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Sample records for activation defines nonpathogenic

  1. Complement sensitivity of Entamoeba histolytica and various nonpathogenic amoeba species.

    PubMed

    Förster, B; Ebert, F; Horstmann, R D

    1994-12-01

    Culture forms of the potentially pathogenic Entamoeba histolytica were compared to those of the nonpathogenic species of E. dispar, E. hartmanni, E. coli, Endolimax nana, and E. moshkovskii regarding the sensitivity to lysis by human complement activated through the alternative pathway. E. dispar was found unique in its complement resistance; all other nonpathogenic isolates resembled E. histolytica in that they were complement sensitive. Thus, a state of complement sensitivity is not a particular property of potentially pathogenic amoebae. PMID:7716404

  2. Susceptibility of pathogenic and nonpathogenic Naegleria ssp

    SciTech Connect

    Whiteman, L.Y.

    1988-01-01

    The susceptibility of four species of Naegleria amoebae to complement-mediated lysis was determined. The amoebicidal activity of normal human serum (NHS) and normal guinea pig serum (NGPS) for Naegleria amoebae was measured by an in vitro cytotoxicity assay. Release of radioactivity from amoebae labeled with {sup 3}H-uridine and visual observation with a compound microscope were used as indices of lysis. Susceptibility or resistance to complement-mediated lysis in vitro correlated with the in vivo pathogenic potential. Nonpathogenic Naegleria amoebae were lysed at a faster rate and at higher cell concentrations than were pathogenic amoebae. Electrophoretic analysis of NHS incubated with pathogenic or nonpathogenic Naegleria spp. demonstrated that amoebae activate the complement cascade resulting in the production of C3 and C5 complement cleavage products. Treatment with papain or trypsin for 1 h, but not with sialidase, increase the susceptibility of highly pathogenic, mouse-passaged N. fowleri to lysis. Treatment with actinomycin D, cycloheximide or various protease inhibitors for 4 h did not increase susceptibility to lysis. Neither a repair process involving de novo protein synthesis nor a complement-inactivating protease appear to account for the increase resistance of N. fowleri amoebae to complement-mediated lysis. A binding study with {sup 125}I radiolabeled C9 indicated that the terminal complement component does not remain stably bound to the membrane of pathogenic amoebae.

  3. Differential effect of immune cells on non-pathogenic Gram-negative bacteria-induced nuclear factor-κB activation and pro-inflammatory gene expression in intestinal epithelial cells

    PubMed Central

    Haller, D; Holt, L; Parlesak, A; Zanga, J; Bäuerlein, A; Sartor, R B; Jobin, C

    2004-01-01

    We have previously shown that non-pathogenic Gram negative bacteria induce RelA phosphorylation, nuclear factor (NF)-κB transcriptional activity and pro-inflammatory gene expression in intestinal epithelial cells (IEC) in vivo and in vitro. In this study, we investigated the molecular mechanism of immune-epithelial cell cross-talk on Gram-negative enteric bacteria-induced NF-κB signalling and pro-inflammatory gene expression in IEC using HT-29/MTX as well as CaCO-2 transwell cultures Interestingly, while differentiated HT-29/MTX cells are unresponsive to non-pathogenic Gram negative bacterial stimulation, interleukin-8 (IL-8) mRNA accumulation is strongly induced in Escherichia coli- but not Bacteroides vulgatus-stimulated IEC cocultured with peripheral blood (PBMC) and lamina propria mononuclear cells (LPMC). The presence of PBMC triggered both E. coli- and B. vulgatus-induced mRNA expression of the Toll-like receptor-4 accessory protein MD-2 as well as endogenous IκBα phosphorylation, demonstrating similar capabilities of these bacteria to induce proximal NF-κB signalling. However, B. vulgatus failed to trigger IκBα degradation and NF-κB transcriptional activity in the presence of PBMC. Interestingly, B. vulgatus- and E. coli-derived lipopolysaccharide-induced similar IL-8 mRNA expression in epithelial cells after basolateral stimulation of HT-29/PBMC cocultures. Although luminal enteric bacteria have adjuvant and antigenic properties in chronic intestinal inflammation, PBMC from patients with active ulcerative colitis and Crohn's disease differentially trigger epithelial cell activation in response to E. coli and E. coli-derived LPS. In conclusion, this study provides evidence for a differential regulation of non-pathogenic Gram-negative bacteria-induced NF-κB signalling and IL-8 gene expression in IEC cocultured with immune cells and suggests the presence of mechanisms that assure hyporesponsiveness of the intestinal epithelium to certain commensally

  4. Defining Adapted Physical Activity: International Perspectives

    ERIC Educational Resources Information Center

    Hutzler, Yeshayahu; Sherrill, Claudine

    2007-01-01

    The purpose of this study was to describe international perspectives concerning terms, definitions, and meanings of adapted physical activity (APA) as (a) activities or service delivery, (b) a profession, and (c) an academic field of study. Gergen's social constructionism, our theory, guided analysis of multiple sources of data via qualitative…

  5. Proteases as Markers for Differentiation of Pathogenic and Nonpathogenic Species of Acanthamoeba

    PubMed Central

    Khan, Naveed A.; Jarroll, Edward L.; Panjwani, Noorjahan; Cao, Zhiyi; Paget, Timothy A.

    2000-01-01

    Acanthamoeba keratitis is a vision-threatening infection caused by pathogenic species of the genus Acanthamoeba. Although not all Acanthamoeba spp. can cause keratitis, it is important to differentiate pathogenic species and isolates from nonpathogens. Since extracellular proteases may play a role in ocular pathology, we used colorimetric, cytopathic, and zymographic assays to assess extracellular protease activity in pathogenic and nonpathogenic Acanthamoeba. Colorimetric assays, using azo-linked protein as a substrate, showed extracellular protease activity in Acanthamoeba-conditioned medium and differentiated pathogenic and nonpathogenic Acanthamoeba. Monolayers of immortalized corneal epithelial cells in four-well plates were used for cytopathic effect (CPE) assays. Pathogenic Acanthamoeba isolates exhibited marked CPE on immortalized corneal epithelial cells, while nonpathogenic isolates did not exhibit CPE. Protease zymography was performed with Acanthamoeba-conditioned medium as well as with Acanthamoeba- plus epithelial-cell-conditioned medium. The zymographic protease assays showed various banding patterns for different strains of Acanthamoeba. In pathogenic Acanthamoeba isolates, all protease bands were inhibited by phenylmethylsulfonyl fluoride (PMSF), suggesting serine type proteases, while in nonpathogenic strains only partial inhibition was observed by using PMSF. The pathogenic Acanthamoeba strains grown under typical laboratory conditions without epithelial cells exhibited one overexpressed protease band of 107 kDa in common; this protease was not observed in nonpathogenic Acanthamoeba strains. The 107-kDa protease exhibited activity over a pH range of 5 to 9.5. PMID:10921939

  6. Phylogenetic and Variable-Number Tandem-Repeat Analyses Identify Nonpathogenic Xanthomonas arboricola Lineages Lacking the Canonical Type III Secretion System

    PubMed Central

    Essakhi, Salwa; Cesbron, Sophie; Fischer-Le Saux, Marion; Bonneau, Sophie; Jacques, Marie-Agnès

    2015-01-01

    Xanthomonas arboricola is conventionally known as a taxon of plant-pathogenic bacteria that includes seven pathovars. This study showed that X. arboricola also encompasses nonpathogenic bacteria that cause no apparent disease symptoms on their hosts. The aim of this study was to assess the X. arboricola population structure associated with walnut, including nonpathogenic strains, in order to gain a better understanding of the role of nonpathogenic xanthomonads in walnut microbiota. A multilocus sequence analysis (MLSA) was performed on a collection of 100 X. arboricola strains, including 27 nonpathogenic strains isolated from walnut. Nonpathogenic strains grouped outside clusters defined by pathovars and formed separate genetic lineages. A multilocus variable-number tandem-repeat analysis (MLVA) conducted on a collection of X. arboricola strains isolated from walnut showed that nonpathogenic strains clustered separately from clonal complexes containing Xanthomonas arboricola pv. juglandis strains. Some nonpathogenic strains of X. arboricola did not contain the canonical type III secretion system (T3SS) and harbored only one to three type III effector (T3E) genes. In the nonpathogenic strains CFBP 7640 and CFBP 7653, neither T3SS genes nor any of the analyzed T3E genes were detected. This finding raises a question about the origin of nonpathogenic strains and the evolution of plant pathogenicity in X. arboricola. T3E genes that were not detected in any nonpathogenic isolates studied represent excellent candidates to be those responsible for pathogenicity in X. arboricola. PMID:26048944

  7. Field efficacy of nonpathogenic Streptomyces species against potato common scab

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reports of potato fields suppressive to common scab (CS) and of association of non-pathogenic streptomycetes with CS resistance suggest that non-pathogenic strains have potential to control or modulate CS disease. Biocontrol potential of non-pathogenic Streptomyces was examined in field experiments ...

  8. Effects of thermal additions on the presence of pathogenic and nonpathogenic free-living amoebae at the Savannah River Laboratory

    SciTech Connect

    Tyndall, R.L.

    1980-01-01

    A study of the effect of thermal additions on the presence of free-living thermophilic amoeba at the Savannah River site was undertaken. Seasonality effects and the influence of varied degrees of thermal enrichment on the numbers and types of thermophilic pathogenic and nonpathogenic amoeba were determined. In addition, the ability of thermophilic nonpathogenic Naegleria to competitively inhibit the growth of the pathogenic Naegleria was defined and related to water quality differences.

  9. Comparative Phylogenomics of Pathogenic and Nonpathogenic Species

    PubMed Central

    Whiston, Emily; Taylor, John W.

    2015-01-01

    The Ascomycete Onygenales order embraces a diverse group of mammalian pathogens, including the yeast-forming dimorphic fungal pathogens Histoplasma capsulatum, Paracoccidioides spp. and Blastomyces dermatitidis, the dermatophytes Microsporum spp. and Trichopyton spp., the spherule-forming dimorphic fungal pathogens in the genus Coccidioides, and many nonpathogens. Although genomes for all of the aforementioned pathogenic species are available, only one nonpathogen had been sequenced. Here, we enhance comparative phylogenomics in Onygenales by adding genomes for Amauroascus mutatus, Amauroascus niger, Byssoonygena ceratinophila, and Chrysosporium queenslandicum—four nonpathogenic Onygenales species, all of which are more closely related to Coccidioides spp. than any other known Onygenales species. Phylogenomic detection of gene family expansion and contraction can provide clues to fungal function but is sensitive to taxon sampling. By adding additional nonpathogens, we show that LysM domain-containing proteins, previously thought to be expanding in some Onygenales, are contracting in the Coccidioides-Uncinocarpus clade, as are the self-nonself recognition Het loci. The denser genome sampling presented here highlights nearly 800 genes unique to Coccidiodes, which have significantly fewer known protein domains and show increased expression in the endosporulating spherule, the parasitic phase unique to Coccidioides spp. These genomes provide insight to gene family expansion/contraction and patterns of individual gene gain/loss in this diverse order—both major drivers of evolutionary change. Our results suggest that gene family expansion/contraction can lead to adaptive radiations that create taxonomic orders, while individual gene gain/loss likely plays a more significant role in branch-specific phenotypic changes that lead to adaptation for species or genera. PMID:26613950

  10. Disparate Proteome Responses of Pathogenic and Non-pathogenic Aspergilli to Human Serum Measured by Activity-Based Protein Profiling (ABPP)

    SciTech Connect

    Wiedner, Susan D.; Ansong, Charles; Webb-Robertson, Bobbie-Jo M.; Pederson, Leeanna M.; Fortuin, Suereta; Hofstad, Beth A.; Shukla, Anil K.; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

    2013-07-01

    Aspergillus fumigatus is the primary pathogen causing the devastating pulmonary disease Invasive Aspergillosis in immunocompromised individuals. Genomic analysis shows high synteny between A. fumigatus and closely related rarely pathogenic Neosartorya fischeri and Aspergillus clavatus genomes. To investigate the presence of unique or highly inducible protein reactivity in the pathogen, we applied activity-based protein profiling to compare protein reactivity of all three fungi over time in minimal media growth and in response to human serum. We found 350 probe-reactive proteins exclusive to A. fumigatus, including known virulence associated proteins, and 13 proteins associated with stress response exclusive to A. fumigatus culture in serum. Though the fungi are highly orthologous, A. fumigatus has significantly more activity across varied biological process. Only 50% of expected orthologs of measured A. fumigatus reactive proteins were observed in N. fischeri and A. clavatus. Human serum induced processes uniquely or significantly represented in A. fumigatus include actin organization and assembly, transport, and fatty acid, cell membrane, and cell wall synthesis. Additionally, signaling proteins regulating vegetative growth, conidiation, and cell wall integrity, required for appropriate cellular response to external stimuli, had higher reactivity over time in A. fumigatus and N. fisheri, but not in A. clavatus. Together, we show that measured proteins and physiological processes identified solely or significantly over-represented in A. fumigatus reveal a unique adaptive response to human protein not found in closely related, but rarely aspergilli. These unique protein reactivity responses may reveal how A. fumigatus initiates pulmonary invasion leading to Invasive Aspergillosis.

  11. The biological activity of structurally defined inositol glycans

    PubMed Central

    Goel, Meenakshi; Azev, Viatcheslav N; d’Alarcao, Marc

    2009-01-01

    Background The inositol glycans (IGs) are glycolipid-derived carbohydrates produced by insulin-sensitive cells in response to insulin treatment. IGs exhibit an array of insulin-like activities including stimulation of lipogenesis, glucose transport and glycogen synthesis, suggesting that they may be involved in insulin signal transduction. However, because the natural IGs are structurally heterogeneous and difficult to purify to homogeneity, an understanding of the relationship between structure and biological activity has relied principally on synthetic IGs of defined structure. Discussion This article briefly describes what is known about the role of IGs in signal transduction and reviews the specific biological activities of the structurally defined IGs synthesized and tested to date. Conclusion A pharmacophore for IG activity begins to emerge from the reviewed data and the structural elements necessary for activity are summarized. PMID:20390053

  12. SNS Devices With Pinhole-Defined Active Regions

    NASA Technical Reports Server (NTRS)

    Hunt, Brian D.; Barner, Jeffrey B.

    1996-01-01

    Superconductor/normal conductor/superconductor (SNS) microbridge devices with pinhole-defined active regions undergoing development. Device includes thin, electrically insulating layer deposited epitaxially, with controlled formation of pinholes, on one of two superconducting layers. Normally conducting metal deposited epitaxially in pinholes and on insulating layer, forming electrical contact between two superconducting layers. Junction resistances and maximum junction voltages expected to be increased.

  13. Non-pathogenic microflora of a spring water with regenerative properties

    PubMed Central

    NICOLETTI, GIOVANNI; CORBELLA, MARTA; JABER, OMAR; MARONE, PIERO; SCEVOLA, DANIELE; FAGA, ANGELA

    2015-01-01

    The Comano spring water (Comano, Italy) has been demonstrated to improve skin regeneration, not only by increasing keratinocyte proliferation and migration, but also by modulating the regenerated collagen and elastic fibers in the dermis. However, such biological properties may not be entirely explained by its mineral composition only. As the non-pathogenic bacterial populations have demonstrated an active role in different biological processes, the potential presence of non-pathogenic bacterial species within the Comano spring water was investigated in order to identify any possible correlation between these bacterial populations and the demonstrated biological properties of this water. The water was collected at the spring using an aseptic procedure and multiple cultures were carried out. A total of 9 different strains were isolated, which were Aeromonas hydrophila, Brevundimonas vesicularis, Chromobacterium violaceum, Citrobacter youngae, Empedobacter brevis, Pantoea agglomerans, Pseudomonas putida, Pseudomonas stutzeri and Streptococcus mitis. All the isolated bacterial strains, although showing a rare potential virulence, demonstrated peculiar and favorable metabolic attitudes in controlling environmental pollution. The therapeutical effects of certain spring waters are currently being proven as correlated not only to their peculiar mineral composition, but also to the complex activity of their resident non-pathogenic bacterial populations. Although the present study provided only preliminary data, some of the non-pathogenic bacterial populations that were identified in the Comano spring water are likely to produce molecular mediators with a role in the wound healing process that, thus far, remain unknown. Numerous other unknown bacterial species, comprehensively termed DNA-rich ‘dark matter’, are likely to contribute to the Comano water regenerative properties as well. Therefore, the non-pathogenic bacterial populations of the Comano spring water are

  14. 20 CFR 220.141 - Substantial gainful activity, defined.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... activities like taking care of one's self, household tasks, hobbies, therapy, school attendance, club...) Substantial work activity. Substantial work activity is work activity that involves doing significant...

  15. 20 CFR 220.141 - Substantial gainful activity, defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... activities like taking care of one's self, household tasks, hobbies, therapy, school attendance, club...) Substantial work activity. Substantial work activity is work activity that involves doing significant...

  16. 20 CFR 220.141 - Substantial gainful activity, defined.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... activities like taking care of one's self, household tasks, hobbies, therapy, school attendance, club...) Substantial work activity. Substantial work activity is work activity that involves doing significant...

  17. 20 CFR 220.141 - Substantial gainful activity, defined.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... activities like taking care of one's self, household tasks, hobbies, therapy, school attendance, club...) Substantial work activity. Substantial work activity is work activity that involves doing significant...

  18. 20 CFR 220.141 - Substantial gainful activity, defined.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... activities like taking care of one's self, household tasks, hobbies, therapy, school attendance, club...) Substantial work activity. Substantial work activity is work activity that involves doing significant...

  19. Proteolytic activation defines distinct lymphangiogenic mechanisms for VEGFC and VEGFD

    PubMed Central

    Bui, Hung M.; Enis, David; Robciuc, Marius R.; Nurmi, Harri J.; Cohen, Jennifer; Chen, Mei; Yang, Yiqing; Dhillon, Veerpal; Johnson, Kathy; Zhang, Hong; Kirkpatrick, Robert; Traxler, Elizabeth; Alitalo, Kari

    2016-01-01

    Lymphangiogenesis is supported by 2 homologous VEGFR3 ligands, VEGFC and VEGFD. VEGFC is required for lymphatic development, while VEGFD is not. VEGFC and VEGFD are proteolytically cleaved after cell secretion in vitro, and recent studies have implicated the protease a disintegrin and metalloproteinase with thrombospondin motifs 3 (ADAMTS3) and the secreted factor collagen and calcium binding EGF domains 1 (CCBE1) in this process. It is not well understood how ligand proteolysis is controlled at the molecular level or how this process regulates lymphangiogenesis, because these complex molecular interactions have been difficult to follow ex vivo and test in vivo. Here, we have developed and used biochemical and cellular tools to demonstrate that an ADAMTS3-CCBE1 complex can form independently of VEGFR3 and is required to convert VEGFC, but not VEGFD, into an active ligand. Consistent with these ex vivo findings, mouse genetic studies revealed that ADAMTS3 is required for lymphatic development in a manner that is identical to the requirement of VEGFC and CCBE1 for lymphatic development. Moreover, CCBE1 was required for in vivo lymphangiogenesis stimulated by VEGFC but not VEGFD. Together, these studies reveal that lymphangiogenesis is regulated by two distinct proteolytic mechanisms of ligand activation: one in which VEGFC activation by ADAMTS3 and CCBE1 spatially and temporally patterns developing lymphatics, and one in which VEGFD activation by a distinct proteolytic mechanism may be stimulated during inflammatory lymphatic growth. PMID:27159393

  20. Ion exchange defines the biological activity of titanate nanotubes.

    PubMed

    Rónavári, Andrea; Kovács, Dávid; Vágvölgyi, Csaba; Kónya, Zoltán; Kiricsi, Mónika; Pfeiffer, Ilona

    2016-05-01

    One-dimensional titanate nanotubes (TiONTs) were subjected to systematic ion exchange to determine the impact of these modifications on biological activities. Ion exchanged TiONTs (with Ag, Mg, Bi, Sb, Ca, K, Sr, Fe, and Cu ions) were successfully synthesized and the presence of the substituted ions was verified by energy dispersive X-ray spectroscopy (EDS). A complex screening was carried out to reveal differences in toxicity to human cells, as well as in antibacterial, antifungal, and antiviral activities between the various modified nanotubes. Our results demonstrated that Ag ion exchanged TiONTs exerted potent antibacterial and antifungal effects against all examined microbial species but were ineffective on viruses. Surprisingly, the antibacterial activity of Cu/TiONTs was restricted to Micrococcus luteus. Most ion exchanged TiONTs did not show antimicrobial activity against the tested bacterial and fungal species. Incorporation of various ions into nanotube architectures lead to mild, moderate, or even to a massive loss of human cell viability; therefore, this type of biological effect exerted by TiONTs can be greatly modulated by ion exchange. These findings further emphasize the contribution of ion exchange in determining not only the physical and chemical characteristics but also the bioactivity of TiONT against different types of living cells. PMID:26972521

  1. Defining Health Activism: From MADD to Mad Activists

    PubMed Central

    Huang, Jean

    2011-01-01

    Health Activism in the 20th Century: A History of Medicine Symposium at Yale University School of Medicine in October 2010 highlighted a variety of issues concerning the social history of medicine, including race, gender, sexual orientation, and disability. A watershed moment in a burgeoning interdisciplinary field, this symposium could pave the way for extensive future discourse. PMID:21451786

  2. Discussing and Defining Sexual Assault: A Classroom Activity

    ERIC Educational Resources Information Center

    Franiuk, Renae

    2007-01-01

    The author devised a classroom activity that facilitates discussion and increases awareness about sexual assault. Students read scenarios involving sexual situations that varied in ambiguity, then labeled whether the situations involved a sexual assault. Students also gave their definitions of sexual assault and completed an evaluation of the…

  3. Twist1 activity thresholds define multiple functions in limb development

    PubMed Central

    Krawchuk, Dayana; Weiner, Shoshana J.; Chen, You-Tzung; Lu, Benson; Costantini, Frank; Behringer, Richard R.; Laufer, Ed

    2010-01-01

    Summary The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1−/− embryos die at midgestation. However, studies on early limb buds found that Twist1−/− mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional alleles to generate a Twist1 allelic series that survives to birth. As Twist1 activity is reduced, limb skeletal defects progress from preaxial polydactyly to girdle reduction combined with hypoplasia, aplasia or mirror symmetry of all limb segments. With reduced Twist1 activity there is striking and progressive upregulation of ectopic Shh expression in the anterior of the limb, combined with an anterior shift in the posterior Shh domain, which is expressed at normal intensity, and loss of the posterior AER. Consequently limb outgrowth is initially impaired, before an ectopic anterior Shh domain expands the AER, promoting additional growth and repatterning. Reducing the dosage of FGF targets of the Etv gene family, which are known repressors of Shh expression in the anterior limb mesenchyme, strongly enhances the anterior skeletal phenotype. Conversely this and other phenotypes are suppressed by reducing the dosage of the Twist1 antagonist Hand2. Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity. PMID:20732316

  4. Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer

    PubMed Central

    Kim, Michael Paul; Zhang, Yun; Lozano, Guillermina

    2015-01-01

    The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve p53 missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may concomitantly gain novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in various model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 in various organ systems are reviewed and their limitations discussed. PMID:26618142

  5. Overexpression of Differentially Expressed Genes Identified in Non-pathogenic and Pathogenic Entamoeba histolytica Clones Allow Identification of New Pathogenicity Factors Involved in Amoebic Liver Abscess Formation.

    PubMed

    Meyer, Martin; Fehling, Helena; Matthiesen, Jenny; Lorenzen, Stephan; Schuldt, Kathrin; Bernin, Hannah; Zaruba, Mareen; Lender, Corinna; Ernst, Thomas; Ittrich, Harald; Roeder, Thomas; Tannich, Egbert; Lotter, Hannelore; Bruchhaus, Iris

    2016-08-01

    We here compared pathogenic (p) and non-pathogenic (np) isolates of Entamoeba histolytica to identify molecules involved in the ability of this parasite to induce amoebic liver abscess (ALA)-like lesions in two rodent models for the disease. We performed a comprehensive analysis of 12 clones (A1-A12) derived from a non-pathogenic isolate HM-1:IMSS-A and 12 clones (B1-B12) derived from a pathogenic isolate HM-1:IMSS-B. "Non-pathogenicity" included the induction of small and quickly resolved lesions while "pathogenicity" comprised larger abscess development that overstayed day 7 post infection. All A-clones were designated as non-pathogenic, whereas 4 out of 12 B-clones lost their ability to induce ALAs in gerbils. No correlation between ALA formation and cysteine peptidase (CP) activity, haemolytic activity, erythrophagocytosis, motility or cytopathic activity was found. To identify the molecular framework underlying different pathogenic phenotypes, three clones were selected for in-depth transcriptome analyses. Comparison of a non-pathogenic clone A1np with pathogenic clone B2p revealed 76 differentially expressed genes, whereas comparison of a non-pathogenic clone B8np with B2p revealed only 19 differentially expressed genes. Only six genes were found to be similarly regulated in the two non-pathogenic clones A1np and B8np in comparison with the pathogenic clone B2p. Based on these analyses, we chose 20 candidate genes and evaluated their roles in ALA formation using the respective gene-overexpressing transfectants. We conclude that different mechanisms lead to loss of pathogenicity. In total, we identified eight proteins, comprising a metallopeptidase, C2 domain proteins, alcohol dehydrogenases and hypothetical proteins, that affect the pathogenicity of E. histolytica. PMID:27575775

  6. 34 CFR 656.3 - What activities define a comprehensive or undergraduate National Resource Center?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What activities define a comprehensive or undergraduate....3 What activities define a comprehensive or undergraduate National Resource Center? A comprehensive... science, technology, engineering, and mathematics fields to achieve foreign language...

  7. 34 CFR 656.3 - What activities define a comprehensive or undergraduate National Resource Center?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What activities define a comprehensive or undergraduate....3 What activities define a comprehensive or undergraduate National Resource Center? A comprehensive... science, technology, engineering, and mathematics fields to achieve foreign language...

  8. 26 CFR 1.103(n)-2T - Private activity bond defined (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Private activity bond defined (temporary). 1.103....103(n)-2T Private activity bond defined (temporary). Q-1: What is the definition of the term “private activity bond”? A-1: In general, for purposes of §§ 1.103(n)-1T through 1.103(n)-6T, the term...

  9. 26 CFR 1.103(n)-2T - Private activity bond defined (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Private activity bond defined (temporary). 1.103....103(n)-2T Private activity bond defined (temporary). Q-1: What is the definition of the term “private activity bond”? A-1: In general, for purposes of §§ 1.103(n)-1T through 1.103(n)-6T, the term...

  10. Serodiagnosis of American trypanosomosis by using nonpathogenic trypanosomatid antigen.

    PubMed Central

    Monteón, V M; Guzmán-Rojas, L; Negrete-García, C; Rosales-Encina, J L; Lopez, P A

    1997-01-01

    Crithidia luciliae, a nonpathogenic trypanosomatid, could provide a good alternative source of antigen for serodiagnosis of Chagas' disease. An enzyme-linked immunosorbent assay showed 100% sensitivity and 83% specificity when 91 human serum samples from Chagas' disease patients and 127 human serum samples from people suffering from toxoplasmosis (21 samples), leishmaniasis (32 samples), systemic rheumatic diseases (33 samples), and heart diseases (41 samples) were tested simultaneously with Trypanosoma cruzi and C. luciliae crude extracts. By Western blotting, an immunodominant band (30 kDa) was recognized by chagasic sera on the C. luciliae crude extract; specificity reached 97% with respect to this protein band. The carbohydrate moieties were not antigenic. PMID:9399545

  11. Overexpression of Differentially Expressed Genes Identified in Non-pathogenic and Pathogenic Entamoeba histolytica Clones Allow Identification of New Pathogenicity Factors Involved in Amoebic Liver Abscess Formation

    PubMed Central

    Lorenzen, Stephan; Schuldt, Kathrin; Bernin, Hannah; Zaruba, Mareen; Lender, Corinna; Ittrich, Harald; Roeder, Thomas; Tannich, Egbert; Lotter, Hannelore; Bruchhaus, Iris

    2016-01-01

    We here compared pathogenic (p) and non-pathogenic (np) isolates of Entamoeba histolytica to identify molecules involved in the ability of this parasite to induce amoebic liver abscess (ALA)-like lesions in two rodent models for the disease. We performed a comprehensive analysis of 12 clones (A1–A12) derived from a non-pathogenic isolate HM-1:IMSS-A and 12 clones (B1–B12) derived from a pathogenic isolate HM-1:IMSS-B. “Non-pathogenicity” included the induction of small and quickly resolved lesions while “pathogenicity” comprised larger abscess development that overstayed day 7 post infection. All A-clones were designated as non-pathogenic, whereas 4 out of 12 B-clones lost their ability to induce ALAs in gerbils. No correlation between ALA formation and cysteine peptidase (CP) activity, haemolytic activity, erythrophagocytosis, motility or cytopathic activity was found. To identify the molecular framework underlying different pathogenic phenotypes, three clones were selected for in-depth transcriptome analyses. Comparison of a non-pathogenic clone A1np with pathogenic clone B2p revealed 76 differentially expressed genes, whereas comparison of a non-pathogenic clone B8np with B2p revealed only 19 differentially expressed genes. Only six genes were found to be similarly regulated in the two non-pathogenic clones A1np and B8np in comparison with the pathogenic clone B2p. Based on these analyses, we chose 20 candidate genes and evaluated their roles in ALA formation using the respective gene-overexpressing transfectants. We conclude that different mechanisms lead to loss of pathogenicity. In total, we identified eight proteins, comprising a metallopeptidase, C2 domain proteins, alcohol dehydrogenases and hypothetical proteins, that affect the pathogenicity of E. histolytica. PMID:27575775

  12. [Non-pathogenic intestinal amoebae: a clinical-analytical overview].

