cell-associated antigens.

    Larson, S R; Atif, S M; Gibbings, S L; Thomas, S M; Prabagar, M G; Danhorn, T; Leach, S M; Henson, P M; Jakubzick, C V

    2016-06-01

    Recently it was shown that circulating Ly6C(+) monocytes traffic from tissue to the draining lymph nodes (LNs) with minimal alteration in their overall phenotype. Furthermore, in the steady state, Ly6C(+) monocytes are as abundant as classical dendritic cells (DCs) within the draining LNs, and even more abundant during inflammation. However, little is known about the functional roles of constitutively trafficking Ly6C(+) monocytes. In this study we investigated whether Ly6C(+) monocytes can efferocytose (acquire dying cells) and cross-present cell-associated antigen, a functional property particularly attributed to Batf3(+) DCs. We demonstrated that Ly6C(+) monocytes intrinsically efferocytose and cross-present cell-associated antigen to CD8(+) T cells. In addition, efferocytosis was enhanced upon direct activation of the Ly6C(+) monocytes through its corresponding TLRs, TLR4 and TLR7. However, only ligation of TLR7, and not TLR4, enhanced cross-presentation by Ly6C(+) monocytes. Overall, this study outlines two functional roles, among others, that Ly6C(+) monocytes have during an adaptive immune response. PMID:26990659

  7. On CO2 pertubation experiments: over-determination of carbonate chemistry reveals inconsistencies

    Hoppe, C. J. M.; Langer, G.; S. D. Rokitta; Wolf-Gladrow, D. A.; Rost, B.

    2010-01-01

    Seawater carbonate chemistry is typically calculated from two measured parameters. Depending on the choice of these input parameters, discrepancies in calculated pCO2 have been recognized by marine chemists, but the significance of this phenomenon for CO2 perturbation experiments has so far not been determined. To mimic different pCO2 scenarios, two common perturbation methods for seawater carbonate chemistry (changing either DIC or TA) were applied using state-of-the-art pr...

  8. Genome-wide Screening Reveals the Genetic Determinants of an Antibiotic Insecticide in Bacillus thuringiensis*

    Liu, Xiao-Yan; Ruan, Li-Fang; Hu, Zhen-Fei; Peng, Dong-hai; Cao, Shi-Yun; Yu, Zi-Niu; Liu, Yao; Zheng, Jin-Shui; Sun, Ming

    2010-01-01

    Thuringiensin is a thermostable secondary metabolite in Bacillus thuringiensis and has insecticidal activity against a wide range of insects. Until now, the regulatory mechanisms and genetic determinants involved in thuringiensin production have remained unclear. Here, we successfully used heterologous expression-guided screening in an Escherichia coli–Bacillus thuringiensis shuttle bacterial artificial chromosome library, to clone the intact thuringiensin synthesis (thu) cluster. Then the th...

  9. Genetic Analyses Reveal Functions for MAP2K3 and MAP2K6 in Mouse Testis Determination.

    Warr, Nick; Siggers, Pam; Carré, Gwenn-Aël; Wells, Sara; Greenfield, Andy

    2016-05-01

    Testis determination in mammals is initiated by expression of SRY in somatic cells of the embryonic gonad. Genetic analyses in the mouse have revealed a requirement for mitogen-activated protein kinase (MAPK) signaling in testis determination: targeted loss of the kinases MAP3K4 and p38 MAPK causes complete XY embryonic gonadal sex reversal. These kinases occupy positions at the top and bottom level, respectively, in the canonical three-tier MAPK-signaling cascade: MAP3K, MAP2K, MAPK. To date, no role in sex determination has been attributed to a MAP2K, although such a function is predicted to exist. Here, we report roles for the kinases MAP2K3 and MAP2K6 in testis determination. C57BL/6J (B6) embryos lacking MAP2K3 exhibited no significant abnormalities of testis development, whilst those lacking MAP2K6 exhibited a minor delay in testis determination. Compound mutants lacking three out of four functional alleles at the two loci also exhibited delayed testis determination and transient ovotestis formation as a consequence, suggestive of partially redundant roles for these kinases in testis determination. Early lethality of double-knockout embryos precludes analysis of sexual development. To reveal their roles in testis determination more clearly, we generated Map2k mutant B6 embryos using a weaker Sry allele (Sry(AKR)). Loss of Map2k3 on this highly sensitized background exacerbates ovotestis development, whilst loss of Map2k6 results in complete XY gonadal sex reversal associated with reduction of Sry expression at 11.25 days postcoitum. Our data suggest that MAP2K6 functions in mouse testis determination, via positive effects on Sry, and also indicate a minor role for MAP2K3. PMID:27009039

  10. Seasonal determinations of algal virus decay rates reveal overwintering in a temperate freshwater pond.

    Long, Andrew M; Short, Steven M

    2016-07-01

    To address questions about algal virus persistence (i.e., continued existence) in the environment, rates of decay of infectivity for two viruses that infect Chlorella-like algae, ATCV-1 and CVM-1, and a virus that infects the prymnesiophyte Chrysochromulina parva, CpV-BQ1, were estimated from in situ incubations in a temperate, seasonally frozen pond. A series of experiments were conducted to estimate rates of decay of infectivity in all four seasons with incubations lasting 21 days in spring, summer and autumn, and 126 days in winter. Decay rates observed across this study were relatively low compared with previous estimates obtained for other algal viruses, and ranged from 0.012 to 11% h(-1). Overall, the virus CpV-BQ1 decayed most rapidly whereas ATCV-1 decayed most slowly, but for all viruses the highest decay rates were observed during the summer and the lowest were observed during the winter. Furthermore, the winter incubations revealed the ability of each virus to overwinter under ice as ATCV-1, CVM-1 and CpV-BQ1 retained up to 48%, 19% and 9% of their infectivity after 126 days, respectively. The observed resilience of algal viruses in a seasonally frozen freshwater pond provides a mechanism that can support the maintenance of viral seed banks in nature. However, the high rates of decay observed in the summer demonstrate that virus survival and therefore environmental persistence can be subject to seasonal bottlenecks. PMID:26943625

  11. Molecular determinants of juvenile hormone action as revealed by 3D QSAR analysis in Drosophila.

    Denisa Liszeková

    Full Text Available BACKGROUND: Postembryonic development, including metamorphosis, of many animals is under control of hormones. In Drosophila and other insects these developmental transitions are regulated by the coordinate action of two principal hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH. While the mode of ecdysone action is relatively well understood, the molecular mode of JH action remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: To gain more insights into the molecular mechanism of JH action, we have tested the biological activity of 86 structurally diverse JH agonists in Drosophila melanogaster. The results were evaluated using 3D QSAR analyses involving CoMFA and CoMSIA procedures. Using this approach we have generated both computer-aided and species-specific pharmacophore fingerprints of JH and its agonists, which revealed that the most active compounds must possess an electronegative atom (oxygen or nitrogen at both ends of the molecule. When either of these electronegative atoms are replaced by carbon or the distance between them is shorter than 11.5 A or longer than 13.5 A, their biological activity is dramatically decreased. The presence of an electron-deficient moiety in the middle of the JH agonist is also essential for high activity. CONCLUSIONS/SIGNIFICANCE: The information from 3D QSAR provides guidelines and mechanistic scope for identification of steric and electrostatic properties as well as donor and acceptor hydrogen-bonding that are important features of the ligand-binding cavity of a JH target protein. In order to refine the pharmacophore analysis and evaluate the outcomes of the CoMFA and CoMSIA study we used pseudoreceptor modeling software PrGen to generate a putative binding site surrogate that is composed of eight amino acid residues corresponding to the defined molecular interactions.

  12. Analysis on Population Level Reveals Trappability of Wild Rodents Is Determined by Previous Trap Occupant.

    Brouard, Marc J; Coulson, Tim; Newman, Chris; Macdonald, David W; Buesching, Christina D

    2015-01-01

    Live trapping is central to the study of small mammals. Thus, any bias needs to be understood and accounted for in subsequent analyses to ensure accurate population estimates. One rarely considered bias is the behavioural response of individuals to the trap, in particular the olfactory cues left behind by previous occupants (PO). We used a data set of 8,115 trap nights spanning 17 separate trapping sessions between August 2002 and November 2013 in Wytham Woods, Oxfordshire, UK to examine if the decision to enter a trap was affected by the PO, if this was detectable in traditional Capture-Mark-Recapture trapping data (i.e., individuals not uniquely marked), and if it was possible for this effect to bias the population estimates obtained. Data were collected on Apodemus sylvaticus, Myodes glareolus, and Microtus agrestis. Three Generalised Linear Models revealed a significant tendency for the three species to enter traps with same-species PO. With, for example, A. sylvaticus 9.1 times more likely to enter a same species PO trap compared to one that contained a M. agrestis in the grassland during the nocturnal period. Simulation highlighted that, when all other factors are equal, the species with the highest PO effect will have the highest capture rate and therefore return more accurate population estimates. Despite the large dataset, certain species-, sex-, and/ or age-combinations were under-represented, and thus no effects of any additional individual-specific characteristics could be evaluated. Uniquely marking individuals would allow for the PO effect to be disentangled from other biases such as trap-shyness and spatial heterogeneity, but may not be possible in all cases and will depend on the aims of the study and the resources available. PMID:26689683

  13. What does Williams Syndrome Reveal about the Determinants of Social Behavior?

    Anna Maaria Järvinen

    2013-06-01

    Full Text Available Growing evidence on autonomic nervous system (ANS function in individuals with Williams syndrome (WS has begun to highlight aberrancies that may have important implications for the social profile characterized by enhanced social motivation and approach. In parallel, neurobiological investigations have identified alterations in the structure, function, and connectivity of the amygdala, as well as prosocial neuropeptide dysregulation, as some of the key neurogenetic features of WS. A recent social approach/withdrawal hypothesis (Kemp and Guastella, 2011 suggests that autonomic cardiac control may play a key role in regulating the relationship between oxytocin and social behavior. This article discusses evidence from these critical, new strands of research into social behavior in WS, to consider the extent to which data on WS may provide novel insight into the determinants of social behavior. Future research directions are suggested.

  14. What does Williams syndrome reveal about the determinants of social behavior?

    Järvinen, Anna M.; Bellugi, Ursula

    2013-01-01

    Growing evidence on autonomic nervous system (ANS) function in individuals with Williams syndrome (WS) has begun to highlight aberrancies that may have important implications for the social profile characterized by enhanced social motivation and approach. In parallel, neurobiological investigations have identified alterations in the structure, function, and connectivity of the amygdala, as well as prosocial neuropeptide dysregulation, as some of the key neurogenetic features of WS. A recent social approach/withdrawal hypothesis (Kemp and Guastella, 2011) suggests that autonomic cardiac control may play a key role in regulating the relationship between oxytocin (OT) and social behavior. This article discusses evidence from these critical, new strands of research into social behavior in WS, to consider the extent to which data on WS may provide novel insight into the determinants of social behavior. Future research directions are suggested. PMID:23825455

  15. Association studies and legume synteny reveal haplotypes determining seed size in Vigna unguiculata

    Mitchell R Lucas

    2013-04-01

    Full Text Available Highly specific seed market classes for cowpea and other grain legumes exists because grain is most commonly cooked and consumed whole. Size, shape, color, and texture are critical features of these market classes and breeders target development of cultivars for market acceptance. Resistance to biotic and abiotic stresses that are absent from elite breeding material are often introgressed through crosses to landraces or wild relatives. When crosses are made between parents with different grain quality characteristics, recovery of progeny with acceptable or enhanced grain quality is problematic. Thus genetic markers for grain quality traits can help in pyramiding genes needed for specific market classes. Allelic variation dictating the inheritance of seed size can be tagged and used to assist the selection of large-seeded lines. In this work we applied SNP genotyping and knowledge of legume synteny to characterize regions of the cowpea genome associated with seed size. These marker-trait associations will enable breeders to use marker based selection approaches to increase the frequency of progeny with large seed. For ~800 samples derived from eight bi-parental populations, QTL analysis was used to identify markers linked to ten trait determinants. In addition, the population structure of 171 samples from the USDA core collection was identified and incorporated into a genome-wide association study which supported more than half of the trait-associated regions important in the bi-parental populations. Seven of the total ten QTL were supported based on synteny to seed size associated regions identified in the related legume soybean. In addition to delivering markers linked to major trait determinants in the context of modern breeding, we provide an analysis of the diversity of the USDA core collection of cowpea to identify genepools, migrants, admixture, and duplicates.

  16. Gene Regulatory Network Analysis Reveals Differences in Site-specific Cell Fate Determination in Mammalian Brain

    Gokhan eErtaylan

    2014-12-01

    Full Text Available Neurogenesis - the generation of new neurons - is an ongoing process that persists in the adult mammalian brain of several species, including humans. In this work we analyze two discrete brain regions: the subventricular zone (SVZ lining the walls of the lateral ventricles; and the subgranular zone (SGZ of the dentate gyrus of the hippocampus in mice and shed light on the SVZ and SGZ specific neurogenesis. We propose a computational model that relies on the construction and analysis of region specific gene regulatory networks from the publicly available data on these two regions. Using this model a number of putative factors involved in neuronal stem cell (NSC identity and maintenance were identified. We also demonstrate potential gender and niche-derived differences based on cell surface and nuclear receptors via Ar, Hif1a and Nr3c1.We have also conducted cell fate determinant analysis for SVZ NSC populations to Olfactory Bulb interneurons and SGZ NSC populations to the granule cells of the Granular Cell Layer. We report thirty-one candidate cell fate determinant gene pairs, ready to be validated. We focus on Ar - Pax6 in SVZ and Sox2 - Ncor1 in SGZ. Both pairs are expressed and localized in the suggested anatomical structures as shown by in situ hybridization and found to physically interact.Finally, we conclude that there are fundamental differences between SGZ and SVZ neurogenesis. We argue that these regulatory mechanisms are linked to the observed differential neurogenic potential of these regions. The presence of nuclear and cell surface receptors in the region specific regulatory circuits indicate the significance of niche derived extracellular factors, hormones and region specific factors such as the oxygen sensitivity, dictating SGZ and SVZ specific neurogenesis.

  17. The Population Genomics of Sunflowers and Genomic Determinants of Protein Evolution Revealed by RNAseq

    Loren H. Rieseberg

    2012-10-01

    determinants of rates of protein evolution and the impact of selection on patterns of polymorphism and divergence.

  18. 17 CFR 270.6c-3 - Exemptions for certain registered variable life insurance separate accounts.

    2010-04-01

    ... account which meets the requirements of paragraph (a) of Rule 6e-2 (17 CFR 270.6e-2) or paragraph (a) of Rule 6e-3(T) (17 CFR 270.6e-3(T)) and registers as an investment company under section 8(a) of the Act... registered variable life insurance separate accounts. 270.6c-3 Section 270.6c-3 Commodity and...

  19. PRINSIP 6C (CHARACTER, CAPACITY, CAPITAL, CONDITION OF ECONOMY, COLLATERAL DAN CONSTRAINT DALAM WIRAUSAHA MAHASISWA

    Henny Sri Astuty

    2015-04-01

    Full Text Available Abstrak: Prinsip 6C (Character, Capacity, Capital, Condition of Economy, Collateral dan Constraint dalam Wirausaha Mahasiswa. Kegiatan wirausaha yang sekarang banyak dilakukan oleh mahasiswa memiliki sisi positif maupun negatif, dari yang berhasil kuliah dan wirausahanya hingga yang gagal semuanya. Untuk ini diperlukan pemahaman tentang prinsip enam C (character, capacity, capital, condition of economy, collateral and constraint yang akan membantu mahasiswa sebagai bekal dalam melakukan kegiatan usahanya. Banyak faktor yang diperoleh dalam prinsip ini yaitu aspek manajemen, pemasaran, produksi, dan keuangan. Kata Kunci: prinsip 6c, wirausaha, mahasiswa Abstract: 6C Principles (Character, Capacity, Capital, Condition of Economy, Collateral and Constraint in Entrepreneurial Students. Entrepreneurial activity that is widely performed by students has two different stories. Some of them are successful on the other hand, the rest of them are fail. Accordingly, it is required an understanding of the 6C principles of the six C (character, capacity, capital, condition of economy, collateral and constraints which will help the students as a preparation in conducting their business activities. Many factors obtained in this principle namely: management, marketing, production, and financial aspects. Keywords: 6C principles, entrepreneurs, students

  20. Integrating total quality management principles with the requirements of DOE Order 5700.6C

    Hedges, D. [Scientific Ecology Group, Inc. (United States)

    1993-03-01

    The Department of Energy has recently required its field offices, contractors, and subcontractors to implement DOE Order 5700.6C, ``Quality Assurance,`` for all work on waste management contracts. The order restructures the 18 criteria of NQA-1 and focuses on the role of management in achieving and assuring quality, performance of activities to achieve and assure quality, and management`s assessment of its performance for the purpose of identifying improvements to be made. The DOE order also introduces elements of the total quality management (TQM) philosophy, which were not present in DOE Order 5700.6B. The research community within DOE has recently issued a document entitled DOE Order 5700.6C Implementation Guide, which is more explicit about the integration of TQM principles with the implementation of DOE Order 5700.6C in research facilities. The Environmental Protection Agency is sponsoring a quality assurance standard (ANSI/ASQC E-4) to replace EPA`s QAMS 005/80. The new standard is consistent with DOE Order 5700.6C, and it also stresses the integration of TQM principles within the quality assurance process. This paper discusses the intent and philosophy of the 10 criteria of the new DOE order, the status of ANSI/ASQC E-4, and how to effectively integrate TQM principles into the quality assurance process as the conversion is made from NQA-1 to DOE Order 5700.6C. The purpose and value of DOE Order 5700.6C Implementation Guide for research will also be discussed.

  1. Modeling reveals bistability and low-pass filtering in the network module determining blood stem cell fate.

    Jatin Narula

    2010-05-01

    Full Text Available Combinatorial regulation of gene expression is ubiquitous in eukaryotes with multiple inputs converging on regulatory control elements. The dynamic properties of these elements determine the functionality of genetic networks regulating differentiation and development. Here we propose a method to quantitatively characterize the regulatory output of distant enhancers with a biophysical approach that recursively determines free energies of protein-protein and protein-DNA interactions from experimental analysis of transcriptional reporter libraries. We apply this method to model the Scl-Gata2-Fli1 triad-a network module important for cell fate specification of hematopoietic stem cells. We show that this triad module is inherently bistable with irreversible transitions in response to physiologically relevant signals such as Notch, Bmp4 and Gata1 and we use the model to predict the sensitivity of the network to mutations. We also show that the triad acts as a low-pass filter by switching between steady states only in response to signals that persist for longer than a minimum duration threshold. We have found that the auto-regulation loops connecting the slow-degrading Scl to Gata2 and Fli1 are crucial for this low-pass filtering property. Taken together our analysis not only reveals new insights into hematopoietic stem cell regulatory network functionality but also provides a novel and widely applicable strategy to incorporate experimental measurements into dynamical network models.

  2. Novel Pneumococcal Serotypes 6C and 6D: Anomaly or Harbinger

    McEllistrem, M. Catherine; Nahm, Moon H.

    2012-01-01

    The discovery of serotypes 6C and 6D, the former of which expanded in the 7-valent pneumococcal protein conjugate vaccine era, illustrates a previously unrecognized limitation of conjugate vaccines: the expansion of unrecognized serotypes could erode the efficacy of a serotype-specific vaccine.

  3. Comparison of Renal Amyloid and Hyaline Glomerulopathy in B6C3F1 Mice: An NTP Retrospective Study.

    Hoane, Jessica S; Johnson, Crystal L; Morrison, James P; Elmore, Susan A

    2016-07-01

    Due to potential misdiagnosis of hyaline glomerulopathy (HG) for amyloidosis, a retrospective study of B6C3F1 mice from the National Toxicology Program (NTP) archives was undertaken to determine whether HG had occurred in prior NTP studies and, if so, whether these 2 glomerular lesions could be routinely discriminated. Kidney slides from 7 amyloid-positive control mice, 2 HG-positive control mice, 3 normal or negative control mice, and 41 potential HG mice (with renal-only deposits previously diagnosed as amyloid) were evaluated using hematoxylin and eosin (H&E), periodic acid Schiff (PAS), Congo red (CR), and Masson's trichrome (MT) stains. Utilizing these techniques, HG was reliably distinguished from amyloidosis. All 41 potential HG mice had glomerular deposits histochemically inconsistent with amyloid; the deposits were PAS positive and CR negative. Four of the 41 mice were selected for transmission electron microscopy of the glomerular deposits; ultrastructurally, the deposits in these animals were consistent with HG and not amyloid. Our findings indicate that HG is a spontaneous lesion in B6C3F1 mice of low occurrence, is commonly misdiagnosed as amyloidosis, and is more likely than amyloid to cause glomerular deposits in mice without evidence of deposits in other tissues. Also, HG can be distinguished from amyloid on H&E evaluation; however, the distinction is improved with use of PAS or CR staining and/or ultraviolet evaluation. PMID:27000376

  4. Specific depletion of Ly6C(hi inflammatory monocytes prevents immunopathology in experimental cerebral malaria.

    Beatrix Schumak

    Full Text Available Plasmodium berghei ANKA (PbA infection of C57BL/6 mice leads to experimental cerebral malaria (ECM that is commonly associated with serious T cell mediated damage. In other parasitic infection models, inflammatory monocytes have been shown to regulate Th1 responses but their role in ECM remains poorly defined, whereas neutrophils are reported to contribute to ECM immune pathology. Making use of the recent development of specific monoclonal antibodies (mAb, we depleted in vivo Ly6C(hi inflammatory monocytes (by anti-CCR2, Ly6G+ neutrophils (by anti-Ly6G or both cell types (by anti-Gr1 during infection with Ovalbumin-transgenic PbA parasites (PbTg. Notably, the application of anti-Gr1 or anti-CCR2 but not anti-Ly6G antibodies into PbTg-infected mice prevented ECM development. In addition, depletion of Ly6C(hi inflammatory monocytes but not neutrophils led to decreased IFNγ levels and IFNγ+CD8+ T effector cells in the brain. Importantly, anti-CCR2 mAb injection did not prevent the generation of PbTg-specific T cell responses in the periphery, whereas anti-Gr1 mAb injection strongly diminished T cell frequencies and CTL responses. In conclusion, the specific depletion of Ly6C(hi inflammatory monocytes attenuated brain inflammation and immune cell recruitment to the CNS, which prevented ECM following Plasmodium infection, pointing out a substantial role of Ly6C+ monocytes in ECM inflammatory processes.

  5. Dissociation of H2 on carbon doped aluminum cluster Al6C

    The dissociation of H2 molecule is the first step for chemical storage of hydrogen, and the energy barrier of the dissociation is the key factor to decide the kinetics of the regeneration of the storage material. As a light element, aluminum is an important candidate component for storage materials with high gravimetric density. This paper investigates the adsorption and dissociation of H2 on carbon doping aluminum cluster Al6C. The study shows that doping carbon into aluminum cluster can significantly change the electronic structure and increase the stability. Al6C has a few stable isomers with close energies and their structures are quite flexible. The molecular adsorption of H2 on Al6C is very weak, but the H2 molecule can be dissociated easily on this cluster. The stable product of the dissociated adsorption is searched and the different paths for the dissociation are investigated. During the dissociation of H2, the structure of the cluster adjusts accordingly, and strong orbital interaction between the hydrogen and the cluster occurs. The calculated energy barrier for the dissociation is only 0.30 eV, which means the dissociation can take place at moderate temperatures

  6. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    Guo, Tai L., E-mail: tlguo1@uga.edu [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Wang, Yunbiao [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102 (China); Xiong, Tao [College of Animal Science, Yangtze University, Jingzhou City, Hubei Province 434025 (China); Ling, Xiao [Institute for Food and Drug Control of Shandong Province, Jinan City, Shandong 250012 (China); Zheng, Jianfeng [Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613 (United States)

    2014-11-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  7. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  8. Small-angle neutron scattering analysis of Mn–C clusters in high-manganese 18Mn–0.6C steel

    Nanometer-scale particles (Mn–C clusters) were analyzed quantitatively using small-angle neutron scattering in 18Mn–0.6C (wt.%) austenite high-manganese steel. The size, number, and volume fraction of the particles were determined as a function of strain (0, 5, 15, 30, 45, 50%) at different temperatures (25 and 100 °C). The diameter of the cluster ranges from 2 to 14 nm in the matrix. The total volume fraction of the cluster significantly increases from 2.7 × 10−6 to 8.7 × 10−6 as the strain increases. Such clustering phenomenon is correlated to the serration behavior under loading in high-manganese steels. - Highlights: • Show Mn-C clustering as function of strain in 18Mn-0.6C TWIP steel. • Determine the size, number, and volume fraction of clusters quantitatively. • Compare the clustering behavior at 25 and 100 °C

  9. General Intermediates for the Synthesis of 6-C-Alkylated DMDP-Related Natural Products

    Chu-Yi Yu

    2013-06-01

    Full Text Available Protected L-homoDMDP en-8 and its C-6 epimer en-7 were prepared through two different pathways starting from the vinylpyrrolidine en-9. Based on the NMR and X-ray analysis, the stereochemistry of homoDMDP at C-6 was confirmed to be consistent with reported data. Compounds en-7 and en-8 are general intermediates for the synthesis of a series of 6-C-alkylated DMDP-related natural products, such as broussonetine G, homoDMDP-7-O-apioside, homoDMDP-7-O-b-D-xyloside and so on.

  10. The chemistry and evolutionary status of HD 62910 (WN6-C4)

    An analysis of the IUE and optical spectra of the WN-C star HD 62910 confirms the classification as WN6-C4, and shows that both the WN and WC lines arise in the same stellar wind. A Sobolev analysis of the observed line strengths gives the following mass abundance ratios: C/N = 0.26, C/He = 0.0024, N/He = 0.01, and H/He = 0.0, consistent with predictions of stellar evolutionary models for the short-lived phase between the WNE and WC stages. 20 refs

  11. Poster: Ocean Literacy Principal 6c. The ocean and humans are inextricably interconnected – Energy

    Society, Blue; Institute, Marine

    2015-01-01

    : BlueSociety.org, Sea for Society and the Marine Institute have developed a number of 'Your Ocean - Your Future' posters that can be used in class to raise awareness and understanding about "the ocean's influence on us and our influence on the ocean". The posters can be used to help learn about the key fundamental concepts about our ocean. Poster 6c. The ocean and humans are inextricably interconnected – Energy: E.U. offshore wind investments topped €4.2 billion in 2014

  12. Interrelationship of interleukin 6, C-reactive protein and Chlamydia pneumoniae IgG antibodies in patients with acute coronary syndromes

    Burazor Ivana; Vojdani Aristo; Burazor Mirko

    2008-01-01

    Background/Aim. Inflammation due to infection could be associated with the development of acute coronary syndromes, clinical manifestations of ongoing atherosclerosis in vessel walls. Our aim was determine whether interleukin 6, C-reactive protein and Chlamydia pneumoniae IgG antibodies are connected with the development of acute coronary syndromes, to evaluate their interrelationship and to examine whether they are predictive of new events and mortality. Methods. This prospective study inclu...

  13. A Naturally-Derived Compound Schisandrin B Enhanced Light Sensation in the pde6c Zebrafish Model of Retinal Degeneration.

    Zhang, Liyun; Xiang, Lue; Liu, Yiwen; Venkatraman, Prahatha; Chong, Leelyn; Cho, Jin; Bonilla, Sylvia; Jin, Zi-Bing; Pang, Chi Pui; Ko, Kam Ming; Ma, Ping; Zhang, Mingzhi; Leung, Yuk Fai

    2016-01-01

    Retinal degeneration is often progressive. This feature has provided a therapeutic window for intervention that may extend functional vision in patients. Even though this approach is feasible, few promising drug candidates are available. The scarcity of new drugs has motivated research to discover novel compounds through different sources. One such example is Schisandrin B (SchB), an active component isolated from the five-flavor fruit (Fructus Schisandrae) that is postulated in traditional Chinese medicines to exert prophylactic visual benefit. This SchB benefit was investigated in this study in pde6cw59, a zebrafish retinal-degeneration model. In this model, the pde6c gene (phosphodiesterase 6C, cGMP-specific, cone, alpha prime) carried a mutation which caused cone degeneration. This altered the local environment and caused the bystander rods to degenerate too. To test SchB on the pde6cw59 mutants, a treatment concentration was first determined that would not cause morphological defects, and would initiate known physiological response. Then, the mutants were treated with the optimized SchB concentration before the appearance of retinal degeneration at 3 days postfertilization (dpf). The light sensation of animals was evaluated at 6 dpf by the visual motor response (VMR), a visual startle that could be initiated by drastic light onset and offset. The results show that the VMR of pde6cw59 mutants towards light onset was enhanced by the SchB treatment, and that the initial phase of the enhancement was primarily mediated through the mutants' eyes. Further immunostaining analysis indicates that the treatment specifically reduced the size of the abnormally large rods. These observations implicate an interesting hypothesis: that the morphologically-improved rods drive the observed VMR enhancement. Together, these investigations have identified a possible visual benefit of SchB on retinal degeneration, a benefit that can potentially be further developed to extend

  14. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet.

    Guo, Tai L; Wang, Yunbiao; Xiong, Tao; Ling, Xiao; Zheng, Jianfeng

    2014-11-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100mg/kg doses (i.p.): the first dose was administered at approximately 2weeks following the initiation of daily GE (20mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. PMID:25178718

  15. 360 degree decompresion and stabilisation of the C6-C7 cervical spine luxation - case study.

    Chrzanowski, Robert; Godlewski, Bartosz; Klauz, Grzegorz; Janeczko, Łukasz

    2012-01-01

    We present the operative technique employed in a young man with cervical spine luxation at the level of C6-C7 with clinical signs of damage to the spinal cord at the level of C5. In order to achieve an optimal therapeutic effect (decompression of neural structures and spinal stabilisation) during one surgical procedure, the positioning of the patient was changed twice during the procedure. Considering the positioning of the patient at the beginning of the procedure, the body position was changed by 360 degrees. The first part of the procedure was performed from an anterior approach with the patient in the supine position. It involved a C6-C7 discectomy and removal of the upper surface of the body of C7, which was protruding into the vertebral canal and compressing the spinal cord. Intraoperative inspection showed that a posterior approach was necessary to reduce the luxation. Therefore, for the second part of the operation, the patient was turned by 180 degrees and placed in the prone position. For the last (third) part of the surgical procedure, the patient was again turned by 180 degrees and placed in the supine position in order to insert an anterior spine fixator. We believe that a procedure utilising different surgical approaches and different positioning of the patient in order to achieve optimal therapeutic effect may be used in selected cases in everyday clinical practice. PMID:23382285

  16. Chemical corrosion of PtRuCu6/C for highly efficient methanol oxidation

    Huang, Meihua; Wu, Chuxin; Guan, Lunhui

    2016-02-01

    Until now, Pt is commonly used as anode catalyst for methanol oxidation in direct methanol fuel cells. Here we report that chemical corrosion of PtRuCu6/C, which was prepared by microwave-polyol technique, promotes the activity of Pt for methanol oxidation. The PtRuCu6/C is chemically corroded, and the obtained sample is denoted as PtRuCu6-A/C. The PtRuCu6-A/C contains a Pt-Ru-Cu core and Pt-Ru shell with surface defects. The PtRuCu6-A/C has surface activity and mass activity 10.6 and 6.0 times higher than those of Pt/C for methanol oxidation. And the surface activity and mass activity of PtRuCu6-A/C are 3.3 and 3.9 times higher than those of PtRu/C for methanol oxidation. The enhanced activity of PtRuCu6-A/C is attributed to the surface defects and the stronger electronic modification of Pt. This facile preparation strategy provides a new route of synthesizing highly active catalysts for methanol oxidation.

  17. Effects of bainitic transformation temperature on microstructure and tensile properties of 0.6C-Si-Mn steel; 0.6C-Si-Mn ko no bisai soshiki to hippari tokusei ni oyobosu benaito hentai ondo no eikyo

    Tomita, Y. [University of Osaka Prefecture, Osaka (Japan). Faculty of Engineering

    1995-06-15

    To acquire excellent mechanical properties of Si-Mn steel by using an austempering treatment to have the steel undergo a bainitic transformation, it is important to identify the effect of its transformation temperature. This paper describes a transformation of 0.6% C-Si-Mn steel at temperatures ranging from 593 K to 673 K, and discussions on the effect of the transformation temperature on the microstructure and tensile properties. The following results were obtained: bainitic ferrite containing very little carbon is produced in layers at any transformation temperature, but a trend was shown that the bainitic ferrite is produced with its width grown larger and denser as the transformation temperature rises; the {gamma}R amount increases remarkably with increasing transformation temperature, and at the same time massive {gamma}R begins to remain in addition to thin film {gamma}R that exists between individual bainitic ferrites; and the result of this experiment revealed that when the transformation temperature is sufficiently high, the fracture elongation increases notably because of the transformation induced plasticity (TRIP) effect of the {gamma}R that occurs effectively during the transformation. 12 refs., 7 figs., 4 tabs.