    PubMed

    Sard, Bárbara Gomila; Navarro, Rafael Toledo; Esteban Sanchis, J Guillermo

    2011-03-01

    Human beings can be parasitized by various species of intestinal amoebae. Entamoeba histolytica is the only intestinal amoeba recognized to be pathogenic, while other amoeba species, E. dispar, E. moshkovskii, E. hartmanni, E. coli, E. polecki, Endolimax nana and Iodamoeba buetschlii are considered to be non-pathogenic. The aim of this review is to synthesize the main morphological characteristics of the trophozoite and cyst stages of each amoeba as the basis for precise microscopical diagnosis. The difficulty of morphological differentiation among species included in the so-called "Entamoeba complex" entails the use of immunological and molecular diagnoses. In addition, a summary of basic epidemiological, therapeutic and prophylactic aspects of these non-pathogenic amoebae is provided. All of these aspects are crucial since these amoebae are usually found to be present in human coproparasitological analyses and must be differentiated from the pathogenic species E. histolytica. Furthermore, they can be used as suitable biological tags of the hygienic state of the environment and the health and hygiene measures of the population. PMID:21458707

  13. Production of anti-fungal volatiles by non-pathogenic Fusarium oxysporum and its efficacy in suppression of verticillium wilt of cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aims: The study aimed to identify volatile organic compounds (VOCs) produced by the non-pathogenic Fusarium oxysporum (Fo) strain CanR-46, and to determine the anti-fungal spectrum and the control efficacy of the Fo-VOCs. Methods: The Fo-VOCs were identified by GC-MS. The antifungal activity of the...

  14. 34 CFR 656.3 - What activities define a comprehensive or undergraduate National Resource Center?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What activities define a comprehensive or undergraduate National Resource Center? 656.3 Section 656.3 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION NATIONAL RESOURCE CENTERS PROGRAM FOR FOREIGN LANGUAGE AND...

  15. 34 CFR 656.3 - What activities define a comprehensive or undergraduate National Resource Center?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false What activities define a comprehensive or undergraduate National Resource Center? 656.3 Section 656.3 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION NATIONAL RESOURCE CENTERS PROGRAM FOR FOREIGN LANGUAGE AND...

  16. Defining Standards and Policies for Promoting Physical Activity in Afterschool Programs

    ERIC Educational Resources Information Center

    Beets, Michael W.; Wallner, Megan; Beighle, Aaron

    2010-01-01

    Background: National guidelines exist that define "quality" afterschool programs (3-6 pm, ASP). No widely adopted national standards/policies exist, however, for ASP providers for the promotion of physical activity (PA). To address this gap, state-level ASP organizations have developed or adopted standards/policies related to PA. The extent to…

  17. Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures

    PubMed Central

    Haller, D; Bode, C; Hammes, W; Pfeifer, A; Schiffrin, E; Blum, S

    2000-01-01

    BACKGROUND AND AIM—Intestinal epithelial cells (IEC) are thought to participate in the mucosal defence against bacteria and in the regulation of mucosal tissue homeostasis. Reactivity of IEC to bacterial signals may depend on interactions with immunocompetent cells. To address the question of whether non-pathogenic bacteria modify the immune response of the intestinal epithelium, we co-cultivated enterocyte-like CaCO-2 cells with human blood leucocytes in separate compartments of transwell cultures.
METHODS—CaCO-2/PBMC co-cultures were stimulated with non-pathogenic bacteria and enteropathogenic Escherichia coli. Expression of tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-8, monocyte chemoattracting protein 1 (MCP-1), and IL-10 was studied by enzyme linked immunosorbent assays (cytokine secretion) and by semiquantitative reverse transcription-polymerase chain reaction.
RESULTS—Challenge of CaCO-2 cells with non-pathogenic E coli and Lactobacillus sakei induced expression of IL-8, MCP-1, IL-1β, and TNF-α mRNA in the presence of underlying leucocytes. Leucocyte sensitised CaCO-2 cells produced TNF-α and IL-1β whereas IL-10 was exclusively secreted by human peripheral blood mononuclear cells. CaCO-2 cells alone remained hyporesponsive to the bacterial challenge. Lactobacillus johnsonii, an intestinal isolate, showed reduced potential to induce proinflammatory cytokines but increased transforming growth factor beta mRNA in leucocyte sensitised CaCO-2 cells. TNF-α was identified as one of the early mediators involved in cellular cross talk. In the presence of leucocytes, discriminative activation of CaCO-2 cells was observed between enteropathogenic E coli and non-pathogenic bacteria.
CONCLUSION—The differential recognition of non-pathogenic bacteria by CaCO-2 cells required the presence of underlying leucocytes. These results strengthen the hypothesis that bacterial signalling at the mucosal surface is dependent on a network of

  18. Characterization of Nonpathogenic, Live, Viral Vaccine Vectors Inducing Potent Cellular Immune Responses

    PubMed Central

    Publicover, Jean; Ramsburg, Elizabeth; Rose, John K.

    2004-01-01

    Experimental vaccines based on recombinant vesicular stomatitis viruses (VSV) expressing foreign viral proteins are protective in several animal disease models. Although these attenuated viruses are nonpathogenic in nonhuman primates when given by nasal, oral, or intramuscular routes, they are pathogenic in mice when given intranasally, and further vector attenuation may be required before human trials with VSV-based vectors can begin. Mutations truncating the VSV glycoprotein (G) cytoplasmic domain from 29 to 9 or 1 amino acid (designated CT9 or CT1, respectively) were shown previously to attenuate VSV growth in cell culture and pathogenesis in mice. Here we show that VSV recombinants carrying either the CT1 or CT9 deletion and expressing the human immunodeficiency virus (HIV) Env protein are nonpathogenic in mice, even when given by the intranasal route. We then carried out a detailed analysis of the CD8+ T-cell responses, including in vivo cytotoxic T-cell activity, induced by these vectors. When given by either the intranasal or intraperitoneal route, the VSV-CT9 vector expressing HIV Env elicited primary and memory CD8+ T-cell responses to Env equivalent to those elicited by recombinant wild-type VSV expressing Env. The VSV-CT1 vector also induced potent CD8+ T-cell responses after intraperitoneal vaccination, but was less effective when given by the intranasal route. The VSV-CT1 vector was also substantially less effective than the VSV-CT9 or wild-type vector at inducing antibody to Env. The VSV-CT9 vector appears ideal because of its lack of pathogenesis, propagation to high titers in vitro, and stimulation of strong cellular and humoral immune responses. PMID:15308726

  19. RE-DEFINING THE ROLES OF SENSORS IN OBJECTIVE PHYSICAL ACTIVITY MONITORING

    PubMed Central

    Chen, Kong Y.; Janz, Kathleen F.; Zhu, Weimo; Brychta, Robert J.

    2011-01-01

    Background As physical activity researchers are increasingly using objective portable devices, this review describes current state of the technology to assess physical activity, with a focus on specific sensors and sensor properties currently used in monitors and their strengths and weakness. Additional sensors and sensor properties desirable for activity measurement and best practices for users and developers also are discussed. Best Practices We grouped current sensors into three broad categories for objectively measuring physical activity: associated body movement, physiology, and context. Desirable sensor properties for measuring physical activity and the importance of these properties in relationship to specific applications are addressed, and the specific roles of transducers and data acquisition systems within the monitoring devices are defined. Technical advancements in sensors, microcomputer processors, memory storage, batteries, wireless communication, and digital filters have made monitors more usable for subjects (smaller, more stable, and longer running time) and for researchers (less costly, higher time resolution and memory storage, shorter download time, and user-defined data features). Future Directions Users and developers of physical activity monitors should learn about the basic properties of their sensors, such as range, accuracy, precision, while considering the data acquisition/filtering steps that may be critical to data quality and may influence the desirable measurement outcome(s). PMID:22157770

  20. Defining Single Molecular Forces Required for Notch Activation Using Nano Yoyo.

    PubMed

    Chowdhury, Farhan; Li, Isaac T S; Ngo, Thuy T M; Leslie, Benjamin J; Kim, Byoung Choul; Sokoloski, Joshua E; Weiland, Elizabeth; Wang, Xuefeng; Chemla, Yann R; Lohman, Timothy M; Ha, Taekjip

    2016-06-01

    Notch signaling, involved in development and tissue homeostasis, is activated at the cell-cell interface through ligand-receptor interactions. Previous studies have implicated mechanical forces in the activation of Notch receptor upon binding to its ligand. Here we aimed to determine the single molecular force required for Notch activation by developing a novel low tension gauge tether (LTGT). LTGT utilizes the low unbinding force between single-stranded DNA (ssDNA) and Escherichia coli ssDNA binding protein (SSB) (∼4 pN dissociation force at 500 nm/s pulling rate). The ssDNA wraps around SSB and, upon application of force, unspools from SSB, much like the unspooling of a yoyo. One end of this nano yoyo is attached to the surface though SSB, while the other end presents a ligand. A Notch receptor, upon binding to its ligand, is believed to undergo force-induced conformational changes required for activating downstream signaling. If the required force for such activation is larger than 4 pN, ssDNA will unspool from SSB, and downstream signaling will not be activated. Using these LTGTs, in combination with the previously reported TGTs that rupture double-stranded DNA at defined forces, we demonstrate that Notch activation requires forces between 4 and 12 pN, assuming an in vivo loading rate of 60 pN/s. Taken together, our study provides a direct link between single-molecular forces and Notch activation. PMID:27167603

  1. Antimycobacterial activity of chemically defined natural substances from the Caribbean flora in Guadeloupe.

    PubMed

    Rastogi, N; Abaul, J; Goh, K S; Devallois, A; Philogène, E; Bourgeois, P

    1998-04-01

    Eight chemically defined, naturally occurring compounds were extracted from the tropical flora of the Caribbean island of Guadeloupe: pilocarpine, an alkaloid from Pilocarpus racemosus; heraclenol and isomeranzin, coumarins from Triphasia trifolia; lochnerin, an indole alkaloid from Rauwolfia biauriculata; ibogaine and voacangine, indole alkaloids from Tabernaemontana citrifolia; texalin, an oxazole from Amyris elemifera; and canellal, a sesquiterpene dialdehyde from Canella winterana. An essential oil fraction from Canella winterana was also tested. The antimycobacterial activity of these substances was tested against Mycobacterium tuberculosis, M. avium and M. kansasii using the Middlebrook 7H11 agar medium, the Bactec 460-TB radiometric methodology, and determination of bacterial viable counts. Three compounds, namely ibogaine, voacangine and texalin, showed antimycobacterial activity. Investigations on the structure-modification and structure-activity relationships of these compounds may help determine new targets for future drug development. PMID:9626931

  2. CXCR4 Activation Defines a New Subgroup of Sonic Hedgehog–Driven Medulloblastoma

    PubMed Central

    Sengupta, Rajarshi; Dubuc, Adrian; Ward, Stacey; Yang, Lihua; Northcott, Paul; Woerner, B. Mark; Kroll, Kirsten; Luo, Jingqin; Taylor, Michael D.; Wechsler-Reya, Robert J.; Rubin, Joshua B.

    2012-01-01

    Medulloblastoma prognosis tends to be poor, despite aggressive therapy, but defining molecular subgroups may identify patients who could benefit from targeted therapies. This study used human gene array and associated clinical data to identify a new molecular subgroup of medulloblastoma characterized by coactivation of the Sonic hedgehog (SHH) and CXCR4 pathways. SHH–CXCR4 tumors were more common in the youngest patients where they were associated with desmoplastic histology. In contrast to tumors activating SHH but not CXCR4, coactivated tumors exhibited greater expression of Math1 and cyclin D1. Treatment with the CXCR4 antagonist AMD3100 inhibited cyclin D1 expression and maximal tumor growth in vivo. Mechanistic investigations revealed that SHH activation stimulated CXCR4 cell surface localization and effector signaling activity, whereas SHH absence caused CXCR4 to assume an intracellular localization. Taken together, our findings define a new medulloblastoma subgroup characterized by a functional interaction between the SHH and CXCR4 pathways, and they provide a rationale to clinically evaluate combined inhibition of SHH and CXCR4 for medulloblastoma treatment. PMID:22052462

  3. HLA-A3 supermotif defined by quantitative structure-activity relationship analysis.

    PubMed

    Guan, Pingping; Doytchinova, Irini A; Flower, Darren R

    2003-01-01

    Activation of a cytotoxic T cell requires specific binding of antigenic peptides to major histocompatibility complex (MHC) molecules. This paper reports a study of peptides binding to members of the HLA-A3 superfamily using a recently developed 2D-QSAR method, called the additive method. Four alleles with high phenotype frequency were included in the study: A*0301, A*1101, A*3101 and A*6801. The influence of each of the 20 amino acids at each position of the peptide on binding was studied. A refined A3 supertype motif was defined in the study. PMID:12646688

  4. Persistence of Pathogenic and Non-Pathogenic Escherichia coli Strains in Various Tropical Agricultural Soils of India.

    PubMed

    Naganandhini, S; Kennedy, Z John; Uyttendaele, M; Balachandar, D

    2015-01-01

    The persistence of Shiga-like toxin producing E. coli (STEC) strains in the agricultural soil creates serious threat to human health through fresh vegetables growing on them. However, the survival of STEC strains in Indian tropical soils is not yet understood thoroughly. Additionally how the survival of STEC strain in soil diverges with non-pathogenic and genetically modified E. coli strains is also not yet assessed. Hence in the present study, the survival pattern of STEC strain (O157-TNAU) was compared with non-pathogenic (MTCC433) and genetically modified (DH5α) strains on different tropical agricultural soils and on a vegetable growing medium, cocopeat under controlled condition. The survival pattern clearly discriminated DH5α from MTCC433 and O157-TNAU, which had shorter life (40 days) than those compared (60 days). Similarly, among the soils assessed, the red laterite and tropical latosol supported longer survival of O157-TNAU and MTCC433 as compared to wetland and black cotton soils. In cocopeat, O157 recorded significantly longer survival than other two strains. The survival data were successfully analyzed using Double-Weibull model and the modeling parameters were correlated with soil physico-chemical and biological properties using principal component analysis (PCA). The PCA of all the three strains revealed that pH, microbial biomass carbon, dehydrogenase activity and available N and P contents of the soil decided the survival of E. coli strains in those soils and cocopeat. The present research work suggests that the survival of O157 differs in tropical Indian soils due to varied physico-chemical and biological properties and the survival is much shorter than those reported in temperate soils. As the survival pattern of non-pathogenic strain, MTCC433 is similar to O157-TNAU in tropical soils, the former can be used as safe model organism for open field studies. PMID:26101887

  5. Persistence of Pathogenic and Non-Pathogenic Escherichia coli Strains in Various Tropical Agricultural Soils of India

    PubMed Central

    Naganandhini, S.; Kennedy, Z. John; Uyttendaele, M.; Balachandar, D.

    2015-01-01

    The persistence of Shiga-like toxin producing E. coli (STEC) strains in the agricultural soil creates serious threat to human health through fresh vegetables growing on them. However, the survival of STEC strains in Indian tropical soils is not yet understood thoroughly. Additionally how the survival of STEC strain in soil diverges with non-pathogenic and genetically modified E. coli strains is also not yet assessed. Hence in the present study, the survival pattern of STEC strain (O157-TNAU) was compared with non-pathogenic (MTCC433) and genetically modified (DH5α) strains on different tropical agricultural soils and on a vegetable growing medium, cocopeat under controlled condition. The survival pattern clearly discriminated DH5α from MTCC433 and O157-TNAU, which had shorter life (40 days) than those compared (60 days). Similarly, among the soils assessed, the red laterite and tropical latosol supported longer survival of O157-TNAU and MTCC433 as compared to wetland and black cotton soils. In cocopeat, O157 recorded significantly longer survival than other two strains. The survival data were successfully analyzed using Double-Weibull model and the modeling parameters were correlated with soil physico-chemical and biological properties using principal component analysis (PCA). The PCA of all the three strains revealed that pH, microbial biomass carbon, dehydrogenase activity and available N and P contents of the soil decided the survival of E. coli strains in those soils and cocopeat. The present research work suggests that the survival of O157 differs in tropical Indian soils due to varied physico-chemical and biological properties and the survival is much shorter than those reported in temperate soils. As the survival pattern of non-pathogenic strain, MTCC433 is similar to O157-TNAU in tropical soils, the former can be used as safe model organism for open field studies. PMID:26101887

  6. Essential requirement of cytochrome c release for caspase activation by procaspase-activating compound defined by cellular models

    PubMed Central

    Seervi, M; Joseph, J; Sobhan, P K; Bhavya, B C; Santhoshkumar, T R

    2011-01-01

    Mitochondrial cytochrome c (cyt. c) release and caspase activation are often impaired in tumors with Bcl-2 overexpression or Bax and Bak-defective status. Direct triggering of cell death downstream of Bax and Bak is an attractive strategy to kill such cancers. Small molecule compounds capable of direct caspase activation appear to be the best mode for killing such tumors. However, there is no precise model to screen such compounds. The currently employed cell-free systems possess the inherent drawback of lacking cellular contents and organelles that operate in integrating cell death signaling. We have developed highly refined cell-based approaches to validate direct caspase activation in cancer cells. Using this approach, we show that PAC-1 (first procaspase-activating compound), the first direct activator of procaspases identified in a cell-free system, in fact requires mitochondrial cyt. c release for triggering caspase activation similar to other antitumor agents. It can induce significant caspase activation and cell death in the absence of Bax and Bak, and in cells overexpressing Bcl-2 and Bcl-xL. This study for the first time defines precise criteria for the validation of direct caspase-activating compounds using specialized cellular models that is expected to accelerate the discovery of potential direct caspase activators. PMID:21900958

  7. Sequencing formally defined reactions for robotic activity: integrating RAPS and GAPPS

    NASA Astrophysics Data System (ADS)

    Slack, Marc G.

    1992-11-01

    Construction of robots which operate in unstructured environments has of late produced a number of approaches for transforming sensor readings into activity in the world. Most of these approaches provide no formal semantics for discussing the way in which the internal state of the robot maps to the desired state of the world. We have been investigating the use of the GAPPS programming language as a mechanism for defining robotic reactions. This work has resulted in the creation of reactive modules which mediate between discrete statements about world states to achieve or maintain and the required continuous activity. While relatively complex goals have been achieved with this approach, the syntax and semantics of the GAPPS language is inappropriate for complicated dynamically changing goals. As a result, we have begun investigating the use of Reactive Action Packages (RAPs) as a mechanism for sequencing the activation of GAPPS-based reactive skills. The motivation for using RAPs is twofold. First, the syntax and semantics of the RAPs language integrates smoothly with a traditional non-linear planning system, allowing the construction and execution of plans for increasingly complex tasks. Second, GAPPS-based reactions fulfill a missing component of a RAPs-based controller system, namely the transformation of discrete RAP primitives (e.g., (maintain grasp ?thing)) into continuous physical activity. This paper presents the approach we are taking and discusses some of the issues involved in integrating these two systems.

  8. The retrieval of self-defining memories is associated with the activation of specific working selves.

    PubMed

    Çili, Soljana; Stopa, Lusia

    2015-01-01

    This article presents two studies that investigated the impact of the retrieval of self-defining memories on individuals' sense of self. Participants recalled positive and/or negative self-defining memories, rated memory characteristics and completed measures focusing on different self-aspects. Study 1 found that participants reported higher state self-esteem after recalling a positive memory than after recalling a negative one. They also reported lower negative self-consistency and higher state self-concept clarity and positive self-consistency, but this result became non-significant after controlling for state self-esteem. Study 2 found that participants reported higher state self-esteem, a marginally higher proportion of recreation/exploration, goals and a marginally lower proportion of achievement goals after recalling a positive memory than after recalling a negative one. They also reported a higher proportion of self-cognitions referring to emotional states after recalling memories from which they had not abstracted meaning than after recalling memories from which they had done this. These findings suggest that the retrieval of vivid, emotional and highly self-relevant memories may be accompanied by the activation of specific self-representations or working selves. They also suggest that the experience of memory-related intrusive images may temporarily influence individuals' sense of self. The implications of these findings for clinical practice are discussed. PMID:24528183

  9. The Race against Protease Activation Defines the Role of ESCRTs in HIV Budding

    PubMed Central

    Bendjennat, Mourad; Saffarian, Saveez

    2016-01-01

    HIV virions assemble on the plasma membrane and bud out of infected cells using interactions with endosomal sorting complexes required for transport (ESCRTs). HIV protease activation is essential for maturation and infectivity of progeny virions, however, the precise timing of protease activation and its relationship to budding has not been well defined. We show that compromised interactions with ESCRTs result in delayed budding of virions from host cells. Specifically, we show that Gag mutants with compromised interactions with ALIX and Tsg101, two early ESCRT factors, have an average budding delay of ~75 minutes and ~10 hours, respectively. Virions with inactive proteases incorporated the full Gag-Pol and had ~60 minutes delay in budding. We demonstrate that during budding delay, activated proteases release critical HIV enzymes back to host cytosol leading to production of non-infectious progeny virions. To explain the molecular mechanism of the observed budding delay, we modulated the Pol size artificially and show that virion release delays are size-dependent and also show size-dependency in requirements for Tsg101 and ALIX. We highlight the sensitivity of HIV to budding “on-time” and suggest that budding delay is a potent mechanism for inhibition of infectious retroviral release. PMID:27280284

  10. De novo DNA demethylation and noncoding transcription define active intergenic regulatory elements.

    PubMed

    Schlesinger, Felix; Smith, Andrew D; Gingeras, Thomas R; Hannon, Gregory J; Hodges, Emily

    2013-10-01

    Deep sequencing of mammalian DNA methylomes has uncovered a previously unpredicted number of discrete hypomethylated regions in intergenic space (iHMRs). Here, we combined whole-genome bisulfite sequencing data with extensive gene expression and chromatin-state data to define functional classes of iHMRs, and to reconstruct the dynamics of their establishment in a developmental setting. Comparing HMR profiles in embryonic stem and primary blood cells, we show that iHMRs mark an exclusive subset of active DNase hypersensitive sites (DHS), and that both developmentally constitutive and cell-type-specific iHMRs display chromatin states typical of distinct regulatory elements. We also observe that iHMR changes are more predictive of nearby gene activity than the promoter HMR itself, and that expression of noncoding RNAs within the iHMR accompanies full activation and complete demethylation of mature B cell enhancers. Conserved sequence features corresponding to iHMR transcript start sites, including a discernible TATA motif, suggest a conserved, functional role for transcription in these regions. Similarly, we explored both primate-specific and human population variation at iHMRs, finding that while enhancer iHMRs are more variable in sequence and methylation status than any other functional class, conservation of the TATA box is highly predictive of iHMR maintenance, reflecting the impact of sequence plasticity and transcriptional signals on iHMR establishment. Overall, our analysis allowed us to construct a three-step timeline in which (1) intergenic DHS are pre-established in the stem cell, (2) partial demethylation of blood-specific intergenic DHSs occurs in blood progenitors, and (3) complete iHMR formation and transcription coincide with enhancer activation in lymphoid-specified cells. PMID:23811145

  11. Contact activation of blood coagulation on a defined kaolin/collagen surface in a microfluidic assay

    PubMed Central

    Zhu, Shu; Diamond, Scott L.

    2014-01-01

    Generation of active Factor XII (FXIIa) triggers blood clotting on artificial surfaces and may also enhance intravascular thrombosis. We developed a patterned kaolin (0 to 0.3 pg/μm2)/type 1 collagen fibril surface for controlled microfluidic clotting assays. Perfusion of whole blood (treated only with a low level of 4 μg/mL of the XIIa inhibitor, corn trypsin inhibitor) drove platelet deposition followed by fibrin formation. At venous wall shear rate (100 s−1), kaolin accelerated onset of fibrin formation by ~100 sec when compared to collagen alone (250 sec vs. 350 sec), with little effect on platelet deposition. Even with kaolin present, arterial wall shear rate (1000 s−1) delayed and suppressed fibrin formation compared to venous wall shear rate. A comparison of surfaces for extrinsic activation (tissue factor TF/collagen) versus contact activation (kaolin/collagen) that each generated equal platelet deposition at 100 s−1 revealed: (1) TF surfaces promoted much faster fibrin onset (at 100 sec) and more endpoint fibrin at 600 sec at either 100 s−1 or 1000 s−1, and (2) kaolin and TF surfaces had a similar sensitivity for reduced fibrin deposition at 1000 s−1 (compared to fibrin formed at 100 s−1) despite differing coagulation triggers. Anti-platelet drugs inhibiting P2Y1, P2Y12, cyclooxygenase-1 or activating IP-receptor or guanylate cyclase reduced platelet and fibrin deposition on kaolin/collagen. Since FXIIa or FXIa inhibition may offer safe antithrombotic therapy, especially for biomaterial thrombosis, these defined collagen/kaolin surfaces may prove useful in drug screening tests or in clinical diagnostic assays of blood under flow conditions. PMID:25303860

  12. De novo DNA demethylation and noncoding transcription define active intergenic regulatory elements

    PubMed Central

    Schlesinger, Felix; Smith, Andrew D.; Gingeras, Thomas R.; Hannon, Gregory J.; Hodges, Emily

    2013-01-01

    Deep sequencing of mammalian DNA methylomes has uncovered a previously unpredicted number of discrete hypomethylated regions in intergenic space (iHMRs). Here, we combined whole-genome bisulfite sequencing data with extensive gene expression and chromatin-state data to define functional classes of iHMRs, and to reconstruct the dynamics of their establishment in a developmental setting. Comparing HMR profiles in embryonic stem and primary blood cells, we show that iHMRs mark an exclusive subset of active DNase hypersensitive sites (DHS), and that both developmentally constitutive and cell-type-specific iHMRs display chromatin states typical of distinct regulatory elements. We also observe that iHMR changes are more predictive of nearby gene activity than the promoter HMR itself, and that expression of noncoding RNAs within the iHMR accompanies full activation and complete demethylation of mature B cell enhancers. Conserved sequence features corresponding to iHMR transcript start sites, including a discernible TATA motif, suggest a conserved, functional role for transcription in these regions. Similarly, we explored both primate-specific and human population variation at iHMRs, finding that while enhancer iHMRs are more variable in sequence and methylation status than any other functional class, conservation of the TATA box is highly predictive of iHMR maintenance, reflecting the impact of sequence plasticity and transcriptional signals on iHMR establishment. Overall, our analysis allowed us to construct a three-step timeline in which (1) intergenic DHS are pre-established in the stem cell, (2) partial demethylation of blood-specific intergenic DHSs occurs in blood progenitors, and (3) complete iHMR formation and transcription coincide with enhancer activation in lymphoid-specified cells. PMID:23811145

  13. High Temperature in Combination with UV Irradiation Enhances Horizontal Transfer of stx2 Gene from E. coli O157:H7 to Non-Pathogenic E. coli

    PubMed Central

    Yue, Wan-Fu; Du, Min; Zhu, Mei-Jun

    2012-01-01

    Background Shiga toxin (stx) genes have been transferred to numerous bacteria, one of which is E. coli O157:H7. It is a common belief that stx gene is transferred by bacteriophages, because stx genes are located on lambdoid prophages in the E. coli O157:H7 genome. Both E. coli O157:H7 and non-pathogenic E. coli are highly enriched in cattle feedlots. We hypothesized that strong UV radiation in combination with high temperature accelerates stx gene transfer into non-pathogenic E. coli in feedlots. Methodology/Principal Findings E. coli O157:H7 EDL933 strain were subjected to different UV irradiation (0 or 0.5 kJ/m2) combination with different temperature (22, 28, 30, 32, and 37°C) treatments, and the activation of lambdoid prophages was analyzed by plaque forming unit while induction of Stx2 prophages was quantified by quantitative real-time PCR. Data showed that lambdoid prophages in E. coli O157:H7, including phages carrying stx2, were activated under UV radiation, a process enhanced by elevated temperature. Consistently, western blotting analysis indicated that the production of Shiga toxin 2 was also dramatically increased by UV irradiation and high temperature. In situ colony hybridization screening indicated that these activated Stx2 prophages were capable of converting laboratory strain of E. coli K12 into new Shiga toxigenic E. coli, which were further confirmed by PCR and ELISA analysis. Conclusions/Significance These data implicate that high environmental temperature in combination with UV irradiation accelerates the spread of stx genes through enhancing Stx prophage induction and Stx phage mediated gene transfer. Cattle feedlot sludge are teemed with E. coli O157:H7 and non-pathogenic E. coli, and is frequently exposed to UV radiation via sunlight, which may contribute to the rapid spread of stx gene to non-pathogenic E. coli and diversity of shiga toxin producing E. coli. PMID:22347461

  14. Degradation of estradiol and ethinyl estradiol by activated sludge and by a defined mixed culture.

    PubMed

    Weber, Stefanie; Leuschner, Prisca; Kämpfer, Peter; Dott, Wolfgang; Hollender, Juliane

    2005-04-01

    The aerobic degradation of the natural hormone 17-beta-estradiol (E2) and the synthetic hormone 17-alpha-ethinyl estradiol (EE2) was investigated in batch experiments with activated sludge from a conventional and a membrane sewage treatment plant. E2 was converted to estrone (E1), the well known metabolite, and further completely transformed within 3 days. The turnover rates of E2 did not differ greatly between conventional and membrane activated sludge. EE2 was persistent in both sludges. By several transfers into fresh E2-medium an enrichment culture could be selected that used E2 as growth substrate. Further enrichment and isolation led to a defined mixed culture consisting of two strains, which were identified by a polyphasic approach as Achromobacter xylosoxidans and Ralstonia sp., respectively. The culture used E2 and E1 as growth substrates and transformed estriol (E3) and 16-alpha-hydroxyestrone but not the xenoestrogens bisphenol A, alpha-zearalenol, mestranol or EE2. The turnover rates of E2 were 0.025-0.1 microg h(-1) cfu(-1) and did not depend on the steroid concentration. PMID:15290133

  15. Measurement of membrane-bound human heme oxygenase-1 activity using a chemically defined assay system.

    PubMed

    Huber, Warren J; Marohnic, Christopher C; Peters, Michelle; Alam, Jawed; Reed, James R; Masters, Bettie Sue Siler; Backes, Wayne L

    2009-04-01

    Heme oxygenase (HO) catalyzes heme degradation in a reaction requiring NADPH-cytochrome P450 reductase (CPR). Although most studies with HO used a soluble 30-kDa form, lacking the C-terminal membrane-binding region, recent reports show that the catalytic behavior of this enzyme is very different if this domain is retained; the overall activity was elevated 5-fold, and the K(m) for CPR decreased approximately 50-fold. The goal of these studies was to accurately measure HO activity using a coupled assay containing purified biliverdin reductase (BVR). This allows measurement of bilirubin formation after incorporation of full-length CPR and heme oxygenase-1 (HO-1) into a membrane environment. When rat liver cytosol was used as the source of partially purified BVR, the reaction remained linear for 2 to 3 min; however, the reaction was only linear for 10 to 30 s when an equivalent amount of purified, human BVR (hBVR) was used. This lack of linearity was not observed with soluble HO-1. Optimal formation of bilirubin was achieved with concentrations of bovine serum albumin (0.25 mg/ml) and hBVR (0.025-0.05 microM), but neither supplement increased the time that the reaction remained linear. Various concentrations of superoxide dismutase had no effect on the reaction; however, when catalase was included, the reactions were linear for at least 4 to 5 min, even at high CPR levels. These results not only show that HO-1-generated hydrogen peroxide leads to a decrease in HO-1 activity but also provide for a chemically defined system to be used to examine the function of full-length HO-1 in a membrane environment. PMID:19131520

  16. Comparative Study of Eis-like Enzymes from Pathogenic and Nonpathogenic Bacteria.

    PubMed

    Green, Keith D; Pricer, Rachel E; Stewart, Megan N; Garneau-Tsodikova, Sylvie

    2015-06-12

    Antibiotic resistance is a growing problem worldwide. Of particular importance is the resistance of Mycobacterium tuberculosis (Mtb) to currently available antibiotics used in the treatment of infected patients. Up-regulation of an aminoglycoside (AG) acetyltransferase, the enhanced intracellular survival (Eis) protein of Mtb (Eis_Mtb), is responsible for resistance to the second-line injectable drug kanamycin A in a number of Mtb clinical isolates. This acetyltransferase is known to modify AGs, not at a single position, as usual for this type of enzyme, but at multiple amine sites. We identified, using in silico techniques, 22 homologues from a wide variety of bacteria, that we then cloned, purified, and biochemically studied. From the selected Eis homologues, 7 showed the ability to modify AGs to various degrees and displayed both similarities and differences when compared to Eis_Mtb. In addition, an inhibitor proved to be active against all homologues tested. Our findings show that this family of acetyltransferase enzymes exists in both mycobacteria and non-mycobacteria and in both pathogenic and nonpathogenic species. The bacterial strains described herein should be monitored for rising resistance rates to AGs. PMID:27622743

  17. Biochemical analysis of plant protection afforded by a nonpathogenic endophytic mutant of Colletotrichum magna

    SciTech Connect

    Redman, R.S.; Rodriguez, R.J. Univ. of Washington, Seattle, WA . Dept. of Botany); Clifton, D.R.; Morrel, J.; Brown, G. ); Freeman, S. . Dept. of Plant Pathology)

    1999-02-01

    A nonpathogenic mutant of Colletotrichum magna (path-1) was previously shown to protect watermelon (Citrullus lanatus) and cucumber (Cucumis sativus) seedlings from anthracnose disease elicited by wild-type C. magna. Disease protection was observed in stems of path-1-colonized cucurbits but not in cotyledons, indicating that path-1 conferred tissue-specific and/or localized protection. Plant biochemical indicators of a localized and systemic (peroxidase, phenylalanine ammonia-lyase, lignin, and salicylic acid) plant-defense response were investigated in anthracnose-resistant and-susceptible cultivars of cucurbit seedlings exposed to four treatments: (1) water (control), (2) path-1 conidia, (3) wild-type conidia, and (4) challenge conditions (inoculation into path-1 conidia for 48 h and then exposure to wild-type conidia). Collectively, these analyses indicated that disease protection in path-1-colonized plants was correlated with the ability of these plants to mount a defense response more rapidly and to equal or greater levels than plants exposed to wild-type C. magna alone. Watermelon plants colonized with path-1 were also protected against disease caused by Colletotrichum orbiculare and Fusarium oxysporum. A model based on the kinetics of plant-defense activation is presented to explain the mechanism of path-1-conferred disease protection.

  18. Uptake of non-pathogenic E. coli by Arabidopsis induces downregulation of heat shock proteins

    PubMed Central

    Schmidt, Susanne; Lonhienne, Thierry GA

    2010-01-01

    We recently demonstrated that non-pathogenic and non-symbiotic microbes E. coli and yeast are taken up by roots and used as a source of nutrients by the plant. Although this process appears to be beneficial for the plant, the nutritional gain of microbe incorporation has to exceed the energy expense of microbe uptake and digestion, and the question remains whether the presence of microbes triggers pathogen- and other stress-induced responses. Here, we present evidence that digesting microbes is accompanied by strong downregulation of genes linked to stress response in Arabidopsis. Genome-wide transcription analysis shows that uptake of E. coli by Arabidopsis roots is accompanied by a pronounced downregulation of heat shock proteins. Plants upregulate heat shock proteins in response to environmental stresses including temperature, salt, light and disease agents including microbial pathogens. The pronounced downregulation of heat shock proteins in the presence of E. coli indicates that uptake and subsequent digestion of microbes does not induce stress. Additionally it suggests that resources devoted to stress resistance in control plants may be re-allocated to the process of microbe uptake and digestion. This observation adds evidences to the notion that uptake of microbes is an active, purposeful and intentional behavior of the plant. PMID:21139429

  19. Biochemical Analysis of Plant Protection Afforded by a Nonpathogenic Endophytic Mutant of Colletotrichum magna1

    PubMed Central

    Redman, Regina S.; Freeman, Stanley; Clifton, David R.; Morrel, Jed; Brown, Gayle; Rodriguez, Rusty J.

    1999-01-01

    A nonpathogenic mutant of Colletotrichum magna (path-1) was previously shown to protect watermelon (Citrullus lanatus) and cucumber (Cucumis sativus) seedlings from anthracnose disease elicited by wild-type C. magna. Disease protection was observed in stems of path-1-colonized cucurbits but not in cotyledons, indicating that path-1 conferred tissue-specific and/or localized protection. Plant biochemical indicators of a localized and systemic (peroxidase, phenylalanine ammonia-lyase, lignin, and salicylic acid) “plant-defense” response were investigated in anthracnose-resistant and -susceptible cultivars of cucurbit seedlings exposed to four treatments: (1) water (control), (2) path-1 conidia, (3) wild-type conidia, and (4) challenge conditions (inoculation into path-1 conidia for 48 h and then exposure to wild-type conidia). Collectively, these analyses indicated that disease protection in path-1-colonized plants was correlated with the ability of these plants to mount a defense response more rapidly and to equal or greater levels than plants exposed to wild-type C. magna alone. Watermelon plants colonized with path-1 were also protected against disease caused by Colletotrichum orbiculare and Fusarium oxysporum. A model based on the kinetics of plant-defense activation is presented to explain the mechanism of path-1-conferred disease protection. PMID:9952476

  20. Biochemical analysis of plant protection afforded by a nonpathogenic endophytic mutant of Colletotrichum magna

    USGS Publications Warehouse

    Redman, R.S.; Freeman, S.; Clifton, D.R.; Morrel, J.; Brown, G.; Rodriguez, R.J.

    1999-01-01

    A nonpathogenic mutant of Colletotrichum magna (path-1) was previously shown to protect watermelon (Citrullus lanatus) and cucumber (Cucumis sativus) seedlings from anthracnose disease elicited by wild-type C. magna. Disease protection was observed in stems of path-1-colonized cucurbits but not in cotyledons, indicating that path-1 conferred tissue-specific and/or localized protection. Plant biochemical indicators of a localized and systemic (peroxidase, phenylalanine ammonia-lyase, lignin, and salicylic acid) 'plant-defense' response were investigated in anthracnose-resistant and -susceptible cultivars of cucurbit seedlings exposed to four treatments: (1) water (control), (2) path-1 conidia, (3) wild-type conidia, and (4) challenge conditions (inoculation into path-1 conidia for 48 h and then exposure to wild-type conidia). Collectively, these analyses indicated that disease protection in path-1 colonized plants was correlated with the ability of these plants to mount a defense response more rapidly and to equal or greater levels than plants exposed to wild-type C. magna alone. Watermelon plants colonized with path-1 were also protected against disease caused by Colletotrichum orbiculare and Fusarium oxysporum. A model based on the kinetics of plant-defense activation is presented to explain the mechanism of path-1-conferred disease protection.

  1. 12 CFR 218.721 - Defined terms relating to the trust and fiduciary activities exception from the definition of...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... limitation, a fee paid— (A) For personal services, tax preparation, or real estate settlement services; (B... DEFINITION OF BROKER IN THE SECURITIES EXCHANGE ACT OF 1934 (REGULATION R) § 218.721 Defined terms relating to the trust and fiduciary activities exception from the definition of “broker.” (a) Defined...

  2. 12 CFR 218.721 - Defined terms relating to the trust and fiduciary activities exception from the definition of...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... limitation, a fee paid— (A) For personal services, tax preparation, or real estate settlement services; (B... DEFINITION OF BROKER IN THE SECURITIES EXCHANGE ACT OF 1934 (REGULATION R) § 218.721 Defined terms relating to the trust and fiduciary activities exception from the definition of “broker.” (a) Defined...

  3. 12 CFR 218.721 - Defined terms relating to the trust and fiduciary activities exception from the definition of...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... limitation, a fee paid— (A) For personal services, tax preparation, or real estate settlement services; (B... DEFINITION OF BROKER IN THE SECURITIES EXCHANGE ACT OF 1934 (REGULATION R) § 218.721 Defined terms relating to the trust and fiduciary activities exception from the definition of “broker.” (a) Defined...

  4. Non-native ligands define the active site of Pennisetum glaucum (L.) R. Br dehydroascorbate reductase.

    PubMed

    Krishna Das, Bhaba; Kumar, Amit; Maindola, Priyank; Mahanty, Srikrishna; Jain, S K; Reddy, Mallireddy K; Arockiasamy, Arulandu

    2016-05-13

    Dehydroascorbate reductase (DHAR), a member of the glutathione-S-transferase (GST) family, reduces dehydroascorbate (DHA) to ascorbate (AsA; Vitamin-C) in a glutathione (GSH)-dependent manner and in doing so, replenishes the critical AsA pool of the cell. To understand the enzyme mechanism in detail, we determined the crystal structure of a plant DHAR from Pennisetum glaucum (PgDHAR) using Iodide-Single Anomalous Dispersion (SAD) and Molecular replacement methods, in two different space groups. Here, we show PgDHAR in complex with two non-native ligands, viz. an acetate bound at the G-site, which resembles the γ-carboxyl moiety of GSH, and a glycerol at the H-site, which shares the backbone of AsA. We also show that, in the absence of bound native substrates, these non-native ligands help define the critical 'hook points' in the DHAR enzyme active site. Further, our data suggest that these non-native ligands can act as the logical bootstrapping points for iterative design of inhibitors/analogs for DHARs. PMID:27067046

  5. From molecular signal activation to locomotion: an integrated, multiscale analysis of cell motility on defined matrices.

    PubMed

    Pathak, Amit; Kumar, Sanjay

    2011-01-01

    The adhesion, mechanics, and motility of eukaryotic cells are highly sensitive to the ligand density and stiffness of the extracellular matrix (ECM). This relationship bears profound implications for stem cell engineering, tumor invasion and metastasis. Yet, our quantitative understanding of how ECM biophysical properties, mechanotransductive signals, and assembly of contractile and adhesive structures collude to control these cell behaviors remains extremely limited. Here we present a novel multiscale model of cell migration on ECMs of defined biophysical properties that integrates local activation of biochemical signals with adhesion and force generation at the cell-ECM interface. We capture the mechanosensitivity of individual cellular components by dynamically coupling ECM properties to the activation of Rho and Rac GTPases in specific portions of the cell with actomyosin contractility, cell-ECM adhesion bond formation and rupture, and process extension and retraction. We show that our framework is capable of recreating key experimentally-observed features of the relationship between cell migration and ECM biophysical properties. In particular, our model predicts for the first time recently reported transitions from filopodial to "stick-slip" to gliding motility on ECMs of increasing stiffness, previously observed dependences of migration speed on ECM stiffness and ligand density, and high-resolution measurements of mechanosensitive protrusion dynamics during cell motility we newly obtained for this study. It also relates the biphasic dependence of cell migration speed on ECM stiffness to the tendency of the cell to polarize. By enabling the investigation of experimentally-inaccessible microscale relationships between mechanotransductive signaling, adhesion, and motility, our model offers new insight into how these factors interact with one another to produce complex migration patterns across a variety of ECM conditions. PMID:21483802

  6. Analyzing the Differences and Preferences of Pathogenic and Nonpathogenic Prokaryote Species

    NASA Astrophysics Data System (ADS)

    Nolen, L.; Duong, K.; Heim, N. A.; Payne, J.

    2015-12-01

    A limited amount of knowledge exists on the large-scale characteristics and differences of pathogenic species in comparison to all prokaryotes. Pathogenic species, like other prokaryotes, have attributes specific to their environment and lifestyles. However, because they have evolved to coexist inside their hosts, the conditions they occupy may be more limited than those of non-pathogenic species. In this study we investigate the possibility of divergent evolution between pathogenic and non-pathogenic species by examining differences that may have evolved as a result of the need to adapt to their host. For this research we analyzed data collected from over 1900 prokaryotic species and performed t-tests using R to quantify potential differences in preferences. To examine the possible divergences from nonpathogenic bacteria, we focused on three variables: cell biovolume, preferred environmental pH, and preferred environmental temperature. We also looked at differences between pathogenic and nonpathogenic species belonging to the same phylum. Our results suggest a strong divergence in abiotic preferences between the two groups, with pathogens occupying a much smaller range of temperatures and pHs than their non-pathogenic counterparts. However, while the median biovolume is different when comparing pathogens and nonpathogens, we cannot conclude that the mean values are significantly different from each other. In addition, we found evidence of convergent evolution, as the temperature and pH preferences of pathogenic bacteria species from different phlya all approach the same values. Pathogenic species do not, however, all approach the same biovolume values, suggesting that specific pH and temperature preferences are more characteristic of pathogens than certain biovolumes.

  7. A Cautionary Tale About Conducting Research on Abstinence Education: How Do State Abstinence Coordinators Define "Sexual Activity?"

    ERIC Educational Resources Information Center

    Bailey, William; Young, Michael; Knickerbocker, Cliff; Doan, Tam

    2002-01-01

    Investigated how state coordinators of abstinence education programs defined "sexual activity." Researchers surveyed Title V abstinence education coordinators from the 50 states, the District of Columbia, and three territories. Of the 17 coordinators providing at least partial responses, none reported having a definition of sexual activity. The…

  8. Genetic analysis of nonpathogenic Agrobacterium tumefaciens mutants arising in crown gall tumors.

    PubMed

    Bélanger, C; Canfield, M L; Moore, L W; Dion, P

    1995-07-01

    Little is known about the effect of the host on the genetic stability of bacterial plant pathogens. Crown gall, a plant disease caused by Agrobacterium tumefaciens, may represent a useful model to study this effect. Indeed, our previous observations on the natural occurrence and origin of nonpathogenic agrobacteria suggest that the host plant might induce loss of pathogenicity in populations of A. tumefaciens. Here we report that five different A. tumefaciens strains initially isolated from apple tumors produced up to 99% nonpathogenic mutants following their reintroduction into axenic apple plants. Two of these five strains were also found to produce mutants on pear and/or blackberry plants. Generally, the mutants of the apple isolate D10B/87 were altered in the tumor-inducing plasmid, harboring either deletions in this plasmid or point mutations in the regulatory virulence gene virG. Most of the mutants originating from the same tumor appeared to be of clonal origin, implying that the host plants influenced agrobacterial populations by favoring growth of nonpathogenic mutants over that of wild-type cells. This hypothesis was confirmed by coinoculation of apple rootstocks with strain D10B/87 and a nonpathogenic mutant. PMID:7601840

  9. Conversion of the pathogenic fungus Colletotrichum magna to a nonpathogenic, endophytic mutualist by gene disruption

    USGS Publications Warehouse

    Redman, R.S.; Ranson, J.C.; Rodriguez, R.J.

    1999-01-01

    Hygromycin-resistant transformants of the cucurbit pathogen Colletotrichum magna (teleomorph: Glomerella magna) were generated by restriction enzyme-mediated integration (REMI) transformation. A rapid pathogenicity assay involving watermelon (Citrullus lanatus) seedlings was developed and 14,400 REMI transformants were screened and assessed for their ability to cause disease, colonize plant tissues, and confer disease resistance against wild-type C. magna. A total of 176 nonpathogenic REMI mutants capable of colonizing cucurbit plants were isolated and assigned to three groups based on their ability to confer disease resistance: phenotype A, 80 to 100% disease protection; phenotype B, 10 to 65% disease protection; and phenotype C, 0 to 4% disease protection. Molecular and genetic analyses of one REMI mutant (R1) indicated that the nonpathogenic phenotype A resulted from a single-site integration. R1 showed a 1:1 segregation of hygromycin resistance and nonpathogenicity and all hygromycin-resistant progeny were nonpathogenic. The integrated vector and 5.5 kb of flanking fungal genomic DNA were isolated from R1 and designated pGMR1. To verify that pGMR1 contained pathogenicity gene sequences, a wild-type isolate of C. magna was transformed with pGMR1 to induce gene disruptions by homologous integration. Approximately 47% of the pGMR1 transformants expressed phenotype A, indicating homologous integration and gene disruption.

  10. Persistence of enterohemorrhagic and non-pathogenic E. coli on spinach leaves and in rhizosphere

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Outbreaks associated with leafy greens have focused attention on the persistence of Escherichia coli O157:H7 on produce. Ecological interactions of E. coli O157:H7 and spinach require detailed characterization. Purpose: Survival of E. coli O157:H7 and non-pathogenic E. coli was evalua...

  11. Defining cure.

    PubMed

    Hilton, Paul; Robinson, Dudley

    2011-06-01

    This paper is a summary of the presentations made as Proposal 2-"Defining cure" to the 2nd Annual meeting of the ICI-Research Society, in Bristol, 16th June 2010. It reviews definitions of 'cure' and 'outcome', and considers the impact that varying definition may have on prevalence studies and cure rates. The difference between subjective and objective outcomes is considered, and the significance that these different outcomes may have for different stakeholders (e.g. clinicians, patients, carers, industry etc.) is discussed. The development of patient reported outcome measures and patient defined goals is reviewed, and consideration given to the use of composite end-points. A series of proposals are made by authors and discussants as to how currently validated outcomes should be applied, and where our future research activity in this area might be directed. PMID:21661023

  12. Early Cytokine Response to Infection with Pathogenic vs Non-Pathogenic Organisms in a Mouse Model of Endodontic Infection.

    PubMed

    Matsui, Aritsune; Stephens, Danielle; Kantarci, Alpdogan; Rittling, Susan R

    2015-01-01

    Using the subcutaneous chamber model of infection, we showed previously that a mixture of four endodontic pathogens (EP: P. intermedia, F. nucleatum, S. intermedius and P. micra) are able to persist without clearance for up to seven days, while a non-pathogenic oral species, S. mitis, was substantially cleared in this time. Here we have compared the cytokine response inside the chambers against these microorganisms. A majority of cytokines tested (17/24) showed different patterns of expression. Several cytokines had a peak of expression at 2 h after infection in response to the EP, while none showed this pattern in S. mitis infections. Chemokines were uniformly present at similar or higher levels in response to S. mitis, with redundant expression of CXCR2 ligands, while several growth/survival factors were present at higher levels in EP infections. Protease activity expressed by EP may be responsible for the lower levels of some chemokines. T-cell associated cytokines were in general expressed at extremely low levels, and did not differ between the two infections. The inflammatory markers IL-6, IL-1α and IL1-β were expressed at similar levels in both infections at early times, while TNFα was preferentially present in S. mitis infections. In EP infected chambers, reciprocal changes in levels of IL-6 and IL-1α were observed at later times suggesting a switch in the inflammatory response. Analysis of the cytokine response to infection with the individual species from the EP mix suggests that P. intermedia drives this inflammatory switch. Together these results show a surprising level of divergence of the host response to pathogenic and non-pathogenic organisms associated with oral infections, and supports a dominant effect of P. intermedia in polymicrobial endodontic infections. PMID:26171605

  13. 17 CFR 247.721 - Defined terms relating to the trust and fiduciary activities exception from the definition of...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., including, without limitation, a fee paid— (A) For personal services, tax preparation, or real estate... AND DEFINITIONS RELATED TO THE EXCEPTIONS FOR BANKS FROM THE DEFINITION OF BROKER § 247.721 Defined terms relating to the trust and fiduciary activities exception from the definition of “broker.”...

  14. 17 CFR 247.721 - Defined terms relating to the trust and fiduciary activities exception from the definition of...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., including, without limitation, a fee paid— (A) For personal services, tax preparation, or real estate... AND DEFINITIONS RELATED TO THE EXCEPTIONS FOR BANKS FROM THE DEFINITION OF BROKER § 247.721 Defined terms relating to the trust and fiduciary activities exception from the definition of “broker.”...

  15. 17 CFR 247.721 - Defined terms relating to the trust and fiduciary activities exception from the definition of...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., including, without limitation, a fee paid— (A) For personal services, tax preparation, or real estate... AND DEFINITIONS RELATED TO THE EXCEPTIONS FOR BANKS FROM THE DEFINITION OF BROKER § 247.721 Defined terms relating to the trust and fiduciary activities exception from the definition of “broker.”...

  16. Progress in defining clinically meaningful changes for clinical trials in nonrenal manifestations of SLE disease activity.

    PubMed

    Choi, Chan-Bum; Liang, Matthew H; Bae, Sang-Cheol

    2016-01-01

    Since the 2002 Dusseldorf meeting, one new agent, Benlysta, has been approved by the US Food and Drug Administration for systemic lupus erythematosus. Experiences from the field in conducting trials of all the agents tested during this period have provided valuable practical insights. There has been incremental progress in defining the minimal clinically important difference (MCID) of key disease manifestations and the view is largely that of the health care providers and not that of the person suffering the disease. This basic methodological work on the MCID should improve the efficiency and the clinical relevance of future trials and their design. PMID:26732314

  17. Systematic Survey of Serine Hydrolase Activity in Mycobacterium tuberculosis Defines Changes Associated with Persistence.

    PubMed

    Ortega, Corrie; Anderson, Lindsey N; Frando, Andrew; Sadler, Natalie C; Brown, Robert W; Smith, Richard D; Wright, Aaron T; Grundner, Christoph

    2016-02-18

    The transition from replication to non-replication underlies much of Mycobacterium tuberculosis (Mtb) pathogenesis, as non- or slowly replicating Mtb are responsible for persistence and poor treatment outcomes. Therapeutic targeting of non-replicating populations is a priority for tuberculosis treatment, but few drug targets in non-replicating Mtb are currently known. Here, we directly measured the activity of the highly diverse and druggable serine hydrolases (SHs) during active replication and non-replication using activity-based proteomics. We predict SH activity for 78 proteins, including 27 proteins with unknown function, and identify 37 SHs that remain active in the absence of replication, providing a set of candidate persistence targets. Non-replication was associated with major shifts in SH activity. These activity changes were largely independent of SH abundance, indicating extensive post-translational regulation of SHs. By probing a large cross-section of druggable Mtb enzyme space during replication and non-replication, we identify new SHs and suggest new persistence targets. PMID:26853625

  18. Defining feasible bounds on muscle activation in a redundant biomechanical task; practical implications of redundancy

    PubMed Central

    Sohn, M. Hongchul; McKay, J. Lucas; Ting, Lena H.

    2013-01-01

    Measured muscle activation patterns often vary significantly from musculoskeletal model predictions that use optimization to resolve redundancy. Although experimental muscle activity exhibits both inter- and intra-subject variability we lack adequate tools to quantify the biomechanical latitude that the nervous system has when selecting muscle activation patterns. Here, we identified feasible ranges of individual muscle activity during force production in a musculoskeletal model to quantify the degree to which biomechanical redundancy allows for variability in muscle activation patterns. In a detailed cat hindlimb model matched to the posture of three cats, we identified the lower and upper bounds on muscle activity in each of 31 muscles during static endpoint force production across different force directions and magnitudes. Feasible ranges of muscle activation were relatively unconstrained across force magnitudes such that only a few (0∼13%) muscles were found to be truly “necessary” (e.g. exhibited non-zero lower bounds) at physiological force ranges. Most muscles were “optional” having zero lower bounds, and frequently had “maximal” upper bounds as well. Moreover, “optional” muscles were never selected by optimization methods that either minimized muscle stress, or that scaled the pattern required for maximum force generation. Therefore, biomechanical constraints were generally insufficient to restrict or specify muscle activation levels for producing a force in a given direction, and many muscle patterns exist that could deviate substantially from one another but still achieve the task. Our approach could be extended to identify the feasible limits of variability in muscle activation patterns in dynamic tasks such as walking. PMID:23489436

  19. Directed Endothelial Progenitor Differentiation from Human Pluripotent Stem Cells Via Wnt Activation Under Defined Conditions.

    PubMed

    Bao, Xiaoping; Lian, Xiaojun; Palecek, Sean P

    2016-01-01

    Efficient derivation of endothelial cells and their progenitors from human pluripotent stem cells (hPSCs) can facilitate studies of human vascular development, disease modeling, drug discovery, and cell-based therapy. Here we provide a detailed protocol for directing hPSCs to functional endothelial cells and their progenitors in a completely defined, growth factor- and serum-free system by temporal modulation of Wnt/β-catenin signaling via small molecules. We demonstrate a 10-day, two-stage process that recapitulates endothelial cell development, in which hPSCs first differentiate to endothelial progenitors that then generate functional endothelial cells and smooth muscle cells. Methods to characterize endothelial cell identity and function are also described. PMID:27590162

  20. Spontaneous cortical activity alternates between motifs defined by regional axonal projections

    PubMed Central

    Mohajerani, Majid H.; Chan, Allen W.; Mohsenvand, Mostafa; LeDue, Jeffrey; Liu, Rui; McVea, David A.; Boyd, Jamie D.; Wang, Yu Tian; Reimers, Mark; Murphy, Timothy H.

    2014-01-01

    In lightly anaesthetized or awake adult mice using millisecond timescale voltage sensitive dye imaging, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing including vision, audition, and touch. Similar cortical networks were found with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality specific sources such as primary sensory areas, and a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area, and a secondary anterior medial sink within the cingulate/secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range mono-synaptic connections between cortical regions. Maps of intracortical mono-synaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity. PMID:23974708

  1. Spontaneous cortical activity alternates between motifs defined by regional axonal projections.

    PubMed

    Mohajerani, Majid H; Chan, Allen W; Mohsenvand, Mostafa; LeDue, Jeffrey; Liu, Rui; McVea, David A; Boyd, Jamie D; Wang, Yu Tian; Reimers, Mark; Murphy, Timothy H

    2013-10-01

    Using millisecond-timescale voltage-sensitive dye imaging in lightly anesthetized or awake adult mice, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing, including vision, audition and touch. We found similar cortical networks with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality-specific sources, such as primary sensory areas, a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area and a secondary anterior medial sink within the cingulate and secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range monosynaptic connections between cortical regions. Maps of intracortical monosynaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity. PMID:23974708

  2. [Investigation of antitumorigenic effects of food-borne non-pathogenic and pathogenic Salmonella enterica strains on MEF, DU145 and HeLa cell lines].

    PubMed

    Altıntaş Kazar, Gamze; Şen, Ece

    2016-07-01

    Basic applications in cancer therapy may fail to eradicate cancer cells completely, they can show toxic affects to healthy cells and development of resistance to antitumor agents may increase tendency to metastasis. Bacterial therapies have the advantage of specific targetting of tumors by selective toxicity, responsiveness to external signals, self-propelling capacity, and the sense of microenvironment. The most interest on the bacterial cancer therapy is about Salmonella spp. with a special emphasis of S.Typhimurium. The aim of this study was to investigate the antitumorigenic effects of food-borne non-pathogenic and pathogenic Salmonella enterica strains on different cell cultures. Non-pathogenic Salmonella Enteriditis (A17) and pathogenic Salmonella Telaviv (A22) strains isolated from chicken carcasses which were put on the market in Edirne province (located at Thrace region of Turkey), and Salmonella Typhimurium ATCC 14028 strain were used in the study. ATCC-derived MEF (mouse embryonic fibroblasts), DU145 (human prostate cancer cells), and HeLa (human cervical cancer cells) cell lines were cocultivated with Salmonella strains of MOI (Multiplicity of infection; number of bacteria:number of cell) of 1000:1, 100:1, 10:1, 1:1, 0.1:1. The cell viability was measured by colorimetric MTT cytotoxicity assay, the percentage of apoptosis was assessed by Tali® Apoptosis Assay-Annexin V Alexa Fluor® 488 kit (Invitrogen, Molecular Probes, Life Technologies, USA), and the caspase-3 activity was determined by colorimetric protease ApoTarget™ kit (Invitrogen, BioSource International, USA). It was shown that non-pathogenic S.Enteriditis (A17) decreased cell viability approximately to 70%, wheras patogenic S.Telaviv (A22) and standart S.Typhimurium ATCC 14028 strains reduced cell viability approximately to 80%. Adversely, it was also observed that pathogenic S.Telaviv (A22) strain induces apoptosis more effectively than non-pathogenic S.Enteriditis (A17) and S

  3. Defining How a Microbial Cell Senses and Responds to a Redox Active Environment

    SciTech Connect

    Kenneth H. Nealson

    2012-06-22

    This grant was for four years, and the work was designed to look at the mechanisms of extracellular electron transfer by the dissimilatory iron reducing bacteria Shewanella oneidensis MR-1, and other closely related Shewanella strains and species. During this work, we defined many of the basic physiological and biochemical properties of the Shewanella group, Much of which was summarized in review articles. We also finished and published the genome sequence of strain MR-1, the first of the shewanellae to have its genome sequenced. Control at the transcriptional and translational level was studied in collaboration with colleagues at PNNL and ANL. We utilized synchrotron X-ray radiation to image both the bacteria and the metal oxide particles via a technique called STXM, synchrotron X-ray absorption (ref. No.9), and X-ray microbeam analysis. We purified several of the cytochromes involved with metal reduction, and improved gene annotation of the MR-1 genome. The conductive appendages (nanowires) of MR-1 were described and characterized. Comparative genomics and biochemistry revealed that the pathway for the utilization of N-acetyl glucosamine in the various strains of Shewanella exhibited great variability, and had a number of previously unknown genes.