  18. Genomic analysis of the Pacific oyster (Crassostrea gigas) reveals possible conservation of vertebrate sex determination in a mollusc.

    Zhang, Na; Xu, Fei; Guo, Ximing

    2014-11-01

    Despite the prevalence of sex in animal kingdom, we have only limited understanding of how sex is determined and evolved in many taxa. The mollusc Pacific oyster Crassostrea gigas exhibits complex modes of sexual reproduction that consists of protandric dioecy, sex change, and occasional hermaphroditism. This complex system is controlled by both environmental and genetic factors through unknown molecular mechanisms. In this study, we investigated genes related to sex-determining pathways in C. gigas through transcriptome sequencing and analysis of female and male gonads. Our analysis identified or confirmed novel homologs in the oyster of key sex-determining genes (SoxH or Sry-like and FoxL2) that were thought to be vertebrate-specific. Their expression profile in C. gigas is consistent with conserved roles in sex determination, under a proposed model where a novel testis-determining CgSoxH may serve as a primary regulator, directly or indirectly interacting with a testis-promoting CgDsx and an ovary-promoting CgFoxL2. Our findings plus previous results suggest that key vertebrate sex-determining genes such as Sry and FoxL2 may not be inventions of vertebrates. The presence of such genes in a mollusc with expression profiles consistent with expected roles in sex determination suggest that sex determination may be deeply conserved in animals, despite rapid evolution of the regulatory pathways that in C. gigas may involve both genetic and environmental factors. PMID:25213692

  19. Heterologous expression, crystallization and preliminary X-ray characterization of CcCel6C, a glycoside hydrolase family 6 enzyme from the basidiomycete Coprinopsis cinerea

    Crystallization of CcCel6C was carried out by the hanging-drop vapour-diffusion method. X-ray diffraction data were collected to 1.6 Å resolution from the crystal. CcCel6C is a gene that encodes a glycoside hydrolase family 6 (GH6) enzyme in the Coprinopsis cinerea genome. In the evolutionary tree of GH6 enzymes, the encoded enzyme was closely related to Cel6B from Humicola insolens, previously called endoglucanase VI, while its amino-acid sequence revealed a region corresponding to the C-terminal active-site-enclosing loop typical of cellobiohydrolase II. Here, the crystallization of CcCel6C produced in Escherichia coli is reported. The square prismatic crystal belonged to the triclinic space group P1, with unit-cell parameters a = 44.04, b = 45.11, c = 48.90 Å, α = 77.81, β = 87.34, γ = 68.79°. Diffraction data were collected to 1.6 Å resolution

  20. Design of a passive UHF RFID tag for the ISO18000-6C protocol

    Wang Yao; Wen Guangjun; Mao Wei; He Yanli; Zhu Xueyong, E-mail: wangyao220597@yahoo.com.cn [RFIC Laboratory CICS, School of Communication and Information Engineering, University of Electronic Science and Technology of China, Chengdu 611731 (China)

    2011-05-15

    This paper presents a new fully integrated wide-range UHF passive RFID tag chip design that is compatible with the ISO18000-6C protocol. In order to reduce the die area, an ultra-low power CMOS voltage regulator without resistors and an area-efficient amplitude shift keying demodulator with a novel adaptive average generator are both adopted. A low power clock generator is designed to guarantee the accuracy of the clock under {+-}4%. As the clock gating technology is employed to reduce the power consumption of the baseband processor, the total power consumption of the tag is about 14 {mu}W with a sensitivity of -9.5 dBm. The detection distance can reach about 5 m under 4 W effective isotropic radiated power. The whole tag is fabricated in TSMC 0.18 {mu}m CMOS technology and the chip size is 880 x 880 {mu}m{sup 2}. (semiconductor integrated circuits)

  1. Design of a passive UHF RFID tag for the ISO18000-6C protocol

    This paper presents a new fully integrated wide-range UHF passive RFID tag chip design that is compatible with the ISO18000-6C protocol. In order to reduce the die area, an ultra-low power CMOS voltage regulator without resistors and an area-efficient amplitude shift keying demodulator with a novel adaptive average generator are both adopted. A low power clock generator is designed to guarantee the accuracy of the clock under ±4%. As the clock gating technology is employed to reduce the power consumption of the baseband processor, the total power consumption of the tag is about 14 μW with a sensitivity of -9.5 dBm. The detection distance can reach about 5 m under 4 W effective isotropic radiated power. The whole tag is fabricated in TSMC 0.18 μm CMOS technology and the chip size is 880 x 880 μm2. (semiconductor integrated circuits)

  2. Studying the Hall-Petch effect regarding sub-micrometer steel (0.6% C

    Rodolfo Rodríguez Baracaldo

    2011-08-01

    Full Text Available This paper study the synthesis and mechanical characterisation of steel (0.6% C having lower than 1 micron grain size. There was severe plastic deformation in high pressure planetary ball milling and consolidation for obtaining bulk samples at temperatures between 350°C and 500°C. Studying grain size evolution showed that samples without subsequent heat treatment retained their nanocrystalline structure. Grain growth was controlled in heat-treated samples due to many nucleation points and the presence of cementite precipitates. The results obtained regarding hardness and grain size satisfactory agreed with the Hall- Petch ratio. The influence of the synthesis and mechanical characterisation techniques used in this work were compared to results mentioned in several references.

  3. Lowest instrumented vertebra selection in Lenke 3C and 6C scoliosis

    Wang, Yu; Bünger, Cody; Zhang, Yanqun;

    2012-01-01

    ), another 11 in Group B (LIV at LAV) and the remaining 18 in Group C (LIV below LAV). At 2-year follow-up, the lumbar vertebrae such as LIV, LIV + 1 and LAV were all more deviated than before surgery in Group A (LIV above LAV), whereas in Group B and C (LIV at and below LAV) they were all less deviated than...... before surgery. No significant differences were found in thoracic or lumbar correction rate, global coronal balance and incidence rate of trunk shift among the three groups. CONCLUSION: In conclusion, in Lenke 3C and 6C scoliosis, post-op lumbar curve behaviour differs due to different choices of LIV...

  4. Genomic Analysis of the Pacific Oyster (Crassostrea gigas) Reveals Possible Conservation of Vertebrate Sex Determination in a Mollusc

    Zhang, Na; Xu, Fei; Guo, Ximing

    2014-01-01

    Despite the prevalence of sex in animal kingdom, we have only limited understanding of how sex is determined and evolved in many taxa. The mollusc Pacific oyster Crassostrea gigas exhibits complex modes of sexual reproduction that consists of protandric dioecy, sex change, and occasional hermaphroditism. This complex system is controlled by both environmental and genetic factors through unknown molecular mechanisms. In this study, we investigated genes related to sex-determining pathways in C...

  5. Molecular mechanisms determining conserved properties of short-term synaptic depression revealed in NSF and SNAP-25 conditional mutants

    Kawasaki, Fumiko; Ordway, Richard W.

    2009-01-01

    Current models of synaptic vesicle trafficking implicate a core complex of proteins comprised of N-ethylmaleimide-sensitive factor (NSF), soluble NSF attachment proteins (SNAPs), and SNAREs in synaptic vesicle fusion and neurotransmitter release. Despite this progress, major challenges remain in establishing the in vivo functions of these proteins and their roles in determining the physiological properties of synapses. The present study employs glutamatergic adult neuromuscular synapses of Dr...

  6. Comparison of the aggregation of homologous β2-microglobulin variants reveals protein solubility as a key determinant of amyloid formation.

    Pashley, Clare L; Hewitt, Eric W; Radford, Sheena E

    2016-02-13

    The mouse and human β2-microglobulin protein orthologs are 70 % identical in sequence and share 88 % sequence similarity. These proteins are predicted by various algorithms to have similar aggregation and amyloid propensities. However, whilst human β2m (hβ2m) forms amyloid-like fibrils in denaturing conditions (e.g. pH2.5) in the absence of NaCl, mouse β2m (mβ2m) requires the addition of 0.3M NaCl to cause fibrillation. Here, the factors which give rise to this difference in amyloid propensity are investigated. We utilise structural and mutational analyses, fibril growth kinetics and solubility measurements under a range of pH and salt conditions, to determine why these two proteins have different amyloid propensities. The results show that, although other factors influence the fibril growth kinetics, a striking difference in the solubility of the proteins is a key determinant of the different amyloidogenicity of hβ2m and mβ2m. The relationship between protein solubility and lag time of amyloid formation is not captured by current aggregation or amyloid prediction algorithms, indicating a need to better understand the role of solubility on the lag time of amyloid formation. The results demonstrate the key contribution of protein solubility in determining amyloid propensity and lag time of amyloid formation, highlighting how small differences in protein sequence can have dramatic effects on amyloid formation. PMID:26780548

  7. Absorption and metabolism of triclosan after application to the skin of B6C3F1 mice.

    Fang, Jia-Long; Vanlandingham, Michelle; Gamboa da Costa, Gonçalo; Beland, Frederick A

    2016-05-01

    Triclosan is used as an antimicrobial agent in personal care products, household items, medical devices, and clinical settings. Humans can receive lifelong exposures to triclosan; however, data on the toxicity and carcinogenicity after topical application are lacking. This study determined the absorption, distribution, metabolism, and excretion of triclosan after application to the skin of B6C3F1 mice. [(14) C(U)]triclosan (10 or 100 mg triclosan/kg body weight) was administered topically to mice in two separate experiments: a vehicle selection experiment using propylene glycol, ethanol, and a generic cosmetic cream, and a toxicokinetic experiment. Mice were killed up to 72 h after triclosan administration, and excreta and tissues were analyzed for radioactivity. Ethanol had the best properties of the vehicles evaluated. Maximum absorption was obtained at approximately 12 h after dosing. Radioactivity appeared in the excreta and in all tissues examined, with the highest levels in the gall bladder and the lowest levels in the brain. Triclosan was metabolized to triclosan sulfate, triclosan glucuronide, 2,4-dichlorophenol, and hydroxytriclosan. The metabolite profile was tissue-dependent and the predominant route of excretion was fecal. The AUC0-∞ and the Cmax of plasma and liver in females were greater than those in males. Slightly lower absorption was observed in mice with Elizabethan collars. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 609-623, 2016. PMID:25410937

  8. Toxicology studies of a chemical mixture of 25 groundwater contaminants. II. Immunosuppression in B6C3F1 mice

    Germolec, D.R.; Yang, R.S.; Ackermann, M.F.; Rosenthal, G.J.; Boorman, G.A.; Blair, P.; Luster, M.I. (National Institutes of Environmental Health Sciences, Research Triangle Park, NC (USA))

    1989-10-01

    Concern over the potential adverse health effects of chemically contaminated groundwater has existed for many years. In general, these studies have focused on retrospective epidemiological studies for cancer risk. In the present studies, immune function was monitored in female B6C3F1 mice exposed to a chemical mixture in drinking water for either 14 or 90 days. The mixture consisted of 25 common groundwater contaminants frequently found near toxic waste dumps, as determined by EPA surveys. None of the animals developed overt signs of toxicity such as body or liver weight changes. Mice exposed to the highest dose of this mixture for 14 or 90 days showed immune function changes which could be related to rapidly proliferating cells, including suppression of hematopoietic stem cells and of antigen-induced antibody-forming cells. Some of these responses, e.g., granulocyte-macrophage colony formation, were also suppressed at lower concentrations of the chemical mixture. There were no effects on T cell function or T and B cell numbers in any of the treatment groups. Altered resistance to challenge with an infectious agent also occurred in mice given the highest concentration, which correlated with the immune function changes. Paired-water studies indicated that the immune effects were related to chemical exposure and not to decreased water intake. These results suggest that long-term exposure to contaminated groundwater may represent a risk to the immune system in humans.

  9. Establishment of a human colorectal cancer cell line P6C with stem cell properties and resistance to chemotherapeutic drugs

    Guan-hua RAO; Hong-min LIU; Bao-wei LI; Jia-jie HAO; Yan-lei YANG; Ming-rong WANG; Xiao-hui WANG

    2013-01-01

    Aim:Cancer stem cells have the capacity to initiate and sustain tumor growth.In this study,we established a CD44+ colorectal cancer stem cell line with particular emphasis on its self-renewal capacity,enhanced tumor initiation and drug resistance.Methods:Fresh colon cancer and paired normal colon tissues were collected from 13 patients who had not received chemotherapy or radiotherapy prior to surgery.Among the 6 single-cell derived clones,only the P6C cell line was cultured for more than 20 passages in serial culture and formed holoclones with high efficiency,and then the stemness gene expression,colony formation,tumorigenicity and drug sensitivities of the P6C cell line were examined.Results:Stemness proteins,including c-Myc,0ct3/4,Nanog,Lgr5,and SOX2,were highly expressed in the P6C cell line.Oct3/4-positive P6C cells mostly generated holoclones through symmetric division,while a small number of P6C cells generated meroclones through asymmetric division.P6C cells stably expressed CD44 and possessed a high capacity to form tumor spheres.A single cellderived sphere was capable of generating xenograft tumors in nude mice.Compared to SW480 and HCT116 colorectal cancer cells,P6C cells were highly resistant to Camptothecin and 5-fluorouracil,the commonly used chemotherapeutic agents to treat colorectal cancers.Conclusion:We established a colorectal cancer stem cell line P6C with a high tumorigenic capacity and the characteristics of normal stem cells.It will benefit the mechanistic studies on cancer stem cells and the development of drugs that specifically target the cancer stem cells.

  10. Genome Editing of Lineage Determinants in Human Pluripotent Stem Cells Reveals Mechanisms of Pancreatic Development and Diabetes.

    Zhu, Zengrong; Li, Qing V; Lee, Kihyun; Rosen, Bess P; González, Federico; Soh, Chew-Li; Huangfu, Danwei

    2016-06-01

    Directed differentiation of human pluripotent stem cells (hPSCs) into somatic counterparts is a valuable tool for studying disease. However, examination of developmental mechanisms in hPSCs remains challenging given complex multi-factorial actions at different stages. Here, we used TALEN and CRISPR/Cas-mediated gene editing and hPSC-directed differentiation for a systematic analysis of the roles of eight pancreatic transcription factors (PDX1, RFX6, PTF1A, GLIS3, MNX1, NGN3, HES1, and ARX). Our analysis not only verified conserved gene requirements between mice and humans but also revealed a number of previously unsuspected developmental mechanisms with implications for type 2 diabetes. These include a role of RFX6 in regulating the number of pancreatic progenitors, a haploinsufficient requirement for PDX1 in pancreatic β cell differentiation, and a potentially divergent role of NGN3 in humans and mice. Our findings support use of systematic genome editing in hPSCs as a strategy for understanding mechanisms underlying congenital disorders. PMID:27133796

  11. Silicon etch using SF6/C4F8/Ar gas mixtures

    While plasmas using mixtures of SF6, C4F8, and Ar are widely used in deep silicon etching, very few studies have linked the discharge parameters to etching results. The authors form such linkages in this report. The authors measured the optical emission intensities of lines from Ar, F, S, SFx, CF2, C2, C3, and CS as a function of the percentage C4F8 in the gas flow, the total gas flow rate, and the bias power. In addition, the ion current density and electron temperature were measured using a floating Langmuir probe. For comparison, trenches were etched of various widths and the trench profiles (etch depth, undercut) were measured. The addition of C4F8 to an SF6/Ar plasma acts to reduce the availability of F as well as increase the deposition of passivation film. Sulfur combines with carbon in the plasma efficiently to create a large optical emission of CS and suppress optical emissions from C2 and C3. At low fractional flows of C4F8, the etch process appears to be controlled by the ion flux more so than by the F density. At large C4F8 fractional flows, the etch process appears to be controlled more by the F density than by the ion flux or deposition rate of passivation film. CF2 and C2 do not appear to cause deposition from the plasma, but CS and other carbon containing molecules as well as ions do

  12. Tensile deformation of a duplex Fe-20Mn-9Al-0.6C steel having the reduced specific weight

    Highlights: → Characterization of deformation of each constituent phase of a duplex high Mn steel. → Austenite deformation mechanism in relation to the stacking fault energy. → Variances of microstructures and phase chemistry affecting the deformation modes. - Abstract: The room temperature deformation characteristics of a duplex Fe-20Mn-9Al-0.6C steel with the reduced specific weight of 6.84 g/cm3 in the fully solutionized state were described in conjunction with the deformation mechanisms of its constituent phases. The phase fraction was insensitive to annealing temperature in the range of 800-1100 deg. C. The ferrite grain size was also nearly unaltered but the austenite grain size slightly increased with increasing annealing temperature. This revealed that there is little window to control the microstructure of the steel by annealing. The steel exhibited a good combination of strength over 800 MPa and ductility over 45% in the present annealing conditions. Ferrite was harder than austenite in this steel. Strain hardening of both phases was monotonic during tensile deformation, but the strain hardening exponent of austenite was higher than that of ferrite, indicating the better strain hardenability of austenite. In addition, the strain hardening exponent of austenite increased but that of ferrite remained unchanged with increasing annealing temperature. The overall strain hardening of the steel followed that of austenite. Considering element partitioning by annealing, the stacking fault energy of austenite of the steel was estimated as ∼70 mJ/m2. Even with the relatively high stacking fault energy, planar glide dominantly occurred in austenite. Neither strain induced martensite nor mechanical twins formed in austenite during tensile deformation. Ferrite exhibited the deformed microstructures typically observed in the wavy glide materials, i.e. dislocation cells. The mechanical properties of the present duplex steel were compared to those of advance high

  13. Sex determination by SRY PCR and sequencing of Tasmanian devil facial tumour cell lines reveals non-allograft transmission.

    Cui, Xianlan; Wang, Yunfeng; Hua, Bobby; Miller, Webb; Zhao, Yan; Cui, Hongyu; Kong, Xiangang

    2016-05-20

    Devil facial tumour disease (DFTD) is an infectious tumour disease and was hypothesised to be transmitted by allograft during biting based on two cytogenetic findings of DFTD tumours in 2006. It was then believed that DFTD tumours were originally from a female devil. In this study the devil sex-determining region Y (SRY) gene was PCR amplified and sequenced, and six pairs of devil SRY PCR primers were used for detection of devil SRY gene fragments in purified DFTD tumour cell lines. Using three pairs of devil SRY PCR primers, devil SRY gene sequence was detected by PCR and sequencing in genomic DNA of DFTD tumour cell lines from six male devils, but not from six female devils. Four out of six DFTD tumour cell lines from male devils contained nucleotides 288-482 of the devil SRY gene, and another two DFTD tumour cell lines contained nucleotides 381-577 and 493-708 of the gene, respectively. These results indicate that the different portions of the SRY gene in the DFTD tumours of the male devils were originally from the male hosts, rejecting the currently believed DFTD allograft transmission theory. The reasons why DFTD transmission was incorrectly defined as allograft are discussed. PMID:27084454

  14. Poly(A) code analyses reveal key determinants for tissue-specific mRNA alternative polyadenylation.

    Weng, Lingjie; Li, Yi; Xie, Xiaohui; Shi, Yongsheng

    2016-06-01

    mRNA alternative polyadenylation (APA) is a critical mechanism for post-transcriptional gene regulation and is often regulated in a tissue- and/or developmental stage-specific manner. An ultimate goal for the APA field has been to be able to computationally predict APA profiles under different physiological or pathological conditions. As a first step toward this goal, we have assembled a poly(A) code for predicting tissue-specific poly(A) sites (PASs). Based on a compendium of over 600 features that have known or potential roles in PAS selection, we have generated and refined a machine-learning algorithm using multiple high-throughput sequencing-based data sets of tissue-specific and constitutive PASs. This code can predict tissue-specific PASs with >85% accuracy. Importantly, by analyzing the prediction performance based on different RNA features, we found that PAS context, including the distance between alternative PASs and the relative position of a PAS within the gene, is a key feature for determining the susceptibility of a PAS to tissue-specific regulation. Our poly(A) code provides a useful tool for not only predicting tissue-specific APA regulation, but also for studying its underlying molecular mechanisms. PMID:27095026

  15. Structural features of class I H-2 antigens revealed by anti-peptide antibodies specific for intracytoplasmic determinants

    Rabbit antisera specific for synthetic peptides corresponding to each of the three intracytoplasmic exons (i.e. exons 6, 7 and 8) of the H-2K/sup b/ gene have been prepared and characterized in terms of their reactivity with class I H-2 molecules. Using lentil lectin-purified glycoproteins isolated from 125I-surface-labelled EL-4 (H-2/sup b/) cells, it has been possible to demonstrate that after clearance of the glycoprotein preparation with either anti-mouse β2-microglobulin, or alloantisera directed against H-2K/sup b/ and D/sup b/, there remains a non-β2-microglobulin-associated (i.e. free) class I heavy chain which can be immunoprecipitated by anti-peptide 8 antisera. This free class I heavy chain has the same 2D gel spot pattern as heavy chains from dimeric H-2K/sup b/, suggesting that conformational alterations resulting from the dissociation of β2-microglobulin, rather than chemical changes, are responsible for the loss of the alloantigenic determinants. Evidence has also been obtained indicating that the reaction of dimeric class I molecules with anti-peptide 6 induces the dissociation of β2-microglobulin, suggesting the potential for significant transmembrane conformational perturbations of the external domains as a result of interactions with the intracytoplasmic region

  16. Determination of the physiological 2:2 TLR5:flagellin activation stoichiometry revealed by the activity of a fusion receptor

    Ivičak-Kocjan, Karolina; Panter, Gabriela; Benčina, Mojca [Laboratory of Biotechnology, National Institute of Chemistry, 1000 Ljubljana (Slovenia); The Centre of Excellence EN-FIST, 1000 Ljubljana (Slovenia); Jerala, Roman, E-mail: roman.jerala@ki.si [Laboratory of Biotechnology, National Institute of Chemistry, 1000 Ljubljana (Slovenia); The Centre of Excellence EN-FIST, 1000 Ljubljana (Slovenia); The Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana (Slovenia)

    2013-05-24

    Highlights: •The chimeric protein fusing flagellin to the TLR5 ectodomain is constitutively active. •Mutation P736H within the BB-loop of TLR5 TIR domain renders the receptor inactive. •The R90D mutation in flagellin inactivated autoactivation of the chimeric protein. •The 2:2 stoichiometry of the TLR5:flagellin complex is physiologically relevant. -- Abstract: Toll-like receptor 5 (TLR5) recognizes flagellin of most flagellated bacteria, enabling activation of the MyD88-dependent signaling pathway. The recently published crystal structure of a truncated zebrafish TLR5 ectodomain in complex with an inactive flagellin fragment indicated binding of two flagellin molecules to a TLR5 homodimer, however this complex did not dimerize in solution. In the present study, we aimed to determine the physiological stoichiometry of TLR5:flagellin activation by the use of a chimeric protein composed of an active flagellin fragment linked to the N-terminus of human TLR5 (SF-TLR5). This construct was constitutively active. Inactivation by the R90D mutation within flagellin demonstrated that autoactivation of the chimeric protein depended solely on the specific interaction between TLR5 and flagellin. Addition of wild-type hTLR5 substantially lowered autoactivation of SF-TLR5 in a concentration dependent manner, an effect which was reversible by the addition of exogenous Salmonella typhimurium flagellin, indicating the biological activity of a TLR5:flagellin complex with a 2:2 stoichiometry. These results, in addition to the combinations of inactive P736H mutation within the BB-loop of the TIR domain of TLR5 and SF-TLR5, further confirm the mechanism of TLR5 activation.

  17. Genome-wide mutagenesis of Xanthomonas axonopodis pv. citri reveals novel genetic determinants and regulation mechanisms of biofilm formation.

    Jinyun Li

    determinants and regulatory mechanism of biofilm formation.

  18. Determination of the physiological 2:2 TLR5:flagellin activation stoichiometry revealed by the activity of a fusion receptor

    Highlights: •The chimeric protein fusing flagellin to the TLR5 ectodomain is constitutively active. •Mutation P736H within the BB-loop of TLR5 TIR domain renders the receptor inactive. •The R90D mutation in flagellin inactivated autoactivation of the chimeric protein. •The 2:2 stoichiometry of the TLR5:flagellin complex is physiologically relevant. -- Abstract: Toll-like receptor 5 (TLR5) recognizes flagellin of most flagellated bacteria, enabling activation of the MyD88-dependent signaling pathway. The recently published crystal structure of a truncated zebrafish TLR5 ectodomain in complex with an inactive flagellin fragment indicated binding of two flagellin molecules to a TLR5 homodimer, however this complex did not dimerize in solution. In the present study, we aimed to determine the physiological stoichiometry of TLR5:flagellin activation by the use of a chimeric protein composed of an active flagellin fragment linked to the N-terminus of human TLR5 (SF-TLR5). This construct was constitutively active. Inactivation by the R90D mutation within flagellin demonstrated that autoactivation of the chimeric protein depended solely on the specific interaction between TLR5 and flagellin. Addition of wild-type hTLR5 substantially lowered autoactivation of SF-TLR5 in a concentration dependent manner, an effect which was reversible by the addition of exogenous Salmonella typhimurium flagellin, indicating the biological activity of a TLR5:flagellin complex with a 2:2 stoichiometry. These results, in addition to the combinations of inactive P736H mutation within the BB-loop of the TIR domain of TLR5 and SF-TLR5, further confirm the mechanism of TLR5 activation

  19. Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice.

    Zheng, Xiao; Ma, Sijing; Kang, An; Wu, Mengqiu; Wang, Lin; Wang, Qiong; Wang, Guangji; Hao, Haiping

    2016-01-01

    The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6C(hi) monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6C(hi) monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6C(hi) monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6C(hi) monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6C(hi) monocytes may serve as the target to enable remote intervention on the depressed brain, and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals. PMID:26783261

  20. Cryogenic etching processes applied to porous low-k materials using SF6/C4F8 plasmas

    Leroy, F.; Zhang, L.; Tillocher, T.; Yatsuda, K.; Maekawa, K.; Nishimura, E.; Lefaucheux, P.; de Marneffe, J.-F.; Baklanov, M. R.; Dussart, R.

    2015-11-01

    Cryogenic etching processes in SF6 and SF6/C4F8 plasmas were successfully applied to porous organosilicate glasses. Such materials are low-k candidates for advanced interconnects. Their integration is very challenging because of plasma induced damage. These two chemistries (SF6 and SF6/C4F8) have demonstrated a promising capability of significantly reducing the damage caused by plasma etching. Desorbed species were analyzed during the wafer warm-up from cryogenic to room temperature by in situ mass spectrometry. An equivalent damage layer (EDL) was evaluated by ex situ Fourier transform infrared (FTIR) spectroscopy and in situ ellipsometry. An anneal step at 350 °C seems efficient to completely desorb the remaining CF x species. Anisotropic profiles were obtained using both chemistries. The selectivity is enhanced using SF6/C4F8 process at low temperature.

  1. MCNPX 2.6.C versus MCNPX and ORIGEN-S: state of the art for reactor core management

    This paper discusses the application of the Monte Carlo burnup code MCNPX-2.6.C for the criticality and depletion reactor core analysis of the Material Testing Research Reactor BR2 in Mol, Belgium. A comparison with the combined MCNP and ORIGEN-S fuel depletion method is presented. The accuracy of both methods, the consumption of calculation time, the depletion capabilities, the advantages and disadvantages of use of both methods are discussed. The accuracy of the criticality calculations by MCNPX-2.6.C is still lower in comparison with the validated MCNP and ORIGEN-S method

  2. Graphical linking of MO multicenter bond index and VB structures. II-5-c rings and 6-c heterocyclic rings

    Bollini, C G; Giambiagi, M

    2001-01-01

    Through the graphical method proposed it is possible to set a link between an MO multicenter bond index and VB structures. The value of the index depends on the order of the atoms involved if they are more than three. For 5-c rings three basic structures are required; the eventually different values are 12. Unlike the 6-c case it may happen that different pairs of basic structures are used to build the same polygon. For the 6-c rings including heteroatoms the original degeneracy of benzene splits leading eventually to 60 different I sub r sub i sub n sub g values.

  3. Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia

    Grau, Tanja; Artemyev, Nikolai O; Rosenberg, Thomas; Dollfus, Hélène; Haugen, Olav H; Cumhur Sener, E; Jurklies, Bernhard; Andreasson, Sten; Kernstock, Christoph; Larsen, Michael; Zrenner, Eberhart; Wissinger, Bernd; Kohl, Susanne

    2011-01-01

    characterization of six missense mutations applying the baculovirus system to express recombinant mutant and wildtype chimeric PDE6C/PDE5 proteins in Sf9 insect cells. Purified proteins were analyzed using Western blotting, phosphodiesterase (PDE) activity measurements as well as inhibition assays by zaprinast and...

  4. HEPATOCARCINOGENICITY OF CHLORAL HYDRATE, 2-CHLOROACETALDEHYDE, AND DICHLOROACETIC ACID IN THE MALE B6C3F1 MOUSE

    Chloral hydrate (CH) and 2-chloroacetaldehyde (CAA) have been identified as chlorination by-products in drinking water. oth chemicals are genotoxic, but their carcinogenic potential had not been adequately tested. hese bioassays were conducted using male B6C3F1 mice exposed to 1 ...

  5. Loss of mitogen-activated protein kinase kinase kinase 4 (MAP3K4 reveals a requirement for MAPK signalling in mouse sex determination.

    Debora Bogani

    2009-09-01

    Full Text Available Sex determination in mammals is controlled by the presence or absence of the Y-linked gene SRY. In the developing male (XY gonad, sex-determining region of the Y (SRY protein acts to up-regulate expression of the related gene, SOX9, a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK signalling pathway in mouse sex determination. Using a forward genetic screen, we identified the recessive boygirl (byg mutation. On the C57BL/6J background, embryos homozygous for byg exhibit consistent XY gonadal sex reversal. The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4, a mitogen-activated protein kinase kinase kinase. Analysis of XY byg/byg gonads at 11.5 d post coitum reveals a growth deficit and a failure to support mesonephric cell migration, both early cellular processes normally associated with testis development. Expression analysis of mutant XY gonads at the same stage also reveals a dramatic reduction in Sox9 and, crucially, Sry at the transcript and protein levels. Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. Finally, we provide evidence that haploinsufficiency for Map3k4 accounts for T-associated sex reversal (Tas. These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and

  6. Revealing of Element-Markers to Characterize Deposit and Determine the Belonging of Ore and Metal Good Samples to the Zhezkazgan-Ulytauskii Ancient Mining and Smelting Centre

    Main objectives of the researched activities carried out within the CRP project are development and adaptation of the nuclear-physical methods complex to analyze the wide range of archaeological samples (ores, slag, metal goods etc.). Kazakhstan is situated in the center of Eurasia continent. Kazakhstan's entrails contain the large deposits of minerals, mining and smelling of which are dated back to Bronze Age. The nuclear-physical methods complex is capable to reveal new possible trade ways of Kazakhstan's ore transportation in the Asian market. It allows comprehending the Kazakhstan's mining and smelting centers' role in Middle and Fore Asia paleoeconomy in the Bronze Era. Base of the revealing of trade ways is the assumption: each of ore deposit has own unique element portrait. Hence, the elemental analysis of ore, slag and metal goods geographically corresponding to same ore region is capable of revealing elemental ratios typical for a chosen deposit. Taldysai settlement, geographically connected to one of the major copper deposits in the world, contains the Zhezkazgan-Ulytauskii mining and smelting center, which was chosen as an ancient metallurgical settlement. Within the CRP project ore, slag and metal good samples collected in the place of ancient settlement Taldysai there were determined contents of 42 chemical elements with the complex of nuclear-physical methods including neutron activation analysis and X-ray fluorescent analysis. Using the analytical complex allows both, extending the range of analyzed elements and obtaining more reliable quantitative data. Obtained data in ore, slag and metal good samples contents show some chemical elements considerably exceeing their average contents in the earth's crust. Possibly, these elements may be used as markers to characterize deposits and determine the belonging of ore and metal good samples to the Zhezkazgan-Ulytauskii mining and smelting center. However, to draw more correct and unambiguous conclusions one

  7. The structure of the complex between a branched pentasaccharide and Thermobacillus xylanilyticus GH-51 arabinofuranosidase reveals xylan-binding determinants and induced fit

    Paës, Gabriel; Skov, Lars K; O'Donohue, Michael J; Rémond, Caroline; Kastrup, Jette Sandholm; Gajhede, Michael; Mirza, Osman

    2008-01-01

    The crystal structure of the family GH-51 alpha- l-arabinofuranosidase from Thermobacillus xylanilyticus has been solved as a seleno-methionyl derivative. In addition, the structure of an inactive mutant Glu176Gln is presented in complex with a branched pentasaccharide, a fragment of its natural...... substrate xylan. The overall structure shows the two characteristic GH-51 domains: a catalytic domain that is folded into a (beta/alpha) 8-barrel and a C-terminal domain that displays jelly roll architecture. The pentasaccharide is bound in a groove on the surface of the enzyme, with the mono arabinosyl...... branch entering a tight pocket harboring the catalytic dyad. Detailed analyses of both structures and comparisons with the two previously determined structures from Geobacillus stearothermophilus and Clostridium thermocellum reveal important details unique to the Thermobacillus xylanilyticus enzyme. In...

  8. Structure-Function Analysis of Friedreich's Ataxia Mutants Reveals Determinants of Frataxin Binding and Activation of the Fe-S Assembly Complex

    Bridwell-Rabb, Jennifer; Winn, Andrew M; Barondeau, David P [TAM

    2012-08-01

    Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease associated with the loss of function of the protein frataxin (FXN) that results from low FXN levels due to a GAA triplet repeat expansion or, occasionally, from missense mutations in the FXN gene. Here biochemical and structural properties of FXN variants, including three FRDA missense mutations (N146K, Q148R, and R165C) and three related mutants (N146A, Q148G, and Q153A), were determined in an effort to understand the structural basis for the loss of function. In vitro assays revealed that although the three FRDA missense mutations exhibited similar losses of cysteine desulfurase and Fe-S cluster assembly activities, the causes for these activation defects were distinct. The R165C variant exhibited a kcat/KM higher than that of native FXN but weak binding to the NFS1, ISD11, and ISCU2 (SDU) complex, whereas the Q148R variant exhibited the lowest kcat/KM of the six tested FXN variants and only a modest binding deficiency. The order of the FXN binding affinities for the SDU Fe-S assembly complex was as follows: FXN > Q148R > N146A > Q148G > N146K > Q153A > R165C. Four different classes of FXN variants were identified on the basis of their biochemical properties. Together, these structure-function studies reveal determinants for the binding and allosteric activation of the Fe-S assembly complex and provide insight into how FRDA missense mutations are functionally compromised.

  9. Comparative transcriptome analysis coupled to X-ray CT reveals sucrose supply and growth velocity as major determinants of potato tuber starch biosynthesis

    Goldstein Ralf

    2010-02-01

    Full Text Available Abstract Background Even though the process of potato tuber starch biosynthesis is well understood, mechanisms regulating biosynthesis are still unclear. Transcriptome analysis provides valuable information as to how genes are regulated. Therefore, this work aimed at investigating transcriptional regulation of starch biosynthetic genes in leaves and tubers of potato plants under various conditions. More specifically we looked at gene expression diurnally in leaves and tubers, during tuber induction and in tubers growing at different velocities. To determine velocity of potato tuber growth a new method based on X-ray Computed Tomography (X-ray CT was established. Results Comparative transcriptome analysis between leaves and tubers revealed striking similarities with the same genes being differentially expressed in both tissues. In tubers, oscillation of granule bound starch synthase (GBSS expression was observed which could be linked to sucrose supply from source leaves. X-ray CT was used to determine time-dependent changes in tuber volume and the growth velocity was calculated. Although there is not a linear correlation between growth velocity and expression of starch biosynthetic genes, there are significant differences between growing and non-growing tubers. Co-expression analysis was used to identify transcription factors positively correlating with starch biosynthetic genes possibly regulating starch biosynthesis. Conclusion Most starch biosynthetic enzymes are encoded by gene families. Co-expression analysis revealed that the same members of these gene families are co-regulated in leaves and tubers. This suggests that regulation of transitory and storage starch biosynthesis in leaves and tubers, respectively, is surprisingly similar. X-ray CT can be used to monitor growth and development of belowground organs and allows to link tuber growth to changes in gene expression. Comparative transcriptome analysis provides a useful tool to identify

  10. Quality Assurance Grading Guidelines for Research and Development at DOE Facilities (DOE Order 5700.6C)

    Powell, T.B.

    1992-01-01

    The quality assurance (QA) requirements for the U.S. Department of Energy (DOE) are established in DOE Order 5700.6C. This order is applicable for all DOE departmental elements, management, and maintenance and operating contractors and requires that documented Quality Assurance Programs (QAPs) are prepared at all levels; it has one attachment. The DOE Office of Energy Research (DOE-ER) has issued a standard to ensure implementation of the full intent of this order in the ER community.

  11. Aespoe Task Force on modelling of groundwater flow and transport of solutes. Review of Task 6C

    This report forms part of an independent review of the specifications, execution and results of Task 6 of the Aespoe Task Force on Modelling of Groundwater Flow and Transport of Solutes, which is seeking to provide a bridge between site characterization (SC) and performance assessment (PA) approaches to solute transport in fractured rock. The present report is concerned solely with Task 6C, which relates to the construction and parametrisation of a block-scale hydrostructural model of the TRUE Block Scale region of the Aespoe Hard Rock laboratory. The task objectives, specifications and outcome are summarised and reviewed. Also, consideration is given to how the hydrostructural model might affect the outcomes of Task 6D and 6E. The main conclusions of this review are summarised below: The Task 6C hydrostructural model is a more comprehensive approach to quantitatively describing a volume of fractured rock than has been achieved hitherto. The idea of including solute retention characteristics as indices attached to individual fractures is an efficient device resulting in a whole volume of fractured rock described by a few spreadsheets. The hydrostructural model is clearly defined and provides a useful test bed for Tasks 6D and 6E. It would have been beneficial if the specifications for Task 6C had been more clearly defined as a hierarchy of requirements, and performance measures had been defined and evaluated to allow comparison of alternative approaches. The device used to reduce connectivity, namely reducing the average size of background fractures, has the effect of producing a final model with an 'unnatural' gap in the overall distribution of fracture sizes. It appears that the exploratory boreholes could be important conductive structures within the region of the 200 m block even though they are segmented into shorter sections by packers. If correct, this implies that the boreholes should be included explicitly in the model if close replication of TRUE Block

  12. The Crystal Structure of the Ivy delta4-16:0-ACP Desaturase Reveals Structural Details of the Oxidized Active Site and Potential Determinants of Regioselectivity

    Guy,J.; Whittle, E.; Kumaran, D.; Lindqvist, Y.; Shanklin, J.

    2007-01-01

    The multifunctional acyl-acyl carrier protein (ACP) desaturase from Hedera helix (English ivy) catalyzes the {Delta}{sup 4} desaturation of 16:0-ACP and the{Delta}{sup 9} desaturation of 18:0-ACP and further desaturates{Delta}{sup 9}-16:1 or {Delta}{sup 9}-18:1 to the corresponding {Delta}{sup 4,9} dienes. The crystal structure of the enzyme has been solved to 1.95{angstrom} resolution, and both the iron-iron distance of 3.2{angstrom} and the presence of a {mu}-oxo bridge reveal this to be the only reported structure of a desaturase in the oxidized FeIII-FeIII form. Significant differences are seen between the oxidized active site and the reduced active site of the Ricinus communis (castor) desaturase; His{sup 227} coordination to Fe2 is lost, and the side chain of Glu{sup 224}, which bridges the two iron ions in the reduced structure, does not interact with either iron. Although carboxylate shifts have been observed on oxidation of other diiron proteins, this is the first example of the residue moving beyond the coordination range of both iron ions. Comparison of the ivy and castor structures reveal surface amino acids close to the annulus of the substrate-binding cavity and others lining the lower portion of the cavity that are potential determinants of their distinct substrate specificities. We propose a hypothesis that differences in side chain packing explains the apparent paradox that several residues lining the lower portion of the cavity in the ivy desaturase are bulkier than their equivalents in the castor enzyme despite the necessity for the ivy enzyme to accommodate three more carbons beyond the diiron site.

  13. A gene-rich linkage map in the dioecious species Actinidia chinensis (kiwifruit) reveals putative X/Y sex-determining chromosomes

    Fraser, Lena G; Tsang, Gianna K; Datson, Paul M; De Silva, H Nihal; Harvey, Catherine F; Gill, Geoffrey P; Crowhurst, Ross N; McNeilage, Mark A

    2009-01-01

    Background The genus Actinidia (kiwifruit) consists of woody, scrambling vines, native to China, and only recently propagated as a commercial crop. All species described are dioecious, but the genetic mechanism for sex-determination is unknown, as is the genetic basis for many of the cluster of characteristics making up the unique fruit. It is, however, an important crop in the New Zealand economy, and a classical breeding program would benefit greatly by knowledge of the trait alleles carried by both female and male parents. The application of marker assisted selection (MAS) in seedling populations would also aid the accurate and efficient development of novel fruit types for the market. Results Gene-rich female, male and consensus linkage maps of the diploid species A. chinensis have been constructed with 644 microsatellite markers. The maps consist of twenty-nine linkage groups corresponding to the haploid number n = 29. We found that sex-linked sequence characterized amplified region (SCAR) markers and the 'Flower-sex' phenotype consistently mapped to a single linkage group, in a subtelomeric region, in a section of inconsistent marker order. The region also contained markers of expressed genes, some of unknown function. Recombination, assessed by allelic distribution and marker order stability, was, in the remainder of the linkage group, in accordance with other linkage groups. Fully informative markers to other genes in this linkage group identified the comparative linkage group in the female map, where recombination ratios determining marker order were similar to the autosomes. Conclusion We have created genetic linkage maps that define the 29 linkage groups of the haploid genome, and have revealed the position and extent of the sex-determining locus in A. chinensis. As all Actinidia species are dioecious, we suggest that the sex-determining loci of other Actinidia species will be similar to that region defined in our maps. As the extent of the non

  14. A gene-rich linkage map in the dioecious species Actinidia chinensis (kiwifruit reveals putative X/Y sex-determining chromosomes

    Gill Geoffrey P

    2009-03-01

    Full Text Available Abstract Background The genus Actinidia (kiwifruit consists of woody, scrambling vines, native to China, and only recently propagated as a commercial crop. All species described are dioecious, but the genetic mechanism for sex-determination is unknown, as is the genetic basis for many of the cluster of characteristics making up the unique fruit. It is, however, an important crop in the New Zealand economy, and a classical breeding program would benefit greatly by knowledge of the trait alleles carried by both female and male parents. The application of marker assisted selection (MAS in seedling populations would also aid the accurate and efficient development of novel fruit types for the market. Results Gene-rich female, male and consensus linkage maps of the diploid species A. chinensis have been constructed with 644 microsatellite markers. The maps consist of twenty-nine linkage groups corresponding to the haploid number n = 29. We found that sex-linked sequence characterized amplified region (SCAR markers and the 'Flower-sex' phenotype consistently mapped to a single linkage group, in a subtelomeric region, in a section of inconsistent marker order. The region also contained markers of expressed genes, some of unknown function. Recombination, assessed by allelic distribution and marker order stability, was, in the remainder of the linkage group, in accordance with other linkage groups. Fully informative markers to other genes in this linkage group identified the comparative linkage group in the female map, where recombination ratios determining marker order were similar to the autosomes. Conclusion We have created genetic linkage maps that define the 29 linkage groups of the haploid genome, and have revealed the position and extent of the sex-determining locus in A. chinensis. As all Actinidia species are dioecious, we suggest that the sex-determining loci of other Actinidia species will be similar to that region defined in our maps. As the

  15. Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F1 mouse model

    Serum levels of cardiac troponins serve as biomarkers of myocardial injury. However, troponins are released into the serum only after damage to cardiac tissue has occurred. Here, we report development of a mouse model of doxorubicin (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive biomarkers of early events of cardiac tissue injury. Male B6C3F1 mice were administered intravenous DOX at 3 mg/kg body weight, or an equivalent volume of saline, once a week for 4, 6, 8, 10, 12, and 14 weeks, resulting in cumulative DOX doses of 12, 18, 24, 30, 36, and 42 mg/kg, respectively. Mice were sacrificed a week following the last dose. A significant reduction in body weight gain was observed in mice following exposure to a weekly DOX dose for 1 week and longer compared to saline-treated controls. DOX treatment also resulted in declines in red blood cell count, hemoglobin level, and hematocrit compared to saline-treated controls after the 2nd weekly dose until the 8th and 9th doses, followed by a modest recovery. All DOX-treated mice had significant elevations in cardiac troponin T concentrations in plasma compared to saline-treated controls, indicating cardiac tissue injury. Also, a dose-related increase in the severity of cardiac lesions was seen in mice exposed to 24 mg/kg DOX and higher cumulative doses. Mice treated with cumulative DOX doses of 30 mg/kg and higher showed a significant decline in heart rate, suggesting drug-induced cardiac dysfunction. Altogether, these findings demonstrate the development of DOX-induced chronic cardiotoxicity in B6C3F1 mice. -- Highlights: ► 24 mg/kg was a cumulative cardiotoxic dose of doxorubicin in male B6C3F1 mice. ► Doxorubicin-induced hematological toxicity was in association with splenomegaly. ► Doxorubicin induced severe testicular toxicity in B6C3F1 male mice.

  16. Steindler flexorplasty to restore elbow flexion in C5-C6-C7 brachial plexus palsy type

    Monreal Ricardo

    2007-07-01

    Full Text Available Abstract Background Loss of elbow flexion due to traumatic palsy of the brachial plexus represents a major functional handicap. Then, the first goal in the treatment of the flail arm is to restore the elbow flexion by primary direct nerve surgery or secondary reconstructive surgery. There are various methods to restore elbow flexion which are well documented in the medical literature but the most known and used is Steindler flexorplasty. This review is intended to detail the author's experience with Steindler flexorplasty to restore elbow flexion in patients with brachial plexus palsy C5-C6-C7 where wrist extensors are paralyzed or weakened. Methods We conducted a retrospective follow-up study of 12 patients with absent or extremely weak elbow flexion (motor grade 2 or less, wrist/finger extensor and triceps palsy associated; who had undergone surgical reconstruction of the flail upper limb by tendon transfer (Steindler flexorplasty and wrist arthrodesis to restore elbow flexion. The aetiology of elbow weakness was in all patients brachial plexus palsy (C5-C6-C7 deficit. Data were collected from medical records and from the information obtained during follow-up visits. Age, sex, preoperative strength (rated on a 0 to 5 scale for the flexors of the elbow, wrist flexors, pronator and triceps, previous surgery, length of follow-up, other associated operative procedures, results and complications were recorded. Results The results are the follows: Eleven patients were found to have very good or good function of the transferred muscles. One patient had mild active flexion of the elbow despite the reconstructive procedure. There were no major intraoperative complications. Two patients experienced transient, intermittent nocturnal ulnar paresthesias postoperatively. In both patients these symptoms subsided without further surgery. Conclusion Our study suggests that in patients with C5-C6-C7 palsy where the wrist and finger extensors are paralyzed or

  17. Thalidomide stimulates splenic IgM antibody response and cytotoxic T lymphocyte activity and alters leukocyte subpopulation numbers in female B6C3F1 mice.

    Karrow, N A; McCay, J A; Brown, R D; Musgrove, D L; Pettit, D A; Munson, A E; Germolec, D R; White, K L

    2000-06-15

    Thalidomide has been shown to have antiinflammatory and, more recently, immunomodulating properties, which are beneficial for the treatment of an ever-increasing list of immune related diseases. Although considerable knowledge regarding thalidomide s antiinflammatory properties has been acquired, relatively little is known about its immunomodulating properties in vivo. In this paper, a panel of immune assays was used to evaluate immunomodulation in female B6C3F1 mice treated intraperitoneally for 28 days with thalidomide (30, 100, or 150 mg/kg/day). Spleen antibody forming cell response was significantly enhanced by 37% in mice treated with 150 mg/kg/day, despite an 8% decrease in the percentage of Ig+ B cells. A significant stimulatory trend was observed for the cytotoxic T cell response across thalidomide treatment groups. An evaluation of the spleen leukocyte subpopulations revealed a 23% increase in the absolute number of CD8+ T cells in the 150 mg/kg treatment group and a 9 and 11% decrease in the absolute number of NK cells in both the 100 and 150 mg/kg thalidomide treatment groups, respectively. These findings demonstrate that, in addition to modulating spleen leukocyte numbers, thalidomide also stimulates murine humoral and cellular immune responses in vivo. PMID:10873712

  18. Mechanisms of carborane 1,6-C2B4H6 high-temperature oxidation in water vapor

    The reactivity of carborane-4 (1,6-C2B4H6) in water vapor at 930-1750 K and 0.02-3.0 MPa is experimentally studied. It is found that carborane-4 is a highly reactive compound: at P = 0.9 MPa and T > 1200 K its reactivity in water vapor exceeds that of propane in air by a factor of 3 to 7. The ignition delay for carborane-4/water vapor mixture decreases with the increasing pressure at T > 1200 K, but is pressure independent at T < 1000 K. It is shown that the ignition delays computed within the proposed detailed oxidation scheme for carborane-4 describe satisfactorily the experimental data in the entire range of the investigated temperatures and pressures

  19. Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility.

    Yen Ling Low

    2010-07-01

    Full Text Available Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway, polymorphisms within the pathway have not been consistently associated with these cancers. We posit that this is due to the complexity of multiple weak genetic effects within the metabolic pathway that can only be effectively detected through multi-variant analysis. We conducted a comprehensive association analysis of the estrogen metabolic pathway by interrogating 239 tagSNPs within 35 genes of the pathway in three tumor samples. The discovery sample consisted of 1,596 breast cancer cases, 719 endometrial cancer cases, and 1,730 controls from Sweden; and the validation sample included 2,245 breast cancer cases and 1,287 controls from Finland. We performed admixture maximum likelihood (AML-based global tests to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three sub-pathways for androgen synthesis, androgen-to-estrogen conversion, and estrogen removal. In the discovery sample, although no single polymorphism was significant after correction for multiple testing, the pathway-based AML global test suggested association with both breast (p(global = 0.034 and endometrial (p(global = 0.052 cancers. Further testing revealed the association to be focused on polymorphisms within the androgen-to-estrogen conversion sub-pathway, for both breast (p(global = 0.008 and endometrial cancer (p(global = 0.014. The sub-pathway association was validated in the Finnish sample of breast cancer (p(global = 0.015. Further tumor subtype analysis demonstrated that the association of the androgen-to-estrogen conversion sub-pathway was confined to postmenopausal women with sporadic estrogen receptor positive tumors (p(global = 0.0003. Gene-based AML analysis suggested CYP19A1 and UGT2B4 to be the major players within the sub-pathway. Our study indicates that the composite

  20. The cooling capabilities of C2F6/C3F8 saturated fluorocarbon blends for the ATLAS silicon tracker

    We investigate and address the performance limitations of the ATLAS silicon tracker fluorocarbon evaporative cooling system operation in the cooling circuits of the barrel silicon microstrip (SCT) sub-detector. In these circuits the minimum achievable evaporation temperatures with C3F8 were higher than the original specification, and were thought to allow an insufficient safety margin against thermal runaway in detector modules subject to a radiation dose initially foreseen for 10 years operation at LHC. We have investigated the cooling capabilities of blends of C3F8 with molar admixtures of up to 25% C2F6, since the addition of the more volatile C2F6 component was expected to allow a lower evaporation temperature for the same evaporation pressure.A custom built recirculator allowed the in-situ preparation of C2F6/C3F8 blends. These were circulated through a representative mechanical and thermal setup reproducing an as-installed ATLAS SCT barrel tracker cooling circuit. Blend molar compositions were verified to a precision of 3.10−3 in a custom ultrasonic instrument.Thermal measurements in a range of C2F6/C3F8 blends were compared with measurements in pure C3F8. These indicated that a blend with 25% C2F6 would allow a reduction in evaporation temperature of around 9oC to below -15oC, even at the highest module power dissipations envisioned after 10 years operation at LHC. Such a reduction would allow more than a factor two in safety margin against temperature dependant leakage power induced thermal runaway.Furthermore, a blend containing up to 25% C2F6 could be circulated without changes to the on-detector elements of the existing ATLAS inner detector evaporative cooling system

  1. Do vehicular emissions dominate the source of C6-C8 aromatics in the megacity Shanghai of eastern China?

    Hongli Wang; Qian Wang; Jianmin Chen; Changhong Chen; Cheng Huang; Liping Qiao; Shengrong Lou

    2015-01-01

    The characteristic ratios of volatile organic compounds (VOCs) to i-pentane,the indicator of vehicular emissions,were employed to apportion the vehicular and non-vehicular contributions to reactive species in urban Shanghai.Two kinds of tunnel experiments,one tunnel with more than 90% light duty gasoline vehicles and the other with more than 60% light duty diesel vehicles,were carried out to study the characteristic ratios of vehicle-related emissions from December 2009 to January 2010.Based on the experiments,the characteristic ratios of C6-C8 aromatics to i-pentane of vehicular emissions were 0.53 ± 0.08 (benzene),0.70 ± 0.12 (toluene),0.41 ± 0.09 (m,p-xylenes),0.16 ± 0.04 (o-xylene),0.023 ± 0.011 (styrene),and 0.15 ± 0.02 (ethylbenzene),respectively.The source apportionment results showed that around 23.3% of C6-C8 aromatics in urban Shanghai were from vehicular emissions,which meant that the non-vehicular emissions had more importance.These findings suggested that emission control of non-vehicular sources,i.e.industrial emissions,should also receive attention in addition to the control of vehicle-related emissions in Shanghai.The chemical removal of VOCs during the transport from emissions to the receptor site had a large impact on the apportionment results.Generally,the overestimation of vehicular contributions would occur when the VOC reaction rate constant with OH radicals (kOH) was larger than that of the vehicular indicator,while for species with smaller kOH than the vehicular indicator,the vehicular contribution would be underestimated by the method of characteristic ratios.

  2. Immunomodulatory effects of black cohosh (Actaea racemosa) extract in female B6C3F1/N mice

    Black cohosh extracts (BCE; Actaea racemosa) are being used worldwide as an alternative to hormone replacement therapy for the management of menstrual and menopausal symptoms, yet the effects of BCE on the immune system are largely unknown. Female B6C3F1/N mice were treated daily with BCE (0, 62.5, 125, 250, 500, or 1000 mg/kg) for 28 days by oral gavage. Liver weights were significantly increased (26–32%) at the 1000 mg/kg dose. Dose-related increases in mean corpuscular volume and mean corpuscular hemoglobin were observed. Decreasing trends were observed in all thymic T cell populations, with the most notable dose-responsive effects on immature thymocytes. In the spleen, dose-related decreases were observed in all cell phenotypes evaluated, reaching the level of statistical significance at the 1000 mg/kg BCE dose. Splenic natural killer (NK) cell numbers were significantly decreased at all BCE doses, with the exception of absolute NK numbers at the 125 mg/kg dose. No effects were observed on T-dependent antibody responses of the humoral immune system, including the antibody-forming cell response to sheep erythrocytes (sRBC) and IgM antibody levels to both sRBC and keyhole limpet hemocyanin. Cytotoxic T cell (TCTL) activity was increased, as was the mixed leukocyte response in one of two studies. Anti-CD3 mediated proliferation and the delayed-type hypersensitivity response were unaffected. No effects were observed on innate immunity or on bone marrow cellularity and colony-forming units. Overall, BCE exposure in B6C3F1/N mice for 28 days at doses up to 1000 mg/kg had minimal immune effects, with the exception of an increased TCTL response

  3. Genotoxicity of malachite green and leucomalachite green in female Big Blue B6C3F1 mice.

    Mittelstaedt, Roberta A; Mei, Nan; Webb, Peggy J; Shaddock, Joseph G; Dobrovolsky, Vasily N; McGarrity, Lynda J; Morris, Suzanne M; Chen, Tao; Beland, Frederick A; Greenlees, Kevin J; Heflich, Robert H

    2004-07-11

    Malachite green, a triphenylmethane dye used in aquaculture as an antifungal agent, is rapidly reduced in vivo to leucomalachite green. Previous studies in which female B6C3F1 mice were fed malachite green produced relatively high levels of liver DNA adducts after 28 days, but no significant induction of liver tumors was detected in a 2-year feeding study. Comparable experiments conducted with leucomalachite green resulted in relatively low levels of liver DNA adducts but a dose-responsive induction of liver tumors. In the present study, we fed transgenic female Big Blue B6C3F1 mice with 450 ppm malachite green and 204 and 408 ppm leucomalachite green (the high doses used in the tumor bioassays) and evaluated genotoxicity after 4 and 16 weeks of treatment. Neither malachite green nor leucomalachite green increased the peripheral blood micronucleus frequency or Hprt lymphocyte mutant frequency at either time point; however, the 16-week treatment with 408 ppm leucomalachite green did increase the liver cII mutant frequency. Similar increases in liver cII mutant frequency were not seen in the mice treated for 16 weeks with malachite green or in female Big Blue rats treated with a comparable dose of leucomalachite green for 16 weeks in a previous study [Mutat. Res. 547 (2004) 5]. These results indicate that leucomalachite green is an in vivo mutagen in transgenic female mouse liver and that the mutagenicities of malachite green and leucomalachite green correlate with their tumorigenicities in mice and rats. The lack of increased micronucleus frequencies and lymphocyte Hprt mutants in female mice treated with leucomalachite green suggests that its genotoxicity is targeted to the tissue at risk for tumor induction. PMID:15238237

  4. Ly6C(hi) Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis.

    Möhle, Luisa; Mattei, Daniele; Heimesaat, Markus M; Bereswill, Stefan; Fischer, André; Alutis, Marie; French, Timothy; Hambardzumyan, Dolores; Matzinger, Polly; Dunay, Ildiko R; Wolf, Susanne A

    2016-05-31

    Antibiotics, though remarkably useful, can also cause certain adverse effects. We detected that treatment of adult mice with antibiotics decreases hippocampal neurogenesis and memory retention. Reconstitution with normal gut flora (SPF) did not completely reverse the deficits in neurogenesis unless the mice also had access to a running wheel or received probiotics. In parallel to an increase in neurogenesis and memory retention, both SPF-reconstituted mice that ran and mice supplemented with probiotics exhibited higher numbers of Ly6C(hi) monocytes in the brain than antibiotic-treated mice. Elimination of Ly6C(hi) monocytes by antibody depletion or the use of knockout mice resulted in decreased neurogenesis, whereas adoptive transfer of Ly6C(hi) monocytes rescued neurogenesis after antibiotic treatment. We propose that the rescue of neurogenesis and behavior deficits in antibiotic-treated mice by exercise and probiotics is partially mediated by Ly6C(hi) monocytes. PMID:27210745

  5. Toxicity and carcinogenicity studies of Caramel Colour IV in F344 rats and B6C3F1 mice.

    MacKenzie, K M; Boysen, B G; Field, W E; Petsel, S R; Chappel, C I; Emerson, J L; Stanley, J

    1992-05-01

    Caramel Colour IV, a type of caramel colour used in the manufacture of cola soft drinks, was evaluated for subchronic and chronic toxicity in rats, and carcinogenicity in Fischer-344 (F344) rats and B6C3F1 mice. In each of the studies, Caramel Colour IV was mixed with demineralized water and the solutions given to the animals ad lib. in the drinking fluid. The concentrations of Caramel Colour IV in the drinking fluid were adjusted periodically to achieve the desired caramel colour intake per kg body weight. In the range-finding studies, groups of 30 rats/sex were given Caramel Colour IV at levels of 0, 15, 20, 25 or 30 g/kg for 13 wk, and groups of 10 male rats were given levels of 0, 2.5, 5, 10 or 15 g/kg for 6 wk followed, for some dose groups, by a 2-wk withdrawal period, and then re-initiation of dosing for another 2 wk. In the rat chronic toxicity study, levels of Caramel Colour IV of 0, 2.5, 5, 7.5 or 10 g/kg were given to groups of 25 rats/sex for 12 months. The test groups in the rat and mouse carcinogenicity studies were composed of 50 animals/sex and each species was given the caramel colour at levels of 0, 0, 2.5, 5 or 10 g/kg for 24 months. In each of the studies, treated animals tended to have dose-related lower water consumption than controls. This was attributed to poor palatability of the drinking fluid, and was generally associated with decreased food consumption and body weights. Rats given caramel colour often had soft or liquid malodorous faeces although there were no treatment-related ante-mortem observations in mice. Blood biochemical changes in the rat (i.e. reduced blood urea nitrogen, alkaline phosphatase and total serum protein) appeared to be related to dietary influences and were not considered toxicologically significant. There were no treatment-related alterations in haematological variables or treatment-related differences in survival or in the incidence of benign or malignant tumours among treated and control groups and no

  6. Structure, phase transitions and molecular motions in ferroelastic (C4H8NH2)SbCl6.(C4H8NH2)Cl

    Bednarska-Bolek, B.; Jakubas, R.; Medycki, W.; Nowak, D.; Zaleski, J.

    2002-04-01

    The crystal structure at 293 K of the new pyrrolidinium chloroantimonate (V) analogue, (C4H8NH2)SbCl6.(C4H8NH2)Cl, has been determined by x-ray diffraction as monoclinic, space group P21/c, Z = 8. The crystal is built up of isolated SbCl6- anions, two types of inequivalent pyrrolidinium cation and isolated Cl- ions. It undergoes five solid-solid phase transitions: at 351/374 K of first-order type (cooling/heating, respectively), at 356 and 152 K second order and at 135/141 and 105/134 K first order, detected by differential scanning calorimetry, dilatometric and dielectric measurements. The ferroelastic domain structure appears between 152 and 135 K. The proton nuclear magnetic resonance second moment and spin-lattice relaxation time of polycrystalline samples were studied over the temperature range 27-410 K. The order-disorder mechanism of the phase transitions at 105 and 374 K connected with the reorientational motion of the pyrrolidinium cations has been confirmed.

  7. The impact of pneumococcal conjugate vaccines on carriage of and disease caused by Streptococcus pneumoniae serotypes 6C and 6D in southern Israel.

    Porat, Nurith; Benisty, Rachel; Givon-Lavi, Noga; Trefler, Ronit; Dagan, Ron

    2016-05-27

    The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) followed by PCV13 resulted in a dramatic reduction in carriage and disease rates of Streptococcus pneumoniae (Sp) serotype 6B (Sp6B) and Sp6A. The structural modifications of the capsule of Sp6A and Sp6B to become Sp6C and Sp6D, respectively, raised a concern that eradication of Sp6A/Sp6B by PCV could be accompanied by an increase in Sp6C/Sp6D. This study examines the dynamics and clonal distribution of Sp6C/Sp6D relative to Sp6A/Sp6B during 1999-2014, pre- and post-PCV implementation. Sp were cultured from Blood/CSF and MEF of children pneumococcal disease, complete elimination of serogroup 6 was found in the PCV era. Similar clonal composition was found for Sp6C and Sp6D pre- and post-PCV. We conclude that Sp6C and Sp6D do not act as replacement serotypes for Sp6A and Sp6B following vaccination with PCV13. The major Sp6C and Sp6D clones present pre-PCV persisted also post-PCV implementation, suggesting that these clones possess an advantage retained post-vaccination. PMID:27113163

  8. Coherent Structure in Solar Wind C$^{6+}$/C$^{4+}$ Ionic Composition Data During the Quiet-Sun Conditions of 2008

    Edmondson, J K; Lepri, S T; Zurbuchen, T H

    2013-01-01

    This analysis offers evidence of characteristic scale sizes in solar wind charge state data measured in-situ for thirteen quiet-sun Carrington rotations in 2008. Using a previously established novel methodology, we analyze the wavelet power spectrum of the charge state ratio C$^{6+}$/C$^{4+}$ measured in-situ by ACE/SWICS for 2-hour and 12-minute cadence. We construct a statistical significance level in the wavelet power spectrum to quantify the interference effects arising from filling missing data in the time series (Edmondson et al. 2013), allowing extraction of significant power from the measured data to a resolution of 24 mins. We analyze each wavelet power spectra for transient coherency, and global periodicities resulting from the superposition of repeating coherent structures. From the significant wavelet power spectra, we find evidence for a general upper-limit on individual transient coherency of $\\sim$10 days. We find evidence for a set of global periodicities between 4-5 hours and 35-45 days. We f...