  4. Defining Active and Reasonable Efforts: Reasonable Efforts to Prevent Placement and Preserve Families.

    ERIC Educational Resources Information Center

    Hunner, Robert J.

    1986-01-01

    Describes development of guidelines to expand understanding of and compliance with both the reasonable efforts requirement of the Adoption Assistance and Child Welfare Act 1980 (P.L. 96-272) and active efforts requirement of the Indian Child Welfare Act 1978 (P.L. 95-608) to help keep Indian families together. (Author/BB)

  5. 26 CFR 1.183-2 - Activity not engaged in for profit defined.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... activities which constitute a trade or business of the taxpayer and under section 212 for expenses incurred... accepted business, economic, and scientific practices, or consultation with those who are expert therein... status such continued losses, if not explainable, as due to customary business risks or reverses, may...

  6. 26 CFR 1.183-2 - Activity not engaged in for profit defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... activities which constitute a trade or business of the taxpayer and under section 212 for expenses incurred... accepted business, economic, and scientific practices, or consultation with those who are expert therein... status such continued losses, if not explainable, as due to customary business risks or reverses, may...

  7. 26 CFR 1.183-2 - Activity not engaged in for profit defined.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... activities which constitute a trade or business of the taxpayer and under section 212 for expenses incurred... accepted business, economic, and scientific practices, or consultation with those who are expert therein... status such continued losses, if not explainable, as due to customary business risks or reverses, may...

  8. 26 CFR 1.183-2 - Activity not engaged in for profit defined.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... activities which constitute a trade or business of the taxpayer and under section 212 for expenses incurred... accepted business, economic, and scientific practices, or consultation with those who are expert therein... status such continued losses, if not explainable, as due to customary business risks or reverses, may...

  9. Histone modifications defining active genes persist after transcriptional and mitotic inactivation.

    PubMed

    Kouskouti, Antigone; Talianidis, Iannis

    2005-01-26

    We examined various histone modifications across the promoter and the coding regions of constitutively active hepatic genes in G0/G1-enriched, mitotically arrested and alpha-amanitin-blocked cells. Gene activation correlated with localized histone hyperacetylation, H3-K4 tri- or dimethylation and H3-K79 dimethylation and localized nucleosome remodeling at the promoter and the 5' portion of the coding regions. Nucleosomes at more downstream locations were monomethylated at H3-K4. CBP, PCAF, Brg-1, SNF2H and FACT were recruited to the coding regions in a gene-specific manner, in a similarly restricted promoter-proximal pattern. Elongator, however, associated with the more downstream regions. While all factors were dissociated from the chromatin after transcriptional inactivation by alpha-amanitin, the histone modifications remained stable. In mitotic cells, histone modifications on parental nucleosomes were preserved and were regenerated in a transcription-dependent manner at the newly deposited nucleosomes, as the cells entered the next G1 phase. The findings suggest that histone modifications may function as molecular memory bookmarks for previously active locations of the genome, thus contributing to the maintenance of active chromatin states through cell division. PMID:15616580

  10. Dynamic Protein Associations Define Two Phases of IL-1β Transcriptional Activation

    PubMed Central

    Zhang, Yue; Saccani, Simona; Shin, Hyunjin; Nikolajczyk, Barbara S.

    2010-01-01

    IL-1β is a key proinflammatory cytokine with roles in multiple diseases. Monocytes package the IL-1β promoter into a “poised architecture” characterized by a histone-free transcription start site and constitutive transcription factor associations. Upon LPS stimulation, multiple proteins inducibly associate with the IL-1β gene. To understand how the complex combination of constitutive and inducible transcription factors activate the IL-1β gene from a poised structure, we measured temporal changes in NF-κB and IFN regulatory factor (IRF) association with IL-1β regulatory elements. Association of the p65 subunit of NF-κB peaks 30–60 min post-monocyte stimulation, and it shortly precedes IRF-4 recruitment to the IL-1β enhancer and maximal mRNA production. In contrast, IRF-8/enhancer association decreases poststimulation. To test the importance of delayed IRF-4/enhancer association, we introduced a mutated PU.1 protein shown to prevent PU.1-mediated IRF-4 recruitment to the enhancer sequence. Mutated PU.1 initially increased IL-1β mRNA followed by decreased mRNA levels 2–3 h poststimulation. Taken together, these data support a dynamic model of IL-1β transcriptional activation in which a combination of IRF-8 and p65 drives the initial phase of IL-1β transcription, while PU.1-mediated IRF-4 recruitment to the enhancer is important for the second phase. We further demonstrate that activation of both NF-κB and IRF-4 depends on CK2 kinase activity. Because IRF-4/enhancer association requires CK2 but not p65 activation, we conclude that CK2 triggers the IRF-4 and p65 pathways independently to serve as a master regulator of IL-1β transcription. PMID:18566416

  11. Model development with defined biological mechanisms for xenobiotic treatment activated sludge at steady state.

    PubMed

    Chong, Nyuk-Min

    2015-06-01

    Activated sludge treatment of a xenobiotic organic compound, much different from treatment of biogenic organics, must be modeled with interactions involving a two-part biomass of degrader and nondegrader, which selectively or competitively grow on a two-part substrate of input xenobiotic and its biogenic metabolites. A xenobiotic treatment model was developed which incorporates kinetics of the growth of degrader and nondegrader, the line dividing metabolites into xenobiotic and biogenic, yields of degrader and nondegrader from utilization of their parts of substrates, and kinetics of degrader reversion to nondegrader due to instability of the degradative element degraders carry. Experimental activated sludge operated for treatment of a xenobiotic generated data for calibration of the model. With the input of influent xenobiotic concentration, mean cell and hydraulic residence times, and calibrated parameters, the model readily outputs concentrations of degrader, nondegrader, and effluent biogenic residue that closely match the results obtained from experiments. PMID:25561268

  12. Structural Waters Define a Functional Channel Mediating Activation of the GPCR, rhodopsin

    SciTech Connect

    Angel, T.; Gupta, S; Jastrzebska, B; Palczewski, K; Chance, M

    2009-01-01

    Structural water molecules may act as prosthetic groups indispensable for proper protein function. In the case of allosteric activation of G protein-coupled receptors (GPCRs), water likely imparts structural plasticity required for agonist-induced signal transmission. Inspection of structures of GPCR superfamily members reveals the presence of conserved embedded water molecules likely important to GPCR function. Coupling radiolytic hydroxyl radical labeling with rapid H2O18 solvent mixing, we observed no exchange of these structural waters with bulk solvent in either ground state or for the Meta II or opsin states. However, the radiolysis approach permitted labeling of selected side chain residues within the transmembrane helices and revealed activation-induced changes in local structural constraints likely mediated by dynamics of both water and protein. These results suggest both a possible general mechanism for water-dependent communication in family A GPCRs based on structural conservation, and a strategy for probing membrane protein structure.

  13. Dual transcriptional activities of SIX proteins define their roles in normal and ectopic eye development.

    PubMed

    Anderson, Abigail M; Weasner, Bonnie M; Weasner, Brandon P; Kumar, Justin P

    2012-03-01

    The SIX family of homeodomain-containing DNA-binding proteins play crucial roles in both Drosophila and vertebrate retinal specification. In flies, three such family members exist, but only two, Sine oculis (So) and Optix, are expressed and function within the eye. In vertebrates, the homologs of Optix (Six3 and Six6) and probably So (Six1 and Six2) are also required for proper eye formation. Depending upon the individual SIX protein and the specific developmental context, transcription of target genes can either be activated or repressed. These activities are thought to occur through physical interactions with the Eyes absent (Eya) co-activator and the Groucho (Gro) co-repressor, but the relative contribution that each complex makes to overall eye development is not well understood. Here, we attempt to address this issue by investigating the role that each complex plays in the induction of ectopic eyes in Drosophila. We fused the VP16 activation and Engrailed repressor domains to both So and Optix, and attempted to generate ectopic eyes with these chimeric proteins. Surprisingly, we find that So and Optix must initially function as transcriptional repressors to trigger the formation of ectopic eyes. Both factors appear to be required to repress the expression of non-retinal selector genes. We propose that during early phases of eye development, SIX proteins function, in part, to repress the transcription of non-retinal selector genes, thereby allowing induction of the retina to proceed. This model of repression-mediated induction of developmental programs could have implications beyond the eye and might be applicable to other systems. PMID:22318629

  14. 26 CFR 1.103(n)-2T - Private activity bond defined (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... in section 103(b)(4) (C) or (D) apply? A-4: Section 103(n)(7)(C) provides that the term “private... activity bond”? A-1: In general, for purposes of §§ 1.103(n)-1T through 1.103(n)-6T, the term “private... from tax under section 103(a) (without application of section 103(n)). See § 1.103-7(b) for...

  15. Defining filled and empty space: reassessing the filled space illusion for active touch and vision.

    PubMed

    Collier, Elizabeth S; Lawson, Rebecca

    2016-09-01

    In the filled space illusion, an extent filled with gratings is estimated as longer than an equivalent extent that is apparently empty. However, researchers do not seem to have carefully considered the terms filled and empty when describing this illusion. Specifically, for active touch, smooth, solid surfaces have typically been used to represent empty space. Thus, it is not known whether comparing gratings to truly empty space (air) during active exploration by touch elicits the same illusionary effect. In Experiments 1 and 2, gratings were estimated as longer if they were compared to smooth, solid surfaces rather than being compared to truly empty space. Consistent with this, Experiment 3 showed that empty space was perceived as longer than solid surfaces when the two were compared directly. Together these results are consistent with the hypothesis that, for touch, the standard filled space illusion only occurs if gratings are compared to smooth, solid surfaces and that it may reverse if gratings are compared to empty space. Finally, Experiment 4 showed that gratings were estimated as longer than both solid and empty extents in vision, so the direction of the filled space illusion in vision was not affected by the nature of the comparator. These results are discussed in relation to the dual nature of active touch. PMID:27233286

  16. An allosteric role for receptor activity-modifying proteins in defining GPCR pharmacology

    PubMed Central

    J Gingell, Joseph; Simms, John; Barwell, James; Poyner, David R; Watkins, Harriet A; Pioszak, Augen A; Sexton, Patrick M; Hay, Debbie L

    2016-01-01

    G protein-coupled receptors are allosteric proteins that control transmission of external signals to regulate cellular response. Although agonist binding promotes canonical G protein signalling transmitted through conformational changes, G protein-coupled receptors also interact with other proteins. These include other G protein-coupled receptors, other receptors and channels, regulatory proteins and receptor-modifying proteins, notably receptor activity-modifying proteins (RAMPs). RAMPs have at least 11 G protein-coupled receptor partners, including many class B G protein-coupled receptors. Prototypic is the calcitonin receptor, with altered ligand specificity when co-expressed with RAMPs. To gain molecular insight into the consequences of this protein–protein interaction, we combined molecular modelling with mutagenesis of the calcitonin receptor extracellular domain, assessed in ligand binding and functional assays. Although some calcitonin receptor residues are universally important for peptide interactions (calcitonin, amylin and calcitonin gene-related peptide) in calcitonin receptor alone or with receptor activity-modifying protein, others have RAMP-dependent effects, whereby mutations decreased amylin/calcitonin gene-related peptide potency substantially only when RAMP was present. Remarkably, the key residues were completely conserved between calcitonin receptor and AMY receptors, and between subtypes of AMY receptor that have different ligand preferences. Mutations at the interface between calcitonin receptor and RAMP affected ligand pharmacology in a RAMP-dependent manner, suggesting that RAMP may allosterically influence the calcitonin receptor conformation. Supporting this, molecular dynamics simulations suggested that the calcitonin receptor extracellular N-terminal domain is more flexible in the presence of receptor activity-modifying protein 1. Thus, RAMPs may act in an allosteric manner to generate a spectrum of unique calcitonin receptor

  17. Changes in everyday function among individuals with psychometrically defined Mild Cognitive Impairment in the ACTIVE Study

    PubMed Central

    Wadley, Virginia G.; Crowe, Michael; Marsiske, Michael; Cook, Sarah E.; Unverzagt, Frederick W.; Rosenberg, Adrienne L.; Rexroth, Daniel

    2007-01-01

    Objectives. Because many individuals with Mild Cognitive Impairment (MCI) will progress to a dementia diagnosis, this population is at high risk for losing functional independence. We examine trajectories of change in everyday function for individuals with cognitive deficits suggestive of MCI. Design. We utilized data from the longitudinal, multi-site Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, which allowed for post-hoc classification of MCI status at baseline using psycho metric definitions for amnestic MCI, non-amnestic MCI, multi-domain MCI, and no MCI. Setting. Six U.S. cities. Participants. 2832 volunteers (mean age 74 years; 26% African American) living independently, recruited from senior housing, community centers, and hospitals and clinics. Measurements. Mixed effect models examined changes in self-reported instrumental and basic activities of daily living (IADLs and ADLs) from the MDS Home Care Interview in 2,358 participants over a three-year period. Results. In models for IADL performance, IADL difficulty, and a Daily Functioning Composite, there was a significant time by MCI classification interaction for each MCI subtype, indicating that all MCI groups showed faster rates of decline in everyday function relative to cognitively normal participants with no MCI. Conclusion. Results demonstrate the importance of MCI as a clinical entity that not only predicts progression to dementia but also predicts functional declines in activities that are key to autonomy and quality of life. MCI classification guidelines should allow for functional changes in MCI, and clinicians should monitor for such changes. Preservation of function may serve as a meaningful outcome for intervention efforts. PMID:17661957

  18. New rabies virus variants for monitoring and manipulating activity and gene expression in defined neural circuits

    PubMed Central

    Osakada, Fumitaka; Mori, Takuma; Cetin, Ali H.; Marshel, James H.; Virgen, Beatriz; Callaway, Edward M.

    2011-01-01

    SUMMARY Glycoprotein-deleted (ΔG) rabies virus is a powerful tool for studies of neural circuit structure. Here we describe the development and demonstrate the utility of new resources that allow experiments directly investigating relationships between the structure and function of neural circuits. New methods and reagents allowed efficient production of twelve novel ΔG rabies variants from plasmid DNA. These new rabies viruses express useful neuroscience tools, including: the Ca++ indicator GCaMP3, for monitoring activity; Channelrhodopsin-2, for photoactivation; allatostatin receptor, for inactivation by ligand application; rtTA, ERT2CreERT2, or FLPo, for control of gene expression. These new tools allow neurons targeted based on their connectivity, to have their function assayed or their activity or gene expression manipulated. Combining these tools with in vivo imaging and optogenetic methods, and/or inducible gene expression in transgenic mice, will facilitate experiments investigating neural circuit development, plasticity, and function that have not been possible with existing reagents. PMID:21867879

  19. Green synthesis of highly stabilized nanocrystalline silver particles by a non-pathogenic and agriculturally important fungus T. asperellum

    NASA Astrophysics Data System (ADS)

    Mukherjee, P.; Roy, M.; Mandal, B. P.; Dey, G. K.; Mukherjee, P. K.; Ghatak, J.; Tyagi, A. K.; Kale, S. P.

    2008-02-01

    A controlled and up-scalable biosynthetic route to nanocrystalline silver particles with well-defined morphology using cell-free aqueous filtrate of a non-pathogenic and commercially viable biocontrol agent Trichoderma asperellum is being reported for the first time. A transparent solution of the cell-free filtrate of Trichoderma asperellum containing 1 mM AgNO3 turns progressively dark brown within 5 d of incubation at 25 °C. The kinetics of the reaction was studied using UV-vis spectroscopy. An intense surface plasmon resonance band at ~410 nm in the UV-vis spectrum clearly reveals the formation of silver nanoparticles. The size of the silver particles using TEM and XRD studies is found to be in the range 13-18 nm. These nanoparticles are found to be highly stable and even after prolonged storage for over 6 months they do not show significant aggregation. A plausible mechanism behind the formation of silver nanoparticles and their stabilization via capping has been investigated using FTIR and surface-enhanced resonance Raman spectroscopy.

  20. Nuclear Pore Proteins Nup153 and Megator Define Transcriptionally Active Regions in the Drosophila Genome

    PubMed Central

    Miura, Kota; Luscombe, Nicholas M.; Akhtar, Asifa

    2010-01-01

    Transcriptional regulation is one of the most important processes for modulating gene expression. Though much of this control is attributed to transcription factors, histones, and associated enzymes, it is increasingly apparent that the spatial organization of chromosomes within the nucleus has a profound effect on transcriptional activity. Studies in yeast indicate that the nuclear pore complex might promote transcription by recruiting chromatin to the nuclear periphery. In higher eukaryotes, however, it is not known whether such regulation has global significance. Here we establish nucleoporins as a major class of global regulators for gene expression in Drosophila melanogaster. Using chromatin-immunoprecipitation combined with microarray hybridisation, we show that Nup153 and Megator (Mtor) bind to 25% of the genome in continuous domains extending 10 kb to 500 kb. These Nucleoporin-Associated Regions (NARs) are dominated by markers for active transcription, including high RNA polymerase II occupancy and histone H4K16 acetylation. RNAi–mediated knock-down of Nup153 alters the expression of ∼5,700 genes, with a pronounced down-regulatory effect within NARs. We find that nucleoporins play a central role in coordinating dosage compensation—an organism-wide process involving the doubling of expression of the male X chromosome. NARs are enriched on the male X chromosome and occupy 75% of this chromosome. Furthermore, Nup153-depletion abolishes the normal function of the male-specific dosage compensation complex. Finally, by extensive 3D imaging, we demonstrate that NARs contribute to gene expression control irrespective of their sub-nuclear localization. Therefore, we suggest that NAR–binding is used for chromosomal organization that enables gene expression control. PMID:20174442

  1. Integrated Interpretation of Geophysical, Geotechnical, and Environmental Monitoring Data to Define Precursors for Landslide Activation

    NASA Astrophysics Data System (ADS)

    Uhlemann, S.; Chambers, J.; Merritt, A.; Wilkinson, P.; Meldrum, P.; Gunn, D.; Maurer, H.; Dixon, N.

    2014-12-01

    To develop a better understanding of the failure mechanisms leading to first time failure or reactivation of landslides, the British Geological Survey is operating an observatory on an active, shallow landslide in North Yorkshire, UK, which is a typical example of slope failure in Lias Group mudrocks. This group and the Whitby Mudstone Formation in particular, show one of the highest landslide densities in the UK. The observatory comprises geophysical (i.e., ERT and self-potential monitoring, P- and S-wave tomography), geotechnical (i.e. acoustic emission and inclinometer), and hydrological and environmental monitoring (i.e. weather station, water level, soil moisture, soil temperature), in addition to movement monitoring using real-time kinematic GPS. In this study we focus on the reactivation of the landslide at the end of 2012, after an exceptionally wet summer. We present an integrated interpretation of the different data streams. Results show that the two lobes (east and west), which form the main focus of the observatory, behave differently. While water levels, and hence pore pressures, in the eastern lobe are characterised by a continuous increase towards activation resulting in significant movement (i.e. metres), water levels in the western lobe are showing frequent drainage events and thus lower pore pressures and a lower level of movement (i.e. tens of centimetres). This is in agreement with data from the geoelectrical monitoring array. During the summer season, resistivities generally increase due to decreasing moisture levels. However, during the summer of 2012 this seasonal pattern was interrupted, with the reactivated lobe displaying strongly decreasing resistivities (i.e. increasing moisture levels). The self-potential and soil moisture data show clear indications of moisture accumulation prior to the reactivation, followed by continuous discharge towards the base of the slope. Using the different data streams, we present 3D volumetric images of

  2. Activity of Defined Mushroom Body Output Neurons Underlies Learned Olfactory Behavior in Drosophila

    PubMed Central

    Owald, David; Felsenberg, Johannes; Talbot, Clifford B.; Das, Gaurav; Perisse, Emmanuel; Huetteroth, Wolf; Waddell, Scott

    2015-01-01

    Summary During olfactory learning in fruit flies, dopaminergic neurons assign value to odor representations in the mushroom body Kenyon cells. Here we identify a class of downstream glutamatergic mushroom body output neurons (MBONs) called M4/6, or MBON-β2β′2a, MBON-β′2mp, and MBON-γ5β′2a, whose dendritic fields overlap with dopaminergic neuron projections in the tips of the β, β′, and γ lobes. This anatomy and their odor tuning suggests that M4/6 neurons pool odor-driven Kenyon cell synaptic outputs. Like that of mushroom body neurons, M4/6 output is required for expression of appetitive and aversive memory performance. Moreover, appetitive and aversive olfactory conditioning bidirectionally alters the relative odor-drive of M4β′ neurons (MBON-β′2mp). Direct block of M4/6 neurons in naive flies mimics appetitive conditioning, being sufficient to convert odor-driven avoidance into approach, while optogenetically activating these neurons induces avoidance behavior. We therefore propose that drive to the M4/6 neurons reflects odor-directed behavioral choice. PMID:25864636

  3. Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity.

    PubMed

    Petiwala, Sakina M; Johnson, Jeremy J

    2015-10-28

    Recently, rosemary extracts standardized to diterpenes (e.g. carnosic acid and carnosol) have been approved by the European Union (EU) and given a GRAS (Generally Recognized as Safe) status in the United States by the Food and Drug Administration (FDA). Incorporation of rosemary into our food system and through dietary selection (e.g. Mediterranean Diet) has increased the likelihood of exposure to diterpenes in rosemary. In consideration of this, a more thorough understanding of rosemary diterpenes is needed to understand its potential for a positive impact on human health. Three agents in particular have received the most attention that includes carnosic acid, carnosol, and rosmanol with promising results of anti-cancer activity. These studies have provided evidence of diterpenes to modulate deregulated signaling pathways in different solid and blood cancers. Rosemary extracts and the phytochemicals therein appear to be well tolerated in different animal models as evidenced by the extensive studies performed for approval by the EU and the FDA as an antioxidant food preservative. This mini-review reports on the pre-clinical studies performed with carnosic acid, carnosol, and rosmanol describing their mechanism of action in different cancers. PMID:26170168

  4. Inducible in vivo DNA footprints define sequences necessary for UV light activation of the parsley chalcone synthase gene.

    PubMed Central

    Schulze-Lefert, P; Dangl, J L; Becker-André, M; Hahlbrock, K; Schulz, W

    1989-01-01

    We began characterization of the protein--DNA interactions necessary for UV light induced transcriptional activation of the gene encoding chalcone synthase (CHS), a key plant defense enzyme. Three light dependent in vivo footprints appear on a 90 bp stretch of the CHS promoter with a time course correlated with the onset of CHS transcription. We define a minimal light responsive promoter by functional analysis of truncated CHS promoter fusions with a reporter gene in transient expression experiments in parsley protoplasts. Two of the three footprinted sequence 'boxes' reside within the minimal promoter. Replacement of 10 bp within either of these 'boxes' leads to complete loss of light responsiveness. We conclude that these sequences define the necessary cis elements of the minimal CHS promoter's light responsive element. One of the functionally defined 'boxes' is homologous to an element implicated in regulation of genes involved in photosynthesis. These data represent the first example in a plant defense gene of an induced change in protein--DNA contacts necessary for transcriptional activation. Also, our data argue strongly that divergent light induced biosynthetic pathways share common regulatory units. Images PMID:2566481

  5. Viral RNA patterns and high viral load reliably define oropharynx carcinomas with active HPV16 involvement.

    PubMed

    Holzinger, Dana; Schmitt, Markus; Dyckhoff, Gerhard; Benner, Axel; Pawlita, Michael; Bosch, Franz X

    2012-10-01

    Oropharyngeal squamous cell carcinomas (OPSCC) that are associated with human papilloma virus (HPV) infection carry a more favorable prognosis than those that are HPV-negative. However, it remains unclear which biomarker(s) can reliably determine which OPSCC specimens are truly driven by HPV infection. In this study, we analyzed 199 fresh-frozen OPSCC specimens for HPV DNA, viral load, RNA expression patterns typical for cervical carcinomas (CxCaRNA(+)), and the HPV-targeted tumor suppressor protein p16(INK4a) as markers for HPV infection. In this set of specimens, there was a 49% prevalence of DNA for the cancer-associated HPV type 16 (HPV(+)). However, there was only a 16% prevalence of high viral load and only a 20% prevalence of CxCaRNA(+), a marker of HPV16 carcinogenic activity. Among the CxCaRNA(+) tumors, 78% of the specimens exhibited overexpression of p16(INK4a), which also occurred in 14% of the HPV-negative tumors. Using a multivariate survival analysis with HPV negativity as the reference group, CxCaRNA(+) as a single marker conferred the lowest risk of death [HR = 0.28, 95% confidence interval (CI), 0.13-0.61] from oropharyngeal cancer, closely followed by high viral load (HR = 0.32, 95% CI, 0.14-0.73). In contrast, a weaker inverse association was found for OPSCC that were HPV(+) and p16(INK4a) high (HR = 0.55, 95% CI, 0.29-1.08). In summary, our findings argued that viral load or RNA pattern analysis is better suited than p16(INK4a) expression to identify HPV16-driven tumors in OPSCC patient populations. PMID:22991302

  6. Safety and efficacy of diphetarsone in the treatment of amoebiasis, non-pathogenic amoebiasis and trichuriasis.

    PubMed

    Keystone, J S; Proctor, E; Glenn, C; McIntyre, L

    1983-01-01

    Eighty-nine patients infected with Entamoeba histolytica, non-pathogenic amoebae or Trichuris trichiura were studied prospectively to determine the safety and efficacy of diphetarsone therapy. An additional 75 patients were studied retrospectively to assess further the efficacy of diphetarsone in the treatment of E. histolytica cyst passers. Side effects were noted in 9% and included gastrointestinal upset, lightheadedness and headache. Transient liver function abnormalities were recorded in 5.6%. diphetarsone was completely effective in the treatment of Dientamoeba fragilis, Entamoeba hartmanni, Iodamoeba buetschlii and Trichuris trichiura. 99% of the patients with E. histolytica, 97% of those with E. coli and 98% of those with Endolimax nana were cured. PMID:6304952

  7. Potential use of continuous cell lines to distinguish between pathogenic and nonpathogenic Listeria spp.

    PubMed Central

    Farber, J M; Speirs, J I

    1987-01-01

    Continuous cell lines were tested for their potential use in distinguishing pathogenic from nonpathogenic Listeria species. Listeria monocytogenes and Listeria ivanovii strains were lethal for mice, and culture filtrates were cytotoxic for cultured cells and hemolytic for sheep erythrocytes, while Listeria innocua, Listeria grayi, and Listeria murrayi strains were negative in all three tests. The eight cell lines tested were all affected but varied in sensitivity, with the Chinese hamster ovary cell line being the most sensitive. Cytolytic effect was noted within minutes of the addition of undiluted filtrates, with optimum titers obtained by 24 h. Images PMID:3114320

  8. The role of substrate specificity and metal binding in defining the activity and structure of an intracellular subtilisin.

    PubMed

    Gamble, Michael; Künze, Georg; Brancale, Andrea; Wilson, Keith S; Jones, D Dafydd

    2012-01-01

    The dimeric intracellular subtilisin proteases (ISPs) found throughout Gram-positive bacteria are a structurally distinct class of the subtilase family. Unlike the vast majority of subtilisin-like proteases, the ISPs function exclusively within the cell, contributing the majority of observed cellular proteolytic activity. Given that they are active within the cell, little is known about substrate specificity and the role of stress signals such as divalent metal ions in modulating ISP function. We demonstrate that both play roles in defining the proteolytic activity of Bacillus clausii ISP and propose the molecular basis of their effects. Enzyme kinetics reveal that one particular synthetic tetrapeptide substrate, Phe-Ala-Ala-Phe-pNA, is hydrolysed with a catalytic efficiency ∼100-fold higher than any other tested. Heat-denatured whole proteins were found to be better substrates for ISP than the native forms. Substrate binding simulations suggest that the S1, S2 and S4 sites form defined binding pockets. The deep S1 cavity and wide S4 site are fully occupied by the hydrophobic aromatic side-chains of Phe. Divalent metal ions, probably Ca(2+), are proposed to be important for ISP activity through structural changes. The presence of >0.01 mM EDTA inactivates ISP, with CD and SEC suggesting that the protein becomes less structured and potentially monomeric. Removal of Ca(2+) at sites close to the dimer interface and the S1 pocket are thought to be responsible for the effect. These studies provide a new insight into the potential physiological function of ISPs, by reconciling substrate specificity and divalent metal binding to associate ISP with the unfolded protein response under stress conditions. PMID:23650602

  9. Colonization of Flax Roots and Early Physiological Responses of Flax Cells Inoculated with Pathogenic and Nonpathogenic Strains of Fusarium oxysporum

    PubMed Central

    Olivain, Chantal; Trouvelot, Sophie; Binet, Marie-Noëlle; Cordier, Christelle; Pugin, Alain; Alabouvette, Claude

    2003-01-01

    Fusarium oxysporum includes nonpathogenic strains and pathogenic strains that can induce necrosis or tracheomycosis in plants. The objective of this study was to compare the abilities of a pathogenic strain (Foln3) and a nonpathogenic strain (Fo47) to colonize flax roots and to induce early physiological responses in flax cell culture suspensions. Both strains colonized the outer cortex of the root; however, plant defense reactions, i.e., the presence of wall appositions, osmiophilic material, and collapsed cells, were less frequent and less intense in a root colonized by Foln3 than by Fo47. Early physiological responses were measured in flax cell suspensions confronted with germinated microconidia of both strains. Both pathogenic (Foln3) and nonpathogenic strains (Fo47) triggered transient H2O2 production in the first few minutes of the interaction, but the nonpathogenic strain also induced a second burst 3 h postinoculation. Ca2+ influx was more intense in cells inoculated with Fo47 than in cells inoculated with Foln3. Similarly, alkalinization of the extracellular medium was higher with Fo47 than with Foln3. Inoculation of the fungi into flax cell suspensions induced cell death 10 to 20 h postinoculation, with a higher percentage of dead cells observed with Fo47 than with Foln3 beginning at 14 h. This is the first report showing that early physiological responses of flax cells can be used to distinguish pathogenic and nonpathogenic strains of the soil-borne fungus F. oxysporum. PMID:12957934

  10. Literature review on the safety of Toyocerin, a non-toxigenic and non-pathogenic Bacillus cereus var. toyoi preparation.