  9. Nasal dosimetry of inspired naphthalene vapor in the male and female B6C3F1 mouse

    Naphthalene vapor is a nasal cytotoxicant in the rat and mouse but is a nasal carcinogen in only the rat. Inhalation dosimetry is a critical aspect of the inhalation toxicology of inspired vapors and may contribute to the species differences in the nasal response. To define the nasal dosimetry of naphthalene in the B6C3F1 male and female mouse, uptake of naphthalene vapor was measured in the surgically isolated upper respiratory tract (URT) at inspiratory flow rates of 25 or 50 ml/min. Uptake was measured at multiple concentrations (0.5, 3, 10, 30 ppm) in controls and mice treated with the cytochrome P450 inhibitor 5-phenyl-1-pentyne. In both sexes, URT uptake efficiency was strongly concentration dependent averaging 90% at 0.5 ppm compared to 50% at 30 ppm (25 ml/min flow rate), indicating saturable processes were involved. Both uptake efficiency and the concentration dependence of uptake were significantly diminished by 5-phenyl-1-pentyne indicating inspired naphthalene vapor is extensively metabolized in the mouse nose with saturation of metabolism occurring at the higher concentrations. A hybrid computational fluid dynamic physiologically based pharmacokinetic model was developed for nasal dosimetry. This model accurately predicted the observed URT uptake efficiencies. Overall, the high URT uptake efficiency of naphthalene in the mouse nose indicates the absence of a tumorigenic response is not attributable to low delivered dose rates in this species

  10. Mathematics revealed

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  11. Revealed Attention

    Masatlioglu, Yusufcan; NAKAJIMA, Daisuke; Ozbay, Erkut Y

    2012-01-01

    The standard revealed preference argument relies on an implicit assumption that a decision maker considers all feasible alternatives. The marketing and psychology literatures, however, provide wellestablished evidence that consumers do not consider all brands in a given market before making a purchase (Limited Attention). In this paper, we illustrate how one can deduce both the decision maker's preference and the alternatives to which she pays attention and inattention from the observed behav...

  12. Revealed Attention

    Yusufcan Masatlioglu; Daisuke Nakajima; Ozbay, Erkut Y

    2012-01-01

    The standard revealed preference argument relies on an implicit assumption that a decision maker considers all feasible alternatives. The marketing and psychology literatures, however, provide well-established evidence that consumers do not consider all brands in a given market before making a purchase (Limited Attention). In this paper, we illustrate how one can deduce both the decision maker's preference and the alternatives to which she pays attention and inattention from the observed beha...

  13. Characterization of uterine granular cell tumors in B6C3F1 mice: a histomorphologic, immunohistochemical, and ultrastructural study.

    Veit, A C; Painter, J T; Miller, R A; Hardisty, J F; Dixon, D

    2008-09-01

    The granular cell tumor is most often a benign neoplasm of uncertain origin. Four uterine granular cell tumors in control and treated female B6C3F1 mice were identified in chronic studies at the National Toxicology Program. Two tumors occurred in untreated control animals and 2 in treated animals receiving different compounds. Tissue sections were evaluated histologically and stained with hematoxylin and eosin, periodic acid-Schiff with diastase resistance, Masson's trichrome, toluidine blue, phosphotungstic acid-hematoxylin, and stained immunohistochemically with a panel of antibodies to muscle (desmin, alpha smooth muscle actin), neural (S-100, neuron specific enolase), epithelial (wide-spectrum cytokeratin), and macrophage (F4/80) markers. The main histomorphologic feature of tumor cells was the presence of abundant cytoplasmic eosinophilic granules that stained positive for periodic acid-Schiff with diastase resistance. Tumors varied in appearance and were comprised of sheets and nests of round to polygonal cells with distinct borders. Nuclei were hyperchromatic, pleomorphic, and centrally to eccentrically located and often contained single nucleoli. Occasional multinucleated giant cells were observed. Tumors were pale pink and homogeneous with trichrome stain and negative with toluidine blue. Three tumors had positive to weakly positive immunoreactivity for desmin, and 1 was positive for alpha smooth muscle actin. Expression of S-100, wide-spectrum cytokeratin, and neuron-specific enolase was negative for all tumors. Ultrastructurally, prominent electron-dense cytoplasmic granules were abundant and contained secondary lysosomes with heterogeneous lysosomal contents. The characteristics of these uterine granular cell tumors were suggestive of a myogenic origin. PMID:18725470

  14. Trichloroethylene-induced gene expression and DNA methylation changes in B6C3F1 mouse liver.

    Yan Jiang

    Full Text Available Trichloroethylene (TCE, widely used as an organic solvent in the industry, is a common contaminant in air, soil, and water. Chronic TCE exposure induced hepatocellular carcinoma in mice, and occupational exposure in humans was suggested to be associated with liver cancer. To understand the role of non-genotoxic mechanism(s for TCE action, we examined the gene expression and DNA methylation changes in the liver of B6C3F1 mice orally administered with TCE (0, 100, 500 and 1000 mg/kg b.w. per day for 5 days. After 5 days TCE treatment at a dose level of 1000 mg/kg b.w., a total of 431 differentially expressed genes were identified in mouse liver by microarray, of which 291 were up-regulated and 140 down-regulated. The expression changed genes were involved in key signal pathways including PPAR, proliferation, apoptosis and homologous recombination. Notably, the expression level of a number of vital genes involved in the regulation of DNA methylation, such as Utrf1, Tet2, DNMT1, DNMT3a and DNMT3b, were dysregulated. Although global DNA methylation change was not detected in the liver of mice exposed to TCE, the promoter regions of Cdkn1a and Ihh were found to be hypo- and hypermethylated respectively, which correlated negatively with their mRNA expression changes. Furthermore, the gene expression and DNA methylation changes induced by TCE were dose dependent. The overall data indicate that TCE exposure leads to aberrant DNA methylation changes, which might alter the expression of genes involved in the TCE-induced liver tumorgenesis.

  15. Effect of atomic sites on electronic and mechanical properties of (Fe,Mo){sub 6}C carbides

    Lv, Z.Q., E-mail: zqlv@ysu.edu.cn [State Key Laboratory of Metastable Material Science and Technology, Yanshan University, Qinhuangdao 066004 (China); College of Mechanical Engineering, Yanshan University, Qinhuangdao 066004 (China); Wang, B. [State Key Laboratory of Metastable Material Science and Technology, Yanshan University, Qinhuangdao 066004 (China); Sun, S.H. [College of Science, Yanshan University, Qinhuangdao 066004 (China); Fu, W.T., E-mail: wtfu@ysu.edu.cn [State Key Laboratory of Metastable Material Science and Technology, Yanshan University, Qinhuangdao 066004 (China)

    2015-11-15

    The phase stability of Fe{sub 3}Mo{sub 3}C-II (Mo at the 48f site) is higher than other phases in the present work. The formation enthalpies of Fe{sub 3}Mo{sub 3}C-II and Fe{sub 2}Mo{sub 4}C are −0.095 and −0.053 eV/atom, respectively. The 16d and 32e sites are comfortable for Fe atoms, and the Mo atoms tend to be at the 48f sites. The electronic characteristics of metal atoms are sensitive to the local short-range order in these crystals. Moreover, the nonmetal C atom is with negative charges (obtaining electrons), and this electronegative phenomenon is also present in some metal atoms (Fe or Mo) in M{sub 6}C. The hardness of Fe{sub 3}Mo{sub 3}C (13.6 GPa) is the highest in these phases, and the hardness of Fe{sub 2}Mo{sub 4}C is 11.7 GPa. The θ{sub D} of Fe{sub 3}Mo{sub 3}C-I (Fe at the 48f site) is 397 K, and that of Fe{sub 3}Mo{sub 3}C-II abruptly changes to 657 K when Mo in the 48f site. - Highlights: • The electronic characteristics of metal atoms are sensitive to the local short-range order in the crystal. • Besides C atom with negative charges, partial metal atoms exist the electronegative phenomenon. • The hardness of Fe{sub 3}Mo{sub 3}C (13.6 GPa) is the highest and Fe{sub 2}Mo{sub 4}C (11.7 GPa) is the second hardest.

  16. Determination of 5 '-leader sequences from radically disparate strains of porcine reproductive and respiratory syndrome virus reveals the presence of highly conserved sequence motifs

    Oleksiewicz, M.B.; Bøtner, Anette; Nielsen, Jens; Storgaard, Torben

    1999-01-01

    We determined the untranslated 5'-leader sequence for three different isolates of porcine reproductive and respiratory syndrome virus (PRRSV): pathogenic European- and American-types, as well as an American-type vaccine strain. 5'-leader from European- and American-type PRRSV differed in length...

  17. Evaluation of gravity field model EIGEN-6C4 by means of various functions of gravity potential, and by GNSS/levelling

    Jan Kostelecký

    2015-06-01

    Full Text Available The combined gravity field model EIGEN-6C4 (Förste et al., 2014 is the latest combined global gravity field model of GFZ Potsdam and GRGS Toulouse. EIGEN-6C4 has been generated including the satellite gravity gradiometry data of the entire GOCE mission (November 2009 till October 2013 and is of maximum spherical degree and order 2190. In this study EIGEN-6C4 has been compared with EGM2008 to its maximum degree and order via gravity disturbances and Tzz part of the Marussi tensor of the second derivatives of the disturbing potential. The emphasis is put on such areas where GOCE data (complete set of gradiometry measurements after reductions in EIGEN-6C4 obviously contributes to an improvement of the gravity field description. GNSS/levelling geoid heights are independent data source for the evaluation of gravity field models. Therefore, we use the GNSS/levelling data sets over the territories of Europe, Czech Republic and Slovakia for the evaluation of EIGEN-6C4 w.r.t. EGM2008.

  18. Aspirin revealed

    Lacey, D.; Hu, X. K.; Loboda, A. V.; Mosey, N. J.; Lipson, R. H.

    2007-03-01

    Experiments are described where the experimental conditions have been optimized to detect aspirin by MALDI mass spectrometry. Although protonated aspirin was not observed by MALDI, sodium and potassium aspirin adducts could be found. Significantly better signals could be obtained by using Rb and Cs salts as cationization sources. Quantum calculations were carried out to determine the structure and energetics of the Li, K, Rb, and Cs alkali--aspirin adducts.

  19. Efficient polymer light-emit ting diodes with violet blue emission based on blends of PSiF6-PPP and PSiFC6C6

    TIAN Renyu; MO Yueqi; PENG Junbiao

    2006-01-01

    Efficient polymer light-emitting diodes (PLEDs) with violet blue emission were fabricated using blends of copolymers of paraphenylene-cosilafluorene (PSiF6-PPP) and polymer of poly (9,9'alkyl-3,6-silafluorene) (PSiFC6C6). The performances of the devices are sensitive to the blend ratio.When the mass ratio of PSiF6-PPP to PSiFC6C6 is 1.96% at luminance of 105 cd.m-2, its electroluminescent (EL) spectrum peaks at 398 nm and full width at half maximum is 67 nm. The improvements of the device performances were due to the energy transfer from PSiFC6C6 to PSiF6-PPP and the balanced injection of electrons and holes.

  20. Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117 overexpression exhibits potential therapeutic implications

    Potti Anil

    2003-01-01

    Full Text Available Abstract Background HER-2/neu and c-kit (CD117 onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. Methods Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. Results Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46% with malignant melanoma were studied with a mean age of 57 years (age range: 15–101 years. The most common histologic type was amelanotic melanoma (n = 62; 30.7% followed by superficial spreading melanoma (n = 54; 26.7%. The depth of penetration of melanoma (Breslow thickness, pT Stage ranged from 0.4 mm (stage pT1 to 8.0 mm (stage pT4A. Mean thickness was 2.6 mm (stage pT3A. The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9% revealed HER-2/neu overexpression, whereas 46 (22.8% revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36. Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. Conclusions The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a

  1. CD11b+Ly6C++Ly6G- cells show distinct function in mice with chronic inflammation or tumor burden

    Källberg Eva

    2012-12-01

    Full Text Available Abstract Background S100A9 has been shown to be important for the function of so called Myeloid Derived Suppressor Cells (MDSC. Cells with a similar phenotype are also involved in pro-inflammatory processes, and we therefore wanted to investigate the gene expression and function of these cells in animals that were either subjected to chronic inflammation, or inoculated with tumors. Methods CD11b+Ly6C++ and Ly6G+ cells were isolated from spleen, tumor tissue or inflammatory granulomas. S100A9, Arginase 1 and iNOS gene expression in the various CD11b+ cell populations was analyzed using Q-PCR. The suppressive activity of the CD11b+ cell populations from different donors was studied in co-culture experiments. Results S100A9 was shown to be expressed mainly in splenic CD11b+Ly6C+G+ cells both at the RNA and protein level. Arginase I and iNOS expression could be detected in both CD11b+Ly6C+Ly6G+ and CD11b+Ly6C+G-/C++G- derived from tumors or a site of chronic inflammation, but was very low in the same cell populations isolated from the spleen. CD11b+ cells isolated from mice with peritoneal chronic inflammation were able to stimulate T lymphocytes, while CD11b+ cells from mice with peritoneal tumors suppressed T cell growth. Conclusion An identical CD11b+Ly6C++G- cell population appears to have the ability to adopt immune stimulatory or immune suppressive functions dependent on the presence of a local inflammatory or tumor microenvironment. Thus, there is a functional plasticity in the CD11b+Ly6C++G- cell population that cannot be distinguished with the current molecular markers.

  2. Identification of a human ABCC10 orthologue in Catharanthus roseus reveals a U12-type intron determinant for the N-terminal domain feature.

    El-Guizani, Taissir; Guibert, Clotilde; Triki, Saida; St-Pierre, Benoit; Ducos, Eric

    2014-04-01

    ABC (ATP-binding cassette) transporters are members of a large superfamily of proteins that utilize ATP hydrolysis to translocate a wide range of substrates across biological membranes. In general, members of C subfamily (ABCC) are structurally characterized by an additional (N-terminal) transmembrane domain (TMD0). Phylogenetic analysis of plant ABCCs separates their protein sequences into three distinct clusters: I and II are plant specific whereas cluster III contains both human and plant ABCCs. Screening of the Plant Medicinal Genomics Resource database allowed us to identify 16 ABCCs partial sequences in Catharanthus roseus; two of which belong to the unique CrABCC1 transcript that we identified in cluster III. Genomic organization of CrABCC1 TMD0 coding sequence displays an AT-AC U12-type intron that is conserved in higher plant orthologues. We showed that CrABCC1, like its human orthologue ABCC10, produces alternative transcripts that encode protein sequences with a truncated form of TMD0 without the first transmembrane span (TM1). Subcellular localization of CrABCC1 TMD0 variants using yellow fluorescent protein fusions reveals that the TM1 is required for a correct routing of the TMD0 to the tonoplast. Finally, the specific repartition of CrABCC1 orthologues in some species suggests that this gene was lost several times during evolution and that its physiological function may, rely on a common feature of multicellular eukaryotes. PMID:24840820

  3. Identification of a human ABCC10 orthologue in Catharanthus roseus reveals a U12-type intron determinant for the N-terminal domain feature

    Taissir El-Guizani; Clotilde Guibert; Saïda Triki; Benoit St-Pierre; Eric Ducos

    2014-04-01

    ABC (ATP-binding cassette) transporters are members of a large superfamily of proteins that utilize ATP hydrolysis to translocate a wide range of substrates across biological membranes. In general, members of C subfamily (ABCC) are structurally characterized by an additional (N-terminal) transmembrane domain (TMD0). Phylogenetic analysis of plant ABCCs separates their protein sequences into three distinct clusters: I and II are plant specific whereas cluster III contains both human and plant ABCCs. Screening of the Plant Medicinal Genomics Resource database allowed us to identify 16 ABCCs partial sequences in Catharanthus roseus; two of which belong to the unique CrABCC1 transcript that we identified in cluster III. Genomic organization of CrABCC1 TMD0 coding sequence displays an AT-AC U12-type intron that is conserved in higher plant orthologues. We showed that CrABCC1, like its human orthologue ABCC10, produces alternative transcripts that encode protein sequences with a truncated form of TMD0 without the first transmembrane span (TM1). Subcellular localization of CrABCC1 TMD0 variants using yellow fluorescent protein fusions reveals that the TM1 is required for a correct routing of the TMD0 to the tonoplast. Finally, the specific repartition of CrABCC1 orthologues in some species suggests that this gene was lost several times during evolution and that its physiological function may, rely on a common feature of multicellular eukaryotes.

  4. Revealing Rembrandt

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  5. Interrogation of the protein-protein interactions between human BRCA2 BRC repeats and RAD51 reveals atomistic determinants of affinity.

    Cole, Daniel J; Rajendra, Eeson; Roberts-Thomson, Meredith; Hardwick, Bryn; McKenzie, Grahame J; Payne, Mike C; Venkitaraman, Ashok R; Skylaris, Chris-Kriton

    2011-07-01

    The breast cancer suppressor BRCA2 controls the recombinase RAD51 in the reactions that mediate homologous DNA recombination, an essential cellular process required for the error-free repair of DNA double-stranded breaks. The primary mode of interaction between BRCA2 and RAD51 is through the BRC repeats, which are ∼35 residue peptide motifs that interact directly with RAD51 in vitro. Human BRCA2, like its mammalian orthologues, contains 8 BRC repeats whose sequence and spacing are evolutionarily conserved. Despite their sequence conservation, there is evidence that the different human BRC repeats have distinct capacities to bind RAD51. A previously published crystal structure reports the structural basis of the interaction between human BRC4 and the catalytic core domain of RAD51. However, no structural information is available regarding the binding of the remaining seven BRC repeats to RAD51, nor is it known why the BRC repeats show marked variation in binding affinity to RAD51 despite only subtle sequence variation. To address these issues, we have performed fluorescence polarisation assays to indirectly measure relative binding affinity, and applied computational simulations to interrogate the behaviour of the eight human BRC-RAD51 complexes, as well as a suite of BRC cancer-associated mutations. Our computational approaches encompass a range of techniques designed to link sequence variation with binding free energy. They include MM-PBSA and thermodynamic integration, which are based on classical force fields, and a recently developed approach to computing binding free energies from large-scale quantum mechanical first principles calculations with the linear-scaling density functional code onetep. Our findings not only reveal how sequence variation in the BRC repeats directly affects affinity with RAD51 and provide significant new insights into the control of RAD51 by human BRCA2, but also exemplify a palette of computational and experimental tools for the

  6. Interrogation of the protein-protein interactions between human BRCA2 BRC repeats and RAD51 reveals atomistic determinants of affinity.

    Daniel J Cole

    2011-07-01

    Full Text Available The breast cancer suppressor BRCA2 controls the recombinase RAD51 in the reactions that mediate homologous DNA recombination, an essential cellular process required for the error-free repair of DNA double-stranded breaks. The primary mode of interaction between BRCA2 and RAD51 is through the BRC repeats, which are ∼35 residue peptide motifs that interact directly with RAD51 in vitro. Human BRCA2, like its mammalian orthologues, contains 8 BRC repeats whose sequence and spacing are evolutionarily conserved. Despite their sequence conservation, there is evidence that the different human BRC repeats have distinct capacities to bind RAD51. A previously published crystal structure reports the structural basis of the interaction between human BRC4 and the catalytic core domain of RAD51. However, no structural information is available regarding the binding of the remaining seven BRC repeats to RAD51, nor is it known why the BRC repeats show marked variation in binding affinity to RAD51 despite only subtle sequence variation. To address these issues, we have performed fluorescence polarisation assays to indirectly measure relative binding affinity, and applied computational simulations to interrogate the behaviour of the eight human BRC-RAD51 complexes, as well as a suite of BRC cancer-associated mutations. Our computational approaches encompass a range of techniques designed to link sequence variation with binding free energy. They include MM-PBSA and thermodynamic integration, which are based on classical force fields, and a recently developed approach to computing binding free energies from large-scale quantum mechanical first principles calculations with the linear-scaling density functional code onetep. Our findings not only reveal how sequence variation in the BRC repeats directly affects affinity with RAD51 and provide significant new insights into the control of RAD51 by human BRCA2, but also exemplify a palette of computational and

  7. Analysis of integrated multiple 'omics' datasets reveals the mechanisms of initiation and determination in the formation of tuberous roots in Rehmannia glutinosa.

    Li, Mingjie; Yang, Yanhui; Li, Xinyu; Gu, Li; Wang, Fengji; Feng, Fajie; Tian, Yunhe; Wang, Fengqing; Wang, Xiaoran; Lin, Wenxiong; Chen, Xinjian; Zhang, Zhongyi

    2015-09-01

    All tuberous roots in Rehmannia glutinosa originate from the expansion of fibrous roots (FRs), but not all FRs can successfully transform into tuberous roots. This study identified differentially expressed genes and proteins associated with the expansion of FRs, by comparing the tuberous root at expansion stages (initiated tuberous root, ITRs) and FRs at the seedling stage (initiated FRs, IFRs). The role of miRNAs in the expansion of FRs was also explored using the sRNA transcriptome and degradome to identify miRNAs and their target genes that were differentially expressed between ITRs and FRs at the mature stage (unexpanded FRs, UFRs, which are unable to expand into ITRs). A total of 6032 genes and 450 proteins were differentially expressed between ITRs and IFRs. Integrated analyses of these data revealed several genes and proteins involved in light signalling, hormone response, and signal transduction that might participate in the induction of tuberous root formation. Several genes related to cell division and cell wall metabolism were involved in initiating the expansion of IFRs. Of 135 miRNAs differentially expressed between ITRs and UFRs, there were 27 miRNAs whose targets were specifically identified in the degradome. Analysis of target genes showed that several miRNAs specifically expressed in UFRs were involved in the degradation of key genes required for the formation of tuberous roots. As far as could be ascertained, this is the first time that the miRNAs that control the transition of FRs to tuberous roots in R. glutinosa have been identified. This comprehensive analysis of 'omics' data sheds new light on the mechanisms involved in the regulation of tuberous roots formation. PMID:26077835

  8. miRNA–target chimeras reveal miRNA 3′-end pairing as a major determinant of Argonaute target specificity

    Moore, Michael J.; Scheel, Troels K. H.; Luna, Joseph M.; Park, Christopher Y.; Fak, John J.; Nishiuchi, Eiko; Rice, Charles M.; Darnell, Robert B.

    2015-01-01

    microRNAs (miRNAs) act as sequence-specific guides for Argonaute (AGO) proteins, which mediate posttranscriptional silencing of target messenger RNAs. Despite their importance in many biological processes, rules governing AGO–miRNA targeting are only partially understood. Here we report a modified AGO HITS-CLIP strategy termed CLEAR (covalent ligation of endogenous Argonaute-bound RNAs)-CLIP, which enriches miRNAs ligated to their endogenous mRNA targets. CLEAR-CLIP mapped ∼130,000 endogenous miRNA–target interactions in mouse brain and ∼40,000 in human hepatoma cells. Motif and structural analysis define expanded pairing rules for over 200 mammalian miRNAs. Most interactions combine seed-based pairing with distinct, miRNA-specific patterns of auxiliary pairing. At some regulatory sites, this specificity confers distinct silencing functions to miRNA family members with shared seed sequences but divergent 3′-ends. This work provides a means for explicit biochemical identification of miRNA sites in vivo, leading to the discovery that miRNA 3′-end pairing is a general determinant of AGO binding specificity. PMID:26602609

  9. Multispectral airborne imagery in the field reveals genetic determinisms of morphological and transpiration traits of an apple tree hybrid population in response to water deficit.

    Virlet, Nicolas; Costes, Evelyne; Martinez, Sébastien; Kelner, Jean-Jacques; Regnard, Jean-Luc

    2015-09-01

    Genetic studies of response to water deficit in adult trees are limited by low throughput of the usual phenotyping methods in the field. Here, we aimed at overcoming this bottleneck, applying a new methodology using airborne multispectral imagery and in planta measurements to compare a high number of individuals.An apple tree population, grafted on the same rootstock, was submitted to contrasting summer water regimes over two years. Aerial images acquired in visible, near- and thermal-infrared at three dates each year allowed calculation of vegetation and water stress indices. Tree vigour and fruit production were also assessed. Linear mixed models were built accounting for date and year effects on several variables and including the differential response of genotypes between control and drought conditions.Broad-sense heritability of most variables was high and 18 quantitative trait loci (QTLs) independent of the dates were detected on nine linkage groups of the consensus apple genetic map. For vegetation and stress indices, QTLs were related to the means, the intra-crown heterogeneity, and differences induced by water regimes. Most QTLs explained 15-20% of variance.Airborne multispectral imaging proved relevant to acquire simultaneous information on a whole tree population and to decipher genetic determinisms involved in response to water deficit. PMID:26208644

  10. Deterministický chaos a jeho fyzikální aplikace-příloha (2.6b) a (2.6c)

    Weinzettl, Vladimír

    Praha : ACADEMIA, 2003, s. 2.6b-2.6c ISBN 80-200-0910-8 R&D Projects: GA ČR GA202/01/1561; GA AV ČR IAA1043003 Institutional research plan: CEZ:AV0Z2043910 Keywords : Arnold transform, deterministic chaos Subject RIV: BA - General Mathematics

  11. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen.

    Baldwin, Susan L; Roeffen, Will; Singh, Susheel K; Tiendrebeogo, Regis W; Christiansen, Michael; Beebe, Elyse; Carter, Darrick; Fox, Christopher B; Howard, Randall F; Reed, Steven G; Sauerwein, Robert; Theisen, Michael

    2016-04-27

    A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-γ and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans. PMID:26994314

  12. A different treatment method applied in a case in which osseous torticolis developed due to C6-C7 old fracture dislocation

    Taser, Omer; Cakmak, Mehmet; Domanic, Unsal; Karamehmetoglu, M.

    2004-01-01

    A report including a diffrent treatment method about a case who had an old fracture-dislocation at the C6-C7 level has been presented. The late results obtained from this case has been discussed under the light of the literature.

  13. NMR structure determination of a synthetic analogue of bacillomycin Lc reveals the strategic role of L-Asn1 in the natural iturinic antibiotics

    Volpon, Laurent; Tsan, Pascale; Majer, Zsuzsa; Vass, Elemer; Hollósi, Miklós; Noguéra, Valérie; Lancelin, Jean-Marc; Besson, Françoise

    2007-08-01

    Iturins are a group of antifungal produced by Bacillus subtilis. All are cyclic lipopeptides with seven α-amino acids of configuration LDDLLDL and one β-amino fatty acid. The bacillomycin L is a member of this family and its NMR structure was previously resolved using the sequence Asp-Tyr-Asn-Ser-Gln-Ser-Thr. In this work, we carefully examined the NMR spectra of this compound and detected an error in the sequence. In fact, Asp1 and Gln5 need to be changed into Asn1 and Glu5, which therefore makes it identical to bacillomycin Lc. As a consequence, it now appears that all iturinic peptides with antibiotic activity share the common β-amino fatty acid 8- L-Asn1- D-Tyr2- D-Asn3 sequence. To better understand the conformational influence of the acidic residue L-Asp1, present, for example in the inactive iturin C, the NMR structure of the synthetic analogue SCP [cyclo ( L-Asp1- D-Tyr2- D-Asn3- L-Ser4- L-Gln5- D-Ser6- L-Thr7-β-Ala8)] was determined and compared with bacillomycin Lc recalculated with the corrected sequence. In both cases, the conformers obtained were separated into two families of similar energy which essentially differ in the number and type of turns. A detailed analysis of both cyclopeptide structures is presented here. In addition, CD and FTIR spectra were performed and confirmed the conformational differences observed by NMR between both cyclopeptides.

  14. Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination

    Grimes, Daniel T.; Keynton, Jennifer L.; Buenavista, Maria T.; Jin, Xingjian; Patel, Saloni H.; Kyosuke, Shinohara; Williams, Debbie J.; Hamada, Hiroshi; Hussain, Rohanah; Nauli, Surya M.; Norris, Dominic P.

    2016-01-01

    During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This ‘nodal flow’ is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo. PMID:27272319

  15. Investigation of specificity determinants in bacterial tRNA-guanine transglycosylase reveals queuine, the substrate of its eucaryotic counterpart, as inhibitor.

    Inna Biela

    Full Text Available Bacterial tRNA-guanine transglycosylase (Tgt catalyses the exchange of the genetically encoded guanine at the wobble position of tRNAs(His,Tyr,Asp,Asn by the premodified base preQ1, which is further converted to queuine at the tRNA level. As eucaryotes are not able to synthesise queuine de novo but acquire it through their diet, eucaryotic Tgt directly inserts the hypermodified base into the wobble position of the tRNAs mentioned above. Bacterial Tgt is required for the efficient pathogenicity of Shigella sp, the causative agent of bacillary dysentery and, hence, it constitutes a putative target for the rational design of anti-Shigellosis compounds. Since mammalian Tgt is known to be indirectly essential to the conversion of phenylalanine to tyrosine, it is necessary to create substances which only inhibit bacterial but not eucaryotic Tgt. Therefore, it seems of utmost importance to study selectivity-determining features within both types of proteins. Homology models of Caenorhabditis elegans Tgt and human Tgt suggest that the replacement of Cys158 and Val233 in bacterial Tgt (Zymomonas mobilis Tgt numbering by valine and accordingly glycine in eucaryotic Tgt largely accounts for the different substrate specificities. In the present study we have created mutated variants of Z. mobilis Tgt in order to investigate the impact of a Cys158Val and a Val233Gly exchange on catalytic activity and substrate specificity. Using enzyme kinetics and X-ray crystallography, we gained evidence that the Cys158Val mutation reduces the affinity to preQ1 while leaving the affinity to guanine unaffected. The Val233Gly exchange leads to an enlarged substrate binding pocket, that is necessary to accommodate queuine in a conformation compatible with the intermediately covalently bound tRNA molecule. Contrary to our expectations, we found that a priori queuine is recognised by the binding pocket of bacterial Tgt without, however, being used as a substrate.

  16. Core phenomenology. TEC report on CRBRP PRA Phase II, Task 6C. Final draft report, Revision 1

    As part of the determination of the risk potential associated with core-damage accident sequences for the CRBRP, a review of the core-damage phenomenology is necessary. How core damage proceeds, its effects on the primary system boundary, and the timing and energetic potential associated with core damage are important to determining the challenge to containment and the ultimate release of fission products to the environment. This chapter addresses the phenomenology related to the core-damage processes and by the use of a core-response event tree, estimates are made of the probability that certain core-response scenarios are followed

  17. Kinetics of reversible addition of cycloalkyl hydroperoxides to C/sub 6/-C/sub 12/ cyclic ketones

    Lipos, V.V.; Bakova, E.A.; Groshina, N.M.; Koshel' , G.N.; Kurkchi, G.A.; Timrot, T.N.

    1985-11-01

    This paper examines the influence of ring size on the reaction of hydroperoxide addition to the C=O bond. The authors investigated the kinetics of hemiperketal formation in the interaction of cycloalkanones C /SUB n/ H /SUB 2n-20/ (n = 6, 8, 12) with cycloalkyl hydroperoxidides C /SUB n/ H /SUB 2n-1/ OOH (n = 6, 8) in the temperature interval 25-50 degrees. The temperature dependence of the rate constants for the forward and reverse reactions of cyclohexanone interaction were determined with cyclohexyl and cyclooctyl hydroperoxides.

  18. A conceptual framework for using DOE 5700. 6C and the other DOE orders as an integrated management system; the Fermilab experience

    Bodnarczuk, M.

    1992-06-01

    In this paper, I describe a conceptual framework that uses DOE Order 5700.6C and more than 140 other DOE Orders as an integrated management system -- but I describe it within the context of the broader sociological and cultural issues of doing research at DOE funded facilities. The conceptual framework has two components. The first involves an interpretation of the 10 criteria of DOE 5700.6C that is tailored for a research environment. The second component involves using the 10 criteria as functional categories that orchestrate and integrate the other DOE Orders into a total management system. The Fermilab approach aims at reducing (or eliminating) the redundancy and overlap within the DOE Orders system at the contractor level.

  19. A conceptual framework for using DOE 5700.6C and the other DOE orders as an integrated management system; the Fermilab experience

    Bodnarczuk, M.

    1992-06-01

    In this paper, I describe a conceptual framework that uses DOE Order 5700.6C and more than 140 other DOE Orders as an integrated management system -- but I describe it within the context of the broader sociological and cultural issues of doing research at DOE funded facilities. The conceptual framework has two components. The first involves an interpretation of the 10 criteria of DOE 5700.6C that is tailored for a research environment. The second component involves using the 10 criteria as functional categories that orchestrate and integrate the other DOE Orders into a total management system. The Fermilab approach aims at reducing (or eliminating) the redundancy and overlap within the DOE Orders system at the contractor level.