    PubMed

    Williams, Lonnie D; Burdock, George A; Jiménez, Guillermo; Castillo, Marisol

    2009-11-01

    Bacillus cereus var. toyoi is a naturally occurring, non-toxigenic and non-pathogenic strain of B. cereus. Safety studies were conducted on a B. toyoi preparation (Toyocerin, including but not limited to enterotoxicity, eye irritation, genotoxicity, acute, subchronic and chronic toxicity studies and human clinical trials. In rabbits, Toyocerin did not exhibit enterotoxicity and was only slightly irritating to the eyes. It was non-mutagenic in an Ames assay at up to 10,000 microg/plate and did not exhibit clastogenic activity in a chromosomal aberration test at up to 450 mg/ml. It was non-toxic in acute and repeated-dose (30 and 60 days and 1 year) toxicity studies in rats and mice at up to 3 x 10(11)spores/kg bw/day. In an eight-day human clinical trial, Toyocerin did not cause any adverse effects in healthy male and female subjects at 1 x 10(9) and 1 x 10(10)spores/kg bw/day. In feeding trials, Toyocerin not cause any adverse effects in rabbits, pigs, chickens, turkeys and cattle at doses ranging from 8.5 x 10(7) to 4 x 10(9)spores/kg bw/day for durations of 2 weeks to 18 months. Taken together, these studies demonstrate that Toyocerin is safe at the doses tested. PMID:19631708

  11. The non-pathogenic Henipavirus Cedar paramyxovirus phosphoprotein has a compromised ability to target STAT1 and STAT2.

    PubMed

    Lieu, Kim G; Marsh, Glenn A; Wang, Lin-Fa; Netter, Hans J

    2015-12-01

    Immune evasion by the lethal henipaviruses, Hendra (HeV) and Nipah virus, is mediated by its interferon (IFN) antagonist P gene products, phosphoprotein (P), and the related V and W proteins, which can target the signal transducer and activator of transcription 1 (STAT1) and STAT2 proteins to inhibit IFN/STAT signaling. However, it is not clear if the recently identified non-pathogenic Henipavirus, Cedar paramyxovirus (CedPV), is also able to antagonize the STAT proteins. We performed comparative studies between the HeV P gene products (P/V/W) and CedPV-P (CedPV does not encode V or W) and demonstrate that differences exist in their ability to engage the STAT proteins using immunoprecipitation and quantitative confocal microscopic analysis. In contrast to HeV-P gene encoded proteins, the ability of CedPV-P to interact with and relocalize STAT1 or STAT2 is compromised, correlating with a reduced capacity to inhibit the mRNA synthesis of IFN-inducible gene MxA. Furthermore, infection studies with HeV and CedPV demonstrate that HeV is more potent than CedPV in inhibiting the IFN-α-mediated nuclear accumulation of STAT1. These results strongly suggest that the ability of CedPV to counteract the IFN/STAT response is compromised compared to HeV. PMID:26526590

  12. Overexpression of specific cysteine peptidases confers pathogenicity to a nonpathogenic Entamoeba histolytica clone.

    PubMed

    Matthiesen, Jenny; Bär, Ann-Katrein; Bartels, Anne-Kathrin; Marien, Dennis; Ofori, Susann; Biller, Laura; Tannich, Egbert; Lotter, Hannelore; Bruchhaus, Iris

    2013-01-01

    Cysteine peptidases (CPs) of Entamoeba histolytica are considered to be important pathogenicity factors. Previous studies have found that under standard axenic culture conditions, only four (ehcp-a1, ehcp-a2, ehcp-a5, and ehcp-a7) out of 35 papain-like ehcp genes present in the E. histolytica genome are expressed at high levels. Little is known about the expression of CPs in E. histolytica during amoebic liver abscess (ALA) formation. In the current study, a quantitative real-time PCR assay was developed to determine the expression of the various ehcp genes during ALA formation in animal models. Increased expression of four ehcp genes (ehcp-a3, -a4, -a10, and -c13) was detected in the gerbil and mouse models. Increased expression of another three ehcp genes (ehcp-a5, -a6, and -a7) was detected in the mouse model only, and two other ehcp genes (ehcp-b8 and -b9) showed increased expression in the gerbil model only. Trophozoites of the nonpathogenic E. histolytica HM-1:IMSS clone A1, which was unable to induce ALAs, were transfected with vectors enabling overexpression of those CPs that are expressed at high levels under culture conditions or during ALA formation. Interestingly, overexpression of ehcp-b8, -b9, and -c13 restored the pathogenic phenotype of the nonpathogenic clone A1 whereas overexpression of various other peptidase genes had no effect on the pathogenicity of this clone. PMID:23532975

  13. Comparative proteomic analysis of pathogenic and non-pathogenic strains from the swine pathogen Mycoplasma hyopneumoniae

    PubMed Central

    2009-01-01

    Background Mycoplasma hyopneumoniae is a highly infectious swine pathogen and is the causative agent of enzootic pneumonia (EP). Following the previous report of a proteomic survey of the pathogenic 7448 strain of swine pathogen, Mycoplasma hyopneumoniae, we performed comparative protein profiling of three M. hyopneumoniae strains, namely the non-pathogenic J strain and the two pathogenic strains 7448 and 7422. Results In 2DE comparisons, we were able to identify differences in expression levels for 67 proteins, including the overexpression of some cytoadherence-related proteins only in the pathogenic strains. 2DE immunoblot analyses allowed the identification of differential proteolytic cleavage patterns of the P97 adhesin in the three strains. For more comprehensive protein profiling, an LC-MS/MS strategy was used. Overall, 35% of the M. hyopneumoniae genome coding capacity was covered. Partially overlapping profiles of identified proteins were observed in the strains with 81 proteins identified only in one strain and 54 proteins identified in two strains. Abundance analysis of proteins detected in more than one strain demonstrates the relative overexpression of 64 proteins, including the P97 adhesin in the pathogenic strains. Conclusions Our results indicate the physiological differences between the non-pathogenic strain, with its non-infective proliferate lifestyle, and the pathogenic strains, with its constitutive expression of adhesins, which would render the bacterium competent for adhesion and infection prior to host contact. PMID:20025764

  14. Defining the role of tyrosine and rational tuning of oxidase activity by genetic incorporation of unnatural tyrosine analogs.

    PubMed

    Yu, Yang; Lv, Xiaoxuan; Li, Jiasong; Zhou, Qing; Cui, Chang; Hosseinzadeh, Parisa; Mukherjee, Arnab; Nilges, Mark J; Wang, Jiangyun; Lu, Yi

    2015-04-15

    While a conserved tyrosine (Tyr) is found in oxidases, the roles of phenol ring pKa and reduction potential in O2 reduction have not been defined despite many years of research on numerous oxidases and their models. These issues represent major challenges in our understanding of O2 reduction mechanism in bioenergetics. Through genetic incorporation of unnatural amino acid analogs of Tyr, with progressively decreasing pKa of the phenol ring and increasing reduction potential, in the active site of a functional model of oxidase in myoglobin, a linear dependence of both the O2 reduction activity and the fraction of H2O formation with the pKa of the phenol ring has been established. By using these unnatural amino acids as spectroscopic probe, we have provided conclusive evidence for the location of a Tyr radical generated during reaction with H2O2, by the distinctive hyperfine splitting patterns of the halogenated tyrosines and one of its deuterated derivatives incorporated at the 33 position of the protein. These results demonstrate for the first time that enhancing the proton donation ability of the Tyr enhances the oxidase activity, allowing the Tyr analogs to augment enzymatic activity beyond that of natural Tyr. PMID:25672571

  15. Recovery of Nonpathogenic Mutant Bacteria from Tumors Caused by Several Agrobacterium tumefaciens Strains: a Frequent Event?▿

    PubMed Central

    Llop, Pablo; Murillo, Jesús; Lastra, Beatriz; López, María M.

    2009-01-01

    We have evaluated the interaction that bacterial genotypes and plant hosts have with the loss of pathogenicity in tumors, using seven Agrobacterium tumefaciens strains inoculated on 12 herbaceous and woody hosts. We performed a screening of the agrobacteria present inside the tumors, looking for nonpathogenic strains, and found a high variability of those strains in this niche. To verify the origin of the putative nonpathogenic mutant bacteria, we applied an efficient, reproducible, and specific randomly amplified polymorphic DNA analysis method. In contrast with previous studies, we recovered a very small percentage (0.01%) of nonpathogenic strains that can be considered true mutants. Of 5,419 agrobacterial isolates examined, 662 were nonpathogenic in tomato, although only 7 (from pepper and tomato tumors induced by two A. tumefaciens strains) could be considered to derive from the inoculated strain. Six mutants were affected in the transferred DNA (T-DNA) region; one of them contained IS426 inserted into the iaaM gene, whereas the whole T-DNA region was apparently deleted in three other mutants, and the virulence of the remaining two mutants was fully restored with the T-DNA genes as well. The plasmid profile was altered in six of the mutants, with changes in the size of the Ti plasmid or other plasmids and/or the acquisition of new plasmids. Our results also suggest that the frequent occurrence of nonpathogenic clones in the tumors is probably due to the preferential growth of nonpathogenic agrobacteria, of either endophytic or environmental origin, but different from the bacterial strain inducing the tumor. PMID:19700547

  16. Distribution and Prevalence of the Australian Non-Pathogenic Rabbit Calicivirus Is Correlated with Rainfall and Temperature

    PubMed Central

    Liu, June; Fordham, Damien A.; Cooke, Brian D.; Cox, Tarnya; Mutze, Greg; Strive, Tanja

    2014-01-01

    Background Australia relies heavily on rabbit haemorrhagic disease virus (RHDV) for the biological control of introduced European wild rabbits Oryctolagus cuniculus, which are significant economic and environmental pests. An endemic non-pathogenic rabbit calicivirus termed RCV–A1 also occurs in wild rabbits in Australian and provides partial protection against lethal RHDV infection, thus interfering with effective rabbit control. Despite its obvious importance for rabbit population management, little is known about the epidemiology of this benign rabbit calicivirus. Methods We determined the continent-wide distribution and prevalence of RCV-A1 by analysing 1,805 serum samples from wild rabbit populations at 78 sites across Australia for the presence of antibodies to RCV-A1 using a serological test that specifically detects RCV-A1 antibodies and does not cross-react with co-occurring RHDV antibodies. We also investigated possible correlation between climate variables and prevalence of RCV-A1 by using generalised linear mixed effect models. Results Antibodies to RCV-A1 were predominantly detected in rabbit populations in cool, high rainfall areas of the south-east and south-west of the continent. There was strong support for modelling RCV-A1 prevalence as a function of average annual rainfall and minimum temperature. The best ranked model explained 26% of the model structural deviance. According to this model, distribution and prevalence of RCV-A1 is positively correlated with periods of above average rainfall and negatively correlated with periods of drought. Implications Our statistical model of RCV-A1 prevalence will greatly increase our understanding of RCV-A1 epidemiology and its interaction with RHDV in Australia. By defining the environmental conditions associated with the prevalence of RCV-A1, it also contributes towards understanding the distribution of similar viruses in New Zealand and Europe. PMID:25486092

  17. Defining "Development".

    PubMed

    Pradeu, Thomas; Laplane, Lucie; Prévot, Karine; Hoquet, Thierry; Reynaud, Valentine; Fusco, Giuseppe; Minelli, Alessandro; Orgogozo, Virginie; Vervoort, Michel

    2016-01-01

    Is it possible, and in the first place is it even desirable, to define what "development" means and to determine the scope of the field called "developmental biology"? Though these questions appeared crucial for the founders of "developmental biology" in the 1950s, there seems to be no consensus today about the need to address them. Here, in a combined biological, philosophical, and historical approach, we ask whether it is possible and useful to define biological development, and, if such a definition is indeed possible and useful, which definition(s) can be considered as the most satisfactory. PMID:26969977

  18. Defining Overweight and Obesity

    MedlinePlus

    ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Defining Adult Overweight and ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs File Formats Help: How ...

  19. Comparative Genomic and Phenotypic Characterization of Pathogenic and Non-Pathogenic Strains of Xanthomonas arboricola Reveals Insights into the Infection Process of Bacterial Spot Disease of Stone Fruits

    PubMed Central

    Garita-Cambronero, Jerson; Palacio-Bielsa, Ana; López, María M.

    2016-01-01

    Xanthomonas arboricola pv. pruni is the causal agent of bacterial spot disease of stone fruits, a quarantinable pathogen in several areas worldwide, including the European Union. In order to develop efficient control methods for this disease, it is necessary to improve the understanding of the key determinants associated with host restriction, colonization and the development of pathogenesis. After an initial characterization, by multilocus sequence analysis, of 15 strains of X. arboricola isolated from Prunus, one strain did not group into the pathovar pruni or into other pathovars of this species and therefore it was identified and defined as a X. arboricola pv. pruni look-a-like. This non-pathogenic strain and two typical strains of X. arboricola pv. pruni were selected for a whole genome and phenotype comparative analysis in features associated with the pathogenesis process in Xanthomonas. Comparative analysis among these bacterial strains isolated from Prunus spp. and the inclusion of 15 publicly available genome sequences from other pathogenic and non-pathogenic strains of X. arboricola revealed variations in the phenotype associated with variations in the profiles of TonB-dependent transporters, sensors of the two-component regulatory system, methyl accepting chemotaxis proteins, components of the flagella and the type IV pilus, as well as in the repertoire of cell-wall degrading enzymes and the components of the type III secretion system and related effectors. These variations provide a global overview of those mechanisms that could be associated with the development of bacterial spot disease. Additionally, it pointed out some features that might influence the host specificity and the variable virulence observed in X. arboricola. PMID:27571391

  20. Comparative Genomic and Phenotypic Characterization of Pathogenic and Non-Pathogenic Strains of Xanthomonas arboricola Reveals Insights into the Infection Process of Bacterial Spot Disease of Stone Fruits.

    PubMed

    Garita-Cambronero, Jerson; Palacio-Bielsa, Ana; López, María M; Cubero, Jaime

    2016-01-01

    Xanthomonas arboricola pv. pruni is the causal agent of bacterial spot disease of stone fruits, a quarantinable pathogen in several areas worldwide, including the European Union. In order to develop efficient control methods for this disease, it is necessary to improve the understanding of the key determinants associated with host restriction, colonization and the development of pathogenesis. After an initial characterization, by multilocus sequence analysis, of 15 strains of X. arboricola isolated from Prunus, one strain did not group into the pathovar pruni or into other pathovars of this species and therefore it was identified and defined as a X. arboricola pv. pruni look-a-like. This non-pathogenic strain and two typical strains of X. arboricola pv. pruni were selected for a whole genome and phenotype comparative analysis in features associated with the pathogenesis process in Xanthomonas. Comparative analysis among these bacterial strains isolated from Prunus spp. and the inclusion of 15 publicly available genome sequences from other pathogenic and non-pathogenic strains of X. arboricola revealed variations in the phenotype associated with variations in the profiles of TonB-dependent transporters, sensors of the two-component regulatory system, methyl accepting chemotaxis proteins, components of the flagella and the type IV pilus, as well as in the repertoire of cell-wall degrading enzymes and the components of the type III secretion system and related effectors. These variations provide a global overview of those mechanisms that could be associated with the development of bacterial spot disease. Additionally, it pointed out some features that might influence the host specificity and the variable virulence observed in X. arboricola. PMID:27571391

  1. Defining Infertility

    MedlinePlus

    ... of the American Society for Reproductive Medicine Defining infertility What is infertility? Infertility is “the inability to conceive after 12 months ... to conceive after 6 months is generally considered infertility. How common is it? Infertility affects 10%-15% ...

  2. Defining Risk.

    ERIC Educational Resources Information Center

    Tholkes, Ben F.

    1998-01-01

    Defines camping risks and lists types and examples: (1) objective risk beyond control; (2) calculated risk based on personal choice; (3) perceived risk; and (4) reckless risk. Describes campers to watch ("immortals" and abdicators), and several "treatments" of risk: avoidance, safety procedures and well-trained staff, adequate insurance, and a…

  3. Co-Activation of Epidermal Growth Factor Receptor and c-MET Defines a Distinct Subset of Lung Adenocarcinomas

    PubMed Central

    Matsubara, Daisuke; Ishikawa, Shumpei; Sachiko, Oguni; Aburatani, Hiroyuki; Fukayama, Masashi; Niki, Toshiro

    2010-01-01

    Epidermal growth factor receptor (EGFR) and MET are molecular targets for lung cancer treatment. The relationships between expression, activation, and gene abnormalities of these two targets are currently unclear. Here, we demonstrate that a panel of 40 lung cancer cell lines could be classified into two groups. Group I was characterized by (1) high phosphorylations of MET and EGFR, (2) frequent mutation or amplification of EGFR, MET, and human epidermal growth factor receptor-2 (HER2), (3) high expressions of bronchial epithelial markers (thyroid transcription factor-1 (TTF-1), MUC1, and Cytokeratin 7 (CK7)); and (4) high expressions of MET, human epidermal growth factor receptor-3, E-cadherin, cyclooxygenase-2, and laminin gamma2. In contrast, Group II exhibited little or no phosphorylation of MET and EGFR; no mutation or amplification of EGFR, MET, and HER2; were triple-negative for TTF-1, MUC1, and CK7; and showed high expressions of vimentin, fibroblast growth factor receptor-1, and transcription factor 8. Importantly, Group I was more sensitive to gefitinib and more resistant to cisplatin and paclitaxel than Group II. The clinical relevance was confirmed in publicly available data on 442 primary lung adenocarcinoma patients; survival benefits by postoperative chemotherapy were seen in only patients with tumors corresponding to Group II. Overall, co-activation of EGFR and MET defines a distinct subgroup of lung carcinoma with characteristic genetic abnormalities, gene expression pattern, and response to chemotherapeutic reagents. PMID:20934974

  4. Rhomboid Enhancer Activity Defines a Subset of Drosophila Neural Precursors Required for Proper Feeding, Growth and Viability

    PubMed Central

    Gresser, Amy L.; Gutzwiller, Lisa M.; Gauck, Mackenzie K.; Hartenstein, Volker; Cook, Tiffany A.; Gebelein, Brian

    2015-01-01

    Organismal growth regulation requires the interaction of multiple metabolic, hormonal and neuronal pathways. While the molecular basis for many of these are well characterized, less is known about the developmental origins of growth regulatory structures and the mechanisms governing control of feeding and satiety. For these reasons, new tools and approaches are needed to link the specification and maturation of discrete cell populations with their subsequent regulatory roles. In this study, we characterize a rhomboid enhancer element that selectively labels four Drosophila embryonic neural precursors. These precursors give rise to the hypopharyngeal sensory organ of the peripheral nervous system and a subset of neurons in the deutocerebral region of the embryonic central nervous system. Post embryogenesis, the rhomboid enhancer is active in a subset of cells within the larval pharyngeal epithelium. Enhancer-targeted toxin expression alters the morphology of the sense organ and results in impaired larval growth, developmental delay, defective anterior spiracle eversion and lethality. Limiting the duration of toxin expression reveals differences in the critical periods for these effects. Embryonic expression causes developmental defects and partially penetrant pre-pupal lethality. Survivors of embryonic expression, however, ultimately become viable adults. In contrast, post-embryonic toxin expression results in fully penetrant lethality. To better define the larval growth defect, we used a variety of assays to demonstrate that toxin-targeted larvae are capable of locating, ingesting and clearing food and they exhibit normal food search behaviors. Strikingly, however, following food exposure these larvae show a rapid decrease in consumption suggesting a satiety-like phenomenon that correlates with the period of impaired larval growth. Together, these data suggest a critical role for these enhancer-defined lineages in regulating feeding, growth and viability. PMID

  5. Rhomboid Enhancer Activity Defines a Subset of Drosophila Neural Precursors Required for Proper Feeding, Growth and Viability.

    PubMed

    Gresser, Amy L; Gutzwiller, Lisa M; Gauck, Mackenzie K; Hartenstein, Volker; Cook, Tiffany A; Gebelein, Brian

    2015-01-01

    Organismal growth regulation requires the interaction of multiple metabolic, hormonal and neuronal pathways. While the molecular basis for many of these are well characterized, less is known about the developmental origins of growth regulatory structures and the mechanisms governing control of feeding and satiety. For these reasons, new tools and approaches are needed to link the specification and maturation of discrete cell populations with their subsequent regulatory roles. In this study, we characterize a rhomboid enhancer element that selectively labels four Drosophila embryonic neural precursors. These precursors give rise to the hypopharyngeal sensory organ of the peripheral nervous system and a subset of neurons in the deutocerebral region of the embryonic central nervous system. Post embryogenesis, the rhomboid enhancer is active in a subset of cells within the larval pharyngeal epithelium. Enhancer-targeted toxin expression alters the morphology of the sense organ and results in impaired larval growth, developmental delay, defective anterior spiracle eversion and lethality. Limiting the duration of toxin expression reveals differences in the critical periods for these effects. Embryonic expression causes developmental defects and partially penetrant pre-pupal lethality. Survivors of embryonic expression, however, ultimately become viable adults. In contrast, post-embryonic toxin expression results in fully penetrant lethality. To better define the larval growth defect, we used a variety of assays to demonstrate that toxin-targeted larvae are capable of locating, ingesting and clearing food and they exhibit normal food search behaviors. Strikingly, however, following food exposure these larvae show a rapid decrease in consumption suggesting a satiety-like phenomenon that correlates with the period of impaired larval growth. Together, these data suggest a critical role for these enhancer-defined lineages in regulating feeding, growth and viability. PMID

  6. Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation

    NASA Astrophysics Data System (ADS)

    Rodrigo-Navarro, Aleixandre; Rico, Patricia; Saadeddin, Anas; Garcia, Andres J.; Salmeron-Sanchez, Manuel

    2014-07-01

    Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications.

  7. Tracking a defined route for O[subscript 2] migration in a dioxygen-activating diiron enzyme

    SciTech Connect

    Song, Woon Ju; Gucinski, Grant; Sazinsky, Matthew H.; Lippard, Stephen J.

    2011-09-08

    For numerous enzymes reactive toward small gaseous compounds, growing evidence indicates that these substrates diffuse into active site pockets through defined pathways in the protein matrix. Toluene/o-xylene monooxygenase hydroxylase is a dioxygen-activating enzyme. Structural analysis suggests two possible pathways for dioxygen access through the {alpha}-subunit to the diiron center: a channel or a series of hydrophobic cavities. To distinguish which is utilized as the O{sub 2} migration pathway, the dimensions of the cavities and the channel were independently varied by site-directed mutagenesis and confirmed by X-ray crystallography. The rate constants for dioxygen access to the diiron center were derived from the formation rates of a peroxodiiron(III) intermediate, generated upon treatment of the diiron(II) enzyme with O2. This reaction depends on the concentration of dioxygen to the first order. Altering the dimensions of the cavities, but not the channel, changed the rate of dioxygen reactivity with the enzyme. These results strongly suggest that voids comprising the cavities in toluene/o-xylene monooxygenase hydroxylase are not artifacts of protein packing/folding, but rather programmed routes for dioxygen migration through the protein matrix. Because the cavities are not fully connected into the diiron active center in the enzyme resting state, conformational changes will be required to facilitate dioxygen access to the diiron center. We propose that such temporary opening and closing of the cavities may occur in all bacterial multicomponent monooxygenases to control O{sub 2} consumption for efficient catalysis. Our findings suggest that other gas-utilizing enzymes may employ similar structural features to effect substrate passage through a protein matrix.

  8. Genetic diversity of non-pathogenic Clavibacter strains isolated from tomato seeds.

    PubMed

    Zaluga, Joanna; Van Vaerenbergh, Johan; Stragier, Pieter; Maes, Martine; De Vos, Paul

    2013-09-01

    Clavibacter michiganensis subsp. michiganensis (Cmm) is a seed-transmitted, quarantine pathogen which causes bacterial wilt and canker of tomato. Despite efforts to prevent seed contamination, new introductions are regularly detected, associated with new regions of tomato seed production. It seems as if the expanding diversity of Cmm also challenges the limited host range. Clavibacter-like isolates from tomato seed are phenotypically similar to Cmm in the common diagnostic semi-selective media and are identified as Cmm in the customary tests but are not pathogenic to tomato. In our first study four representatives formed a separate cluster in gyrB sequence analysis and in MALDI-TOF MS. Their presence on seed prevents clear judgment on the health status of tomato seeds. As their nature and function are unclear we aimed to investigate and compare them to Cmm. Twenty strains described as Clavibacter-like isolated from tomato seed and not pathogenic to tomato plantlets were selected. Leaf spots, wilting or cankers were not induced after local or systemic inoculation. Tomato stems were not colonized nor was there evidence of survival in tomato stems. Total DNA-DNA hybridization and sequence analysis of gyrB and dnaA proved that they belong to the Cm species but can be unambiguously separated from Cmm. Some of the genes encoding virulence determinants in Cmm strains were also detected in some of the non-pathogenic isolates. Moreover, Cmm strains formed a coherent group, while non-pathogenic Cm strains were heterogenic. The latter was confirmed by BOX-PCR. We speculate that tomato seeds likely represent a larger reservoir of unexplored Clavibacter diversity. PMID:23768656

  9. Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections

    PubMed Central

    Greenwood, Edward J. D.; Schmidt, Fabian; Kondova, Ivanela; Niphuis, Henk; Hodara, Vida L.; Clissold, Leah; McLay, Kirsten; Guerra, Bernadette; Redrobe, Sharon; Giavedoni, Luis D.; Lanford, Robert E.; Murthy, Krishna K.; Rouet, François; Heeney, Jonathan L.

    2015-01-01

    The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in ‘natural host’ species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections. PMID:26360709

  10. Genome and secretome analyses provide insights into keratin decomposition by novel proteases from the non-pathogenic fungus Onygena corvina.

    PubMed

    Huang, Yuhong; Busk, Peter Kamp; Herbst, Florian-Alexander; Lange, Lene

    2015-11-01

    Poultry processing plants and slaughterhouses produce huge quantities of feathers and hair/bristle waste annually. These keratinaceous wastes are highly resistant to degradation. Onygena corvina, a non-pathogenic fungus, grows specifically on feathers, hooves, horn, and hair in nature. Hence, the proteases secreted by O. corvina are interesting in view of their potential relevance for industrial decomposition of keratinaceous wastes. We sequenced and assembled the genome of O. corvina and used a method called peptide pattern recognition to identify 73 different proteases. Comparative genome analysis of proteases in keratin-degrading and non-keratin-degrading fungi indicated that 18 putative secreted proteases from four protease families (M36, M35, M43, and S8) may be responsible for keratin decomposition. Twelve of the 18 predicted protease genes could be amplified from O. corvina grown on keratinaceous materials and were transformed into Pichia pastoris. One of the recombinant proteases belonging to the S8 family showed high keratin-degrading activity. Furthermore, 29 different proteases were identified by mass spectrometry in the culture broth of O. corvina grown on feathers and bristle. The culture broth was fractionated by ion exchange chromatography to isolate active fractions with five novel proteases belonging to three protease families (S8, M28, and M3). Enzyme blends composed of three of these five proteases, one from each family, showed high degree of degradation of keratin in vitro. A blend of novel proteases, such as those we discovered, could possibly find a use for degrading keratinaceous wastes and provide proteins, peptides, and amino acids as valuable ingredients for animal feed. PMID:26177915

  11. A high-resolution lake sediment record of glacier activity from SE Greenland defines abrupt Holocene cooling events

    NASA Astrophysics Data System (ADS)

    Balascio, N. L.; Bradley, R. S.; D'Andrea, W. J.

    2013-12-01

    Orbital driven changes in high latitude summer insolation during the Holocene are responsible for the primary millennial-scale climate trends in the Arctic. Following deglaciation, maximum summer temperatures generally occurred during the early to mid-Holocene and declined through the late Holocene. Superimposed on this gradual cooling trend are centennial- and decadal-scale intervals that indicate more rapid perturbations of the arctic climate system. Highly resolved sedimentary records from terrestrial and marine sites help to better characterize climate system dynamics during the Holocene and investigate forcing and feedback mechanism that operate on different timescales. Reconstructing glacial activity can provide valuable paleoclimate information about trends in summer temperature and/or winter precipitation. Proglacial lakes contain sediment archives of meltwater input from glaciers and typically have high sedimentation rates preserving detailed information on glacial activity. However, interpreting proglacial sedimentary records can be difficult because 1) there may be significant input of sediment from non-glacial sources, 2) there is often a lack of organic material for radiocarbon dating, and 3) not all glaciers are sensitive to rapid climatic changes. Here we present a c. 10 cal ka BP record of glacier activity from Kulusuk Lake (65.6°N, 37.1°W; 202 m a.s.l.), a proglacial lake in southeast Greenland that is well constrained by radiocarbon dates and shows a clear signal of changes in glacial input throughout the Holocene. Kulusuk Lake is presently fed by meltwater from two cirque glaciers. It has a small catchment and no other significant source of sediment input. A 3.5 m sediment core contains distinct lithologic changes defined by grain size, magnetic susceptibility, organic content, and scanning XRF data. During the early Holocene, an overall decrease in meltwater input from 8.7-7.7 ka indicates the retreat of the glaciers in response to regional

  12. Difference between Escherichia coli O157:H7 and non-pathogenic E. coli: survival and growth in seasonings.

    PubMed

    Yokoigawa, K; Takikawa, A; Kawai, H

    1999-01-01

    We examined the survival and growth of Escherichia coli O157:H7 cells incubated with several seasonings, in comparison with those of non-pathogenic E. coli. The cells were incubated at 25 degrees C for 24 h with several concentrations of NaCl, sucrose, soy sauce, worcester sauce and tomato ketchup, and their survival ratios were determined. The E. coli O157:H7 strains showed relatively higher survival ratios in 0.5-1.0 M sucrose, 25% soy sauce and 12.5-50% worcester sauce than the non-pathogenic strains, but slightly lower survival ratios in 0.5-2.0 M NaCl. A noteworthy difference between E. coli O157:H7 and the non-pathogenic strains was that incubation in the presence of 12.5% soy sauce allowed the growth of E. coli O157:H7 strains but reduced the viable cell numbers of non-pathogenic E. coli strains. PMID:16232665

  13. Defining RNA motif–aminoglycoside interactions via two-dimensional combinatorial screening and structure–activity relationships through sequencing

    PubMed Central

    Velagapudi, Sai Pradeep; Disney, Matthew D.

    2013-01-01

    RNA is an extremely important target for the development of chemical probes of function or small molecule therapeutics. Aminoglycosides are the most well studied class of small molecules to target RNA. However, the RNA motifs outside of the bacterial rRNA A-site that are likely to be bound by these compounds in biological systems is largely unknown. If such information were known, it could allow for aminoglycosides to be exploited to target other RNAs and, in addition, could provide invaluable insights into potential bystander targets of these clinically used drugs. We utilized two-dimensional combinatorial screening (2DCS), a library-versus-library screening approach, to select the motifs displayed in a 3 × 3 nucleotide internal loop library and in a 6-nucleotide hairpin library that bind with high affinity and selectivity to six aminoglycoside derivatives. The selected RNA motifs were then analyzed using structure–activity relationships through sequencing (StARTS), a statistical approach that defines the privileged RNA motif space that binds a small molecule. StARTS allowed for the facile annotation of the selected RNA motif–aminoglycoside interactions in terms of affinity and selectivity. The interactions selected by 2DCS generally have nanomolar affinities, which is higher affinity than the binding of aminoglycosides to a mimic of their therapeutic target, the bacterial rRNA A-site. PMID:23719281

  14. Defining RNA motif-aminoglycoside interactions via two-dimensional combinatorial screening and structure-activity relationships through sequencing.

    PubMed

    Velagapudi, Sai Pradeep; Disney, Matthew D

    2013-10-15

    RNA is an extremely important target for the development of chemical probes of function or small molecule therapeutics. Aminoglycosides are the most well studied class of small molecules to target RNA. However, the RNA motifs outside of the bacterial rRNA A-site that are likely to be bound by these compounds in biological systems is largely unknown. If such information were known, it could allow for aminoglycosides to be exploited to target other RNAs and, in addition, could provide invaluable insights into potential bystander targets of these clinically used drugs. We utilized two-dimensional combinatorial screening (2DCS), a library-versus-library screening approach, to select the motifs displayed in a 3×3 nucleotide internal loop library and in a 6-nucleotide hairpin library that bind with high affinity and selectivity to six aminoglycoside derivatives. The selected RNA motifs were then analyzed using structure-activity relationships through sequencing (StARTS), a statistical approach that defines the privileged RNA motif space that binds a small molecule. StARTS allowed for the facile annotation of the selected RNA motif-aminoglycoside interactions in terms of affinity and selectivity. The interactions selected by 2DCS generally have nanomolar affinities, which is higher affinity than the binding of aminoglycosides to a mimic of their therapeutic target, the bacterial rRNA A-site. PMID:23719281

  15. Gardnerella vaginalis Subgroups Defined by cpn60 Sequencing and Sialidase Activity in Isolates from Canada, Belgium and Kenya.

    PubMed

    Schellenberg, John J; Paramel Jayaprakash, Teenus; Withana Gamage, Niradha; Patterson, Mo H; Vaneechoutte, Mario; Hill, Janet E

    2016-01-01

    Increased abundance of Gardnerella vaginalis and sialidase activity in vaginal fluid is associated with bacterial vaginosis (BV), a common but poorly understood clinical entity associated with poor reproductive health outcomes. Since most women are colonized with G. vaginalis, its status as a normal member of the vaginal microbiota or pathogen causing BV remains controversial, and numerous classification schemes have been described. Since 2005, sequencing of the chaperonin-60 universal target (cpn60 UT) has distinguished four subgroups in isolate collections, clone libraries and deep sequencing datasets. To clarify potential clinical and diagnostic significance of cpn60 subgroups, we undertook phenotypic and molecular characterization of 112 G. vaginalis isolates from three continents. A total of 36 subgroup A, 33 B, 35 C and 8 D isolates were identified through phylogenetic analysis of cpn60 sequences as corresponding to four "clades" identified in a recently published study, based on sequencing 473 genes across 17 isolates. cpn60 subgroups were compared with other previously described molecular methods for classification of Gardnerella subgroups, including amplified ribosomal DNA restriction analysis (ARDRA) and real-time PCR assays designed to quantify subgroups in vaginal samples. Although two ARDRA patterns were observed in isolates, each was observed in three cpn60 subgroups (A/B/D and B/C/D). Real-time PCR assays corroborated cpn60 subgroups overall, but 13 isolates from subgroups A, B and D were negative in all assays. A putative sialidase gene was detected in all subgroup B, C and D isolates, but only in a single subgroup A isolate. In contrast, sialidase activity was observed in all subgroup B isolates, 3 (9%) subgroup C isolates and no subgroup A or D isolates. These observations suggest distinct roles for G. vaginalis subgroups in BV pathogenesis. We conclude that cpn60 UT sequencing is a robust approach for defining G. vaginalis subgroups within the

  16. Gardnerella vaginalis Subgroups Defined by cpn60 Sequencing and Sialidase Activity in Isolates from Canada, Belgium and Kenya

    PubMed Central

    Schellenberg, John J.; Paramel Jayaprakash, Teenus; Withana Gamage, Niradha; Patterson, Mo H.; Vaneechoutte, Mario; Hill, Janet E.

    2016-01-01

    Increased abundance of Gardnerella vaginalis and sialidase activity in vaginal fluid is associated with bacterial vaginosis (BV), a common but poorly understood clinical entity associated with poor reproductive health outcomes. Since most women are colonized with G. vaginalis, its status as a normal member of the vaginal microbiota or pathogen causing BV remains controversial, and numerous classification schemes have been described. Since 2005, sequencing of the chaperonin-60 universal target (cpn60 UT) has distinguished four subgroups in isolate collections, clone libraries and deep sequencing datasets. To clarify potential clinical and diagnostic significance of cpn60 subgroups, we undertook phenotypic and molecular characterization of 112 G. vaginalis isolates from three continents. A total of 36 subgroup A, 33 B, 35 C and 8 D isolates were identified through phylogenetic analysis of cpn60 sequences as corresponding to four “clades” identified in a recently published study, based on sequencing 473 genes across 17 isolates. cpn60 subgroups were compared with other previously described molecular methods for classification of Gardnerella subgroups, including amplified ribosomal DNA restriction analysis (ARDRA) and real-time PCR assays designed to quantify subgroups in vaginal samples. Although two ARDRA patterns were observed in isolates, each was observed in three cpn60 subgroups (A/B/D and B/C/D). Real-time PCR assays corroborated cpn60 subgroups overall, but 13 isolates from subgroups A, B and D were negative in all assays. A putative sialidase gene was detected in all subgroup B, C and D isolates, but only in a single subgroup A isolate. In contrast, sialidase activity was observed in all subgroup B isolates, 3 (9%) subgroup C isolates and no subgroup A or D isolates. These observations suggest distinct roles for G. vaginalis subgroups in BV pathogenesis. We conclude that cpn60 UT sequencing is a robust approach for defining G. vaginalis subgroups within

  17. Nonpathogenic SIV and Pathogenic HIV Infections Associate with Disparate Innate Cytokine Signatures in Response to Mycobacterium bovis BCG

    PubMed Central

    Gasper, Melanie A.; Biswas, Shameek P.; Fisher, Bridget S.; Ehnert, Stephanie C.; Sherman, David R.; Sodora, Donald L.

    2016-01-01

    Infections with mycobacteria, including Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis (M. bovis) BCG, are a leading cause of morbidity and mortality for HIV-infected persons. In contrast to HIV, nonpathogenic SIV infections of sooty mangabeys are characterized by a lack of clinical disease including an absence of opportunistic infections. The goal of this study was to identify innate immune responses to M. bovis BCG maintained during nonpathogenic lentiviral infections through a comparison of functional responses during pathogenic HIV or nonpathogenic SIV infections. Monocytes were evaluated for their ability to express key anti-mycobacterial cytokines TNF-α and IL-12 following a six-hour ex vivo BCG exposure. While HIV-infection was associated with a decreased percentage of IL-12-producing monocytes, nonpathogenic SIV-infection was associated with an increased percentage of monocytes producing both cytokines. Gene expression analysis of PBMC following ex vivo BCG exposure identified differential expression of NK cell-related genes and several cytokines, including IFN-γ and IL-23, between HIV-infected and control subjects. In contrast, SIV-infected and uninfected-control mangabeys exhibited no significant differences in gene expression after BCG exposure. Finally, differential gene expression patterns were identified between species, with mangabeys exhibiting lower IL-6 and higher IL-17 in response to BCG when compared to humans. Overall, this comparison of immune responses to M. bovis BCG identified unique immune signatures (involving cytokines IL-12, TNF-α, IL-23, IL-17, and IL-6) that are altered during HIV, but maintained or increased during nonpathogenic SIV infections. These unique cytokine and transcriptome signatures provide insight into the differential immune responses to Mycobacteria during pathogenic HIV-infection that may be associated with an increased incidence of mycobacterial co-infections. PMID:27505158

  18. Comparative Genomics of Pathogenic and Nonpathogenic Strains of Xanthomonas arboricola Unveil Molecular and Evolutionary Events Linked to Pathoadaptation

    PubMed Central

    Cesbron, Sophie; Briand, Martial; Essakhi, Salwa; Gironde, Sophie; Boureau, Tristan; Manceau, Charles; Fischer-Le Saux, Marion; Jacques, Marie-Agnès

    2015-01-01

    The bacterial species Xanthomonas arboricola contains plant pathogenic and nonpathogenic strains. It includes the pathogen X. arboricola pv. juglandis, causing the bacterial blight of Juglans regia. The emergence of a new bacterial disease of J. regia in France called vertical oozing canker (VOC) was previously described and the causal agent was identified as a distinct genetic lineage within the pathovar juglandis. Symptoms on walnut leaves and fruits are similar to those of a bacterial blight but VOC includes also cankers on trunk and branches. In this work, we used comparative genomics and physiological tests to detect differences between four X. arboricola strains isolated from walnut tree: strain CFBP 2528 causing walnut blight (WB), strain CFBP 7179 causing VOC and two nonpathogenic strains, CFBP 7634 and CFBP 7651, isolated from healthy walnut buds. Whole genome sequence comparisons revealed that pathogenic strains possess a larger and wider range of mobile genetic elements than nonpathogenic strains. One pathogenic strain, CFBP 7179, possessed a specific integrative and conjugative element (ICE) of 95 kb encoding genes involved in copper resistance, transport and regulation. The type three effector repertoire was larger in pathogenic strains than in nonpathogenic strains. Moreover, CFBP 7634 strain lacked the type three secretion system encoding genes. The flagellar system appeared incomplete and nonfunctional in the pathogenic strain CFBP 2528. Differential sets of chemoreceptor and different repertoires of genes coding adhesins were identified between pathogenic and nonpathogenic strains. Besides these differences, some strain-specific differences were also observed. Altogether, this study provides valuable insights to highlight the mechanisms involved in ecology, environment perception, plant adhesion and interaction, leading to the emergence of new strains in a dynamic environment. PMID:26734033

  19. The Sugarcane Defense Protein SUGARWIN2 Causes Cell Death in Colletotrichum falcatum but Not in Non-Pathogenic Fungi

    PubMed Central

    Franco, Flávia P.; Santiago, Adelita C.; Henrique-Silva, Flávio; de Castro, Patrícia Alves; Goldman, Gustavo H.; Moura, Daniel S.; Silva-Filho, Marcio C.

    2014-01-01

    Plants respond to pathogens and insect attacks by inducing and accumulating a large set of defense-related proteins. Two homologues of a barley wound-inducible protein (BARWIN) have been characterized in sugarcane, SUGARWIN1 and SUGARWIN2 (sugarcane wound-inducible proteins). Induction of SUGARWINs occurs in response to Diatraea saccharalis damage but not to pathogen infection. In addition, the protein itself does not show any effect on insect development; instead, it has antimicrobial activities toward Fusarium verticillioides, an opportunistic fungus that usually occurs after D. saccharalis borer attacks on sugarcane. In this study, we sought to evaluate the specificity of SUGARWIN2 to better understand its mechanism of action against phytopathogens and the associations between fungi and insects that affect plants. We used Colletotrichum falcatum, a fungus that causes red rot disease in sugarcane fields infested by D. saccharalis, and Ceratocystis paradoxa, which causes pineapple disease in sugarcane. We also tested whether SUGARWIN2 is able to cause cell death in Aspergillus nidulans, a fungus that does not infect sugarcane, and in the model yeast Saccharomyces cerevisiae, which is used for bioethanol production. Recombinant SUGARWIN2 altered C. falcatum morphology by increasing vacuolization, points of fractures and a leak of intracellular material, leading to germling apoptosis. In C. paradoxa, SUGARWIN2 showed increased vacuolization in hyphae but did not kill the fungi. Neither the non-pathogenic fungus A. nidulans nor the yeast S. cerevisiae was affected by recombinant SUGARWIN2, suggesting that the protein is specific to sugarcane opportunistic fungal pathogens. PMID:24608349

  20. The sugarcane defense protein SUGARWIN2 causes cell death in Colletotrichum falcatum but not in non-pathogenic fungi.

    PubMed

    Franco, Flávia P; Santiago, Adelita C; Henrique-Silva, Flávio; de Castro, Patrícia Alves; Goldman, Gustavo H; Moura, Daniel S; Silva-Filho, Marcio C

    2014-01-01

    Plants respond to pathogens and insect attacks by inducing and accumulating a large set of defense-related proteins. Two homologues of a barley wound-inducible protein (BARWIN) have been characterized in sugarcane, SUGARWIN1 and SUGARWIN2 (sugarcane wound-inducible proteins). Induction of SUGARWINs occurs in response to Diatraea saccharalis damage but not to pathogen infection. In addition, the protein itself does not show any effect on insect development; instead, it has antimicrobial activities toward Fusarium verticillioides, an opportunistic fungus that usually occurs after D. saccharalis borer attacks on sugarcane. In this study, we sought to evaluate the specificity of SUGARWIN2 to better understand its mechanism of action against phytopathogens and the associations between fungi and insects that affect plants. We used Colletotrichum falcatum, a fungus that causes red rot disease in sugarcane fields infested by D. saccharalis, and Ceratocystis paradoxa, which causes pineapple disease in sugarcane. We also tested whether SUGARWIN2 is able to cause cell death in Aspergillus nidulans, a fungus that does not infect sugarcane, and in the model yeast Saccharomyces cerevisiae, which is used for bioethanol production. Recombinant SUGARWIN2 altered C. falcatum morphology by increasing vacuolization, points of fractures and a leak of intracellular material, leading to germling apoptosis. In C. paradoxa, SUGARWIN2 showed increased vacuolization in hyphae but did not kill the fungi. Neither the non-pathogenic fungus A. nidulans nor the yeast S. cerevisiae was affected by recombinant SUGARWIN2, suggesting that the protein is specific to sugarcane opportunistic fungal pathogens. PMID:24608349

  1. Defining chaos

    SciTech Connect

    Hunt, Brian R.; Ott, Edward

    2015-09-15

    In this paper, we propose, discuss, and illustrate a computationally feasible definition of chaos which can be applied very generally to situations that are commonly encountered, including attractors, repellers, and non-periodically forced systems. This definition is based on an entropy-like quantity, which we call “expansion entropy,” and we define chaos as occurring when this quantity is positive. We relate and compare expansion entropy to the well-known concept of topological entropy to which it is equivalent under appropriate conditions. We also present example illustrations, discuss computational implementations, and point out issues arising from attempts at giving definitions of chaos that are not entropy-based.

  2. Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications.

    PubMed

    Ardini, Elena; Menichincheri, Maria; Banfi, Patrizia; Bosotti, Roberta; De Ponti, Cristina; Pulci, Romana; Ballinari, Dario; Ciomei, Marina; Texido, Gemma; Degrassi, Anna; Avanzi, Nilla; Amboldi, Nadia; Saccardo, Maria Beatrice; Casero, Daniele; Orsini, Paolo; Bandiera, Tiziano; Mologni, Luca; Anderson, David; Wei, Ge; Harris, Jason; Vernier, Jean-Michel; Li, Gang; Felder, Eduard; Donati, Daniele; Isacchi, Antonella; Pesenti, Enrico; Magnaghi, Paola; Galvani, Arturo

    2016-04-01

    Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non-small cell lung cancers (NSCLC) as well as other tumor types and their oncogenic relevance as actionable targets has been demonstrated by the efficacy of selective kinase inhibitors such as crizotinib, ceritinib, and alectinib. More recently, low-frequency rearrangements of TRK kinases have been described in NSCLC, colorectal carcinoma, glioblastoma, and Spitzoid melanoma. Entrectinib, whose discovery and preclinical characterization are reported herein, is a novel, potent inhibitor of ALK, ROS1, and, importantly, of TRK family kinases, which shows promise for therapy of tumors bearing oncogenic forms of these proteins. Proliferation profiling against over 200 human tumor cell lines revealed that entrectinib is exquisitely potent in vitro against lines that are dependent on the drug's pharmacologic targets. Oral administration of entrectinib to tumor-bearing mice induced regression in relevant human xenograft tumors, including the TRKA-dependent colorectal carcinoma KM12, ROS1-driven tumors, and several ALK-dependent models of different tissue origins, including a model of brain-localized lung cancer metastasis. Entrectinib is currently showing great promise in phase I/II clinical trials, including the first documented objective responses to a TRK inhibitor in colorectal carcinoma and in NSCLC. The drug is, thus, potentially suited to the therapy of several molecularly defined cancer settings, especially that of TRK-dependent tumors, for which no approved drugs are currently available. Mol Cancer Ther; 15(4); 628-39. ©2016 AACR. PMID:26939704

  3. Glycoprotein of Nonpathogenic Rabies Viruses Is a Key Determinant of Human Cell Apoptosis

    PubMed Central

    Préhaud, Christophe; Lay, Stéphanie; Dietzschold, Bernhard; Lafon, Monique

    2003-01-01

    We showed that, unlike pathogenic rabies virus (RV) strain CVS, attenuated RV strain ERA triggers the caspase-dependent apoptosis of human cells. Furthermore, we observed that the induction of apoptosis is correlated with a particular virus antigen distribution: the overexpression of the viral G protein on the cell surface, with continuous localization on the cytoplasmic membrane, and large cytoplasmic inclusions of the N protein. To determine whether one of these two major RV proteins (G and N proteins) triggers apoptosis, we constructed transgenic Jurkat T-cell lines that drive tetracycline-inducible gene expression to produce the G and N proteins of ERA and CVS individually. The induction of ERA G protein (G-ERA) expression but not of ERA N protein expression resulted in apoptosis, and G-ERA was more efficient at triggering apoptosis than was CVS G protein. To test whether other viral proteins participated in the induction of apoptosis, human cells were infected with recombinant RV in which the G protein gene from the attenuated strain had been replaced by its virulent strain counterpart (CVS). Only RV containing the G protein from the nonpathogenic RV strain was able to trigger the apoptosis of human cells. Thus, the ability of RV strains to induce apoptosis is largely determined by the viral G protein. PMID:12970438

  4. Single-molecule analysis of the major glycopolymers of pathogenic and non-pathogenic yeast cells

    NASA Astrophysics Data System (ADS)

    El-Kirat-Chatel, Sofiane; Beaussart, Audrey; Alsteens, David; Sarazin, Aurore; Jouault, Thierry; Dufrêne, Yves F.

    2013-05-01

    Most microbes are coated with carbohydrates that show remarkable structural variability and play a crucial role in mediating microbial-host interactions. Understanding the functions of cell wall glycoconjugates requires detailed knowledge of their molecular organization, diversity and heterogeneity. Here we use atomic force microscopy (AFM) with tips bearing specific probes (lectins, antibodies) to analyze the major glycopolymers of pathogenic and non-pathogenic yeast cells at molecular resolution. We show that non-ubiquitous β-1,2-mannans are largely exposed on the surface of native cells from pathogenic Candida albicans and C. glabrata, the former species displaying the highest glycopolymer density and extensions. We also find that chitin, a major component of the inner layer of the yeast cell wall, is much more abundant in C. albicans. These differences in molecular properties, further supported by flow cytometry measurements, may play an important role in strengthening cell wall mechanics and immune interactions. This study demonstrates that single-molecule AFM, combined with immunological and fluorescence methods, is a powerful platform in fungal glycobiology for probing the density, distribution and extension of specific cell wall glycoconjugates. In nanomedicine, we anticipate that this new form of AFM-based nanoglycobiology will contribute to the development of sugar-based drugs, immunotherapeutics, vaccines and diagnostics.

  5. Living biointerfaces based on non-pathogenic bacteria support stem cell differentiation

    PubMed Central

    Hay, Jake J.; Rodrigo-Navarro, Aleixandre; Hassi, Karoliina; Moulisova, Vladimira; Dalby, Matthew J.; Salmeron-Sanchez, Manuel

    2016-01-01

    Lactococcus lactis, a non-pathogenic bacteria, has been genetically engineered to express the III7–10 fragment of human fibronectin as a membrane protein. The engineered L. lactis is able to develop biofilms on different surfaces (such as glass and synthetic polymers) and serves as a long-term substrate for mammalian cell culture, specifically human mesenchymal stem cells (hMSC). This system constitutes a living interface between biomaterials and stem cells. The engineered biofilms remain stable and viable for up to 28 days while the expressed fibronectin fragment induces hMSC adhesion. We have optimised conditions to allow long-term mammalian cell culture, and found that the biofilm is functionally equivalent to a fibronectin-coated surface in terms of osteoblastic differentiation using bone morphogenetic protein 2 (BMP-2) added to the medium. This living bacteria interface holds promise as a dynamic substrate for stem cell differentiation that can be further engineered to express other biochemical cues to control hMSC differentiation. PMID:26902619

  6. Living biointerfaces based on non-pathogenic bacteria support stem cell differentiation

    NASA Astrophysics Data System (ADS)

    Hay, Jake J.; Rodrigo-Navarro, Aleixandre; Hassi, Karoliina; Moulisova, Vladimira; Dalby, Matthew J.; Salmeron-Sanchez, Manuel

    2016-02-01

    Lactococcus lactis, a non-pathogenic bacteria, has been genetically engineered to express the III7-10 fragment of human fibronectin as a membrane protein. The engineered L. lactis is able to develop biofilms on different surfaces (such as glass and synthetic polymers) and serves as a long-term substrate for mammalian cell culture, specifically human mesenchymal stem cells (hMSC). This system constitutes a living interface between biomaterials and stem cells. The engineered biofilms remain stable and viable for up to 28 days while the expressed fibronectin fragment induces hMSC adhesion. We have optimised conditions to allow long-term mammalian cell culture, and found that the biofilm is functionally equivalent to a fibronectin-coated surface in terms of osteoblastic differentiation using bone morphogenetic protein 2 (BMP-2) added to the medium. This living bacteria interface holds promise as a dynamic substrate for stem cell differentiation that can be further engineered to express other biochemical cues to control hMSC differentiation.

  7. 20 CFR 404.418 - “Noncovered remunerative activity outside the United States,” defined.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... United States,â defined. 404.418 Section 404.418 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... (b) He carries on a trade or business outside the United States (other than the performance of... earnings from self-employment (see § 404.1052) if the trade or business were carried on in the...

  8. Defining GERD.

    PubMed Central

    Sontag, S. J.

    1999-01-01

    "It is not the death of GERD that I seek, but that it turns from its evil ways and follows the path of righteousness." The reflux world is fully aware of what GERD is and what GERD does. What the world does not know, however, is the answer to the most important yet least asked question surrounding GERD's raison-d'etre: Why is GERD here and why do we have it? What GERD is: abnormal gastric reflux into the esophagus that causes any type of mischief. What GERD does: causes discomfort and/or pain with or without destroying the mucosa; causes stricture or stenosis, preventing food from being swallowed; sets the stage for the development of esophageal adenocarcinoma; invades the surrounding lands to harass the peaceful oropharyngeal, laryngeal and broncho-pulmonary territories; reminds us that we are not only human, but that we are dust and ashes. Why GERD is here: We propose three separate and distinct etiologies of GERD, and we offer the following three hypotheses to explain why, after 1.5 million years of standing erect, we have evolved into a species (specifically Homosapiens sapiens) that is destined to live with the scourge of GERD. Hypothesis 1: congenital. The antireflux barrier, comprising the smooth-muscled lower esophageal sphincter, the skeletal-muscled right crural diaphragm and the phreno-esophageal ligament does not completely develop due to a developmental anomaly or incomplete gestation. Hypothesis 2: acute trauma: The antireflux barrier in adults suffering acute traumatic injury to the abdomen or chest is permanently disrupted by unexpected forces, such as motor vehicle accidents (with steering wheel crush impact), blows to the abdomen (from activities such as boxing, etc.), heavy lifting or moving (e.g., pianos, refrigerators) or stress positions (e.g., hand stands on parallel gym bars). The trauma creates a hiatal hernia that renders the antireflux mechanism useless and incapable of preventing GERD. Hypothesis 3: chronic trauma: The antireflux barrier

  9. Molecular interactions of the intrinsic activation complex of coagulation: binding of native and activated human factors IX and X to defined phospholipid vesicles.

    PubMed

    Burri, B J; Edgington, T S; Fair, D S

    1987-02-20

    The assembly of proteins of the intrinsic activation complex has been partially elucidated. In the present study we examine the association of gamma-carboxylated serine proteinase zymogens factors IX and X, and their proteolytically activated counterparts factors IXa and Xa to unilamellar lipid vesicles of defined composition using three types of physical measurement. Utilizing relative light scatter to estimate the dissociation constants for binding in the presence of calcium ions, it appears that factor IXa (0.93 +/- 0.37 microM) may preferentially associate with phospholipids relative to factor IX (0.35 +/- 0.08 microM). In contrast, factor X (0.34 +/- 0.14 microM), the substrate for factor IXa, appears to bind to phospholipid with a higher affinity than factor Xa (0.58 +/- 0.13 microM). These observations are compatible with the hypothesized dynamics where the forward 'traffic' is facilitated by favoring the association of factor IXa with factor X. The dissociation constants were estimated by molecular exclusion chromatography (1.1 - 2.5 microM) and do not reflect these relative and ordered differences in association with lipid vesicles. Quasi-elastic light scatter analyses indicate that each protein appears to saturate the same vesicle surface, consistent with competition for similar surface lipids, although the molecular shell formed by factor Xa (36 A) is smaller, suggesting that it has a different packing on the phospholipid surface than the other proteins (64-79 A). The pattern of preferential affinities for phospholipid is consistent with a kinetically functional forward traffic through the reaction precursors to products, and suggests that these preferential affinities may assist in the ordering of the four proteins in the intrinsic activation complex. PMID:3493031

  10. Comparative Transcriptional Analysis of Homologous Pathogenic and Non-Pathogenic Lawsonia intracellularis Isolates in Infected Porcine Cells

    PubMed Central

    Vannucci, Fabio A.; Foster, Douglas N.; Gebhart, Connie J.

    2012-01-01

    Lawsonia intracellularis is the causative agent of proliferative enteropathy. This disease affects various animal species, including nonhuman primates, has been endemic in pigs, and is an emerging concern in horses. Non-pathogenic variants obtained through multiple passages in vitro do not induce disease, but bacterial isolates at low passage induce clinical and pathological changes. We hypothesize that genes differentially expressed between pathogenic (passage 10) and non-pathogenic (passage 60) L. intracellularis isolates encode potential bacterial virulence factors. The present study used high-throughput sequencing technology to characterize the transcriptional profiling of a pathogenic and a non-pathogenic homologous L. intracellularis variant during in vitro infection. A total of 401 genes were exclusively expressed by the pathogenic variant. Plasmid-encoded genes and those involved in membrane transporter (e.g. ATP-binding cassette), adaptation and stress response (e.g. transcriptional regulators) were the categories mostly responsible for this wider transcriptional landscape. The entire gene repertoire of plasmid A was repressed in the non-pathogenic variant suggesting its relevant role in the virulence phenotype of the pathogenic variant. Of the 319 genes which were commonly expressed in both pathogenic and non-pathogenic variants, no significant difference was observed by comparing their normalized transcription levels (fold change±2; p<0.05). Unexpectedly, these genes demonstrated a positive correlation (r2 = 0.81; p<0.05), indicating the involvement of gene silencing (switching off) mechanisms to attenuate virulence properties of the pathogenic variant during multiple cell passages. Following the validation of these results by reverse transcriptase-quantitative PCR using ten selected genes, the present study represents the first report characterizing the transcriptional profile of L. intracellularis. The complexity of the virulence phenotype was

  11. Comparative transcriptional analysis of homologous pathogenic and non-pathogenic Lawsonia intracellularis isolates in infected porcine cells.