  20. A conceptual framework for using DOE 5700.6C and the other DOE orders as an integrated management system; the Fermilab experience

    In this paper, I describe a conceptual framework that uses DOE Order 5700.6C and more than 140 other DOE Orders as an integrated management system -- but I describe it within the context of the broader sociological and cultural issues of doing research at DOE funded facilities. The conceptual framework has two components. The first involves an interpretation of the 10 criteria of DOE 5700.6C that is tailored for a research environment. The second component involves using the 10 criteria as functional categories that orchestrate and integrate the other DOE Orders into a total management system. The Fermilab approach aims at reducing (or eliminating) the redundancy and overlap within the DOE Orders system at the contractor level

  1. Sequential excitation energy transfer from naphthalene cascading through titan yellow to fluorescein sodium mediated by (C16Naph(2,6)C4N+) vesicles

    The sequential excitation energy transfer has been studied in a C16Naph(2,6)C4N+, titan yellow (TY) and fluorescein sodium (FS) ternary aqueous covesicle system. The sequential arrays of chromophores with regulated distance, orders, and orientations were constructed on a non-covalent self-organization system through amphiphilic and electrostatic interaction in aqueous media. The naphthalene group, embedded in the interior of the vesicles, TY and FS anchored on surface of the covesicles through electrostatic interaction, which were employed as donor, mediator and acceptor, respectively, based on overlapping absorption and emission spectra. The sequential energy transfer from naphthalene cascading through TY mediator to FS has been studied in the C16Naph(2,6)C4N+, TY and FS ternary aqueous covesicle system. This sequential excitation energy transfer offers a good model for photoenergy transmission system mimicking photosynthetic systems

  2. Phylogenetic analysis of Amphioxus genes of the proprotein convertase family, including aPC6C, a marker of epithelial fusions during embryology

    Stéphanie Bertrand, Alain Camasses, Mathilde Paris, Nicholas D. Holland, Hector Escriva

    2006-01-01

    Full Text Available The proprotein convertases (PCs comprise a family of subtilisin-like endoproteases that activate precursor proteins (including, prohormones, growth factors, and adhesion molecules during their transit through secretory pathways or at the cell surface. To explore the evolution of the PC gene family in chordates, we made a phylogenetic analysis of PC genes found in databases, with special attention to three PC genes of the cephalochordate amphioxus, the closest living invertebrate relative to the vertebrates. Since some vertebrate PC genes are essential for early development, we investigated the expression pattern of the C isoform of the amphioxus PC6 gene (aPC6C. In amphioxus embryos and larvae, aPC6C is expressed at places where epithelia fuse. Several kinds of fusions occur: ectoderm-to-ectoderm during neurulation; mesoderm-to-ectoderm during formation of the preoral ciliated pit; and endoderm-to-ectoderm during formation of the mouth, pharyngeal slits, anus, and external opening of the club-shaped gland. Presumably, at all these sites, aPC6C is activating proteins favoring association between previously disjunct cell populations.

  3. Thalidomide enhances both primary and secondary host resistances to Listeria monocytogenes infection by a neutrophil-related mechanism in female B6C3F1 mice

    Previously, we have reported that thalidomide can modulate the immune responses in female B6C3F1 mice. Furthermore, thalidomide immunomodulation increased primary host resistance to intravenously infected Listeria monocytogenes. The present study was intended to evaluate the mechanisms underlying the enhanced host resistance to L. monocytogenes by focusing on the neutrophils. Female B6C3F1 mice were treated intraperitoneally with thalidomide (100 mg/kg) for 15 days. Exposure to thalidomide increased the numbers of neutrophils in the spleens and livers of L. monocytogenes-infected mice when compared to the L. monocytogenes-infected control mice. Additionally, the percentage of neutrophils was also significantly increased after Thd treatment in L. monocytogenes-infected mice. Further studies using antibodies to deplete corresponding cells indicated that thalidomide-mediated increase in primary host resistance (both the moribundity and colony counts in the liver and spleen) to L. monocytogenes infection was due to its effect on neutrophils but not CD8+ T cells or NK cells. Finally, Thd exposure also increased host resistance to secondary host resistance to L. monocytogenes infection, and depletion of neutrophils abolished the protective effect. In conclusion, thalidomide enhanced host resistance to both primary and secondary L. monocytogenes infections by a neutrophil-related mechanism in female B6C3F1 mice

  4. Thalidomide enhances both primary and secondary host resistances to Listeria monocytogenes infection by a neutrophil-related mechanism in female B6C3F1 mice.

    Guo, Tai L; Chi, Rui P; Karrow, Niel A; Zhang, Ling X; Pruett, Stephen B; Germolec, Dori R; White, Kimber L

    2005-12-15

    Previously, we have reported that thalidomide can modulate the immune responses in female B6C3F1 mice. Furthermore, thalidomide immunomodulation increased primary host resistance to intravenously infected Listeria monocytogenes. The present study was intended to evaluate the mechanisms underlying the enhanced host resistance to L. monocytogenes by focusing on the neutrophils. Female B6C3F1 mice were treated intraperitoneally with thalidomide (100 mg/kg) for 15 days. Exposure to thalidomide increased the numbers of neutrophils in the spleens and livers of L. monocytogenes-infected mice when compared to the L. monocytogenes-infected control mice. Additionally, the percentage of neutrophils was also significantly increased after Thd treatment in L. monocytogenes-infected mice. Further studies using antibodies to deplete corresponding cells indicated that thalidomide-mediated increase in primary host resistance (both the moribundity and colony counts in the liver and spleen) to L. monocytogenes infection was due to its effect on neutrophils but not CD8+ T cells or NK cells. Finally, Thd exposure also increased host resistance to secondary host resistance to L. monocytogenes infection, and depletion of neutrophils abolished the protective effect. In conclusion, thalidomide enhanced host resistance to both primary and secondary L. monocytogenes infections by a neutrophil-related mechanism in female B6C3F1 mice. PMID:15921716

  5. Nido-Carborane building-block reagents. 3. Cyclic and open-chain oligomers incorporating -CB4H6C - units. Crown carboranes

    The open-chain dialkynes EtC≡C(CH2)nC≡CEt (n = 4, 6), the trialkyne HC≡C(CH2)5C≡CH, and the cyclic dialkynes CH2(CH2)4C≡C(CH2)nC≡C (n = 4-6) were treated with B5H9 and (C2H5)3 to give the corresponding nido-carborane oligomers, in which the original -C≡C- units are converted to -CB4H6C- nido-carborane cages. In each case, all available -C≡C- groups were transformed to carborane moieties. No partially converted products (having both carborane and -C≡C- groups in the chain) were found; when the B5H9/-C≡C- ratio employed was 2+ and oxidative fusion, forming products incorporating C4B8 cages. The cyclic bis(carborane) CH2(CH2)4CB4H6C(CH2)5CB4H6C is an air-stable oil that can be deprotonated but does not under metal-promoted oxidative fusion. All products were characterized by 11B and 1H NMR, infrared, visible-uv, and mass spectroscopy, and the 13C NMR spectra of linear bis(carboranes) are reported. 9 references, 7 figures, 4 tables

  6. Structure, ferroelectric ordering, and semiempirical quantum calculations of lanthanide based metal-organic framework: [Nd(C4H5O6)(C4H4O6)][3H2O

    Ahmad, Bhat Zahoor; Want, Basharat

    2016-04-01

    We investigate the structure and ferroelectric behavior of a lanthanide based metal-organic framework (MOF), [Nd(C4H5O6)(C4H4O6)][3H2O]. X-ray crystal structure analyses reveal that it crystallizes in the P41212 space group with Nd centres, coordinated by nine oxygen atoms, forming a distorted capped square antiprismatic geometry. The molecules, bridged by tartrate ligands, form a 2D chiral structure. The 2D sheets are further linked into a 3D porous framework via strong hydrogen-bonding scheme (O-H…O ≈ 2.113 Å). Dielectric studies reveal two anomalies at 295 K and 185 K. The former is a paraelectric-ferroelectric transition, and the later is attributed to the freezing down of the motion of the hydroxyl groups. The phase transition is of second order, and the spontaneous polarization in low temperature phase is attributed to the ordering of protons of hydroxyl groups. The dielectric nonlinearity parameters have been calculated using Landau- Devonshire phenomenological theory. In addition, the most recent semiempirical models, Sparkle/PM7, Sparkle/RM1, and Sparkle/AM1, are tested on the present system to assay the accuracy of semiempirical quantum approaches to predict the geometries of solid MOFs. Our results show that Sparkle/PM7 model is the most accurate to predict the unit cell structure and coordination polyhedron geometry. The semiempirical methods are also used to calculate different ground state molecular properties.

  7. Overcoming recruitment barriers revealed high readiness to participate and low dropout rate among people with schizophrenia in a randomized controlled trial testing the effect of a Guided Self-Determination intervention

    Jørgensen, Rikke; Munk-Jørgensen, Povl; Lysaker, Paul H;

    2014-01-01

    BACKGROUND: Recruitment is one of the most serious challenges in performing randomized controlled trials. Often clinical trials with participants diagnosed with schizophrenia are terminated prematurely because of recruitment challenges resulting in a considerable waste of resources in the form of...... time, funding, and the participants' efforts. Dropout rates in schizophrenia trials are also high.Recruitment challenges are often due to patients not wanting to participate in research but can also be due to clinicians' concerns regarding individuals diagnosed with schizophrenia as participants in...... research. This paper reports how overcoming recruitment challenges not related to patients revealed high readiness to take part and low dropout rates in a one year long randomized controlled trial testing Guided Self-Determination (GSD) among outpatients with schizophrenia receiving treatment in Assertive...

  8. Analysis of a pair of END+ and END- viruses derived from the same bovine viral diarrhea virus stock reveals the amino acid determinants in Npro responsible for inhibition of type I interferon production.

    Kozasa, Takashi; Abe, Yuri; Mitsuhashi, Kazuya; Tamura, Tomokazu; Aoki, Hiroshi; Ishimaru, Masatoshi; Nakamura, Shigeyuki; Okamatsu, Masatoshi; Kida, Hiroshi; Sakoda, Yoshihiro

    2015-05-01

    The Exaltation of Newcastle disease virus (END) phenomenon is induced by the inhibition of type I interferon in pestivirus-infected cells in vitro, via proteasomal degradation of cellular interferon regulatory factor (IRF)-3 with the property of the viral autoprotease protein N(pro). Reportedly, the amino acid residues in the zinc-binding TRASH motif of N(pro) determine the difference in characteristics between END-phenomenon-positive (END(+)) and END-phenomenon-negative (END(-)) classical swine fever viruses (CSFVs). However, the basic mechanism underlying this function in bovine viral diarrhea virus (BVDV) has not been elucidated from the genomic differences between END(+) and END(-) viruses using reverse genetics till date. In the present study, comparison of complete genome sequences of a pair of END(+) and END(-) viruses isolated from the same virus stock revealed that there were only four amino acid substitutions (D136G, I2623V, D3148G and D3502Y) between two viruses. Based on these differences, viruses with and without mutations at these positions were generated using reverse genetics. The END assay, measurements of induced type I interferon and IRF-3 detection in cells infected with these viruses revealed that the aspartic acid at position 136 in the zinc-binding TRASH motif of N(pro) was required to inhibit the production of type I interferon via the degradation of cellular IRF-3, consistently with CSFV. PMID:25648277

  9. Sl. prosin6c6, prozim6c6

    Valčáková, Pavla

    Warszawa : Instytut Slawistyki PAN, Fundacja Slawistyczna, 2014 - (Jakubowicz, M.; Raszewska-Zurek, B.), s. 125-129 ISBN 978-83-64031-07-6 Institutional support: RVO:68378092 Keywords : Slavic languages * names of the winter month * etymology Subject RIV: AI - Linguistics

  10. Enhancement of the Hepatotoxicity of chloroform in B6C3F1 mice by corn oil: implications for chloroform carcinogenesis

    Bull, R.J.; Brown, J.M.; Meierhenry, E.A.; Jorgenson, T.A.; Robinson, M.; Stober, J.A.

    1986-11-01

    A recent study of the ability of chloroform in drinking water to produce cancer reported that male Osborne-Mendel rats developed renal tumors, but that female B6C3F1 mice failed to develop hepatocellular carcinomas. The results obtained in the male Osborne-Mendel rats were comparable to those observed in an earlier study sponsored by the National Cancer Institute (NCI). On the other hand, the lack of an increased incidence of hepatocellular carcinomas in female B6C3F1 mice was in sharp contrast to previously reported results. The doses of chloroform used were comparable to that which produced an 85% incidence in the NCI study. The authors have investigated the extent to which the vehicle might be responsible for the different results in these two studies by examining the differential effects of chloroform when it was administered by gavage using corn oil versus a 2% Emulphor suspension as the vehicle. Male and female B6C3F1 mice were administered chloroform at 60, 130, and 270 mg/kg per day for 90 days. At sacrifice, body and organ weights were measured, and blood was recovered to perform the following serum chemistry measurements (in order of priority): glutamate oxalacetate transaminase (SGOT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and triglyceride (TG) levels. The liver was sectioned for histopathological examination. These data indicate that administration of chloroform by corn oil gavage results in more marked hepatotoxic effects than observed when it is provided in an aqueous suspension. A major difference between two recent carcinogenesis bioassays of chloroform in this same mouse strain was the vehicle used.

  11. Relative Apoptosis-inducing Potential of Homeopa-thic Condurango 6C and 30C in H460 Lung Cancer Cells In vitro

    Sikdar Sourav

    2014-03-01

    Full Text Available Objectives: In homeopathy, it is claimed that more homeopathically-diluted potencies render more protective/curative effects against any disease condition. Potentized forms of Condurango are used successfully to treat digestive problems, as well as esophageal and stomach cancers. However, the comparative efficacies of Condurango 6C and 30C, one diluted below and one above Avogadro’s limit (lacking original drug molecule, respectively, have not been critically analyzed for their cell-killing (apoptosis efficacy against lung cancer cells in vitro, and signalling cascades have not been studied. Hence, the present study was undertaken. Methods: 3-(4,5-dimethylthiazol-2-yl-2,5-diphenylte- trazolium bromide (MTT assays were conducted on H460-non-small-cell lung cancer (NSCLC cells by using a succussed ethyl alcohol vehicle (placebo as a control. Studies on cellular morphology, cell cycle regulation, generation of reactive oxygen species (ROS, changes in mitochondrial membrane potential (MMP, and DNA-damage were made, and expressions of related signaling markers were studied. The observations were done in a “blinded” manner. Results: Both Condurango 6C and 30C induced apoptosis via cell cycle arrest at subG0/G1 and altered expressions of certain apoptotic markers significantly in H460 cells. The drugs induced oxidative stress through ROS elevation and MMP depolarization at 18-24 hours. These events presumably activated a caspase-3-mediated signalling cascade, as evidenced by reverse transcriptase- polymerase chain reaction (RT-PCR, western blot and immunofluorescence studies at a late phase (48 hours in which cells were pushed towards apoptosis. Conclusion: Condurango 30C had greater apoptotic effect than Condurango 6C as claimed in the homeopathic doctrine.

  12. Body weight considerations in the B6C3F1 mouse and the use of dietary control to standardize background tumor incidence in chronic bioassays

    In B6C3F1 mice, the rate of body growth influences susceptibility to liver neoplasia and large variations in body weight can complicate the interpretation of bioassay data. The relationship between body weight and liver tumor incidence was calculated for historical control populations of male and female ad libitum-fed mice (approx. 2750 and 2300 animals, respectively) and in populations of male and female mice which had been subjected to forced body weight reduction due to either dietary restriction or exposure to noncarcinogenic chemicals (approx. 1600 and 1700, respectively). Resulting tumor risk data were then used to construct idealized weight curves for male and female B6C3F1 mice; these curves predict a terminal background liver tumor incidence of 15-20%. Use of dietary control to manipulate body growth of male B6C3F1 mice to fit the idealized weight curve was evaluated in a 2-year bioassay of chloral hydrate. Cohorts of mice were successfully maintained at weights approximating their idealized target weights throughout the study. These mice exhibited less body weight variation than their ad libitum-fed counterparts (e.g., standard deviations of body weight were 1.4 and 3.4 g for respective control groups at 36 weeks). Historical control body weight and tumor risk data from the two male mouse populations were utilized to predict background liver tumor rates for each experimental group of the chloral hydrate study. The predicted background tumor rates closely matched the observed rates for both the dietary controlled and ad libitum-fed chloral hydrate control groups when each mouse was evaluated according to either its weekly food consumption or its weekly change in body weight

  13. A modification potential method of calculating total cross sections of electrons scattering from complex molecules C2H6, C2F6, C6H6 and C6F6 at 100 eV-5000 eV

    Shi De-Heng; Sun Jin-Feng; Zhu Zun-Lue; Liu Yu-Fang; Yang Xiang-Dong

    2006-01-01

    A complex optical model potential modified by incorporating the concept of bonded atom, which takes into consideration the overlapping effect of electron clouds between two atoms in a molecule, is first employed to calculate the total cross sections for electrons scattering from such complex molecules as C2H6, C2F6, C6H6 and C6F6 using the additivity rule model at Hartree-Fock level over the energy range from 100 eV to 5000 eV. The total cross sections are quantitatively compared with those obtained by experiments wherever available, and they are in good agreement with each other over a wide energy range. It is shown that the modified potential together with the additivity rule model is completely suitable for the calculation of total cross sections of electrons scattering from such complex molecules as C2H6, C2F6, C6H6 and C6F6 above 200 eV-300 eV.

  14. Differential Induction of Ly6G and Ly6C Positive Myeloid Derived Suppressor Cells in Chronic Kidney and Liver Inflammation and Fibrosis

    Höchst, Bastian; Mikulec, Julita; Baccega, Tania; Metzger, Christina; Welz, Meike; Peusquens, Julia; Tacke, Frank; Knolle, Percy; Kurts, Christian; Diehl, Linda; Ludwig-Portugall, Isis

    2015-01-01

    CD11b+Gr1+ myeloid derived suppressor cells (MDSC) are known to be very potent suppressors of T cell immunity and can be further stratified into granulocytic MDSC and monocytic MDSC in mice based on expression of Ly6G or Ly6C, respectively. Here, using these markers and functional assays, we aimed to identify whether MDSC are induced during chronic inflammation leading to fibrosis in both kidney and liver and whether additional markers could more specifically identify these MDSC subsets. In a...

  15. Pi-class glutathione-S-transferase-positive hepatocytes in aging B6C3F1 mice undergo apoptosis induced by dietary restriction.

    Muskhelishvili, L; Turturro, A.; Hart, R W; James, S J

    1996-01-01

    Liver sections from aging ad libitum-fed and diet-restricted B6C3F1 male mice were evaluated immunohistochemically for pi-class glutathione S-transferase (GST-II). GST-II immunostaining of hepatocytes was diffuse and occurred in periportal regions of hepatic acinus, whereas perivenous areas were weakly stained or were stain-free. Expression of GST-II was significantly diminished in diet-restricted mice in all age groups and was associated with a marked decrease in liver tumor development. As ...

  16. Degradation of Swainsonine by the NADP-Dependent Alcohol Dehydrogenase A1R6C3 in Arthrobacter sp. HW08

    Yan Wang

    2016-05-01

    Full Text Available Swainsonine is an indolizidine alkaloid that has been found in locoweeds and some fungi. Our previous study demonstrated that Arthrobacter sp. HW08 or its crude enzyme extract could degrade swainsonie efficiently. However, the mechanism of swainsonine degradation in bacteria remains unclear. In this study, we used label-free quantitative proteomics method based on liquid chromatography-electrospray ionization-tandem mass spectrometry to dissect the mechanism of swainsonine biodegradation by Arthrobacter sp. HW08. The results showed that 129 differentially expressed proteins were relevant to swainsonine degradation. These differentially expressed proteins were mostly related to the biological process of metabolism and the molecular function of catalytic activity. Among the 129 differentially expressed proteins, putative sugar phosphate isomerase/epimerase A1R5X7, Acetyl-CoA acetyltransferase A0JZ95, and nicotinamide adenine dinucleotide phosphate (NADP-dependent alcohol dehydrogenase A1R6C3 were found to contribute to the swainsonine degradation. Notably, NADP-dependent alcohol dehyrodgenase A1R6C3 appeared to play a major role in degrading swainsonine, but not as much as Arthrobacter sp. HW08 did. Collectively, our findings here provide insights to understand the mechanism of swainsonine degradation in bacteria.

  17. Salivaricin D, a novel intrinsically trypsin-resistant lantibiotic from Streptococcus salivarius 5M6c isolated from a healthy infant.

    Birri, Dagim Jirata; Brede, Dag Anders; Nes, Ingolf F

    2012-01-01

    In this work, we purified and characterized a newly identified lantibiotic (salivaricin D) from Streptococcus salivarius 5M6c. Salivaricin D is a 34-amino-acid-residue peptide (3,467.55 Da); the locus of the gene encoding this peptide is a 16.5-kb DNA segment which contains genes encoding the precursor of two lantibiotics, two modification enzymes (dehydratase and cyclase), an ABC transporter, a serine-like protease, immunity proteins (lipoprotein and ABC transporters), a response regulator, and a sensor histidine kinase. The immunity gene (salI) was heterologously expressed in a sensitive indicator and provided significant protection against salivaricin D, confirming its immunity function. Salivaricin D is a naturally trypsin-resistant lantibiotic that is similar to nisin-like lantibiotics. It is a relatively broad-spectrum bacteriocin that inhibits members of many genera of Gram-positive bacteria, including the important human pathogens Streptococcus pyogenes and Streptococcus pneumoniae. Thus, Streptococcus salivarius 5M6c may be a potential biological agent for the control of oronasopharynx-colonizing streptococcal pathogens or may be used as a probiotic bacterium. PMID:22101034

  18. A CHRONIC INHALATION STUDY OF METHYL BROMIDE TOXICITY IN B6C3F1 MICE. (FINAL REPORT TO THE NATIONAL TOXICOLOGY PROGRAM)

    HABER, S.B.

    1987-06-26

    This report provides a detailed account of a two year chronic inhalation study of methyl bromide toxicity in B6C3Fl mice conducted for the National Toxicology Program. Mice were randomized into three dose groups (10, 33 and 100 ppm methyl bromide) and one control group (0 ppm) per sex and exposed 5 days/week, 6 hours/day, for a total of 103 weeks. Endpoints included body weight; clinical signs and mortality, and at 6, 15 and 24 months of exposure, animals were sacrificed for organ weights, hematology and histopathology. In addition, a subgroup of animals in each dosage group was monitored for neurobehavioral and neuropathological changes. After only 20 weeks of exposure, 48% of the males and 12% of the females in the 100 ppm group had died. Exposures were terminated in that group and the surviving mice were observed for the duration of the study. Exposure of B6C3Fl mice to methyl bromide, even for only 20 weeks, produced significant changes in growth rate, mortality, organ weights and neurobehavioral functioning. These changes occurred in both males and females, but were more pronounced in males.

  19. Degradation of Swainsonine by the NADP-Dependent Alcohol Dehydrogenase A1R6C3 in Arthrobacter sp. HW08

    Wang, Yan; Zhai, A’guan; Zhang, Yanqi; Qiu, Kai; Wang, Jianhua; Li, Qinfan

    2016-01-01

    Swainsonine is an indolizidine alkaloid that has been found in locoweeds and some fungi. Our previous study demonstrated that Arthrobacter sp. HW08 or its crude enzyme extract could degrade swainsonie efficiently. However, the mechanism of swainsonine degradation in bacteria remains unclear. In this study, we used label-free quantitative proteomics method based on liquid chromatography-electrospray ionization-tandem mass spectrometry to dissect the mechanism of swainsonine biodegradation by Arthrobacter sp. HW08. The results showed that 129 differentially expressed proteins were relevant to swainsonine degradation. These differentially expressed proteins were mostly related to the biological process of metabolism and the molecular function of catalytic activity. Among the 129 differentially expressed proteins, putative sugar phosphate isomerase/epimerase A1R5X7, Acetyl-CoA acetyltransferase A0JZ95, and nicotinamide adenine dinucleotide phosphate (NADP)-dependent alcohol dehydrogenase A1R6C3 were found to contribute to the swainsonine degradation. Notably, NADP-dependent alcohol dehyrodgenase A1R6C3 appeared to play a major role in degrading swainsonine, but not as much as Arthrobacter sp. HW08 did. Collectively, our findings here provide insights to understand the mechanism of swainsonine degradation in bacteria. PMID:27196926

  20. Fine precipitation scenarios of AlZnMg(Cu) alloys revealed by advanced atomic-resolution electron microscopy study Part I: Structure determination of the precipitates in AlZnMg(Cu) alloys

    Although they are among the most important precipitation-hardened materials for industry applications, the high-strength AlZnMg(Cu) alloys have thus far not yet been understood adequately about their underlying precipitation scenarios in relation with the properties. This is partly due to the fact that the structures of a number of different precipitates involved in electron microscopy in association with quantitative image simulations have to be employed; a systematic study of these hardening precipitates in different alloys is also necessary. In Part I of the present study, it is shown that there are five types of structurally different precipitates including the equilibrium η-phase precipitate. Using two state-of-the-art atomic-resolution imaging techniques in electron microscopy in association with quantitative image simulations, we have determined and clarified all the unknown precipitate structures. It is demonstrated that atomic-resolution imaging can directly suggest approximate structure models, whereas quantitative image analysis can refine the structure details that are much smaller than the resolution of the microscope. This combination is crucially important for solving the difficult structure problems of the strengthening precipitates in AlZnMg(Cu) alloys. - Highlights: Part I: • We determine and verify all the key precipitate structures in AlMgZn(Cu) alloys. • We employ aberration-corrected scanning transmission electron microscopy (STEM). • We use aberration-corrected high-resolution TEM (HRTEM) for the investigations. • We obtain atomic-resolution images of the precipitates and model their structures. • We refine all precipitate structures with quantitative image simulation analysis. Part II: • The hardening precipitates in AlZnMg alloys shall be classified into two groups. • Two precipitation scenarios coexist in the alloys. • The precipitation behavior of such an alloy depends on the alloy's composition. • Very detailed

  1. Effects of rare earth addition on microstructure and mechanical properties of a Fe–15Mn–1.5Al–0.6C TWIP steel

    The microstructure and mechanical properties of a Fe–15Mn–1.5Al–0.6C TWIP steel with and without rare earth (RE) addition were investigated. The RE-alloyed steel showed both improved tensile strength and total elongation (TEL). Optical microscopy and electron back-scattered diffraction (EBSD) characterizations showed that the RE-alloyed steel possessed a more homogeneous microstructure and a larger fraction of high-angle grain boundaries, which increased the TEL. Meanwhile, EBSD and transmission electron microscope (TEM) analyses indicated that the RE-alloyed steel exhibited more uniform distributed annealing twins and secondary annealing twins with a thickness of 10–20 nm appeared in some grains, which resulted in the higher tensile strength

  2. Benzene metabolite levels in blood and bone marrow of B6C3F{sub 1} mice after low-level exposure

    Bechtold, W.E.; Strunk, M.R.; Thornton-Manning, J.R. [and others

    1995-12-01

    Studies at the Inhalation Toxicology Research Institute (ITRI) have explored the species-specific uptake and metabolism of benzene. Results have shown that metabolism is dependent on both dose and route of administration. Of particular interest were shifts in the major metabolic pathways as a function of exposure concentration. In these studies, B6C3F{sub 1} mice were exposed to increasing levels of benzene by either gavage or inhalation. As benzene internal dose increased, the relative amounts of muconic acid and hydroquinone decreased. In contrast, the relative amount of catechol increased with increasing exposure. These results show that the relative levels of toxic metabolites are a function of exposure level. Based on these results and assuming a linear relationship between exposure concentration and levels of bone marrow metabolites, it would be difficult to detect an elevation of any phenolic metabolites above background after occupational exposures to the OSHA Permissible Exposure Limit of 1 ppm benzene.

  3. Influence of Al on the fatigue crack growth behavior of Fe–22Mn–(3Al)–0.6C TWIP steels

    Ma, Penghui [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); National Engineering Research Center for Equipment and Technology of Cold Strip Rolling, Yanshan University, Qinhuangdao 066004 (China); Qian, Lihe, E-mail: dlhqian@yahoo.com [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); National Engineering Research Center for Equipment and Technology of Cold Strip Rolling, Yanshan University, Qinhuangdao 066004 (China); Meng, Jiangying [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); Liu, Shuai; Zhang, Fucheng [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); National Engineering Research Center for Equipment and Technology of Cold Strip Rolling, Yanshan University, Qinhuangdao 066004 (China)

    2015-10-01

    The influence of Al on fatigue crack growth (FCG) behavior of the high-Mn austenitic twinning-induced plasticity (TWIP) steel was investigated by conducting FCG tests on Fe–22Mn–0Al–0.6C and Fe–22Mn–3Al–0.6C TWIP steels (hereafter, referred to as 0Al and 3Al TWIP steel, respectively). The FCG tests were performed at stress ratio of 0.1 under the control of stress intensity factor range using three-point bending specimens. Excepting that the traditional two-dimensional (2D) observation methods (optical, scanning and transmission electron microscopes) were used to observe the crack paths, fracture surfaces and microstructure features, a high-resolution synchrotron X-ray computed tomography was also applied to observe the three-dimensional (3-D) crack morphology. The results indicate that the FCG resistance of the 0Al TWIP steel is superior to that of 3Al TWIP steel in the near threshold regime. Observed from the 2D crack paths and 3D crack morphologies, it can be found that the crack surface roughness and crack deflection of the 0Al steel are greater than those of 3Al steel. It is suggested that the degree of roughness-induced crack closure decreases with the addition of Al. And the 0Al steel shows much larger plastic zone sizes ahead of the crack tip than the 3Al steel, suggesting that plasticity-induced crack closure may also play an important role in decreasing the FCG rate in the 0Al steel. By excluding the crack closure effects, the 0Al steel still exhibits a higher effective crack growth threshold value than the 3Al steel; this is considered to be due to the higher planarity of slip in the 0Al steel than in the 3Al steel, and the mechanical twins generated in the 0Al steel reduce the stress concentration at crack tip.

  4. Influence of Al on the fatigue crack growth behavior of Fe–22Mn–(3Al)–0.6C TWIP steels

    The influence of Al on fatigue crack growth (FCG) behavior of the high-Mn austenitic twinning-induced plasticity (TWIP) steel was investigated by conducting FCG tests on Fe–22Mn–0Al–0.6C and Fe–22Mn–3Al–0.6C TWIP steels (hereafter, referred to as 0Al and 3Al TWIP steel, respectively). The FCG tests were performed at stress ratio of 0.1 under the control of stress intensity factor range using three-point bending specimens. Excepting that the traditional two-dimensional (2D) observation methods (optical, scanning and transmission electron microscopes) were used to observe the crack paths, fracture surfaces and microstructure features, a high-resolution synchrotron X-ray computed tomography was also applied to observe the three-dimensional (3-D) crack morphology. The results indicate that the FCG resistance of the 0Al TWIP steel is superior to that of 3Al TWIP steel in the near threshold regime. Observed from the 2D crack paths and 3D crack morphologies, it can be found that the crack surface roughness and crack deflection of the 0Al steel are greater than those of 3Al steel. It is suggested that the degree of roughness-induced crack closure decreases with the addition of Al. And the 0Al steel shows much larger plastic zone sizes ahead of the crack tip than the 3Al steel, suggesting that plasticity-induced crack closure may also play an important role in decreasing the FCG rate in the 0Al steel. By excluding the crack closure effects, the 0Al steel still exhibits a higher effective crack growth threshold value than the 3Al steel; this is considered to be due to the higher planarity of slip in the 0Al steel than in the 3Al steel, and the mechanical twins generated in the 0Al steel reduce the stress concentration at crack tip

  5. Inflammatory and chloracne-like skin lesions in B6C3F1 mice exposed to 3,3',4,4'-tetrachloroazobenzene for 2 years

    Exposure to dioxin and dioxin-like compounds (DLCs) has been connected to the induction of chloracne in humans and animals. 3,3',4,4'-Tetrachloroazobenzene (TCAB) is an environmental contaminant that induces chloracne in humans. TCAB has been studied only to a limited extent in laboratory animals. While performing a 2-year gavage study in B6C3F1 mice to evaluate the toxic and carcinogenic effects of TCAB, we also explored potential chloracnegenic properties. Groups of 50 male and 50 female B6C3F1 mice were exposed by gavage to TCAB at dose levels of 0, 3, 10 and 30 mg/kg for 5 days a week for 2 years. The animals developed treatment-related gross inflammatory skin lesions, which were characterized histologically by inflammation, fibrosis, hyperplasia, and ulcers. Additionally, many of the animals developed follicular dilatation and sebaceous gland atrophy, consistent with chloracne-like lesions. This current 2-year study supports recently published papers showing susceptibility to chloracne in mouse strains other than hairless mice. The chloracne-like lesions were not clinically evident; therefore, our study highlights the need for careful examination of the skin in order to identify subtle lesions consistent with chloracne-like changes in rodents exposed to dioxin and DLCs. Since previous short-term studies did not demonstrate any skin lesions, we suggest that reliable assessment of all safety issues involving dioxin and DLCs requires evaluation following chronic exposure. Such studies in animal models will help to elucidate the mechanisms of dioxin-related health hazards.

  6. Sex-dependent differences in the disposition of 2,4-dichlorophenoxyacetic acid in Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters.