    PubMed

    Vannucci, Fabio A; Foster, Douglas N; Gebhart, Connie J

    2012-01-01

    Lawsonia intracellularis is the causative agent of proliferative enteropathy. This disease affects various animal species, including nonhuman primates, has been endemic in pigs, and is an emerging concern in horses. Non-pathogenic variants obtained through multiple passages in vitro do not induce disease, but bacterial isolates at low passage induce clinical and pathological changes. We hypothesize that genes differentially expressed between pathogenic (passage 10) and non-pathogenic (passage 60) L. intracellularis isolates encode potential bacterial virulence factors. The present study used high-throughput sequencing technology to characterize the transcriptional profiling of a pathogenic and a non-pathogenic homologous L. intracellularis variant during in vitro infection. A total of 401 genes were exclusively expressed by the pathogenic variant. Plasmid-encoded genes and those involved in membrane transporter (e.g. ATP-binding cassette), adaptation and stress response (e.g. transcriptional regulators) were the categories mostly responsible for this wider transcriptional landscape. The entire gene repertoire of plasmid A was repressed in the non-pathogenic variant suggesting its relevant role in the virulence phenotype of the pathogenic variant. Of the 319 genes which were commonly expressed in both pathogenic and non-pathogenic variants, no significant difference was observed by comparing their normalized transcription levels (fold change±2; p<0.05). Unexpectedly, these genes demonstrated a positive correlation (r(2) = 0.81; p<0.05), indicating the involvement of gene silencing (switching off) mechanisms to attenuate virulence properties of the pathogenic variant during multiple cell passages. Following the validation of these results by reverse transcriptase-quantitative PCR using ten selected genes, the present study represents the first report characterizing the transcriptional profile of L. intracellularis. The complexity of the virulence phenotype was

  12. Genetic islands in pome fruit pathogenic and non-pathogenic Erwinia species and related plasmids

    PubMed Central

    Llop, Pablo

    2015-01-01

    New pathogenic bacteria belonging to the genus Erwinia associated with pome fruit trees (Erwinia, E. piriflorinigrans, E. uzenensis) have been increasingly described in the last years, and comparative analyses have found that all these species share several genetic characteristics. Studies at different level (whole genome comparison, virulence genes, plasmid content, etc.) show a high intraspecies homogeneity (i.e., among E. amylovora strains) and also abundant similarities appear between the different Erwinia species: presence of plasmids of similar size in the pathogenic species; high similarity in several genes associated with exopolysaccharide production and hence, with virulence, as well as in some other genes, in the chromosomes. Many genetic similarities have been observed also among some of the plasmids (and genomes) from the pathogenic species and E. tasmaniensis or E. billingiae, two epiphytic species on the same hosts. The amount of genetic material shared in this genus varies from individual genes to clusters, genomic islands and genetic material that even may constitute a whole plasmid. Recent research on evolution of erwinias point out the horizontal transfer acquisition of some genomic islands that were subsequently lost in some species and several pathogenic traits that are still present. How this common material has been obtained and is efficiently maintained in different species belonging to the same genus sharing a common ecological niche provides an idea of the origin and evolution of the pathogenic Erwinia and the interaction with non-pathogenic species present in the same niche, and the role of the genes that are conserved in all of them. PMID:26379649

  13. Prevalences of pathogenic and non-pathogenic Vibrio parahaemolyticus in mollusks from the Spanish Mediterranean Coast

    PubMed Central

    Lopez-Joven, Carmen; de Blas, Ignacio; Furones, M. Dolores; Roque, Ana

    2015-01-01

    Vibrio parahaemolyticus is a well-recognized pathogen of humans. To better understand the ecology of the human-pathogenic variants of this bacterium in the environment, a study on the prevalence in bivalves of pathogenic variants (tlh+ and tdh+ and/or trh+) versus a non-pathogenic one (only tlh+ as species marker for V. parahaemolyticus), was performed in two bays in Catalonia, Spain. Environmental factors that might affect dynamics of both variants of V. parahaemolyticus were taken into account. The results showed that the global prevalence of total V. parahaemolyticus found in both bays was 14.2% (207/1459). It was, however, significantly dependent on sampling point, campaign (year) and bivalve species. Pathogenic variants of V. parahaemolyticus (tdh+ and/or trh+) were detected in 3.8% of the samples (56/1459), meaning that the proportion of bivalves who contained tlh gene were contaminated by pathogenic V. parahaemolyticus strains is 27.1% (56/207). Moreover, the presence of pathogenic V. parahaemolyticus (trh+) was significantly correlated with water salinity, thus the probability of finding pathogenic V. parahaemolyticus decreased 1.45 times with every salinity unit (ppt) increased. Additionally, data showed that V. parahaemolyticus could establish close associations with Ruditapes spp. (P-value < 0.001), which could enhance the transmission of illness to human by pathogenic variants, when clams were eaten raw or slightly cooked. This study provides information on the abundance, ecology and characteristics of total and human-pathogenic V. parahaemolyticus variants associated with bivalves cultured in the Spanish Mediterranean Coast. PMID:26284033

  14. The Use of Cytochrome C Oxidase Enzyme Activity and Immunohistochemistry in Defining Mitochondrial Injury in Kidney Disease.

    PubMed

    Zsengellér, Zsuzsanna K; Rosen, Seymour

    2016-09-01

    The renal biopsy is a dynamic way of looking at renal disease, and tubular elements are an important part of this analysis. The mitochondria in 20 renal biopsies were examined by immunohistochemical (electron transport chain enzyme: cytochrome C oxidase IV [COX IV]) and enzyme histochemical methods (COX), both by light and electron microscopy. The distal convoluted tubules and thick ascending limbs showed the greatest intensity in the COX immunostains and enzyme activity in controls. The degree of mitochondrial COX protein and enzyme activity diminished as the tubules became atrophic. With proximal hypertrophic changes, there was great variation in both COX activity and protein expression. In contrast, in three cases of systemic lupus erythematosus, biopsied for high-grade proteinuria, the activity was consistently upregulated, whereas protein expression remained normal. These unexpected findings of heterogeneous upregulation in hypertrophy and the dyssynchrony of protein expression and activity may indicate mitochondrial dysregulation. Functional electron microscopy showed COX activity delineated by the intense mitochondrial staining in normal or hypertrophic proximal tubules. With atrophic changes, residual small mitochondria with diminished activity could be seen. With mitochondrial size abnormalities (enlargement and irregularity, adefovir toxicity), activity persisted. In the renal biopsy, mitochondrial analysis is feasible utilizing immunohistochemical and enzyme histochemical techniques. PMID:27578326

  15. Endosomal localization of phospholipase D 1a and 1b is defined by the C-termini of the proteins, and is independent of activity.

    PubMed

    Hughes, W E; Parker, P J

    2001-06-15

    The factors regulating the activity of cellular phospholipase D (PLD) have been well characterized; however, the cellular distribution of specific PLD isoforms and the factors defining localization are less clear. Two specific PLD1 isoforms, PLD1a and PLD1b, are shown in the present study to be localized in endosomal compartments with early endosomal autoantigen 1, internalizing epidermal growth factor receptor (ErbB1) and lysobisphosphatidic acid. Novel C-terminal splice variants of PLD1, PLD1a2 and PLD1b2, do not exhibit this endosomal localization. Studies using catalytically inactive and C-terminal deletion mutants of the four PLD1 isoforms led to the conclusion that the C-terminus plays an important part in the catalytic activity of PLD1, but that the endosomal localization of PLD1a and PLD1b is defined by the C-terminus and not catalytic activity. PMID:11389680

  16. In vitro assays for assessment of androgenic and estrogenic activity of defined mixtures and complex environment samples

    EPA Science Inventory

    Point sources of potentially endocrine active compounds to aquatic environments such as waste water treatment plants, pulp and paper mills, and animal feeding operations invariably contain complex mixtures of chemicals. The current study investigates the use of targeted in vitro ...

  17. A Defined Terminal Region of the E. coli Chromosome Shows Late Segregation and High FtsK Activity

    PubMed Central

    Meile, Jean-Christophe; Stouf, Mathieu; Capiaux, Hervé; Mercier, Romain; Lesterlin, Christian; Hallet, Bernard; Cornet, François

    2011-01-01

    Background The FtsK DNA-translocase controls the last steps of chromosome segregation in E. coli. It translocates sister chromosomes using the KOPS DNA motifs to orient its activity, and controls the resolution of dimeric forms of sister chromosomes by XerCD-mediated recombination at the dif site and their decatenation by TopoIV. Methodology We have used XerCD/dif recombination as a genetic trap to probe the interaction of FtsK with loci located in different regions of the chromosome. This assay revealed that the activity of FtsK is restricted to a ∼400 kb terminal region of the chromosome around the natural position of the dif site. Preferential interaction with this region required the tethering of FtsK to the division septum via its N-terminal domain as well as its translocation activity. However, the KOPS-recognition activity of FtsK was not required. Displacement of replication termination outside the FtsK high activity region had no effect on FtsK activity and deletion of a part of this region was not compensated by its extension to neighbouring regions. By observing the fate of fluorescent-tagged loci of the ter region, we found that segregation of the FtsK high activity region is delayed compared to that of its adjacent regions. Significance Our results show that a restricted terminal region of the chromosome is specifically dedicated to the last steps of chromosome segregation and to their coupling with cell division by FtsK. PMID:21799784

  18. Defining the Active Fraction of Daptomycin against Methicillin-Resistant Staphylococcus aureus (MRSA) Using a Pharmacokinetic and Pharmacodynamic Approach

    PubMed Central

    Garonzik, Samira M.; Lenhard, Justin R.; Forrest, Alan; Holden, Patricia N.; Bulitta, Jϋrgen B.; Tsuji, Brian T.

    2016-01-01

    Our objective was to study the pharmacodynamics of daptomycin in the presence of varying concentrations of human serum (HS) in vitro to quantify the fraction of daptomycin that is ‘active’. Time kill experiments were performed with daptomycin (0 to 256 mg/L) against two MRSA strains at log-phase growth, in the presence of HS (0%, 10%, 30%, 50%, 70%) combined with Mueller-Hinton broth. Daptomycin ≥ 2 mg/L achieved 99.9% kill within 8 h at all HS concentrations; early killing activity was slightly attenuated at higher HS concentrations. After 1 h, bacterial reduction of USA300 upon exposure to daptomycin 4 mg/L ranged from -3.1 to -0.5 log10CFU/mL in the presence of 0% to 70% HS, respectively. Bactericidal activity was achieved against both strains at daptomycin ≥ 4 mg/L for all fractions of HS exposure. A mechanism-based mathematical model (MBM) was developed to estimate the active daptomycin fraction at each %HS, comprising 3 bacterial subpopulations differing in daptomycin susceptibility. Time-kill data were fit with this MBM with excellent precision (r2 >0.95). The active fraction of daptomycin was estimated to range from 34.6% to 25.2% at HS fractions of 10% to 70%, respectively. Despite the reported low unbound fraction of daptomycin, the impact of protein binding on the activity of daptomycin was modest. The active fraction approach can be utilized to design in vitro experiments and to optimize therapeutic regimens of daptomycin in humans. PMID:27284923

  19. High Heregulin Expression Is Associated with Activated HER3 and May Define an Actionable Biomarker in Patients with Squamous Cell Carcinomas of the Head and Neck

    PubMed Central

    Shames, David S.; Carbon, Juliet; Walter, Kim; Jubb, Adrian M.; Kozlowski, Cleopatra; Januario, Tom; An, Do; Fu, Ling; Xiao, Yuanyuan; Raja, Rajiv; Jiang, Brittany; Malekafzali, Ashi; Stern, Howard; Settleman, Jeff; Wilson, Timothy R.; Hampton, Garret M.; Yauch, Robert L.; Pirzkall, Andrea; Amler, Lukas C.

    2013-01-01

    Purpose Tumors with oncogenic dependencies on the HER family of receptor tyrosine kinases (RTKs) often respond well to targeted inhibition. Our previous work suggested that many cell lines derived from squamous cell carcinomas of the head and neck (SCCHNs) depend on autocrine signaling driven by HER2/3 dimerization and high-level co-expression of HRG. Additionally, results from a Phase I trial of MEHD7495A, a dual-action antibody that blocks ligand binding to EGFR and HER3, suggest that high-level HRG expression was associated with clinical response in SCCHN patients. Here we explore the hypothesis that high-level HRG expression defines a subpopulation of SCCHNs with activated HER3. Experimental Design qRT-PCR expression profiling was performed on >750 tumors of diverse origin, including >150 therapy-naïve, primary, and recurrent SCCHNs. Activated HER3, defined by immunoprecipitation of phospho-HER3, was compared to HRG expression in SCCHN samples. Paracrine versus autocrine expression was evaluated using RNA-in situ hybridization. Results SCCHN tumors express the highest levels of HRG compared to a diverse collection of other tumor types. We show that high HRG expression is associated with activated HER3, whereas low HRG expression is associated with low HER3 activation in SCCHN tumors. Furthermore, HRG expression is higher in recurrent SCCHN compared to patient-matched therapy naïve specimens. Conclusions HRG expression levels define a biologically distinct subset of SCCHN patients. We propose that high-level expression of HRG is associated with constitutive activation of HER3 in SCCHN and thus defines an actionable biomarker for interventions targeting HER3. PMID:23468880

  20. Defining the Active Ingredients of Interactive Computer Play Interventions for Children with Neuromotor Impairments: A Scoping Review

    ERIC Educational Resources Information Center

    Levac, Danielle; Rivard, Lisa; Missiuna, Cheryl

    2012-01-01

    Rehabilitation researchers who investigate complex interventions are challenged to describe the "active ingredients" of their interventions: the reason(s) why a treatment is expected to be effective. Interactive Computer Play (ICP) is an emerging complex intervention in rehabilitation practice and research. The purpose of this scoping review is to…

  1. Flavonol Activation Defines an Unanticipated Ligand-Binding Site in the Kinase-RNase Domain of IRE1

    SciTech Connect

    Wiseman, R. Luke; Zhang, Yuhong; Lee, Kenneth P.K.; Harding, Heather P.; Haynes, Cole M.; Price, Joshua; Sicheri, Frank; Ron, David

    2010-08-18

    Signaling in the most conserved branch of the endoplasmic reticulum (ER) unfolded protein response (UPR) is initiated by sequence-specific cleavage of the HAC1/XBP1 mRNA by the ER stress-induced kinase-endonuclease IRE1. We have discovered that the flavonol quercetin activates yeast IRE1's RNase and potentiates activation by ADP, a natural activating ligand that engages the IRE1 nucleotide-binding cleft. Enzyme kinetics and the structure of a cocrystal of IRE1 complexed with ADP and quercetin reveal engagement by quercetin of an unanticipated ligand-binding pocket at the dimer interface of IRE1's kinase extension nuclease (KEN) domain. Analytical ultracentrifugation and crosslinking studies support the preeminence of enhanced dimer formation in quercetin's mechanism of action. These findings hint at the existence of endogenous cytoplasmic ligands that may function alongside stress signals from the ER lumen to modulate IRE1 activity and at the potential for the development of drugs that modify UPR signaling from this unanticipated site.

  2. In Vitro Assays for Assessment of Androgenic and Estrogenic Activity of Defined Mixtures and Complex Environmental Samples

    EPA Science Inventory

    Point sources of endocrine active compounds to aquatic environments such as waste water treatment plants, pulp and paper mills, and animal feeding operations invariably contain complex mixtures of chemicals. The current study investigates the use of targeted in vitro assays des...

  3. Analytic Hierarchy Process to Define the Most Important Factors and Related Technologies for Empowering Elderly People in Taking an Active Role in their Health.

    PubMed

    Fico, G; Gaeta, E; Arredondo, M T; Pecchia, L

    2015-09-01

    Successful management of health conditions in older population is determined by strategic involvement of a professional team of careers and by empowering patients and their caregivers to take over a central role and responsibility in the daily management of condition. Identifying, structuring and ranking the most important needs related to these aspects could pave the way for improved strategies in designing systems and technological solutions supporting user empowerment. This paper presents the preliminary results of a study aiming to elicit these needs. Healthcare professionals, working together in the European and Innovation Partnership on Active and Healthy Ageing (EIP-AHA) initiative, have defined a set of needs and factors that have been organized in two hierarchies around the concepts of patient activation and proactive and prepared care team, defined in the Chronic Care Model. The two hierarchies have been mapped, by a team of experts in computer science, with technologies and solutions that could facilitate the achievement of the identified needs. PMID:26254254

  4. Review of screening guidelines for non-AIDS-defining malignancies: evolving issues in the era of highly active antiretroviral therapy.

    PubMed

    Tyerman, Zachary; Aboulafia, David M

    2012-01-01

    HIV-associated morbidity and mortality have declined dramatically in the era of HAART. Through direct and indirect benefits of HAART, people with HIV/AIDS are living longer, developing less AIDS-defining cancers and more cancers commonly seen in the seronegative population. Herein, we review cancer screening strategies for people living with HIV and compare and contrast them with those of the general population. The most noticeable differences occur in anal and cervical cancer screening. Although anal cancer is uncommon in the general population, it is more prevalent in men who have sex with men and people at high risk for human papillomavirus infection, especially those infected with HIV. To address this, we recommend that a digital rectal exam and a visual inspection be performed annually. In addition, an anal Pap test should be performed soon after the diagnosis of HIV infection, with follow-up testing every six months until two normal tests. Abnormal cytological results are then investigated with high-resolution anoscopy and biopsy of suspicious lesions. In screening for cervical cancer, a Pap test should be performed during the anogenital exam after initial HIV diagnosis, with a second Pap six months later, then annually if the results are normal. A colposcopy should follow an abnormal result. Human papillomavirus testing as a screening method for cervical cancer in women with HIV can also be efficacious. In lung cancer screening, preliminary data suggest that low-dose computerized tomography may play an important role, but further research is needed. Screening for breast and colon cancer should follow guidelines for the general population. Early screening for prostate cancer based on a diagnosis of HIV lacks clear benefit. PMID:22297500

  5. A role for the thermal environment in defining co-stimulation requirements for CD4(+) T cell activation.

    PubMed

    Zynda, Evan R; Grimm, Melissa J; Yuan, Min; Zhong, Lingwen; Mace, Thomas A; Capitano, Maegan; Ostberg, Julie R; Lee, Kelvin P; Pralle, Arnd; Repasky, Elizabeth A

    2015-01-01

    Maintenance of normal core body temperature is vigorously defended by long conserved, neurovascular homeostatic mechanisms that assist in heat dissipation during prolonged, heat generating exercise or exposure to warm environments. Moreover, during febrile episodes, body temperature can be significantly elevated for at least several hours at a time. Thus, as blood cells circulate throughout the body, physiologically relevant variations in surrounding tissue temperature can occur; moreover, shifts in core temperature occur during daily circadian cycles. This study has addressed the fundamental question of whether the threshold of stimulation needed to activate lymphocytes is influenced by temperature increases associated with physiologically relevant increases in temperature. We report that the need for co-stimulation of CD4+ T cells via CD28 ligation for the production of IL-2 is significantly reduced when cells are exposed to fever-range temperature. Moreover, even in the presence of sufficient CD28 ligation, provision of extra heat further increases IL-2 production. Additional in vivo and in vitro data (using both thermal and chemical modulation of membrane fluidity) support the hypothesis that the mechanism by which temperature modulates co-stimulation is linked to increases in membrane fluidity and membrane macromolecular clustering in the plasma membrane. Thermally-regulated changes in plasma membrane organization in response to physiological increases in temperature may assist in the geographical control of lymphocyte activation, i.e., stimulating activation in lymph nodes rather than in cooler surface regions, and further, may temporarily and reversibly enable CD4+ T cells to become more quickly and easily activated during times of infection during fever. PMID:26131730

  6. Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site

    NASA Astrophysics Data System (ADS)

    Wang, Xizhuo; Wang, Youjun; Zhou, Yandong; Hendron, Eunan; Mancarella, Salvatore; Andrake, Mark D.; Rothberg, Brad S.; Soboloff, Jonathan; Gill, Donald L.

    2014-02-01

    STIM1 and STIM2 are widely expressed endoplasmic reticulum (ER) Ca2+ sensor proteins able to translocate within the ER membrane to physically couple with and gate plasma membrane Orai Ca2+ channels. Although they are structurally similar, we reveal critical differences in the function of the short STIM-Orai-activating regions (SOAR) of STIM1 and STIM2. We narrow these differences in Orai1 gating to a strategically exposed phenylalanine residue (Phe-394) in SOAR1, which in SOAR2 is substituted by a leucine residue. Remarkably, in full-length STIM1, replacement of Phe-394 with the dimensionally similar but polar histidine head group prevents both Orai1 binding and gating, creating an Orai1 non-agonist. Thus, this residue is critical in tuning the efficacy of Orai activation. While STIM1 is a full Orai1-agonist, leucine-replacement of this crucial residue in STIM2 endows it with partial agonist properties, which may be critical for limiting Orai1 activation stemming from its enhanced sensitivity to store-depletion.

  7. Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site

    PubMed Central

    Wang, Xizhuo; Wang, Youjun; Zhou, Yandong; Hendron, Eunan; Mancarella, Salvatore; Andrake, Mark D.; Rothberg, Brad S.; Soboloff, Jonathan; Gill, Donald L.

    2014-01-01

    STIM1 and STIM2 are widely expressed endoplasmic reticulum (ER) Ca2+ sensor proteins able to translocate within the ER membrane to physically couple with and gate plasma membrane Orai Ca2+ channels. Although structurally similar, we reveal critical differences in the function of the short STIM-Orai activating regions (SOAR) from STIM1 and STIM2. We narrowed these differences in Orai1 gating to a strategically exposed phenylalanine residue (Phe-394) in SOAR1, which in SOAR2 is substituted by a leucine residue. Remarkably, in full-length STIM1, replacement of Phe-394 with the dimensionally similar but polar histidine headgroup, prevents both Orai1 binding and gating, creating an Orai1 non-agonist. Thus, this residue is critical in tuning the efficacy of Orai activation. While STIM1 is a full Orai1-agonist, leucine-replacement of this crucial residue in STIM2 endows it with partial agonist properties, which may be critical for limiting Orai1 activation stemming from its enhanced sensitivity to store-depletion. PMID:24492416

  8. Associations between Physical Activity and Obesity Defined by Waist-To-Height Ratio and Body Mass Index in the Korean Population

    PubMed Central

    Lee, On; Lee, Duck-chul; Lee, Sukho; Kim, Yeon Soo

    2016-01-01

    Objective This study investigated the associations between physical activity and the prevalence of obesity determined by waist-to-height ratio (WHtR) and body mass index (BMI). Methods This is the first study to our knowledge on physical activity and obesity using a nationally representative sample of South Korean population from The Korea National Health and Nutrition Examination Survey. We categorized individuals into either non-obese or obese defined by WHtR and BMI. Levels of moderate-to-vigorous physical activity were classified as ‘Inactive’, ‘Active’, and ‘Very active’ groups based on the World Health Organization physical activity guidelines. Multivariable logistic regression was used to examine the associations between physical activity and the prevalence of obesity. Results Physical activity was significantly associated with a lower prevalence of obesity using both WHtR and BMI. Compared to inactive men, odds ratios (ORs) (95% confidence intervals [CIs]) for obesity by WHtR ≥0.50 were 0.69 (0.53–0.89) in active men and 0.76 (0.63–0.91) in very active men (p for trend = 0.007). The ORs (95% CIs) for obesity by BMI ≥25 kg/m2 were 0.78 (0.59–1.03) in active men and 0.82 (0.67–0.99) in very active men (p for trend = 0.060). The ORs (95% CIs) for obesity by BMI ≥30 kg/m2 were 0.40 (0.15–0.98) in active men and 0.90 (0.52–1.56) in very active men (p for trend = 0.978). Compared to inactive women, the ORs (95% CIs) for obesity by WHtR ≥0.50 were 0.94 (0.75–1.18) in active women and 0.84 (0.71–0.998) in very active women (p for trend = 0.046). However, no significant associations were found between physical activity and obesity by BMI in women. Conclusions We found more significant associations between physical activity and obesity defined by WHtR than BMI. However, intervention studies are warranted to investigate and compare causal associations between physical activity and different obesity measures in various populations

  9. The transcriptional PPARβ/δ network in human macrophages defines a unique agonist-induced activation state

    PubMed Central

    Adhikary, Till; Wortmann, Annika; Schumann, Tim; Finkernagel, Florian; Lieber, Sonja; Roth, Katrin; Toth, Philipp M.; Diederich, Wibke E.; Nist, Andrea; Stiewe, Thorsten; Kleinesudeik, Lara; Reinartz, Silke; Müller-Brüsselbach, Sabine; Müller, Rolf

    2015-01-01

    Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a lipid ligand-inducible transcription factor with established metabolic functions, whereas its anti-inflammatory function is poorly understood. To address this issue, we determined the global PPARβ/δ-regulated signaling network in human monocyte-derived macrophages. Besides cell type-independent, canonical target genes with metabolic and immune regulatory functions we identified a large number of inflammation-associated NFκB and STAT1 target genes that are repressed by agonists. Accordingly, PPARβ/δ agonists inhibited the expression of multiple pro-inflammatory mediators and induced an anti-inflammatory, IL-4-like morphological phenotype. Surprisingly, bioinformatic analyses also identified immune stimulatory effects. Consistent with this prediction, PPARβ/δ agonists enhanced macrophage survival under hypoxic stress and stimulated CD8+ T cell activation, concomitantly with the repression of immune suppressive target genes and their encoded products CD274 (PD-1 ligand), CD32B (inhibitory Fcγ receptor IIB) and indoleamine 2,3-dioxygenase 1 (IDO-1), as well as a diminished release of the immune suppressive IDO-1 metabolite kynurenine. Comparison with published data revealed a significant overlap of the PPARβ/δ transcriptome with coexpression modules characteristic of both anti-inflammatory and pro-inflammatory cytokines. Our findings indicate that PPARβ/δ agonists induce a unique macrophage activation state with strong anti-inflammatory but also specific immune stimulatory components, pointing to a context-dependent function of PPARβ/δ in immune regulation. PMID:25934804

  10. Atomic force microscopy investigations of heterogeneities in the adhesion energies measured between pathogenic and non-pathogenic Listeria species and silicon nitride as they correlate to virulence and adherence

    PubMed Central

    Park, Bong-Jae; Abu-Lail, Nehal I.

    2011-01-01

    Atomic force microscopy (AFM) was used to probe heterogeneities in adhesion energies measured between pathogenic and non-pathogenic species of Listeria and silicon nitride in water at four levels. Adhesion energies were quantified on individual bacterial cells (cell level), bacterial cells that belonged to an individual Listeria strain but varied in their cultures (strain level), bacterial cells that belonged to an individual Listeria species but varied in their strain type (species level) and on bacterial cells that belonged to the Listeria genus but varied in their species type (genus level). To quantify heterogeneities in the adhesion energies, a heterogeneity index was defined based on quantified standard errors of mean. At the cell level, spatial variations in the adhesion energies were not observed. For the strain, species and genus levels, the heterogeneity index increased with increase in the adhesion energies. At the species level, heterogeneity index increased with strain virulence. PMID:21623482

  11. Can we define an asymptotic value for the ice active surface site density for heterogeneous ice nucleation?

    NASA Astrophysics Data System (ADS)

    Niedermeier, Dennis; Augustin-Bauditz, Stefanie; Hartmann, Susan; Wex, Heike; Ignatius, Karoliina; Stratmann, Frank

    2015-05-01

    The immersion freezing behavior of droplets containing size-segregated, monodisperse feldspar particles was investigated. For all particle sizes investigated, a leveling off of the frozen droplet fraction was observed reaching a plateau within the heterogeneous freezing temperature regime (T >- 38°C). The frozen fraction in the plateau region was proportional to the particle surface area. Based on these findings, an asymptotic value for ice active surface site density ns, which we named ns⋆, could be determined for the investigated feldspar sample. The comparison of these results with those of other studies not only elucidates the general feasibility of determining such an asymptotic value but also shows that the value of ns⋆ strongly depends on the method of the particle surface area determination. However, such an asymptotic value might be an important input parameter for atmospheric modeling applications. At least it shows that care should be taken when ns is extrapolated to lower or higher temperature.

  12. Can we define an asymptotic value for the ice active surface site density for heterogeneous ice nucleation?

    NASA Astrophysics Data System (ADS)

    Niedermeier, Dennis; Augustin-Bauditz, Stefanie; Hartmann, Susan; Wex, Heike; Ignatius, Karoliina; Stratmann, Frank

    2015-04-01

    The formation of ice in atmospheric clouds has a substantial influence on the radiative properties of clouds as well as on the formation of precipitation. Therefore much effort has been made to understand and quantify the major ice formation processes in clouds. Immersion freezing has been suggested to be a dominant primary ice formation process in low and mid-level clouds (mixed-phase cloud conditions). It also has been shown that mineral dust particles are the most abundant ice nucleating particles in the atmosphere and thus may play an important role for atmospheric ice nucleation (Murray et al., 2012). Additionally, biological particles like bacteria and pollen are suggested to be potentially involved in atmospheric ice formation, at least on a regional scale (Murray et al., 2012). In recent studies for biological particles (SNOMAX and birch pollen), it has been demonstrated that freezing is induced by ice nucleating macromolecules and that an asymptotic value for the mass density of these ice nucleating macromolecules can be determined (Hartmann et al., 2013; Augustin et al., 2013, Wex et al., 2014). The question arises whether such an asymptotic value can also be determined for the ice active surface site density ns, a parameter which is commonly used to describe the ice nucleation activity of e.g., mineral dust. Such an asymptotic value for ns could be an important input parameter for atmospheric modeling applications. In the presented study, we therefore investigated the immersion freezing behavior of droplets containing size-segregated, monodisperse feldspar particles utilizing the Leipzig Aerosol Cloud Interaction Simulator (LACIS). For all particle sizes considered in the experiments, we observed a leveling off of the frozen droplet fraction reaching a plateau within the heterogeneous freezing temperature regime (T > -38°C) which was proportional to the particle surface area. Based on these findings, we could determine an asymptotic value for the ice

  13. Using constitutive activity to define appropriate high-throughput screening assays for orphan g protein-coupled receptors.