    Griffin, R J; Godfrey, V B; Kim, Y C; Burka, L T

    1997-09-01

    2,4-Dichlorophenoxyacetic acid (2,4-D), a widely used broadleaf herbicide, is under investigation in a study of peroxisome proliferators. To supplement that study, male and female rats, mice, and hamsters were dosed with 14C-2,4-D orally at 5 and 200 mg/kg and tissue distributions were determined. Blood, liver, kidney, muscle, skin, fat, brain, testes, and ovaries were examined. At early time points tissues from female rats consistently contained higher amounts of radioactivity than did corresponding tissues from males (up to 9 times). By 72 hr, tissue levels were equivalent and males and females had excreted equal amounts of radioactivity. This sex difference was absent in mice. In hamsters, males had higher tissue levels than females. Taurine, glycine, and glucuronide conjugates of 2,4-D were excreted along with parent. Metabolite profiles differed between species qualitatively and quantitatively; however, differences between sexes were minimal. Plasma elimination curves were generated in male and female rats after iv and oral administration. Kinetic analysis revealed significant differences in elimination and exposure parameters consistent with a greater ability to clear 2,4-D by male rats relative to females. This suggests that at equivalent doses, female rats are exposed to higher concentrations of 2,4-D for a longer time than males and may be more susceptible to 2,4-D-induced toxicity. These sex-dependent variations in the clearance of 2,4-D in rats and hamsters may indicate a need for sex-specific models to accurately assess human health risks. PMID:9311622

  7. Differential induction of Ly6G and Ly6C positive myeloid derived suppressor cells in chronic kidney and liver inflammation and fibrosis.

    Bastian Höchst

    Full Text Available CD11b+Gr1+ myeloid derived suppressor cells (MDSC are known to be very potent suppressors of T cell immunity and can be further stratified into granulocytic MDSC and monocytic MDSC in mice based on expression of Ly6G or Ly6C, respectively. Here, using these markers and functional assays, we aimed to identify whether MDSC are induced during chronic inflammation leading to fibrosis in both kidney and liver and whether additional markers could more specifically identify these MDSC subsets. In an adenine-induced model of kidney inflammation/fibrosis suppressive Ly6Gpos MDSC were induced. The suppressive function within the Ly6G+ MDSC population was exclusively present in IFNγRβ expressing cells. In contrast, in chronic inflammation in the liver induced by bile duct ligation, suppressive capacity was exclusively present in the Ly6Cpos MDSC subset. Gene expression analyses confirmed the differential origins and regulation of those MDSC subsets. Additionally, depletion of MDSC in either kidney or liver fibrosis enhanced fibrosis markers, indicating a protective role for MDSC in organ fibrosis. Thus, our data demonstrate that during liver inflammation and kidney fibrosis MDSC with similar function arise bearing a distinct marker profile and arising from different cell populations.

  8. Spectroscopic (FT-IR, FT-Raman) and quantum mechanical studies of 3t-pentyl-2r,6c-diphenylpiperidin-4-one thiosemicarbazone

    Savithiri, S.; Arockia doss, M.; Rajarajan, G.; Thanikachalam, V.; Bharanidharan, S.; Saleem, H.

    2015-02-01

    In this study, the molecular structure and vibrational spectra of 3t-pentyl2r,6c-diphenylpiperidin-4-one thiosemicarbazone (PDPOTSC) were studied. The ground-state molecular geometry was ascertained by using the density functional theory (DFT)/B3LYP method using 6-31++G(d,p) as a basis set. The vibrational (FT-IR and FT-Raman) spectra of PDPOTSC were computed using DFT/B3LYP and HF methods with 6-31++G(d,p) basis set. The fundamental vibrations were assigned on the basis of the total energy distribution (TED ⩾ 10%) of the vibrational modes, calculated with scaled quantum mechanics (SQM) methods PQS program. The electrical dipole moment (μ) and first hyperpolarizability (βo) values have been computed using DFT/B3LYP and HF methods. The calculated result (βo) shows that the title molecule might have nonlinear optical (NLO) behavior. Atomic charges of C, N, S and molecular electrostatic potential (MEP) were calculated using B3LYP/6-31G++(d,p). The HOMO-LUMO energies were calculated and natural bonding orbital (NBO) analysis has also been carried out.

  9. The effect of cesium carbonate on 1-(3-methoxycarbonyl)propyl-1-phenyl[6,6]C61 aggregation in films

    Surface-pressure versus molecular area isotherms, X-ray reflectivity, and X-ray near-total reflection fluorescence were used to study the properties of 1-(3-methoxycarbonyl)propyl-1-phenyl[6,6]C61 (PCBM) that was pre-mixed with cesium carbonate and spread as a film at the air-water interface. The pre-mixed PCBM with cesium carbonate demonstrated a strikingly strong effect on the organization of the film. Whereas films formed from pure PCBM solution were rough due to strong inter-molecular interactions, the films formed from the mixture were much smoother. This indicates that the cesium carbonate moderates the inter-molecular interactions among PCBM molecules, hinting that the cesium diffusion observed in inverted organic photovoltaic structures and the likely ensuing ionic Cs-PCBM interaction decrease aggregation tendency of PCBM. This implies that the use of cesium salts affects the morphology of the organic layer and consequently improves the efficiency of these devices

  10. Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis

    Okita, Kohei; Tokino, Takashi; Nishimori, Hiroyuki [Univ. of Tokyo (Japan)] [and others

    1996-04-15

    Carnitine is an essential cofactor for oxidation of mitochondrial fatty acids. Carnitine deficiency results in failure of energy production by mitochondria and leads to metabolic encephalopathy, lipid-storage myopathy, and cardiomyopathy. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, inherits the JVS phenotype in autosomal recessive fashion, through a mutant allele mapped to mouse chromosome 11. As a step toward identifying the gene responsible for JVS by positional cloning, we attempted to refine the jvs locus in the mouse by detailed linkage analysis with 13 microsatellite markers, using 190 backcross progeny. Among the 13 loci tested, 5 (defined by markers D11Mit24, D11Mit111,D11Nds9, D11Mit86, and D11Mit23) showed no recombination, with a maximum lod score of 52.38. Our results implied that the jvs gene can be sought on mouse chromosome 11 within a genetic distance no greater than about 1.6 cM. 21 refs., 2 figs.

  11. The 'revealed preferences' theory: Assumptions and conjectures

    Being kind of intuitive psychology the 'Revealed-Preferences'- theory based approaches towards determining the acceptable risks are a useful method for the generation of hypotheses. In view of the fact that reliability engineering develops faster than methods for the determination of reliability aims the Revealed-Preferences approach is a necessary preliminary help. Some of the assumptions on which the 'Revealed-Preferences' theory is based will be identified and analysed and afterwards compared with experimentally obtained results. (orig./DG)

  12. Elevated interleukin-9 receptor expression and response to interleukins-9 and -7 in thymocytes during radiation-induced T-cell lymphomagenesis in B6C3F1 mice

    Full text: Dysregulation of cytokine receptor expression and responsiveness to cytokines is hypothesized to play an important role in the development and expansion of preneoplastic cells or progression of neoplastic cells during the early and late stages of leukemogenesis. To determine the crucial changes in initiated cells that confer significant growth during the early stage of radiation-induced lymphomagenesis, we examined both the expression of receptors for thymus-derived cytokines and thymocyte response to cytokines before the onset of T cell lymphomas in B6C3F1 mice after split-dose irradiation. After irradiation, thymic T cell subsets underwent delayed regeneration consisting of two phases as determined by receptor expression. The first phase occurred within one week post-irradiation and was accompanied by transient expansion of T cell subsets strongly expressing receptor genes for IL-1, IL-2, IL-6, IL-7, IL-15 and TNF. The second phase occurred 12 weeks after irradiation and was characterized by increased expression of IL9R. Thymocytes from non-irradiated control mice were unresponsive to IL-9. However, IL-9 acted synergistically with IL-7 and PHA to stimulate the proliferation of irradiated cells during the second post-irradiation phase. Moreover, these cells showed hyper-responsiveness to IL-7 or PHA alone compared to age-matched non-irradiated control thymocytes. These results suggest that the unusual expression of IL-9 receptors and/or increased responsiveness of thymocytes to cytokines are key processes in the development of radiation-induced T cell lymphomas

  13. The effects of Si on the mechanical twinning and strain hardening of Fe–18Mn–0.6C twinning-induced plasticity steel

    The stacking-fault energy (SFE), dislocation slip, mechanical twinning, strain hardening, and yield and tensile strengths were systemically investigated in Fe–18Mn–0.6C–1.5Si twinning-induced plasticity (TWIP) steel. The results were also compared with those for Fe–18Mn–0.6C and Fe–18Mn–0.6C–1.5Al TWIP steels. The SFE decreased by 4 mJ m−2 per 1 wt.% Si. The addition of Si increased both the yield strength, due mainly to solid solution hardening, and the tensile strength, owing to the high strain hardening that occurred while maintaining a large elongation of over 60%. To examine this high strain hardening, especially at low strains, the volume fractions of the primary and secondary mechanical twins were quantitatively evaluated by combining the merits of electron backscattered diffractometry and transmission electron microscopy. The volume fractions of both the primary and secondary twins were the highest in the Fe–18Mn–0.6C–1.5Si TWIP steel, which had the lowest SFE of the three TWIP steels. In particular, the volume fraction of the secondary mechanical twins increased rapidly with the addition of Si. The contributions of dislocation storage, mechanical twinning and dynamic strain aging (DSA) to the strain hardening were also quantitatively evaluated in the three TWIP steels. The Si-added TWIP steel had the highest strain hardening, due mainly to the active primary and secondary twinning, and experienced negligible DSA. In contrast, the Al-added TWIP steel exhibited the lowest strain hardening due to the reductions in both the mechanical twinning and DSA

  14. Toxicokinetics of chloral hydrate in ad libitum-fed, dietary-controlled, and calorically restricted male B6C3F1 mice following short-term exposure

    Chloral hydrate is widely used as a sedative in pediatric medicine and is a by-product of water chlorination and a metabolic intermediate in the biotransformation of trichloroethylene. Chloral hydrate and its major metabolite, trichloroacetic acid, induce liver tumors in B6C3F1 mice, a strain that can exhibit high rates of background liver tumor incidence, which is associated with increased body weight. This report describes the influence of diet and body weight on the acute toxicity, hepatic enzyme response, and toxickinetics of chloral hydrate as part of a larger study investigating the carcinogenicity of chloral hydrate in ad libitum-fed and dietary controlled mice. Dietary control involves moderate food restriction to maintain the test animals at an idealized body weight. Mice were dosed with chloral hydrate at 0, 50, 100, 250, 500, and 1000 mg/kg daily, 5 days/week, by aqueous gavage for 2 weekly dosing cycles. Three diet groups were used: ad libitum, dietary control, and 40% caloric restriction. Both dietary control and caloric restriction slightly reduced acute toxicity of high doses of chloral hydrate and potentiated the induction of hepatic enzymes associated with peroxisome proliferation. Chloral hydrate toxicokinetics were investigated using blood samples obtained by sequential tail clipping and a microscale gas chromatography technique. It was rapidly cleared from serum within 3 h of dosing. Trichloroacetate was the major metabolite in serum in all three diet groups. Although the area under the curve values for serum trichloroacetate were slightly greater in the dietary controlled and calorically restricted groups than in the ad libitum-fed groups, this increase did not appear to completely account for the potentiation of hepatic enzyme induction by dietary restriction

  15. Expression of ovarian microsomal epoxide hydrolase and glutathione S-transferase during onset of VCD-induced ovotoxicity in B6C3F1 mice

    4-vinylcyclohexene diepoxide (VCD) specifically destroys small pre-antral follicles in the rodent ovary. VCD can be detoxified to an inactive tetrol by microsomal epoxide hydrolase (mEH), or by conjugation to glutathione (GSH) by glutathione S-transferase (GST). Formation of VCD-GSH adducts in the mouse ovary 4 h after VCD exposure (0.57 mmol/kg/day) has been demonstrated. Because the mouse ovary expresses both mEH and GST, expression of mEH and GST pi and mu during a time-course of VCD-induced ovotoxicity was evaluated in a neonatal mouse ovarian culture system. Ovaries from postnatal day 4 (PND4) B6C3F1 mice were incubated with VCD (15 μM) for 2, 4, 6, 8, 10, 12, or 15 days. Following incubation, ovaries were histologically evaluated, or assessed for mRNA or protein expression. VCD did not cause follicle loss (p > 0.05) on days 2, 4, or 6 of culture. At days 8, 10, 12, and 15, VCD reduced (p < 0.05) both primordial and primary follicle numbers. Increased (p < 0.05) expression of mEH, GST pi and GST mu mRNA was detected after 4 days of VCD exposure. This expression was reduced on days 6 and 8, when follicle loss was underway, but increased (p < 0.05) after 10 days of exposure. mEH and GST pi proteins were elevated (p < 0.05) following 8 days of VCD-exposure however there was no increase in GST mu protein. These findings suggest that with continuous exposure to VCD, increased expression of detoxification enzymes may participate in retarding the onset of follicle loss, but that this loss cannot ultimately be prevented

  16. In Utero exposure to genistein enhanced intranasal house dust mite allergen-induced respiratory sensitization in young adult B6C3F1 mice.

    Guo, Tai L; Meng, Andrew H

    2016-06-24

    Despite many hypothesized benefits of dietary isoflavone genistein (GEN) deriving from soy-based products, questions surrounding GEN's developmental immunotoxic effects are increasing. To understand how in utero GEN exposure may modulate postnatal respiratory sensitization, we conducted a time course study using a common household allergen (house dust mites: HDM; 10μg/mouse) following intranasal instillation, a physiological route of allergen exposure. GEN was administered to dams by gavage from gestational day 14 to parturition at a physiologically relevant dose (20mg/kg bw). Female and male offspring were sensitized with HDM allergens beginning about one month prior to sacrifice followed by challenges with three weekly doses of HDM extracts, and they were euthanized at day 3 following the final HDM exposure at four different time points (postnatal day (PND) 80, 120, 160, and 200). In utero GEN combined with postnatal HDM exposures (GEN+HDM) increased total IgE production in both young female and male B6C3F1 offspring (e.g., PND 80 in females and PND 120 in males). Increased antigen-specific IgG1, IgG2a and IgG2b levels were also observed at various time points in both female and male offspring. In addition, increases in macrophage number in bronchoalveolar lavage fluid of both female and male GEN+HDM offspring at PND 80 and PND 120, respectively, were observed when compared to the vehicle group. For T cells, an increase over the vehicle in female GEN+HDM offspring was observed at PND 80. Due to similar patterns of increases, it seems likely that GEN+HDM-induced increases in total IgE and macrophages are related. Overall, in utero GEN plus later-life HDM exposures exert increases in total IgE and HDM-specific IgG production as well as macrophage recruitments to the lung in young adult mice. PMID:27113705

  17. Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water.

    Frawley, Rachel P; Smith, Matthew J; White, Kimber L; Elmore, Susan A; Herbert, Ron; Moore, Rebecca; Staska, Lauren M; Behl, Mamta; Hooth, Michelle J; Kissling, Grace E; Germolec, Dori R

    2016-09-01

    Tungsten is a naturally occurring, high-tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent. Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models. The objective of this study was to assess potential immunotoxicity of sodium tungstate dihydrate (STD), a drinking water contaminant. Female B6C3F1/N mice received 0-2000 mg STD/L in their drinking water for 28 d, and were evaluated for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity. Three different parameters of cell-mediated immunity were similarly affected at 1000 mg STD/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased 32%, and 21%, respectively. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg STD/L, the absolute numbers of CD3(+) T-cell progenitor cells in bone marrow were increased 86%, but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. STD-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues. These data suggest exposure to STD in drinking water may adversely affect cell-mediated immunity. PMID:27223060

  18. NTP Toxicology and Carcinogenesis Studies of 1,3-Butadiene (CAS No. 106-99-0) in B6C3F1 Mice (Inhalation Studies).

    1984-08-01

    1,3-Butadiene is used as an intermediate in the production of elastomers, polymers, and other chemicals. Of the 1,3-butadiene used in 1978, 44% was used to manufacture styrene-butadiene rubber (a substitute for natural rubber, produced by copolymerization of 1,3-butadiene with styrene), and 19% was used to produce polybutane elastomer (a substance that increases resistance of tire products to wear, heat degradation, and blowouts). Chloroprene monomer, derived from 1,3-butadiene, is used exclusively to manufacture neoprene elastomers for non-tire and latex applications. Commercial nitrile rubber, used largely in rubber hoses, seals, and gaskets for automobiles, is a copolymer of 1,3-butadiene and acrylonitrile. Acrylonitrile- butadiene- styrene resins, usually containing 20%-30% 1,3-butadiene by weight, are used to make parts for automobiles and appliances. Other polymer uses include specialty polybutadiene polymers, thermoplastic elastomers, nitrile barrier resins, and K resins(R). 1,3-Butadiene is used as an intermediate in the production of a variety of industrial chemicals, including two fungicides, captan and captofol. It is approved by the U.S. Food and Drug Administration for use in the production of adhesives used in articles for packaging, transporting, or holding food; in components of paper and paperboard that are in contact with dry food; and as a modifier in the production of semigrid and rigid vinyl chloride plastic food-contact articles. No information was located on the levels of monomer or on its elution rate from any of the commercially available polymers. It is not known if unreacted 1,3-butadiene migrated from packaging materials. Male and female B6C3F1 mice were exposed to air containing 1,3-butadiene (greater than 99% pure) at concentrations of 0-8,000 ppm in 15-day and 14-week inhalation studies. In the 15-day studies, survival was unaffected by dose, and no pathologic effects were observed; slight decreases in mean body weight occurred at the

  19. Toxicity and carcinogenicity of methyl isobutyl ketone in F344N rats and B6C3F1 mice following 2-year inhalation exposure

    Methyl isobutyl ketone (MIBK) is primarily used as a denaturant for rubbing alcohol, as a solvent and in the manufacture of methyl amyl alcohol. Inhalation of vapors is the most likely route of exposure in the work place. In order to evaluate the potential of MIBK to induce toxic and carcinogenic effects following chronic exposure, groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MIBK at concentrations of 0, 450, 900, or 1800 ppm by inhalation, 6 h/day, 5 days per week for 2 years. Survival was decreased in male rats at 1800 ppm. Body weight gains were decreased in male rats at 900 and 1800 ppm and in female mice at 1800 ppm. The primary targets of MIBK toxicity and carcinogenicity were the kidney in rats and the liver in mice. In male rats, there was increased mineralization of the renal papilla at all exposure concentrations. The incidence of chronic progressive nephropathy (CPN) was increased at 1800 ppm and the severity was increased in all exposed groups. There were also increases in renal tubule hyperplasia at all exposure concentrations, and in adenoma and adenoma or carcinoma (combined) at 1800 ppm; these lesions are thought to represent a continuum in the progression of proliferative lesions in renal tubule epithelium. These increases may have resulted from the increased severity of CPN, either through α2μ-globulin-dependent or -independent mechanisms. An increase in mononuclear cell leukemia at 1800 ppm was an uncertain finding. Adrenal medulla hyperplasia was increased at 1800 ppm, and there was a positive trend for increases in benign or malignant pheochromocytomas (combined). In female rats, there were increases in the incidence of CPN in all exposure concentrations and in the severity at 1800 ppm, indicating that CPN was increased by mechanisms in addition to those related to α2μ-globulin. There were renal mesenchymal tumors, which have not been observed in historical control animals, in two female rats at 1800 ppm. The

  20. Toxicity and carcinogenicity of methyl isobutyl ketone in F344N rats and B6C3F1 mice following 2-year inhalation exposure.

    Stout, Matthew D; Herbert, Ronald A; Kissling, Grace E; Suarez, Fernando; Roycroft, Joseph H; Chhabra, Rajendra S; Bucher, John R

    2008-02-28

    Methyl isobutyl ketone (MIBK) is primarily used as a denaturant for rubbing alcohol, as a solvent and in the manufacture of methyl amyl alcohol. Inhalation of vapors is the most likely route of exposure in the work place. In order to evaluate the potential of MIBK to induce toxic and carcinogenic effects following chronic exposure, groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MIBK at concentrations of 0, 450, 900, or 1800ppm by inhalation, 6h/day, 5 days per week for 2 years. Survival was decreased in male rats at 1800ppm. Body weight gains were decreased in male rats at 900 and 1800ppm and in female mice at 1800ppm. The primary targets of MIBK toxicity and carcinogenicity were the kidney in rats and the liver in mice. In male rats, there was increased mineralization of the renal papilla at all exposure concentrations. The incidence of chronic progressive nephropathy (CPN) was increased at 1800ppm and the severity was increased in all exposed groups. There were also increases in renal tubule hyperplasia at all exposure concentrations, and in adenoma and adenoma or carcinoma (combined) at 1800ppm; these lesions are thought to represent a continuum in the progression of proliferative lesions in renal tubule epithelium. These increases may have resulted from the increased severity of CPN, either through alpha2micro-globulin-dependent or -independent mechanisms. An increase in mononuclear cell leukemia at 1800ppm was an uncertain finding. Adrenal medulla hyperplasia was increased at 1800ppm, and there was a positive trend for increases in benign or malignant pheochromocytomas (combined). In female rats, there were increases in the incidence of CPN in all exposure concentrations and in the severity at 1800ppm, indicating that CPN was increased by mechanisms in addition to those related to alpha2micro-globulin. There were renal mesenchymal tumors, which have not been observed in historical control animals, in two female rats at 1800ppm. The

  1. Effects of dietary fish oil on the depletion of carcinogenic PAH-DNA adduct levels in the liver of B6C3F1 mouse.

    Guo-Dong Zhou

    Full Text Available Many carcinogenic polycyclic aromatic hydrocarbons (PAHs and their metabolites can bind covalently to DNA. Carcinogen-DNA adducts may lead to mutations in critical genes, eventually leading to cancer. In this study we report that fish oil (FO blocks the formation of DNA adducts by detoxification of PAHs. B6C3F1 male mice were fed a FO or corn oil (CO diet for 30 days. The animals were then treated with seven carcinogenic PAHs including benzo(apyrene (BaP with one of two doses via a single intraperitoneal injection. Animals were terminated at 1, 3, or 7 d after treatment. The levels of DNA adducts were analyzed by the (32P-postlabeling assay. Our results showed that the levels of total hepatic DNA adducts were significantly decreased in FO groups compared to CO groups with an exception of low PAH dose at 3 d (P = 0.067. Total adduct levels in the high dose PAH groups were 41.36±6.48 (Mean±SEM and 78.72±8.03 in 10(9 nucleotides (P = 0.011, respectively, for the FO and CO groups at 7 d. Animals treated with the low dose (2.5 fold lower PAHs displayed similar trends. Total adduct levels were 12.21±2.33 in the FO group and 24.07±1.99 in the CO group, P = 0.008. BPDE-dG adduct values at 7 d after treatment of high dose PAHs were 32.34±1.94 (CO group and 21.82±3.37 (FO group in 10(9 nucleotides with P value being 0.035. Low dose groups showed similar trends for BPDE-dG adduct in the two diet groups. FO significantly enhanced gene expression of Cyp1a1 in both the high and low dose PAH groups. Gstt1 at low dose of PAHs showed high levels in FO compared to CO groups with P values being 0.014. Histological observations indicated that FO played a hepatoprotective role during the early stages. Our results suggest that FO has a potential to be developed as a cancer chemopreventive agent.

  2. Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells.

    Rusin, Scott F; Schlosser, Kate A; Adamo, Mark E; Kettenbach, Arminja N

    2015-10-13

    Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry-based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c-dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2-dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity. PMID:26462736

  3. NTP Carcinogenesis Bioassay of Propyl Gallate (CAS No. 121-79-9) in F344/N Rats and B6C3F1 Mice (Feed Study).

    1982-12-01

    Propyl gallate is a white to nearly white odorless powder having a slightly bitter taste. Solutions of propyl gallate turn dark in the presence of iron or iron salts. Propyl gallate has been used since 1948 as an antioxidant to stabilize cosmetics, food packaging materials, and foods containing fats. As an additive, it may be found in edible fats, oils, mayonnaise, shortening, baked goods, candy, dried meat, fresh pork sausage, and dried milk, and it is used in hair grooming products, pressure-sensitive adhesives, lubricating oil additives, and transforming oils. A NTP Carcinogenesis bioassay of propyl gallate was conducted by feeding diets containing 6,000 or 12,000 ppm propyl gallate to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 untreated rats and 50 untreated mice of each sex served as controls. Survival of rats and mice was not adversely affected by propyl gallate, but mean body weights of dosed rats and mice of each sex were lower than those of the controls. At 104 weeks, mean body weights of low-and high-dose rats were 4% and 8% lower than those of the controls for males and 11% and 19% lower than those of the controls for females. Similarly, mean body weights of low-and high-dose mice were 5% and 8% lower than those of the controls for males and 11% (both dose groups) lower than those of the controls for females. Thyroid follicular-cell adenomas or carcinomas (combined) occurred in male rats with a statistically significant (P<0.05) positive trend, but the incidences in the dosed groups were not statistically significant in direct comparisons with the control groups. Moreover, the incidence of high-dose male rats with follicular-cell tumors (3/50, 6%) was not statistically different from the historical control rate (14/584, 2.4%) for the laboratory that conducted this bioassay. Rare tumors (an astrocytoma or a glioma) were found in the brains of two low-dose female rats. The incidence of all brain tumors in the

  4. NTP Toxicology and Carcinogenesis Studies of Coumarin (CAS No. 91-64-5) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    1993-09-01

    Coumarin is the basic structure of numerous naturally occurring compounds with important and diverse physiological activities. More than a thousand coumarin derivatives have been described, varying from simple coumarins containing alkyl and hydroxyl side chains to complex coumarins with benzoyl, furanoyl, pyranoyl, or alkylphosphorothionyl substituents. Coumarin and 3,4-dihydrocoumarin were nominated by the Food and Drug Administration and the National Cancer Institute for study because of the widespread use of coumarin in perfumes, cosmetics, and other products as a fragrance, continued interest in coumarin compounds as flavor-enhancing agents for foods, and the interest in structure-activity relationships of this important group of compounds. Coumarin is believed to be metabolized to a 3,4-epoxide intermediate, which may be responsible for its toxic effects, while 3,4-dihydrocoumarin, which lacks the 3,4-double bond, is not considered likely to form an epoxide intermediate. Toxicity and carcinogenicity studies were conducted by administering coumarin (97% pure) in corn oil by gavage to groups of male and female F344/N rats and B6C3F1 mice for 16 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, Drosophila melanogaster, and B6C3F1 mice. 16-DAY STUDY IN RATS: Groups of five male and five female rats received coumarin in corn oil by gavage at doses of 0, 25, 50, 100, 200, or 400 mg per kg body weight, 5 days a week for a total of 12 doses in a 16-day period. All female rats and four male rats receiving 400 mg/kg died. The mean body weight gains and final mean body weights of surviving dosed male and female rats were similar to those of the controls. There were no clinical signs of organ-specific toxicity, and there was no evidence of impaired blood coagulation from measurements of capillary clotting time or prothrombin and activated partial thromboplastin time. 16-DAY STUDY IN MICE

  5. Differential Surface Expression of CD18 and CD44 by Neutrophils in Bone Marrow and Spleen Contributed to the Neutrophilia in Thalidomide-treated Female B6C3F1 Mice1

    Auttachoat, Wimolnut; Zheng, Jian Feng; Chi, Rui P.; Meng, Andrew; Guo, Tai L.

    2006-01-01

    Previously, we have reported that thalidomide (Thd) can enhance neutrophil function in female B6C3F1 mice. The present study was intended to evaluate the mechanisms underlying the enhanced neutrophil responses following Thd treatment intraperitoneally (100 mg/kg) for 14 or 28 days. Treatment with Thd increased the numbers of neutrophils in the spleen, peripheral blood, bone marrow, peritoneal cavity and lung of female B6C3F1 mice when compared to the vehicle control mice. Thd treatment for 14...

  6. Cellular basis of the immunohematologic defects observed in short-term semiallogeneic B6C3F1→C3H chimeras: evidence for host-versus-graft reaction initiated by radioresistant T cells

    Lethally irradiated C3Hf mice reconstituted with a relatively low dose (2 x 106) of B6C3F1 bone marrow cells (B6C3F1→C3Hf chimeras) frequently manifest immunohematologic deficiencies during the first month following injection of bone marrow cells. They show slow recovery of antibody-forming potential to sheep red blood cells (SRBC) as compared to that observed in syngeneic (C3Hf→C3Hf or B6C3F1→B6C3F1) chimeras. They also show a deficiency of B-cell activity as assessed by antibody response to SRBC following further reconstitution with B6C3F1-derived thymus cells 1 week after injection of bone marrow cells. A significant fraction of B6C3F1→C3Hf chimeras was shown to manifest a sudden loss of cellularity of spleens during the second week following injection of bone marrow cells even though cellularity was restored to the normal level within 1 week. The splenic mononuclear cells recovered from such chimeras almost invariably showed strong cytotoxicity against target cells expressing donor-type specific H-2 antigens (H-2/sup b/) when assesed by 51Cr-release assay in vitro. The effector cells responsible for the observed anti-donor specific cytotoxicity were shown to be residual host-derived T cells. These results indicate strongly that residual host T cells could develop anti-donor specific cytotoxicity even after exposure to a supralethal dose (1050 R) of radiation and that the immunohematologic disturbances observed in shortterm F1 to parent bone marrow chimeras (B6C3F1→C3Hf) were due to host-versus-graft reaction (HVGR) initiated by residual host T cells. The implication of these findings on the radiobiological nature of the residual T cells and the persistence of potentially anti-donor reactive T-cell clones in long-surviving allogeneic bone marrow chimeras was discussed

  7. Nitrogen incorporation in saturated aliphatic C6-C8 hydrocarbons and ethanol in low-pressure nitrogen plasma generated by a hollow cathode discharge ion source.

    Usmanov, Dilshadbek T; Chen, Lee Chuin; Hiraoka, Kenzo; Wada, Hiroshi; Nonami, Hiroshi; Yamabe, Shinichi

    2016-06-01

    Ion/molecule reactions of saturated hydrocarbons (n-hexane, cyclohexane, n-heptane, n-octane and isooctane) in 28-Torr N2 plasma generated by a hollow cathode discharge ion source were investigated using an Orbitrap mass spectrometer. It was found that the ions with [M+14](+) were observed as the major ions (M: sample molecule). The exact mass analysis revealed that the ions are nitrogenated molecules, [M+N](+) formed by the reactions of N3 (+) with M. The reaction, N3 (+) + M → [M+N](+) + N2 , were examined by the density functional theory calculations. It was found that N3 (+) abstracts the H atom from hydrocarbon molecules leading to the formation of protonated imines in the forms of R'R″CNH2 (+) (i.e. C-H bond nitrogenation). This result is in accord with the fact that elimination of NH3 is the major channel for MS/MS of [M+N](+) . That is, nitrogen is incorporated in the C-H bonds of saturated hydrocarbons. No nitrogenation was observed for benzene and acetone, which was ascribed to the formation of stable charge-transfer complexes benzene⋅⋅⋅⋅N3 (+) and acetone⋅⋅⋅⋅N3 (+) revealed by density functional theory calculations. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27270868

  8. Protective effects of the fermented milk Kefir on X-ray irradiation-induced intestinal damage in B6C3F1 mice

    Gastrointestinal damage associated with radiation therapy is currently an inevitable outcome. The protective effect of Kefir was assessed for its usefulness against radiation-induced gastrointestinal damage. A Kefir supernatant was diluted by 2- or 10-fold and administered for 1 week prior to 8 Gray (Gy) X-ray irradiation at a dose rate of 2 Gy/min, with an additional 15d of administration post-irradiation. The survival rate of control mice with normal drinking water dropped to 70% on days 4 through 9 post-irradiation. On the other hand, 100% of mice in the 10- and 2-fold-diluted Kefir groups survived up to day 9 post-irradiation (p<0.05 and p<0.01, respectively). Examinations for crypt regeneration against 8, 10 and 12 Gy irradiation at a dose rate of 4 Gy/min revealed that the crypt number was significantly increased in the mice administered both diluted Kefir solutions (p<0.01 for each). Histological and immunohistochemical examinations revealed that the diluted Kefir solutions protected the crypts from radiation, and promoted crypt regeneration. In addition, lyophilized Kefir powder was found to significantly recover the testis weights (p<0.05), but had no effects on the body and spleen weights, after 8 Gy irradiation. These findings suggest that Kefir could be a promising candidate as a radiation-protective agent. (author)

  9. A quadruple mutant of Arabidopsis reveals a β-carotene hydroxylation activity for LUT1/CYP97C1 and a regulatory role of xanthophylls on determination of the PSI/PSII ratio

    Fiore Alessia

    2012-04-01

    Full Text Available Abstract Background Xanthophylls are oxygenated carotenoids playing an essential role as structural components of the photosynthetic apparatus. Xanthophylls contribute to the assembly and stability of light-harvesting complex, to light absorbance and to photoprotection. The first step in xanthophyll biosynthesis from α- and β-carotene is the hydroxylation of ε- and β-rings, performed by both non-heme iron oxygenases (CHY1, CHY2 and P450 cytochromes (LUT1/CYP97C1, LUT5/CYP97A3. The Arabidopsis triple chy1chy2lut5 mutant is almost completely depleted in β-xanthophylls. Results Here we report on the quadruple chy1chy2lut2lut5 mutant, additionally carrying the lut2 mutation (affecting lycopene ε-cyclase. This genotype lacks lutein and yet it shows a compensatory increase in β-xanthophylls with respect to chy1chy2lut5 mutant. Mutant plants show an even stronger photosensitivity than chy1chy2lut5, a complete lack of qE, the rapidly reversible component of non-photochemical quenching, and a peculiar organization of the pigment binding complexes into thylakoids. Biochemical analysis reveals that the chy1chy2lut2lut5 mutant is depleted in Lhcb subunits and is specifically affected in Photosystem I function, showing a deficiency in PSI-LHCI supercomplexes. Moreover, by analyzing a series of single, double, triple and quadruple Arabidopsis mutants in xanthophyll biosynthesis, we show a hitherto undescribed correlation between xanthophyll levels and the PSI-PSII ratio. The decrease in the xanthophyll/carotenoid ratio causes a proportional decrease in the LHCII and PSI core levels with respect to PSII. Conclusions The physiological and biochemical phenotype of the chy1chy2lut2lut5 mutant shows that (i LUT1/CYP97C1 protein reveals a major β-carotene hydroxylase activity in vivo when depleted in its preferred substrate α-carotene; (ii xanthophylls are needed for normal level of Photosystem I and LHCII accumulation.

  10. Plan of study to determine if the isotopic ratios [delta]15 N and [delta]18 O can reveal the sources of nitrate discharged by the Mississippi River into the Gulf of Mexico

    Battaglin, William A.; Kendall, Carol; Goolsby, Donald A.; Boyer, Laurie L.

    1997-01-01

    Nitrate and other nutrients discharged from the Mississippi River basin are suspected of causing a zone of depleted dissolved oxygen (hypoxic zone) in the Gulf of Mexico each summer. The hypoxic zone may have an adverse effect on aquatic life and commercial fisheries. Commercial fertilizers are the dominant source of nitrogen input to the Mississippi basin. Other nitrogen sources include animal waste, fixation of atmospheric nitrogen by legumes, precipitation, domestic and industrial effluent, and the soil. The inputs of nitrogen from most of these sources to the Mississippi basin can be estimated and the outputs in surface water can be measured. However, nitrogen from each source is affected differently by physical, chemical, and biological processes that control nitrogen cycling in terrestrial and aquatic systems. Hence, the relative contributions from the various sources of nitrogen to nitrate load in the Mississippi River are unknown because the different sources may not contribute proportionally to their inputs in the basin. It may be possible to determine the relative contributions of the major sources of nitrate in river water using the stable isotopic ratios d15N and d18O of the nitrate ion. A few researchers have used the d15N and/or d18O isotope ratios to determine sources of nitrate in ground water, headwater catchments, and small rivers, but little is known about the isotopic composition of nitrate in larger rivers. The objective of this study is to measure the isotopic composition of nitrate and suspended organic matter in the Mississippi River and its major tributaries, in discharge to the Gulf of Mexico, and in streamflow from smaller watersheds that have distinct sources of nitrogen (row crops, animal wastes, and urban effluents) or are minimally impacted by man (undeveloped). Samples from seven sites on the Mississippi River and its tributaries and from 17 sites in smaller watersheds within the Mississippi River basin will be analyzed for d15N and

  11. Tumor Volume and Metabolism of Prostate Cancer Determined by Proton Magnetic Resonance Spectroscopic Imaging at 3T Without Endorectal Coil Reveal Potential Clinical Implications in the Context of Radiation Oncology

    Purpose: To determine whether a relationship exists between the tumor volume (TV) or relative choline content determined using magnetic resonance spectroscopy imaging (MRSI) at 3T and the clinical prognostic parameters for patients with localized prostate cancer (PCa). Methods and Materials: A total of 72 men (mean age, 67.8 ± 6.2 years) were stratified as having low-risk (n = 26), intermediate-risk (n = 24), or high-risk (n = 22) PCa. MRSI was performed at 3T using a phased-array coil. Spectra are expressed as the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamines plus creatine/citrate ratios. The mean ratio of the most pathologic voxels and the MRSI-based TV were also determined. Results: The mean values of the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamine plus creatine/citrate ratios were greater for Stage T2b or greater tumors vs. Stage T2a or less tumors: 7.53 ± 13.60 vs. 2.31 ± 5.65 (p = .018), 8.98 ± 14.58 vs. 2.56 ± 5.70 (p = .016), and 10.32 ± 15.47 vs. 3.55 ± 6.16 (p = .014), respectively. The mean MRSI-based TV for Stage T2b or greater and Stage T2a or less tumors was significantly different (2.23 ± 2.62 cm3 vs. 1.26 ± 2.06 cm3, respectively; p = .030). This TV correlated with increased prostate-specific antigen levels (odds ratio, 1.293; p = .012). Patients with high-risk PCa had a larger TV than did the patients with intermediate-risk PCa. A similar result was found for the intermediate-risk group compared with the low-risk group (odds ratio, 1.225; p = .041). Conclusion: Biomarkers expressing the relative choline content and TV were significant parameters for the localization of PCa and could be helpful for determining the prognosis more accurately.

  12. Age, introduction of solid feed and weaning are more important determinants of gut bacterial succession in piglets than breed and nursing mother as revealed by a reciprocal cross-fostering model.

    Bian, Gaorui; Ma, Shouqing; Zhu, Zhigang; Su, Yong; Zoetendal, Erwin G; Mackie, Roderick; Liu, Junhua; Mu, Chunlong; Huang, Ruihua; Smidt, Hauke; Zhu, Weiyun

    2016-05-01

    A reciprocal cross-fostering model with an obese typical Chinese piglet breed and a lean Western breed was used to identify genetic and maternal effects on the acquisition and development gut bacteria from birth until after weaning. Pyrosequencing of 16S rRNA genes results revealed an age- and diet-dependent bacterial succession process in piglets. During the first 3 days after birth, the bacterial community was relatively simple and dominated by Firmicutes with 79% and 65% relative abundance for Meishan and Yorkshire piglets, respectively. During the suckling period until day 14, the piglet breed and the nursing mother lead to increasing differentiation of the fecal bacterial community, with specific bacteria taxa associated with breed, and others with the nursing sow most likely due to its milk composition. Although the effect of nursing mother and the breed were evident through the suckling period, the introduction of solid feed and subsequent weaning were the major events occurring that dominated succession of the gut microbiota in the early life of piglets. This piglet cross-fostering model is a useful tool for studying the effects of diet, host genetics and the environment on the development and acquisition of the gut microbiota and over longer studies the subsequent impact on growth, health and performance of pigs. PMID:26940746

  13. Toxicology and carcinogenesis studies of tetralin (CAS No. 119-64-2) in F344/N rats and B6C3F1 mice (inhalation studies).

    2011-04-01

    Tetralin is used as an industrial solvent primarily for naphthalene, fats, resins, oils, and waxes; as a solvent and stabilizer for shoe polishes and floor waxes; as a solvent for pesticides, rubber, asphalt, and aromatic hydrocarbons (e.g., anthracene); as a dye solvent carrier in the textile industry; as a substitute for turpentine in lacquers, paints, and varnishes; in paint thinners and as a paint remover; in alkali-resistant lacquers for cleaning printing ink from rollers and type; as a constituent of motor fuels and lubricants; for the removal of naphthalene in gas distribution systems; and as an insecticide for clothes moths. Tetralin was nominated by the National Cancer Institute for carcinogenicity and disposition studies because of its structure, high production volume, and high potential for worker and consumer exposure. Male and female F344/N rats and B6C3F1 mice were exposed to tetralin (at least 97% pure) by inhalation for 2 weeks, 3 months, or 2 years; male NCI Black Reiter (NBR) rats were exposed to tetralin by inhalation for 2 weeks. Male NBR rats do not produce 2u-globulin; the NBR rats were included to study the relationship of 2u-globulin and renal lesion induction. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male (F344/N and NBR) and five female (F344/N) rats were exposed to tetralin at air concentrations of 0, 7.5, 15, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 12 exposures. All rats survived to the end of the studies. The final mean body weight of female rats exposed to 120 ppm and mean body weight gains of female rats exposed to 30 ppm or greater were significantly less than those of the chamber controls. Final mean body weights of exposed groups of male NBR rats and mean body weight gains of all exposed groups of male rats were significantly less than those of the chamber controls. Dark

  14. Toxicology and carcinogenesis studies of methylphenidate hydrochloride (Cas No. 298-59-9) in F344/N rats and B6C3F1 mice (feed studies). Technical report series

    NONE

    1995-07-01

    Toxicology and carcinogenicity studies were conducted by administration of methylphenidate hydrochloride in feed to groups of 70 F344/N rats of each sex at doses of 0, 100, 500, or 1,0000 ppm and to groups of 70 B6C3F1 mice of each sex at doses of 0, 50, 250, or 500 ppm. Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of methylphenidate hydrochloride in male or female F344/N rats receiving 100, 500, or 1,000 ppm. There was some evidence of carcinogenic activity in male and female B6C3F1 mice, based on the occurrence of hepatocellular neoplasms. Treatment of female rats with methylphenidate hydrochloride was associated with a decrease in the incidence of mammary gland fibroadenomas. Administration of methylphenidate hydrochloride to male and female mice resulted in increased incidence of eosinophilic foci in the liver.

  15. Proverbs Reveal Culture Diversity

    Hou, Rong

    2013-01-01

    Through the analysis of property of culture and proverb, it can be known that proverb can help one to understand a culture. The way proverb reveals culture diversity can be connected with the patterns of value dimension, which conveys the information of a culture’s deep meaning. From the perspective of uncertainty-avoidance, it can be seen that although Ireland and America both are low-uncertainty-avoidance cultures, they mainly have different life attitudes, because that Americans put more e...

  16. Evaluation of on-line pyrolysis coupled to isotope ratio mass spectrometry for the determination of position-specific (13)C isotope composition of short chain n-alkanes (C6-C12).

    Gilbert, Alexis; Yamada, Keita; Yoshida, Naohiro

    2016-06-01

    We measured (13)C intramolecular isotopic composition of commercially available short-chain hydrocarbons (n-C6-n-C12) using (13)C-NMR. Results show that the main variation is between the terminal and the sub-terminal C-atom positions. Site-preference (difference in δ(13)C values between terminal and sub-terminal C-atom positions) among all the samples varies between -12.2‰ and +8.4‰. Comparison of these results with those obtained using on-line pyrolysis coupled with GC-C-IRMS show that the thermal cracking of hydrocarbons occurs with a good isotopic fidelity between terminal and sub-terminal C-atom positions of the starting material and the related pyrolysis products (methane and ethylene). On-line pyrolysis coupled with GC-C-IRMS can thus be used for tracing hydrocarbons biogeochemical processes. PMID:27130103

  17. Comparative Analysis of Novel Complement-Targeted Inhibitors, MiniFH, and the Natural Regulators Factor H and Factor H-like Protein 1 Reveal Functional Determinants of Complement Regulation.

    Harder, Markus J; Anliker, Markus; Höchsmann, Britta; Simmet, Thomas; Huber-Lang, Markus; Schrezenmeier, Hubert; Ricklin, Daniel; Lambris, John D; Barlow, Paul N; Schmidt, Christoph Q

    2016-01-15

    The serum proteins factor H (FH), consisting of 20 complement control protein modules (CCPs), and its splice product FH-like protein 1 (FHL-1; consisting of CCPs 1-7) are major regulators of the alternative pathway (AP) of complement activation. The engineered version of FH, miniFH, contains only the N- and C-terminal portions of FH linked by an optimized peptide and shows ∼ 10-fold higher ex vivo potency. We explored the hypothesis that regulatory potency is enhanced by unmasking of a ligand-binding site in the C-terminal CCPs 19-20 that is cryptic in full-length native FH. Therefore, we produced an FH variant lacking the central domains 10-15 (FHΔ10-15). To explore how avidity affects regulatory strength, we generated a duplicated version of miniFH, termed midiFH. We compared activities of FHΔ10-15 and midiFH to miniFH, FH, and FHL-1. Relative to FH, FHΔ10-15 exhibited an altered binding profile toward C3 activation products and a 5-fold-enhanced complement regulation on a paroxysmal nocturnal hemoglobinuria patient's erythrocytes. Contrary to dogma, FHL-1 and FH exhibited equal regulatory activity, suggesting that the role of FHL-1 in AP regulation has been underestimated. Unexpectedly, a substantially increased avidity for complement opsonins, as seen in midiFH, did not potentiate the inhibitory potential on host cells. In conclusion, comparisons of engineered and native FH-based regulators have identified features that determine high AP regulatory activity on host cells. Unrestricted availability of FH CCPs 19-20 and an optimal spatial orientation between the N- and C-terminal FH regions are key. PMID:26643478

  18. Revealing the programming process

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...

  19. TypeScript revealed

    Maharry, Dan

    2013-01-01

    TypeScript Revealed is a quick 100-page guide to Anders Hejlsberg's new take on JavaScript. With this brief, fast-paced introduction to TypeScript, .NET, Web and Windows 8 application developers who are already familiar with JavaScript will easily get up to speed with TypeScript and decide whether or not to start incorporating it into their own development. TypeScript is 'JavaScript for Application-scale development'; a superset of JavaScript that brings to it an additional object-oriented-like syntax familiar to .NET programmers that compiles down into simple, clean JavaScript that any browse

  20. Chemistry of plutonium revealed

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. In this paper the work carried out at Berkeley from the spring of 1942 to the summer of 1945 is described briefly. The aqueous chemistry of plutonium is quite remarkable. Important insights were obtained from tracer experiments, but the full complexity was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were based on aqueous solutions, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, an equilibrium was rapidly established among the four aqueous oxidation states, while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element are reported

  1. Revealing Cosmic Rotation

    Yadav, Amit P S; Keating, Brian G

    2012-01-01

    Cosmological Birefringence (CB), a rotation of the polarization plane of radiation coming to us from distant astrophysical sources, may reveal parity violation in either the electromagnetic or gravitational sectors of the fundamental interactions in nature. Until only recently this phenomenon could be probed with only radio observations or observations at UV wavelengths. Recently, there is a substantial effort to constrain such non-standard models using observations of the rotation of the polarization plane of cosmic microwave background (CMB) radiation. This can be done via measurements of the $B$-modes of the CMB or by measuring its TB and EB correlations which vanish in the standard model. In this paper we show that $EB$ correlations-based estimator is the best for upcoming polarization experiments. The $EB$ based estimator surpasses other estimators because it has the smallest noise and of all the estimators is least affected by systematics. Current polarimeters are optimized for the detection of $B$-mode...

  2. Android Emotions Revealed

    Vlachos, Evgenios; Schärfe, Henrik

    2012-01-01

    This work presents a method for designing facial interfaces for sociable android robots with respect to the fundamental rules of human affect expression. Extending the work of Paul Ekman towards a robotic direction, we follow the judgment-based approach for evaluating facial expressions to test in...... which case an android robot like the Geminoid|DK –a duplicate of an Original person- reveals emotions convincingly; when following an empirical perspective, or when following a theoretical one. The methodology includes the processes of acquiring the empirical data, and gathering feedback on them. Our...... findings are based on the results derived from a number of judgments, and suggest that before programming the facial expressions of a Geminoid, the Original should pass through the proposed procedure. According to our recommendations, the facial expressions of an android should be tested by judges, even in...

  3. Radiotoxicity of systemically administered [211At]astatide in B6C3F1 and BALB/C (NU/NU) mice: A long-term survival study with histologic analysis

    Purpose: The present study undertook to establish the dose (LD) of systemically administered (via tail vein) sodium [211At]astatide that would kill 10% (LD10) of exposed animals in two mouse models and to evaluate the resulting histologic lesions. Methods and Materials: Three dose escalation experiments were carried out using groups of 10 3- to 4-week-old, 20 ± 2 g B6C3F1 mice, and one dose escalation experiment was carried out with groups of 10 4- to 6-week-old, 22 ± 2 g BALB/c (nu/nu) mice. All animals were weighed daily and checked twice daily for general health; autopsies were performed within 12 h of death. Results: The LD10 (95% confidence interval) level of free [211At]astatide at 360 days was 15.1 μCi (5.2-19.1 μCi) in B6C3F1 mice and was associated with a 37.8% weight difference from saline controls (p 10 at 360 days was 7.7 μCi (0-14.2 μCi), while a dose of 10 μCi (0.42 μCi g-1) was associated with a 9.44% weight difference vs. saline controls (p 211At]astatide activity levels were associated with severe bone marrow depression, testicular atrophy, focal alopecia, and nuclear atypia of the epidermoid mucosa of the fore-stomach in the B6C3F1 mice; at activity levels approximating LD10 at 360 days, mild changes in the heart, liver, stomach, and spleen were observed. For BALB/c (nu/nu) mice, administration of 10 μCi was associated at autopsy with mild histologic lesions in the heart, stomach, liver, and spleen. Conclusions: These studies provide a basis for the design of further investigations of [211At]-labeled compounds as therapeutic agents.

  4. Synthesis, structural characterization, and spectroscopy of the cadmium-cadmium bonded molecular species Ar'CdCdAr' (Ar' = C6H3-2,6-(C6H3-2,6-Pri2)2).

    Zhu, Zhongliang; Fischer, Roland C; Fettinger, James C; Rivard, Eric; Brynda, Marcin; Power, Philip P

    2006-11-29

    The synthesis and first structural characterization of a cadmium-cadmium bonded molecular compound Ar'CdCdAr' (Ar' = C6H3-2,6-(C6H3-2,6-Pri2)2) are reported. The existence of the Cd-Cd bond was established by 113Cd NMR spectroscopy and X-ray diffraction (Cd-Cd = 2.6257(5) A). Like its group 12 analogue Ar'ZnZnAr', DFT calculations showed that Ar'CdCdAr' had significant p-character in the Cd-Cd sigma-bonding HOMO. PMID:17117840

  5. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen

    Baldwin, Susan L; Roeffen, Will; Singh, Susheel K;

    2016-01-01

    A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the......, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN...

  6. Spatial interactions determine temporal feature integration as revealed by unmasking

    Michael H. Herzog

    2006-01-01

    Full Text Available Feature integration is one of the most fundamental problems in neuroscience. In a recent contribution, we showed that a trailing grating can diminish the masking effects one vernier exerts on another, preceding vernier. Here, we show that this temporal unmasking depends on neural spatial interactions related to the trailing grating. Hence, our paradigm allows us to study the spatio-temporal interactions underlying feature integration.

  7. Eye Movements Reveal Dynamics of Task Control

    Mayr, Ulrich; Kuhns, David; Rieter, Miranda

    2013-01-01

    With the goal to determine the cognitive architecture that underlies flexible changes of control settings, we assessed within-trial and across-trial dynamics of attentional selection by tracking of eye movements in the context of a cued task-switching paradigm. Within-trial dynamics revealed a switch-induced, discrete delay in onset of…

  8. Toxicity and Carcinogenicity of Ozone in Combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and Dibutyl Phthalate in B6C3F1 Mice for 16 and 32 Weeks

    MIN YOUNG KIM; M YUNG CHO

    2009-01-01

    Objective To evaluate the toxic and carcinogenic potential of ozone alone or in combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyddyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP). Methods Male and female B6C3F1 mice were exposed,through inhalation,intravenous administration and diet,to 0.5 ppm of ozone,1.0 mg/kg of NNK and 5000 ppm of DBP,individually and in combination for 16 and 32 weeks. Results No treatment-related death was seen,but significant differences in body and organ weights between control and treated mice were observed during the study.No incidence of lung tumor incidence was recorded in mice exposed to either ozone alone or combined treatment.Oviductal carcinomas were observed in female mice exposed to ozone or DBP alone for 16 weeks and ozone in combination with NNK and DBP for 32 weeks. Conclusion Although ozone alone and in conjunction with NNK and/or DBP does not induce lung cancer under our experimental conditions,they induce oviductal carcinomas in B6C3F1 mice.

  9. DOE 5700.6C, 10CFR830.120, DOE-ER-STD-6001-92, and Covey-based TQM: A historical perspective on current issues in research environments

    Bodnarczuk, M

    1994-06-01

    Three years ago there were no standards or published guidelines for quality in research environments. Today, one standard has been published, and three guidelines documents are in final draft form and about to be published. In this paper, I describe the events that led to the writing of DOE 5700.6C, 10CFR830.120, and DOE-ER-STD-6001-92, focusing on the cultural barriers that arose (largely in the community of quality assurance professionals) during this process. I go on to describe why I believe that implementing DOE 5700.6C and 10CFR830.120 must be pushed even further toward an approach that embodies the Malcolm Baldrige National Quality Award and why even this is not far enough. The reason is because the most crucial aspect of successfully implementing a quality initiative is to base it on a cohesive, unified foundation of organizational and individual values and beliefs. Stephen Covey`s 7 Habits of Highly Effective People and Principle Centered Leadership provide such a foundations.

  10. NTP Toxicity Studies of Sodium Cyanide (CAS No. 143-33-9) Administered by Dosed Water to F344/N Rats and B6C3F1 Mice.

    1993-11-01

    Cyanide and its salts are used extensively in industry and manufacturing and are found in water and food consumed by humans. Chronic exposure to low levels of cyanide is suspected to be responsible for various neuropathic and thyrotoxic conditions in humans. Data in the literature indicate that long-term exposure to near-lethal concentrations of cyanide may produce lesions in rodents similar to those linked to chronic cyanide exposure in humans. However, few data are available on the effects of subchronic exposure to cyanide concentrations that are not acutely toxic. To address this lack of data, 13-week toxicity studies on cyanide were conducted with male and female F344/N rats and B6C3F1 mice administered low doses of sodium cyanide in drinking water. Animals were evaluated for histopathology, clinical chemistry, hematology, urine chemistry, and reproductive toxicity. In addition, the mutagenicity of sodium cyanide was assessed in Salmonella typhimurium. Groups of 10 rats and 10 mice per sex were administered sodium cyanide in drinking water at concentrations of 0, 3, 10, 30, 100, and 300 ppm for 13 weeks. No deaths attributed to sodium cyanide administration occurred in either species. In animals exposed to 300 ppm, male rats had slightly lower final mean body weights and mean body weight gains and female mice had slightly lower final mean body weights than the respective controls. Water consumption by rats and mice in the 100 and 300 ppm groups was 10% to 30% lower than that by the controls; however, no clinical signs attributable to sodium cyanide administration or to dehydration were observed. No gross or microscopic changes specifically related to cyanide toxicity occurred at any site in males or females of either species. In particular, no lesions were found in the brain or thyroid gland. Differences between absolute and relative organ weights of exposed and control animals were minor and sporadic and were not exposure concentration dependent; these

  11. Puerto Rico Revealed Preference data

    National Oceanic and Atmospheric Administration, Department of Commerce — Revealed preference models provide insights into recreational angler behavior and the economic value of recreational fishing trips. Revealed preference data is...

  12. Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice

    Previously, we have reported that thalidomide (Thd) can enhance neutrophil function in female B6C3F1 mice. The present study was intended to evaluate the mechanisms underlying the enhanced neutrophil responses following Thd treatment intraperitoneally (100 mg/kg) for 14 or 28 days. Treatment with Thd increased the numbers of neutrophils in the spleen, peripheral blood, bone marrow, peritoneal cavity and lungs of female B6C3F1 mice when compared to the vehicle control mice. Thd treatment for 14 days increased the percentage and the number of neutrophils in the spleen in the first 8 h (peaking at 2 h) after the last Thd treatment, and it returned to the baseline after 24 h. However, Thd treatment for 28 days increased the percentage and number of neutrophils in the spleen even at the 24-h time point after the last Thd treatment. These neutrophils were demonstrated to be functional by the myeloperoxidase activity assay. Further studies have ruled out the possibility of an increased bone marrow granulopoiesis following Thd treatment. Flow cytometric analysis of the surface expression of adhesion molecules suggested that Thd treatment for either 14 or 28 days decreased the surface expression of either CD18 or CD44 by bone marrow neutrophils. On the other hand, the surface expression of both CD18 and CD44 by splenic neutrophils was increased following Thd treatment for 28 days but not for 14 days. No effect was produced for other cell surface molecules such as CD62L and CD11a. It was possible that decreased surface expressions of CD18 and CD44 facilitated neutrophils' release from the bone marrow; increased surface expressions of CD44 and CD18 by splenic neutrophils after 28 days of Thd treatment increased their ability to remain in the periphery. Taken together, Thd treatment increased neutrophils in female B6C3F1 mice, at least partially, through differentially modulating the surface expression of CD18 and CD44 by the neutrophils in the bone marrow and spleen

  13. Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice.

    Auttachoat, Wimolnut; Zheng, Jian Feng; Chi, Rui P; Meng, Andrew; Guo, Tai L

    2007-02-01

    Previously, we have reported that thalidomide (Thd) can enhance neutrophil function in female B6C3F1 mice. The present study was intended to evaluate the mechanisms underlying the enhanced neutrophil responses following Thd treatment intraperitoneally (100 mg/kg) for 14 or 28 days. Treatment with Thd increased the numbers of neutrophils in the spleen, peripheral blood, bone marrow, peritoneal cavity and lungs of female B6C3F1 mice when compared to the vehicle control mice. Thd treatment for 14 days increased the percentage and the number of neutrophils in the spleen in the first 8 h (peaking at 2 h) after the last Thd treatment, and it returned to the baseline after 24 h. However, Thd treatment for 28 days increased the percentage and number of neutrophils in the spleen even at the 24-h time point after the last Thd treatment. These neutrophils were demonstrated to be functional by the myeloperoxidase activity assay. Further studies have ruled out the possibility of an increased bone marrow granulopoiesis following Thd treatment. Flow cytometric analysis of the surface expression of adhesion molecules suggested that Thd treatment for either 14 or 28 days decreased the surface expression of either CD18 or CD44 by bone marrow neutrophils. On the other hand, the surface expression of both CD18 and CD44 by splenic neutrophils was increased following Thd treatment for 28 days but not for 14 days. No effect was produced for other cell surface molecules such as CD62L and CD11a. It was possible that decreased surface expressions of CD18 and CD44 facilitated neutrophils' release from the bone marrow; increased surface expressions of CD44 and CD18 by splenic neutrophils after 28 days of Thd treatment increased their ability to remain in the periphery. Taken together, Thd treatment increased neutrophils in female B6C3F1 mice, at least partially, through differentially modulating the surface expression of CD18 and CD44 by the neutrophils in the bone marrow and spleen. PMID

  14. Kinematic viscosity and speed of sound in gaseous CO, CO2, SiF4, SF6, C4F8, and NH3 from 220 K to 375 K and pressures up to 3.4 MPa

    An acoustic Greenspan viscometer was used to measure the kinematic viscosity and speed of sound in the gases: CO, CO2, SiF4, SF6, C4F8, and NH3. The measurements cover the temperature range 220 K to 375 K, and pressures up to 3.4 MPa or 80% of the saturation pressure. The viscometer was calibrated at 298.16 K using five reference gases, Ar, He, N2, CH4, and C3H8, for which the viscosity and the speed of sound are known. With this calibration, we estimated the relative standard uncertainty of the kinematic viscosity ur(η/ρ) = 0.006 and the uncertainty of speed of sound ur(c) = 0.0001, except for very low pressures where the signal-to-noise ratio deteriorates and quality factor for the Helmholtz mode is ≤20

  15. Mammalian phylogeny reveals recent diversification rate shifts

    Stadler, Tanja

    2011-01-01

    Phylogenetic trees of present-day species allow investigation of the rate of evolution that led to the present-day diversity. A recent analysis of the mammalian phylogeny challenged the view of explosive mammalian evolution after the Cretaceous–Tertiary (K/T) boundary (65 Mya). However, due to lack of appropriate methods, the diversification (speciation minus extinction) rates in the more recent past of mammalian evolution could not be determined. In this paper, I provide a method that reveal...

  16. Revealed Cores: Characterizations and Structure

    Stefano Vannucci

    2010-01-01

    Characterizations of the choice functions that select the cores or the externally stable cores induced by an underlying revealed dominance digraph are provided. Relying on such characterizations, the basic order-theoretic structure of the corresponding sets of revealed cores is also analyzed

  17. NTP Carcinogenesis Bioassay of L-Ascorbic Acid (Vitamin C) (CAS No. 50-81-7) in F344/N Rats and B6C3F1 Mice (Feed Study).

    1983-03-01

    L-Ascorbic acid is essential for many physiologic functions in animals and humans, mostly biochemical reactions involving oxidation. L-Ascorbic acid is approved for use as a dietary supplement and chemical preservative by the U.S. Food and Drug Administration and is on the FDA's list of substances generally recognized as safe. L-Ascorbic acid may be used in soft drinks as an antioxidant for flavor ingredients, in meat and meat-containing products, for curing and pickling, in flour to improve baking quality, in beer as a stabilizer, in fats and oils as an antioxidant, and in a wide variety of foods for vitamin C enrichment. L-Ascorbic acid may also find use in stain removers, hair waving preparations; plastics manufacture, photography, and water treatment. A NTP Carcinogenesis bioassay of L-ascorbic acid (>97% pure) was conducted by administering diets containing 25,000 or 50,000 ppm L-ascorbic acid to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Controls consisted of 50 untreated rats and untreated mice of each sex. Fifty-thousand ppm is the highest dose recommended for chronic studies. Survival of dosed and control female rats and of dosed and control female mice were comparable. Survival of high-dose male rats was slightly greater than that of the controls (P=0.087). Survival of high-dose male mice was significantly greater (P=0.009) than that of the controls. Throughout most of the study, mean body weights of dosed female rats and dosed female mice were lower than those of the controls. Final body weights were comparable among groups, except for the high-dose female rats (0.07) than those in the controls, the trend test was not significant (P>/=0.07), and no increases were observed for male rats. Under the conditions of this bioassay, L-ascorbic acid was not carcinogenic for male and female F344/N rats or male and female B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative

  18. A New Rerouting Technique for the Extensor Pollicis Longus in Palliative Treatment for Wrist and Finger Extension Paralysis Resulting From Radial Nerve and C5C6C7 Root Injury.

    Laravine, Jennifer; Cambon-Binder, Adeline; Belkheyar, Zoubir

    2016-03-01

    Wrist and finger extension paralysis is a consequence of an injury to the radial nerve or the C5C6C7 roots. Despite these 2 different levels of lesions, palliative treatment for this type of paralysis depends on the same tendon transfers. A large majority of the patients are able to compensate for a deficiency of the extension of the wrist and fingers. However, a deficiency in the opening of the first web space, which could be responsible for transfers to the abductor pollicis longus, the extensor pollicis brevis, and the extensor pollicis longus (EPL), frequently exists. The aim of this work was to evaluate the feasibility of a new EPL rerouting technique outside of Lister's tubercle. Another aim was to verify whether this technique allows a better opening of the thumb-index pinch in this type of paralysis. In the first part, we performed an anatomic study comparing the EPL rerouting technique and the frequently used technique for wrist and finger extension paralyses. In the second part, we present 2 clinical cases in which this new technique will be practiced. Preliminary results during this study favor the EPL rerouting technique. This is a simple and reproducible technique that allows for good opening of the first web space in the treatment of wrist and finger extension paralysis. PMID:26709570

  19. Ntp technical report on toxicity, reproductive, and developmental studies of 60-Hz magnetic fields, administered by whole body exposure to F344/N rats, Sprague-Dawley rats, and B6C3F1 mice. Toxicity report series

    Boorman, G.A.

    1996-09-01

    Electric and magnetic fields are associated with the production, transmission, and use of electricity; thus the potential for human exposure is high. These electric and magnetic fields are predominantly of low frequency (60 Hz) and generally of low intensity. The prevailing view among physicists is that exposure to these low-frequency, low-intensity fields does not pose a health hazard. However, this view has been challenged by reports linking magnetic field exposure to the development of leukemia and other cancers. Because multiple epidemiologic studies suggested a potential for increased cancer rates with increasing exposure, and because of public concern, the effects of 60-Hz magnetic field exposure were examined in F344/N rats and B6C3F1 mice in 8-week full-body-exposure studies. Animals were evaluated for hematology and clinical chemistry (rats only) parameters, pineal gland hormone concentrations, and histopathology. Additional studies were performed in Sprague-Dawley rats to examine teratologic and reproductive effects of magnetic field exposure.

  20. Ground-based solar absorption measurements of CH{sub 4}, CO, C{sub 2}H{sub 6}, C2H2 and HCN in the tropics

    Petersen, Anna K.; Warneke, Thorsten; Velasco, Voltaire; Notholt, Justus [Institute of Environmental Physics (IUP), University of Bremen (Germany); Schrems, Otto [Alfred Wegener Institute for Polar and Marine Research (AWI), Bremerhaven (Germany)

    2007-07-01

    The composition of the tropical atmosphere and its change is of significant importance for global climate. Currently large uncertainties in the budgets of many trace gases in the tropics exist, mainly due to a lack of measurements in the tropics. We have performed solar absorption Fourier Transform InfraRed measurements at Paramaribo, Suriname (5.83 N, 55.17 W) during four consecutive dry seasons, starting in autumn 2004. Currently these are the only remote sensing measurements performed in the inner-tropics over a longer time period. In the case of methane these measurements represent the only tropical ground-based remote sensing data of sufficient precision to validate satellite retrievals of CH4. Here we present first results on methane (CH{sub 4}) and trace gases related to biomass burning. Methane retrievals are compared with model simulations, satellite retrievals from SCIAMACHY and in situ data. In addition we investigate the pollution from biomass burning using CO, C{sub 2}H{sub 6}, C{sub 2}H{sub 2} and HCN. Backwardtrajectories and global fire maps were used to identify the origin of the polluted air masses. Correlations between the different gases are analysed and compared to literature data.

  1. Radioprotective effects of miso (fermented soy bean paste) against radiation in B6C3F1 mice. Increased small intestinal crypt survival, crypt lengths and prolongation of average time to death

    The radioprotective effect of miso, a fermentation product from soy bean, was investigated with reference to the survival time, crypt survival and jejunum crypt length in male B6C3F1 mice. Miso at three different fermentation stages (early-, medium- and long-term fermented miso) was mixed in MF diet into biscuits at 10% and was administered from 1 week before irradiation. Animal survival in the long-term fermented miso group was significantly prolonged as compared with the short-term fermented miso and MF cases after 8 Gy of 60Co-γ-ray irradiation at a dose rate of 2 Gy min-1. Delay in mortality was evident in all three miso groups, with significantly increased survival. At doses of 10 and 12 Gy X-irradiation at a dose rate of 4 Gy min-1, the treatment with long-term fermented miso significantly increased crypt survival. Also the protective influence against irradiation in terms of crypt lengths in the long-term fermented miso group was significantly greater than in the short-term or medium-term fermented miso and MF diet groups. Thus, prolonged fermentation appears to be very important for protection against radiation effects. (author)

  2. Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90 days of exposure to hexavalent chromium in drinking water

    Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90 days of exposure to 0, 0.3, 4, 14, 60, 170 or 520 mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose–response modeling identified > 80% of the differentially expressed genes exhibited sigmoidal dose–response curves with EC50 values ranging from 10 to 100 mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC50 values 50 of 47 mg/L SDD.

  3. Implementation guide for use with suspect/counterfeit items: Requirements of DOE O 440.1, worker protection management; 10 CFR 830.120; and DOE 5700.6C, quality assurance

    Department of Energy (DOE) Order (O) 440.1, Worker Protection Management For DOE Federal and Contractors Employees, [7] sets forth requirements for DOE and its contractors to implement suspect and counterfeit items (S/CI) controls as part of the quality assurance (QA) programs required by 10 Code of Federal Regulations (CFR) 830.120 [8] or DOE 5700.6C, Quality Assurance [9]. DOE G-830.120, Implementation Guide for Use with 10 CFR Part 830.120, Quality Assurance, [10] provides additional guidance on establishing and implementing effective QA processes to control S/CIs. DOE O 232.1, Occurrence Reporting and Processing of Operations, [11] specifies requirements for reporting S/CIs under the DOE Occurrence Reporting and Processing System (ORPS). DOE promulgated the requirements and guidance to control or eliminate the hazards posed by S/CIs, which can lead to unexpected equipment failures and undue risks to the DOE mission, the environment, and personnel. This Guide is a compendium of information contained in the referenced DOE directives and other documents concerning S/CI controls. It incorporates, updates, and supersedes earlier guidance issued in Plan for the Suspect/Counterfeit Products Issue in the Department of Energy, dated October 1993, [4] and in memoranda issued by Defense Programs (DP) [12-16] and other DOE program offices. This guidance was developed to strengthen the procurement process, identify and eliminate S/CIs, and improve the reporting of S/CIs. The information in this Guide, when implemented by DOE and its contractors, will satisfy the S/CI requirements contained in the referenced DOE directives

  4. FTIR time-series of biomass burning products (HCN, C2H6, C2H2, CH3OH, and HCOOH) at Reunion Island (21° S, 55° E) and comparisons with model data

    Vigouroux, C.; Stavrakou, T.; Whaley, C.; Dils, B.; Duflot, V.; Hermans, C.; Kumps, N.; Metzger, J.-M.; Scolas, F.; Vanhaelewyn, G.; Müller, J.-F.; Jones, D. B. A.; Li, Q.; De Mazière, M.

    2012-11-01

    Reunion Island (21° S, 55° E), situated in the Indian Ocean at about 800 km east of Madagascar, is appropriately located to monitor the outflow of biomass burning pollution from Southern Africa and Madagascar, in the case of short-lived compounds, and from other Southern Hemispheric landmasses such as South America, in the case of longer-lived species. Ground-based Fourier transform infrared (FTIR) solar absorption observations are sensitive to a large number of biomass burning products. We present in this work the FTIR retrieval strategies, suitable for very humid sites such as Reunion Island, for hydrogen cyanide (HCN), ethane (C2H6), acetylene (C2H2), methanol (CH3OH), and formic acid (HCOOH). We provide their total columns time-series obtained from the measurements during August-October 2004, May-October 2007, and May 2009-December 2010. We show that biomass burning explains a large part of the observed seasonal and interannual variability of the chemical species. The correlations between the daily mean total columns of each of the species and those of CO, also measured with our FTIR spectrometer at Reunion Island, are very good from August to November (R ≥ 0.86). This allows us to derive, for that period, the following enhancement ratios with respect to CO: 0.0047, 0.0078, 0.0020, 0.012, and 0.0046 for HCN, C2H6, C2H2, CH3OH, and HCOOH, respectively. The HCN ground-based data are compared to the chemical transport model GEOS-Chem, while the data for the other species are compared to the IMAGESv2 model. We show that using the HCN/CO ratio derived from our measurements (0.0047) in GEOS-Chem reduces the underestimation of the modeled HCN columns compared with the FTIR measurements. The comparisons between IMAGESv2 and the long-lived species C2H6 and C2H2 indicate that the biomass burning emissions used in the model (from the GFED3 inventory) are probably underestimated in the late September-October period for all years of measurements, and especially in

  5. Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

    Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. Cmax and AUC∞ increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC∞ for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain:plasma ratios were

  6. Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

    Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Johnson, Jerry D.; Hong, S. Peter [Battelle Memorial Institute, Columbus, OH 43201 (United States); Robinson, Veronica Godfrey [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Gibbs, Seth; Graves, Steven W. [Battelle Memorial Institute, Columbus, OH 43201 (United States); Hooth, Michelle J.; Smith, Cynthia S. [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)

    2013-09-01

    Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ∞} increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ∞} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain

  7. Urticarial vasculitis reveals unsuspected thyroiditis.

    Ferreira, Olga; Mota, Alberto; Baudrier, Teresa; Azevedo, Filomena

    2012-01-01

    A 38-year-old woman presented with erythematous, violaceous plaques with a serpiginous and unusual appearance located on the left shoulder, left thigh, and right buttock, evolving for 5 days, which eventually became generalized. A skin biopsy revealed leukocytoclastic vasculitis and a diagnosis of urticarial vasculitis was made. The complete blood count, biochemistry, complement levels, and other immunological test results were unremarkable. However, antithyroid antibody titers were increased. Despite having normal thyroid function tests and an absence of specific symptoms, the patient underwent a thyroid ultrasound, which revealed features of thyroiditis, and was subsequently referred to an endocrinologist. Several diseases can be associated with urticarial vasculitis, namely infections and autoimmune connective-tissue disorders such as systemic lupus erythematosus and Sjögren syndrome. Thyroiditis is an uncommon association. PMID:23000939

  8. Decision Making and Revealed Preference

    de la Rosa, Leonidas Enrique

    If our decision-making processes are to some extent shaped by evolutionary pressures and our environment is different from that to which we adapted, some of our choices will not be in our best interest. But revealed preference is the only tool that we have so far to conduct a normative analysis. ....... Given advances in evolutionary psychology and neuroscience, I propose one way to model those evolutionary pressures that will hopefully prove useful in expanding normative economics.......If our decision-making processes are to some extent shaped by evolutionary pressures and our environment is different from that to which we adapted, some of our choices will not be in our best interest. But revealed preference is the only tool that we have so far to conduct a normative analysis...

  9. Lipid sorting revealed by SANS

    We have investigated the lipid sorting in a binary small unilamellar vesicle (SUV) composed of cone-shaped (1,2-dihexanoyl-sn-glycero-3-phosphocholine: DHPC) and cylinder-shaped (1,2-dipalmitoyl-sn-glycero-3-phosphocholine: DPPC) lipids. In order to reveal the lipid sorting we adopted a contrast matching technique of small angle neutron scattering (SANS), which extracts the distribution of deuterated lipids in the bilayer quantitatively. The SANS profile of deuterated SUVs at the contrast matching condition showed a characteristic scattering profile, indicating an asymmetric distribution of cone-shaped lipids in the bilayer. The fitting of the observed SANS profile revealed that most DHPC molecules are localized in the outer leaflet, which supports that the shape of the lipid is strongly coupled with the membrane curvature. We compared the obtained asymmetric distribution of the cone-shaped lipids in the bilayer with the theoretical prediction based on the curvature energy model. (author)

  10. Revealing and Concealing in Antiquity

    Secrecy and the act of concealing and revealing knowledge effectually segregate the initiated and the uninitiated. The act of sharing or hiding knowledge plays a central role in all human relations private or public, political or religious. This volume explores the concept of secrecy and its impl...... the concept of secrecy and its potential for illuminating the agendas behind identity constructions, political propaganda, literary works, religous practices and shared history....

  11. NTP Carcinogenesis Studies of Food Grade Geranyl Acetate (71% Geranyl Acetate, 29% Citronellyl Acetate) (CAS No. 105-87-3) in F344/N Rats and B6C3F1 Mice (Gavage Study).

    1987-10-01

    Geranyl acetate (3,7-dimethyl-2,6-octadiene-1-ol acetate) is a colorless liquid prepared by fractional distillation of selected essential oils or by acetylation of geraniol. It is a natural constituent of more than 60 essential oils, including Ceylon citronella, palmarosa, lemon grass, petit grain, neroli bigarade, geranium, coriander, carrot, and sassafras. Geranyl acetate is used primarily as a component of perfumes for creams and soaps and as a flavoring ingredient. On the U.S. Food and Drug Administration's list of substances "generally recognized as safe," the Food Chemicals Codex (1972) specifies that geranyl acetate must contain at least 90% total esters. Carcinogenesis studies of food-grade geranyl acetate (containing approximately 29% citronellyl acetate) were conducted by administering the test chemical in corn oil by gavage to groups of 50 male and 50 female F344/N rats at doses of 1,000 or 2,000 mg/kg body weight and to groups of 50 male and 50 female B6C3F1 mice at doses of 500 or 1,000 mg/kg. Doses were administered five times per week for 103 weeks. Groups of 50 rats and 50 mice of each sex received corn oil by gavage on the same dosing schedule and served as vehicle controls. The cumulative toxicity of geranyl acetate in the 2-year study was indicated by the significantly shorter survival of high dose male rats (control, 34/50; low dose, 29/50; high dose, 18/50) and of high dose male mice (control, 31/50; low dose, 32/50; high dose, 0/50) and of dosed female mice (38/50; 15/50; 0/50) when compared with controls. Throughout most of the 2-year study, mean body weights of high dose rats and mice of each sex were lower than those of the controls. The occurrence of retinopathy or cataracts in the high dose male rats and low dose female rats as compared with the controls does not appear to be related to the administration of geranyl acetate but rather the proximity of the rats to fluorescent light. The incidence of retinopathy or cataracts (combined) was

  12. Determinants of marriage dissolution

    Rahim, Mohd Amirul Rafiq Abu; Shafie, Siti Aishah Mohd; Hadi, Az'lina Abdul; Razali, Nornadiah Mohd; Azid @ Maarof, Nur Niswah Naslina

    2015-10-01

    Nowadays, the number of divorce cases among Muslim couples is very worrisome whereby the total cases reported in 2013 increased by half of the total cases reported in the previous year. The questions on the true key factors of dissolution of marriage continue to arise. Thus, the objective of this study is to reveal the factors that contribute to the dissolution of marriage. A total of 181 cases and ten potential determinants were included in this study. The potential determinants considered were age at marriage of husband and wife, educational level of husband and wife, employment status of husband and wife, income of husband and wife, the number of children and the presence at a counseling session. Logistic regression analysis was used to analyze the data. The findings revealed that four determinants, namely the income of husband and wife, number of children and the presence at a counselling session were significant in predicting the likelihood of divorce among Muslim couples.

  13. Transparency masters for mathematics revealed

    Berman, Elizabeth

    1980-01-01

    Transparency Masters for Mathematics Revealed focuses on master diagrams that can be used for transparencies for an overhead projector or duplicator masters for worksheets. The book offers information on a compilation of master diagrams prepared by John R. Stafford, Jr., audiovisual supervisor at the University of Missouri at Kansas City. Some of the transparencies are designed to be shown horizontally. The initial three masters are number lines and grids that can be used in a mathematics course, while the others are adaptations of text figures which are slightly altered in some instances. The

  14. The chemistry of plutonium revealed

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. Important insights were obtained from tracer experiments, but the full complexity of plutonium chemistry was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were aqueous solution based, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, it was found that an equilibrium was rapidly established among the four aqueous oxidation states while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element will be reported

  15. Plan competitions reveal entrepreneurial talent

    Madison, Alison L.

    2011-05-15

    Monthly economic diversity column for Tri-City Herald business section. Excerpt below: There’s something to be said for gaining valuable real-world experience in a structured, nurturing environment. Take for instance learning to scuba dive in the comfort of my resort pool rather than immediately hanging out with sharks while I figure out little things like oxygen tanks and avoiding underwater panic attacks. Likewise, graduate students are getting some excellent, supportive real-world training through university business plan competitions. These competitions are places where smart minds, new technologies, months of preparation and coaching, and some healthy pre-presentation jitters collide to reveal not only solid new business ideas, but also some promising entrepreneurial talent. In fact, professionals from around our region descend upon college campuses every spring to judge these events, which help to bridge the gap between academics and the real technology and business-driven economy.

  16. Archimedes: Accelerator Reveals Ancient Text

    Archimedes (287-212 BC), who is famous for shouting 'Eureka' (I found it) is considered one of the most brilliant thinkers of all times. The 10th-century parchment document known as the 'Archimedes Palimpsest' is the unique source for two of the great Greek's treatises. Some of the writings, hidden under gold forgeries, have recently been revealed at the Stanford Synchrotron Radiation Laboratory at SLAC. An intense x-ray beam produced in a particle accelerator causes the iron in original ink, which has been partly erased and covered, to send out a fluorescence glow. A detector records the signal and a digital image showing the ancient writings is produced. Please join us in this fascinating journey of a 1,000-year-old parchment from its origin in the Mediterranean city of Constantinople to a particle accelerator in Menlo Park.

  17. Interior Evolution of Ceres Revealed by Dawn

    Raymond, Carol A.; Park, Ryan S.; Konopliv, Alex S.; Bland, Michael T.; Marchi, Simone; Castillo-Rogez, Julie C.; McCord, Thomas B.; Jaumann, Ralf; Russell, Christopher T.; Prettyman, Thomas H.

    2015-11-01

    Dawn's exploration of Ceres has revealed its geophysical characteristics, informing the processes that have shaped it. Dawn has determined the average diameter of Ceres to be 940 km, smaller than the previously estimated 975 km [1]. This implies a density of 2160 kg/m3, indicating that Ceres is less differentiated than predicted [2]. The low-degree gravity field is consistent with the body being in hydrostatic equilibrium and the magnitude of J2 implies some central condensation. Ceres' entire surface is cratered, implying the lack of a thick (10's of km) water ice layer at the surface. Variability in Ceres' crater morphology indicates that the near-surface layer has variable strength and rheology, likely due to heterogeneity in the near-surface mixture of rock, ice and salt. The lack of a number of expected large impact basins on Ceres can be interpreted to be the result of viscous relaxation, resurfacing or a combination of both. These data provide insights into Ceres' thermal evolution and mechanical properties, which appear to be unique to this warm, icy body.[1] Thomas, P. C., et al., Differentiation of the asteroid Ceres as revealed by its shape, Nature, 437, 224-226, 2005; [2] McCord et al., Ceres: Its Origin, Evolution and Structure and Dawn's Potential Contribution, Space Sci Rev DOI 10.1007/s11214-010-9729-9, 2011.

  18. Transcriptome classification reveals molecular subtypes in psoriasis

    Ainali Chrysanthi

    2012-09-01

    Full Text Available Abstract Background Psoriasis is an immune-mediated disease characterised by chronically elevated pro-inflammatory cytokine levels, leading to aberrant keratinocyte proliferation and differentiation. Although certain clinical phenotypes, such as plaque psoriasis, are well defined, it is currently unclear whether there are molecular subtypes that might impact on prognosis or treatment outcomes. Results We present a pipeline for patient stratification through a comprehensive analysis of gene expression in paired lesional and non-lesional psoriatic tissue samples, compared with controls, to establish differences in RNA expression patterns across all tissue types. Ensembles of decision tree predictors were employed to cluster psoriatic samples on the basis of gene expression patterns and reveal gene expression signatures that best discriminate molecular disease subtypes. This multi-stage procedure was applied to several published psoriasis studies and a comparison of gene expression patterns across datasets was performed. Conclusion Overall, classification of psoriasis gene expression patterns revealed distinct molecular sub-groups within the clinical phenotype of plaque psoriasis. Enrichment for TGFb and ErbB signaling pathways, noted in one of the two psoriasis subgroups, suggested that this group may be more amenable to therapies targeting these pathways. Our study highlights the potential biological relevance of using ensemble decision tree predictors to determine molecular disease subtypes, in what may initially appear to be a homogenous clinical group. The R code used in this paper is available upon request.

  19. Reveal for Salmonella test system.

    Bird, C B; Miller, R L; Miller, B M

    1999-01-01

    The Reveal for Salmonella (RSS) test system is a presumptive qualitative test that detects the presence of Salmonella organisms in foods within 21 h total testing time, allowing the user to release negative products 24 h earlier than when using other rapid test kits. Foods are enriched with a proprietary resuscitation medium called Revive and then selectively enriched with either Selenite Cystine or Rappaport-Vassiliadis selective media. The enriched culture is used to inoculate the RSS detection device, which initiates a lateral flow through a reagent zone containing anti-Salmonella antibodies conjugated to colloidal gold particles that capture antigens present in the culture. The antigen-antibody complex migrates farther and is captured by an additional anti-Salmonella antibody, causing the colloidal gold to precipitate and form a visual line, indicating a positive result. A procedural control line also will form regardless of the presence of Salmonella organisms to indicate the test is working properly. Existing AOAC Official Methods for Salmonella organisms require a 48 h enrichment before testing. Hence, a food product has to be held before release, adding extra cost to the company and the consumer. The RSS test system was evaluated by quantitative spiking studies. Although AOAC encourages inclusion of naturally contaminated foods, almost all microbiological AOAC validation studies have been performed with artificially contaminated foods for absolute control over the study. The RSS test system is designed to test many food types for Salmonella organisms and has a limit of detection of 5-10 colony-forming units (cfu)/25 g with a false-negative rate of < 1% and a false-positive rate of < 5.0%. It showed an 81% overall agreement with the traditional procedure of the U.S. Department of Agriculture's Food Safety Inspection Service. PMID:10367381

  20. POSITIVE MOTIVATION DETERMINANTS IN PSYCHOLOGY

    Svyatoslav Vasilyevich KOTOV

    2015-01-01

    The paper considered the study of determinants of moti-vation and operation achievement. The paper revealed (with description in details) the following factors: want for competence and self-determination, orientation in purpose of live, values, self-efficacy, resilience, and in-trinsic motivation. The study rationalized psychology regularities in the above determinants and the part they played in shaping resilience, personal mental wellbeing and further reinforcement of achievement motivation...

  1. Determining impurities

    A method of determining the content of impurities in organic-origin natural fibrous materials, in which a specimen of said material is compacted to a surface density of from 0.05 to 50 g/cm2, whereupon it is exposed to the effect of a soft gamma-radiation, the mass attenuation coefficient (μ) is determined and the percentage content (Csub(A)) of impurities is assessed. The method has applications in the textile industry. (author)

  2. Focus groups reveal consumer ambivalence.

    1983-01-01

    According to qualitative research, Salvadoreans are ambivalent about the use of contraceptives. Since complete responsibility for management of the CSM project was accepted by the Association Demografica Salvadorena (ADS), the agency which operates the contraceptive social marketing project in El Salvador, in November 1980, the need for decisions in such areas as product price increases, introduction of new condom brands, promotion of the vaginal foaming tablet, and assessment of product sales performance had arisen. The ICSMP funded market research, completed during 1983, was intended to provide the data on which such decisions by ADS could be based. The qualitative research involved 8 focus groups, comprised of men and women, aged 18-45, contraceptive users and nonusers, from the middle and lower socioeconomic strata of the city of San Salvador and other suburban areas. In each group a moderator led discussion of family planning and probed respondents for specific attitudes, knowledge, and behavior regarding the use of contraceptives. To assess attitudes at a more emotional level, moderators asked respondents to "draw" their ideas on certain issues. A marked discrepancy was revealed between respondents' intellectual responses to the issues raised in group discussion, as opposed to their feelings expressed in the drawings. Intellectually, participants responded very positively to family planning practice, but when they were asked to draw their perceptions, ambivalent feelings emerged. Drawings of both the user and the nonuser convey primarily negative aspects for either choice. The user is tense and moody toward her children; the nonuser loses her attractiveness and "dies." Figures also show drawings of some of the attitudes of single and married male participants. 1 drawing shows an incomplete and a complete circle, symbolizing a sterilized man (incomplete) and a nonsterilized man (complete). Another picture depicts a chained man who has lost his freedom

  3. Gender determination in populus

    McLetchie, D.N. [Univ. of Kentucky, Lexington, KY (United States). Dept. of Biological Sciences; Tuskan, G.A. [Oak Ridge National Lab., TN (United States)

    1994-12-31

    Gender, the expression of maleness or femaleness, in dioecious plants has been associated with changes in morphology, physiology, ecological position, and commercial importance of several species, including members of the Salicaceae family. Various mechanisms have been proposed to explain the expression of gender in Salicaceae, including sex chromosomes, simple Mendelian genes, quantitative genes, environment, and genotype-by-environment interactions. Published reports would favor a genetic basis for gender. The objective of this study was to identify molecular markers associated with gender in a segregating family of hybrid poplars. Bulked segregant analysis and chi-squared analysis were used to test for the occurrence of sex chromosomes, individual loci, and chromosome ratios (i.e., ploidy levels) as the mechanisms for gender determination. Examination of 2488 PCR based RAPD markers from 1219 primers revealed nine polymorphic bands between male and female bulked samples. However, linkage analysis indicated that none of these markers were significantly associated with gender. Chisquared results for difference in male-to-female ratios between diploid and triploid genotypes also revealed no significant differences. These findings suggest gender is not controlled via sex chromosomes, simple Mendelian loci or ratios of autosome to gender-determining loci. It is possible that gender is determined genetically by regions of the genome not sampled by the tested markers or by a complex of loci operating in an additive threshold manner or in an epistatic manner. It is also possible that gender is determined environmentally at an early zygote stage, canalizing gender expression.

  4. Radioactivity reveals how crisps mix

    Many of the ''fluids'' processed in the food industry have strange flow properties that cannot easily be predicted. This is an important question in industry, since engineers need to know how such systems flow through pipes in production plants or how different components mix together. To counter this lack of knowledge, the fluids are generally processed for longer than necessary, which often proves expensive and may affect the quality of the final product. The University of Birmingham Positron Imaging Centre has developed a powerful technique to study the behaviour of crisps, yoghurt and ice cream - together with many other granular materials and viscous fluids - in a variety of industrial processes. In one case, the group labelled a single crisp using a positron-emitting radioisotope and added it to a rotating drum full of crisps. By tracking the movement of the labelled crisp, they could determine how uniformly the crisps were exposed to the flavouring that was added in the mixing process. In this article the author describes the research at the university's Positron Imaging Centre. (UK)

  5. Parámetros astrofísicos fundamentales de 6 cúmulos de la Nube Mayor de Magallanes en el rango de transición entre 200 y 700 millones de años

    Piatti, A. E.; Bica, E.; Geisler, D.; Clariá, J. J.

    Complementing our recent Washington photometric studies on intermediate age and young Large Magellanic Cloud (LMC) clusters, we present in this work new results for 6 previously unstudied star clusters in the transition range 200-700 Myr. We study NGC 1836, NGC 1860 and NGC 1865, which are projected on the LMC bar; SL 444, also located in the central disc but outside the bar, and LW 224 and SL 548, both located in the outer disc. We derive ages and metallicities from extracted T1 versus C-T1 colour-magnitude diagrams (CMDs), using theoretical isochrones recently computed for the Washington system. For the metallicity determinations, these CMDs are particularly sensitive. We also estimate ages and metallicities of the surrounding fields of NGC 1860 and NGC 1865 by employing the δT1 index and theoretical isochrones.

  6. HUBBLE REVEALS 'BACKWARDS' SPIRAL GALAXY

    2002-01-01

    Astronomers have found a spiral galaxy that may be spinning to the beat of a different cosmic drummer. To the surprise of astronomers, the galaxy, called NGC 4622, appears to be rotating in the opposite direction to what they expected. Pictures by NASA's Hubble Space Telescope helped astronomers determine that the galaxy may be spinning clockwise by showing which side of the galaxy is closer to Earth. A Hubble telescope photo of the oddball galaxy is this month's Hubble Heritage offering. The image shows NGC 4622 and its outer pair of winding arms full of new stars [shown in blue]. Astronomers are puzzled by the clockwise rotation because of the direction the outer spiral arms are pointing. Most spiral galaxies have arms of gas and stars that trail behind as they turn. But this galaxy has two 'leading' outer arms that point toward the direction of the galaxy's clockwise rotation. To add to the conundrum, NGC 4622 also has a 'trailing' inner arm that is wrapped around the galaxy in the opposite direction it is rotating. Based on galaxy simulations, a team of astronomers had expected that the galaxy was turning counterclockwise. NGC 4622 is a rare example of a spiral galaxy with arms pointing in opposite directions. What caused this galaxy to behave differently from most galaxies? Astronomers suspect that NGC 4622 interacted with another galaxy. Its two outer arms are lopsided, meaning that something disturbed it. The new Hubble image suggests that NGC 4622 consumed a small companion galaxy. The galaxy's core provides new evidence for a merger between NGC 4622 and a smaller galaxy. This information could be the key to understanding the unusual leading arms. Galaxies, which consist of stars, gas, and dust, rotate very slowly. Our Sun, one of many stars in our Milky Way Galaxy, completes a circuit around the Milky Way every 250 million years. NGC 4622 resides 111 million light-years away in the constellation Centaurus. The pictures were taken in May 2001 with Hubble

  7. Density,Viscosity,Refractive Index,and Speed of Sound in Binary Mixtures of Pyridine and 1-Alkanols(C6,C7,C8,C10)at 303.15 K

    ALI Anwar; TARIQ Mohd; NABI Firdosa; SHAHJAHAN

    2008-01-01

    The densities(ρ),viscosities(η),refractive indices(nD),and speeds of sound(u),of binary mixtures of pyridine with 1-hexanoi,1-heptanol,1-octanol and 1-decanol,including those of pure liquids,were measured over the entire composition range at 303.15 K and atmospheric pressure.From these experimental data,the values of excess molar volumes(VE),deviations in isentropic compressibilities(△ks),viscosities(△η),molar refractions(△Rm),apparent and partial molar volumes(Vφ,2 and V0φ,2 ),apparent and partial molar compressibilities(Kφ,2 and K0φ,2 ),of alkanols in pyridine and their corresponding deviations(△V and △K)were calculated.The variations of these parameters with composition of the mixtures suggest that the strength of interactions in these mixtures follow the order:1-hexanol 1-heptanol 1-octanol 1-decanol.All the excess and deviation functions were fitted to Redlich-Kister polynomial equation to determine the fitting coefficients and the standard deviations.

  8. Abrasive supply for ancient Egypt revealed

    In the framework of the major research scheme 'Synchronization of Civilizations in the Eastern Mediterranean Region in the 2nd Millennium B.C' instrumental neutron activation analysis (INAA) was used to determine 30 elements in pumice from archaeological excavations to reveal their specific volcanic origin. In ancient time, the widespread pumiceous products of several eruptions in the Aegean region have been used as abrasive tools and were therefore popular trade objects. The correlation of such archaeological findings to a specific eruption of known age would therefore allow to certify a maximum age of the respective stratum ('dating by first appearance'). Pumices from the Aegean region can easily be distinguished by their trace element distribution patterns. This has been shown by previous studies of the group. The elements Al, Ba, Ca, Ce, Co, Cr, Cs, Dy, Eu, Fe, Hf, K, La, Lu, Mn, Na, Nd, Rb, Sb, Sc, Sm, Ta, Tb, Th, Ti, U, V, Yb, Zr and Zn were determined in 16 samples of pumice lumps from excavations in Tell-el-Dab'a and Tell-el-Herr (Egypt). Two irradiation cycles and five measurement runs were applied. To show the accuracy of the results obtained, typical samples of the most important pumice sources in the Aegean region, particularly from Milos, Nisyros, Kos and Thera were analyzed together with the Egyptian samples of unknown origin. A reliable identification of the samples is achieved by comparing these results to the database compiled in previous studies. The geographical positions of these islands are shown. Within the error range, most of the elements determined in typical representatives of Milos, Nisyros, Kos and Santorini were in perfect agreement with values from the literature. On the basis of the Cluster graphics presented, it is possible to relate unknown pumice to its primary source, just by comparing the relation of a few elements, like Ta-Eu and Th-Hf. One concludes that all samples except one can be related to the Minoan eruption of Thera

  9. Gas-rich mergers and feedback are ubiqitous amongst starbursting radio galaxies, as revealed by JVLA, IRAM PdBI and Herschel

    Ivison, R J; Amblard, A; Arumugam, V; De Breuck, C; Emonts, B H C; Feain, I; Greve, T R; Haas, M; Ibar, E; Jarvis, M J; Kovaks, A; Lehnert, M D; Nesvadba, N P H; Rottgering, H J A; Seymour, N; Wylezalek, D

    2012-01-01

    We report new, sensitive observations of two z ~ 3-3.5 FIR-luminous radio galaxies, 6C1909+72 and B3J2330+3927, in 12CO J=1-0 with the Karl Jansky VLA and at 100-500um using Herschel, alongside new and archival 12CO J=4-3 observations from IRAM PdBI. We introduce a new colour-colour diagnostic plot to constrain the redshifts of several distant, dusty galaxies in our target fields. A bright SMG near 6C1909+72 likely shares the same node or filament as the signpost AGN, but it is not detected in CO despite ~20,000 km/s of velocity coverage. Also in the 6C1909+72 field, a large, red dust feature spanning ~500 kpc is aligned with the radio jet. We suggest several processes by which metal-rich material may have been transported, favouring a collimated outflow reminiscent of the jet-oriented metal enrichment seen in local cluster environments. Our interferometric imaging reveals a gas-rich companion to B3J2330+3927; indeed, all bar one of the eight z >~ 2 radio galaxies (or companions) detected in CO provide some e...

  10. Quantitative determination of four constituents of Tinospora sps. by a reversed-phase HPLC-UV-DAD method. Broad-based studies revealing variation in content of four secondary metabolites in the plant from different eco-geographical regions of India.

    Ahmed, S M; Manhas, L R; Verma, V; Khajuria, R K

    2006-09-01

    This paper describes the separation and quantitation of important markers, such as 20beta-hydroxyecdysone, tinosporaside, cordioside, and columbin, present in three species of Tinospora viz, T. cordifolia, T. malabrica, and T. crispa. A reverse-phase (RP) high-performance liquid chromatography (HPLC)-UV-diode array detection (DAD) method employing gradient elution is thus developed. The marker compounds isolated from 70% ethanolic extract of T. cordfolia by repeated column chromatography are identified on the basis of (1)H NMR, (13)C NMR, and mass spectral data. The compounds are separated on a RP (RP-18, 5 microm, 250 x 4.6-mm i.d.) column using water-acetonitrile gradient and are detected by the HPLC-UV-DAD method. The calibration curves that result from marker compounds in the concentration range of 100-2000 ng on column exhibit a good correlation (r(2) > or = 0.99978). The method is successfully applied to separate and study the content of four marker compounds in 40 different accessions of three Tinospora species collected from different regions of India. The studies reveal that the maximum amount of the marker compounds is present in Tinospora cordifolia species, especially from accessions collected from higher altitudes of the Jammu province (North India). PMID:16959127