    PubMed

    Ngo, Tony; Coleman, James L J; Smith, Nicola J

    2015-01-01

    Orphan G protein-coupled receptors represent an underexploited resource for drug discovery but pose a considerable challenge for assay development because their cognate G protein signaling pathways are often unknown. In this methodological chapter, we describe the use of constitutive activity, that is, the inherent ability of receptors to couple to their cognate G proteins in the absence of ligand, to inform the development of high-throughput screening assays for a particular orphan receptor. We specifically focus on a two-step process, whereby constitutive G protein coupling is first determined using yeast Gpa1/human G protein chimeras linked to growth and β-galactosidase generation. Coupling selectivity is then confirmed in mammalian cells expressing endogenous G proteins and driving accumulation of transcription factor-fused luciferase reporters specific to each of the classes of G protein. Based on these findings, high-throughput screening campaigns can be performed on the already miniaturized mammalian reporter system. PMID:25563179

  14. Identification of glycosomes and metabolic end products in pathogenic and nonpathogenic strains of Cryptobia salmositica (Kinetoplastida: Bodonidae).

    PubMed

    Ardelli, B F; Witt, J D; Woo, P T

    2000-08-10

    Whole cell lysates of pathogenic and nonpathogenic strains of Cryptobia salmositica were subjected to subcellular fractionation using differential and isopycnic centrifugation in sucrose. The glycolytic enzymes hexokinase, fructose-1,6-biphosphate aldolase, triosephosphate isomerase, glucosephosphate isomerase and glyceraldehyde-3-phosphate-dehydrogenase and the peroxisomal enzyme catalase were associated with a microbody that had a buoyant density in sucrose of 1.21 g cm-3. Lactate dehydrogenase was detected in whole cell lysates, but not in purified organelles. A microbody with a positive reaction for catalase was detected in electron microscope sections of the pathogenic and nonpathogenic strains. These catalase-containing microbodies fused with lipid bodies and vacuoles, arose by division from pre-existing microbodies and expelled their contents into the cytoplasm of the cell. Both strains also modified the catalase content in their microbodies. Under aerobic conditions, they metabolized glucose to pyruvate and lactate. We conclude that part of the glycolytic pathway in C. salmositica is compartmentalized in a microbody called the glycosome. PMID:10986644

  15. Identification and characterization of non-pathogenic Fusarium oxysporum capable of increasing and decreasing Fusarium wilt severity.

    PubMed

    Forsyth, Leanne M; Smith, Linda J; Aitken, Elizabeth A B

    2006-08-01

    Fusarium wilt of banana is a potentially devastating disease throughout the world. Options for control of the causal organism, Fusarium oxysporum f.sp. cubense (Foc) are limited. Suppressive soil sites have previously been identified where, despite the presence of Foc, Fusarium wilt does not develop. In order to understand some aspects of this disease suppression, endophytic Fusarium oxysporum isolates were obtained from banana roots. These isolates were genetically characterized and compared with an isolate of Fusarium oxysporum previously identified as being capable of suppressing Fusarium wilt of banana in glasshouse trials. Three additional isolates were selected for glasshouse trials to assess suppression of Fusarium wilt in two different cultivars of banana, Cavendish and Lady Finger. One isolate (BRIP 29089) was identified as a potential biocontrol organism, reducing the disease severity of Fusarium wilt in Lady Finger and Cavendish cultivars. Interestingly, one isolate (BRIP 45952) increased Fusarium wilt disease severity on Cavendish. The implications of an isolate of Fusarium oxysporum, non-pathogenic on banana, increasing disease severity and the potential role of non-pathogenic isolates of Fusarium oxysporum in disease complexes are discussed. PMID:16891106

  16. Defining torpor in free-ranging bats: experimental evaluation of external temperature-sensitive radiotransmitters and the concept of active temperature.

    PubMed

    Willis, C K R; Brigham, R M

    2003-07-01

    A variety of definitions involving body temperature (Tb), metabolic rate and behavior have been used to define torpor in mammals and birds. This problem is confounded in some studies of free-ranging animals that employ only skin temperature (Tsk), a measure that approximates but may not precisely reflect Tb. We assess the accuracy of Tsk in the context of a recent definition for torpor called active temperature. We compared the active temperatures of individual big brown bats (Eptesicus fuscus), which aggregate in cavities, with solitary, foliage-roosting hoary bats (Lasiurus cinereus). In captive big brown bats, we compared Tsk and core Tb at a range of ambient temperatures for clustered and solitary roosting animals, compared Tsk and Tb during arousal from torpor, and quantified the effect of flight on warming from torpor. Hoary bats had significantly lower active temperatures than big brown bats despite having the same normothermic Tsk. Tsk was significantly lower than Tb during normothermia but often greater than Tb during torpor. Flight increased the rate of warming from torpor. This effect was more pronounced for Tsk than Tb. This suggests that bats could rely on heat generated by flight muscles to complete the final stages of arousal. Using active temperature to define torpor may underestimate torpor due to ambient cooling of external transmitters or animals leaving roosts while still torpid. Conversely, active temperature may also overestimate shallow torpor use if it is recorded during active arousal when shivering and non-shivering thermogenesis warm external transmitters. Our findings illuminate the need for laboratory studies that quantify the relationship between metabolic rate and Tsk over a range of ambient temperatures. PMID:12764630

  17. Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization.

    PubMed

    Yamamoto, N; Naraparaju, V R

    1998-06-01

    Freund's adjuvant produced severe inflammation that augments development of antibodies. Thus, mixed administration of antigens with adjuvant was not required as long as inflammation was induced in the hosts. Since macrophage activation for phagocytosis and antigen processing is the first step of antibody development, inflammation-primed macrophage activation plays a major role in immune development. Therefore, macrophage activating factor should act as an adjuvant for immunization. The inflammation-primed macrophage activation process is the major macrophage activating cascade that requires participation of serum vitamin D3-binding protein (DBP; human DBP is known as Gc protein) and glycosidases of B and T lymphocytes. Stepwise incubation of Gc protein with immobilized beta-galactosidase and sialidase efficiently generated the most potent macrophage activating factor (designated GcMAF) we have ever encountered. Administration of GcMAF (20 or 100 pg/mouse) resulted in stimulation of the progenitor cells for extensive mitogenesis and activation of macrophages. Administration of GcMAF (100 pg/mouse) along with immunization of mice with sheep red blood cells (SRBC) produced a large number of anti-SRBC antibody secreting splenic cells in 2-4 days. Thus, GcMAF has a potent adjuvant activity for immunization. Although malignant tumours are poorly immunogenic, 4 days after GcMAF-primed immunization of mice with heat-killed Ehrlich ascites tumour cells, the ascites tumour was no longer transplantable in these mice. PMID:9682967

  18. Nonpathogenic CCR2-tropic SIVrcm after serial passage and its effect on SIVmac infection of Indian rhesus macaques

    PubMed Central

    Ling, Binhua; Veazey, Ronald S.; Marx, Preston A.

    2015-01-01

    The natural host of SIVrcm is the red-capped mangabey (Cercocebus torquatus torquatus). Although this virus infects macaques and human PBMCs, its pathogenic potential is unknown. We serially passaged SIVrcm through 9 rhesus macaques to assess its potential for virulence. SIVrcm infected all macaques with peak viremia 2 weeks postinfection yet viral loads decreased to undetectable levels about one month after inoculation. Remarkably, SIVrcm replication and virulence did not increase following 7 serial passages. While CD4+ T cells in the gut were decreased in early infection, proportions of memory CD4+CCR5+ T cells were not affected. Three SIVrcm-infected macaques were subsequently challenged with SIVmac251 to assess the potential for superinfection. Interestingly, animals previously infected with SIVrcm had 100 fold lower levels of SIVmac251 in plasma compared to naive animals inoculated with SIVmac251. These results suggest that SIVrcm is nonpathogenic and may be useful for examining effective immune responses in SIV infection. PMID:18662820

  19. Cokeromyces recurvatus identified in lung biopsy: case report of a non-pathogenic fungus, highlighting its potential histologic mimics.

    PubMed

    Agaronov, Maksim; Ratkiewicz, Irene; Lawlor, Michael; Cartun, Richard W; Aslanzadeh, Jaber; Fiel-Gan, Mary

    2015-01-01

    We report a case of aspiration in a patient with gastric outlet obstruction due to pancreatic adenocarcinoma, in which three large yeasts were identified on tissue biopsy of the lung infiltrate. The histologic sections of the yeasts showed densely eosinophilic, round to oval, thick-walled structures with frayed borders and intra-cystic bluish inclusions. There was a background of mixed neutrophilic and eosinophilic infiltrate along with focal tissue necrosis. Our initial differential diagnoses included the usual large yeasts such as Cryptococcus, Coccidioides, and Blastomyces. Immunohistochemistry revealed reactivity to the Blastomyces antibody. Mycology studies eventually identified the organism as Cokeromyces recurvatus. Anti-fungal treatment was withheld with spontaneous resolution of the infiltrates. This case demonstrates the importance of using culture to speciate organisms identified on tissue, separating pathogens from non-pathogens and non-living artifacts in order for appropriate management. PMID:25887878

  20. A new role for the nonpathogenic nonsynonymous single-nucleotide polymorphisms of acetylcholinesterase in the treatment of Alzheimer's disease: a computational study.

    PubMed

    Saravanaraman, Ponne; Chinnadurai, Raj Kumar; Boopathy, Rathanam

    2014-08-01

    Single-nucleotide polymorphisms (SNPs) are implicated in the complexity of understanding the genetics of diseases and their therapeutics. Here we have attempted to determine the impact of nonsynonymous SNPs (nsSNPs) on structure, dynamics, and ligand-binding properties of the human acetylcholinesterase (hAChE) protein, which has been targeted in the treatment of Alzheimer's disease. Of the reported 153 SNPs, 4 nsSNPs, namely, A415G, P104A, V302E, and Y119H, were prioritized to be functionally unfavorable by SIFT and PolyPhen algorithms. Molecular dynamics simulation revealed these nsSNP forms to be structurally stable, and they are also considered functionally active as they lie away from the catalytic triad. However, the aromatic amino acids lining the active-site gorge exhibited altered degrees of side chain dihedral angles. Such conformational alterations were evaluated for their ability to interfere with binding of hAChE inhibitors. The inhibitors (donepezil, galantamine, rivastigmine, and tacrine) were oriented differently in comparison to the native because of the steric hindrance offered by the altered dihedral angles. Interestingly, huperzine A alone exhibited higher efficiency in its binding to the AChE and retained similar orientation irrespective of the polymorphisms since the orientation of Asp74 involved in its binding and trafficking remained unaltered in all protein forms. Therefore, we conclude that nsSNPs confer changes to the dynamicity of proteins, which in turn affects their ligand-binding properties rather than their stability. Considering the diverse polymorphic nature of hAChE, while contemplating any structure-based drug design, the common, nonpathogenic nsSNPs should be considered for the utmost efficacy of drugs. PMID:24611490

  1. Correlation Between Radiation Dose to {sup 18}F-FDG-PET Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

    SciTech Connect

    Rose, Brent S.; Liang Yun; Lau, Steven K.; Jensen, Lindsay G.; Yashar, Catheryn M.; Hoh, Carl K.; Mell, Loren K.

    2012-07-15

    Purpose: To test the hypothesis that radiation dose to {sup 18}F-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG-PET)-defined active bone marrow (BM{sub ACT}) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. Methods and Materials: The conditions of 26 women with cervical cancer who underwent {sup 18}F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BM{sub ACT} was defined as the subregion of total bone marrow (BM{sub TOT}) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BM{sub INACT}) was defined as BM{sub TOT} - BM{sub ACT}. Generalized linear modeling was used to test the correlation between BM{sub ACT} and BM{sub INACT} dose-volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC). Results: Increased BM{sub ACT} mean dose was significantly associated with decreased log(WBC) nadir ({beta} = -0.04; 95% CI, -0.07to -0.01; p = 0.009), decreased log(ANC) nadir ({beta} = -0.05; 95% CI, -0.08 to -0.02; p = 0.006), decreased hemoglobin nadir ({beta} = -0.16; 95% CI, -0.27 to -0.05; p = 0.010), and decreased platelet nadir ({beta} = -6.16; 95% CI, -9.37 to -2.96; p < 0.001). By contrast, there was no association between BM{sub INACT} mean dose and log(WBC) nadir ({beta} = -0.01; 95% CI, -0.06 to 0.05; p = 0.84), log(ANC) nadir ({beta} = -0.03; 95% CI, -0.10 to 0.04; p = 0.40), hemoglobin nadir ({beta} = -0.09; 95% CI, -0.31 to 0.14; p = 0.452), or platelet nadir ({beta} = -3.47; 95% CI, -10.44 to 3.50; p = 0.339). Conclusions: Irradiation of BM subregions with higher {sup 18}F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BM{sub ACT} subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify

  2. Draft Genome Sequence of the Dimorphic Fungus Sporothrix pallida, a Nonpathogenic Species Belonging to Sporothrix, a Genus Containing Agents of Human and Feline Sporotrichosis

    PubMed Central

    D’Alessandro, Enrico; Giosa, Domenico; Huang, Lilin; Zhang, Jing; Gao, Wenchao; Brankovics, Balazs; Oliveira, Manoel Marques Evangelista; Scordino, Fabio; Lo Passo, Carla; Criseo, Giuseppe; van Diepeningen, Anne D.; Huang, Huaiqiu; de Hoog, G. Sybren

    2016-01-01

    Sporothrix pallida is considered to be a mostly avirulent environmental fungus, phylogenetically closely related to the well-known pathogen Sporothrix schenckii. Here, we present the first assembly of its genome, which provides a valuable resource for future comparative genomic studies between nonpathogenic and pathogenic Sporothrix spp. PMID:27034494

  3. Early events in tissues during infection with pathogenic (SIVmac239) and nonpathogenic (SIVmac1A11) molecular clones of simian immunodeficiency virus.

    PubMed Central

    Lackner, A. A.; Vogel, P.; Ramos, R. A.; Kluge, J. D.; Marthas, M.

    1994-01-01

    The extent of virus replication, tissue distribution, localization of virus within tissues, and the presence of pathological lesions was examined early after experimental infection of rhesus monkeys with simian immunodeficiency virus (SIV). Three strains of SIV were used: molecularly cloned pathogenic SIVmac239; molecularly cloned nonpathogenic SIVmac1A11; and uncloned pathogenic SIVmac. The major targets of infection in all animals at 2 weeks postinoculation were the thymus and spleen. The distribution of virus within lymphoid organs varied with the viral inoculum: nonpathogenic SIVmac1A11 was present primarily within lymphoid follicles and in the thymic cortex; SIVmac239 was present primarily within periarteriolar lymphoid sheaths in the spleen, the paracortex of lymph nodes, and the medulla of the thymus; uncloned SIVmac was present in all these areas but tended to parallel the distribution of SIVmac239. Animals inoculated with nonpathogenic SIVmac1A11 had fewer SIV-positive cells by in situ hybridization and after 13 weeks postinoculation, virus was undetectable in any tissue from these animals. No significant pathological abnormalities were recognized in animals inoculated with this nonpathogenic virus. In contrast, nearly half of the animals inoculated with either SIVmac or SIVmac239 developed significant pathological lesions, including opportunistic infections by 13 weeks postinoculation, highlighting the virulence of these viruses. Our results indicate marked differences in tissue distribution between pathogenic and nonpathogenic molecular clones of SIV during the acute phase of infection. The most striking differences were the absence of SIVmac1A11 from the central nervous system and thymic medulla. The prominent early involvement of the thymus suggests that infection of this organ is a key event in the induction of immune suppression by SIV. Images Figure 1 Figure 2 Figure 3 PMID:8053500

  4. Defining the paramedic process.

    PubMed

    Carter, Holly; Thompson, James

    2015-01-01

    The use of a 'process of care' is well established in several health professions, most evidently within the field of nursing. Now ingrained within methods of care delivery, it offers a logical approach to problem solving and ensures an appropriate delivery of interventions that are specifically suited to the individual patient. Paramedicine is a rapidly advancing profession despite a wide acknowledgement of limited research provisions. This frequently results in the borrowing of evidence from other disciplines. While this has often been useful, there are many concerns relating to the acceptable limit of evidence transcription between professions. To date, there is no formally recognised 'process of care'-defining activity within the pre-hospital arena. With much current focus on the professional classification of paramedic work, it is considered timely to formally define a formula that underpins other professional roles such as nursing. It is hypothesised that defined processes of care, particularly the nursing process, may have features that would readily translate to pre-hospital practice. The literature analysed was obtained through systematic searches of a range of databases, including Ovid MEDLINE, Cumulative Index to Nursing and Allied Health. The results demonstrated that the defined process of care provides nursing with more than just a structure for practice, but also has implications for education, clinical governance and professional standing. The current nursing process does not directly articulate to the complex and often unstructured role of the paramedic; however, it has many principles that offer value to the paramedic in their practice. Expanding the nursing process model to include the stages of Dispatch Considerations, Scene Assessment, First Impressions, Patient History, Physical Examination, Clinical Decision-Making, Interventions, Re-evaluation, Transport Decisions, Handover and Reflection would provide an appropriate model for pre

  5. Structural Analysis and Anticoagulant Activities of the Novel Sulfated Fucan Possessing a Regular Well-Defined Repeating Unit from Sea Cucumber

    PubMed Central

    Wu, Mingyi; Xu, Li; Zhao, Longyan; Xiao, Chuang; Gao, Na; Luo, Lan; Yang, Lian; Li, Zi; Chen, Lingyun; Zhao, Jinhua

    2015-01-01

    Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC–MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2) and (1→3)-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan) contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants. PMID:25871288

  6. Capsules from Pathogenic and Non-Pathogenic Cryptococcus spp. Manifest Significant Differences in Structure and Ability to Protect against Phagocytic Cells

    PubMed Central

    Araujo, Glauber de S.; Fonseca, Fernanda L.; Pontes, Bruno; Torres, Andre; Cordero, Radames J. B.; Zancopé-Oliveira, Rosely M.; Casadevall, Arturo; Viana, Nathan B.; Nimrichter, Leonardo; Rodrigues, Marcio L.; Garcia, Eloi S.; de Souza, Wanderley; Frases, Susana

    2012-01-01

    Capsule production is common among bacterial species, but relatively rare in eukaryotic microorganisms. Members of the fungal Cryptococcus genus are known to produce capsules, which are major determinants of virulence in the highly pathogenic species Cryptococcus neoformans and Cryptococcus gattii. Although the lack of virulence of many species of the Cryptococcus genus can be explained solely by the lack of mammalian thermotolerance, it is uncertain whether the capsules from these organisms are comparable to those of the pathogenic cryptococci. In this study, we compared the characteristic of the capsule from the non-pathogenic environmental yeast Cryptococcus liquefaciens with that of C. neoformans. Microscopic observations revealed that C. liquefaciens has a capsule visible in India ink preparations that was also efficiently labeled by three antibodies generated to specific C. neoformans capsular antigens. Capsular polysaccharides of C. liquefaciens were incorporated onto the cell surface of acapsular C. neoformans mutant cells. Polysaccharide composition determinations in combination with confocal microscopy revealed that C. liquefaciens capsule consisted of mannose, xylose, glucose, glucuronic acid, galactose and N-acetylglucosamine. Physical chemical analysis of the C. liquefaciens polysaccharides in comparison with C. neoformans samples revealed significant differences in viscosity, elastic properties and macromolecular structure parameters of polysaccharide solutions such as rigidity, effective diameter, zeta potential and molecular mass, which nevertheless appeared to be characteristics of linear polysaccharides that also comprise capsular polysaccharide of C. neoformans. The environmental yeast, however, showed enhanced susceptibility to the antimicrobial activity of the environmental phagocytes, suggesting that the C. liquefaciens capsular components are insufficient in protecting yeast cells against killing by amoeba. These results suggest that capsular

  7. RESPONSES OF OYSTER (CRASSOSTREA VIRGINICA) HEMOCYTES TO NONPATHOGENIC AND CLINICAL ISOLATES OF VIBRIO PARAHAEMOLYTICUS

    EPA Science Inventory

    Bacterial uptake by oysters (Crassostrea virginica) and bactericidal activity of oyster hemocytes were studied using four environmental isolates and three clinical isolates of Vibrio parahaemolyticus. Clinical isolates (2030, 2062, 2107) were obtained from gastroenteritis patien...

  8. Glycodendrimersomes from Sequence-Defined Janus Glycodendrimers Reveal High Activity and Sensor Capacity for the Agglutination by Natural Variants of Human Lectins.

    PubMed

    Zhang, Shaodong; Xiao, Qi; Sherman, Samuel E; Muncan, Adam; Ramos Vicente, Andrea D M; Wang, Zhichun; Hammer, Daniel A; Williams, Dewight; Chen, Yingchao; Pochan, Darrin J; Vértesy, Sabine; André, Sabine; Klein, Michael L; Gabius, Hans-Joachim; Percec, Virgil

    2015-10-21

    A library of eight amphiphilic Janus glycodendrimers (Janus-GDs) presenting D-lactose (Lac) and a combination of Lac with up to eight methoxytriethoxy (3EO) units in a sequence-defined arrangement was synthesized via an iterative modular methodology. The length of the linker between Lac and the hydrophobic part of the Janus-GDs was also varied. Self-assembly by injection from THF solution into phosphate-buffered saline led to unilamellar, monodisperse glycodendrimersomes (GDSs) with dimensions predicted by Janus-GD concentration. These GDSs provided a toolbox to measure bioactivity profiles in agglutination assays with sugar-binding proteins (lectins). Three naturally occurring forms of the human adhesion/growth-regulatory lectin galectin-8, Gal-8S and Gal-8L, which differ by the length of linker connecting their two active domains, and a single amino acid mutant (F19Y), were used as probes to study activity and sensor capacity. Unpredictably, the sequence of Lac on the Janus-GDs was demonstrated to determine bioactivity, with the highest level revealed for a Janus-GD with six 3EO groups and one Lac. A further increase in Lac density was invariably accompanied by a substantial decrease in agglutination, whereas a decrease in Lac density resulted in similar or lower bioactivity and sensor capacity. Both changes in topology of Lac presentation of the GDSs and seemingly subtle alterations in protein structure resulted in different levels of bioactivity, demonstrating the presence of regulation on both GDS surface and lectin. These results illustrate the applicability of Janus-GDs to dissect structure-activity relationships between programmable cell surface models and human lectins in a highly sensitive and physiologically relevant manner. PMID:26421463

  9. Neogenin, Defined as a GD3-associated Molecule by Enzyme-mediated Activation of Radical Sources, Confers Malignant Properties via Intracytoplasmic Domain in Melanoma Cells.

    PubMed

    Kaneko, Kei; Ohkawa, Yuki; Hashimoto, Noboru; Ohmi, Yuhsuke; Kotani, Norihiro; Honke, Koichi; Ogawa, Mitsutaka; Okajima, Tetsuya; Furukawa, Keiko; Furukawa, Koichi

    2016-08-01

    To investigate mechanisms for increased malignant properties in malignant melanomas by ganglioside GD3, enzyme-mediated activation of radical sources and subsequent mass spectrometry were performed using an anti-GD3 antibody and GD3-positive (GD3+) and GD3-negative (GD3-) melanoma cell lines. Neogenin, defined as a GD3-neighbored molecule, was largely localized in lipid/rafts in GD3+ cells. Silencing of neogenin resulted in the reduction of cell growth and invasion activity. Physical association between GD3 and neogenin was demonstrated by immunoblotting of the immunoprecipitates with anti-neogenin antibody from GD3+ cell lysates. The intracytoplasmic domain of neogenin (Ne-ICD) was detected in GD3+ cells at higher levels than in GD3- cells when cells were treated by a proteasome inhibitor but not when simultaneously treated with a γ-secretase inhibitor. Exogenous GD3 also induced increased Ne-ICD in GD3- cells. Overexpression of Ne-ICD in GD3- cells resulted in the increased cell growth and invasion activity, suggesting that Ne-ICD plays a role as a transcriptional factor to drive malignant properties of melanomas after cleavage with γ-secretase. γ-Secretase was found in lipid/rafts in GD3+ cells. Accordingly, immunocyto-staining revealed that GD3, neogenin, and γ-secretase were co-localized at the leading edge of GD3+ cells. All these results suggested that GD3 recruits γ-secretase to lipid/rafts, allowing efficient cleavage of neogenin. ChIP-sequencing was performed to identify candidates of target genes of Ne-ICD. Some of them actually showed increased expression after expression of Ne-ICD, probably exerting malignant phenotypes of melanomas under GD3 expression. PMID:27288875

  10. Controllable assembly of well-defined monodisperse Au nanoparticles on hierarchical ZnO microspheres for enhanced visible-light-driven photocatalytic and antibacterial activity

    NASA Astrophysics Data System (ADS)

    Wang, Yuan; Fang, Hua-Bin; Zheng, Yan-Zhen; Ye, Rongqin; Tao, Xia; Chen, Jian-Feng

    2015-11-01

    A high-efficiency visible-light-driven photocatalyst composed of homogeneously distributed Au nanoparticles (AuNPs) well-defined on hierarchical ZnO microspheres (ZMS) via a controllable layer-by-layer self-assembly technique is demonstrated. The gradual growth of the characteristic absorption bands of Au loaded on ZnO in the visible light region with an increasing number of assemblies indicates the enhancement of the light harvesting ability of the ZMS/Au composites as well as the reproducibility and controllability of the entire assembly process. Results on the photoelectrochemical performance characterized by EIS and transient photocurrent response spectra indicate that the ZMS/Au composites possess increased photoinduced charge separation and transfer efficiency compared to the pure ZMS film. As a result, the hybrid composites exhibited enhanced decomposition activity for methylene blue and salicylic acid as well as antibacterial activity in killing S. aureus and E. coli under visible light irradiation. It can be noted that well-distributed Au components even at a rather low Au/ZnO weight ratio of ~1.2% also exhibited extraordinary photocatalysis. Such a facile and controllable self-assembly approach may be viable for preparing high-performance visible-light-driven ZMS/Au photocatalysts in a simple and controllable way, and consequently, the technology may extend to other plasmon-enhanced heterostructures made of nanostructured semiconductors and noble metals for great potential application in environmental protection.A high-efficiency visible-light-driven photocatalyst composed of homogeneously distributed Au nanoparticles (AuNPs) well-defined on hierarchical ZnO microspheres (ZMS) via a controllable layer-by-layer self-assembly technique is demonstrated. The gradual growth of the characteristic absorption bands of Au loaded on ZnO in the visible light region with an increasing number of assemblies indicates the enhancement of the light harvesting ability of

  11. Nonpathogenic Binucleate Rhizoctonia spp. and Benzothiadiazole Protect Cotton Seedlings Against Rhizoctonia Damping-Off and Alternaria Leaf Spot in Cotton.

    PubMed

    Jabaji-Hare, Suha; Neate, Stephen M

    2005-09-01

    ABSTRACT Recent reports have shown induction of resistance to Rhizoctonia root rot using nonpathogenic strains of binucleate Rhizoctonia spp. (np-BNR). This study evaluates the biocontrol ability of several np-BNR isolates against root and foliar diseases of cotton in greenhouse trials, provides evidence for induced systemic resistance (ISR) as a mechanism in this biocontrol, and compares the disease control provided by np-BNR with that provided by the chemical inducer benzothiadiazole (BTH). Pretreatment of cotton seedlings with np-BNR isolates provided good protection against pre- and post-emergence damping-off caused by a virulent strain of Rhizoctonia solani (AG-4). Seedling stand of protected cotton was significantly higher (P < 0.05) than that of nonprotected seedlings. Several np-BNR isolates significantly reduced disease severity. The combination of BTH and np-BNR provided significant protection against seedling rot and leaf spot in cotton; however, the degree of disease reduction was comparable to that obtained with np-BNR treatment alone. Significant reduction in leaf spot symptoms caused by Alternaria macrospora occurred on cotyledons pretreated with np-BNR or sprayed with BTH, and the np- BNR-treated seedlings had significantly less leaf spot than BTH-treated seedlings. The results demonstrate that np-BNR isolates can protect cotton from infections caused by both root and leaf pathogens and that disease control was superior to that observed with a chemical inducer. PMID:18943300

  12. Prevention of immunodeficiency virus induced CD4+ T-cell depletion by prior infection with a non-pathogenic virus

    SciTech Connect

    TerWee, Julie A.; Carlson, Jennifer K.; Sprague, Wendy S.; Sondgeroth, Kerry S.; Shropshire, Sarah B.; Troyer, Jennifer L.; VandeWoude, Sue

    2008-07-20

    Immune dysregulation initiated by a profound loss of CD4+ T-cells is fundamental to HIV-induced pathogenesis. Infection of domestic cats with a non-pathogenic lentivirus prevalent in the puma (puma lentivirus, PLV or FIV{sub PCO}) prevented peripheral blood CD4+ T-cell depletion caused by subsequent virulent FIV infection. Maintenance of this critical population was not associated with a significant decrease in FIV viremia, lending support to the hypothesis that direct viral cytopathic effect is not the primary cause of immunodeficiency. Although this approach was analogous to immunization with a modified live vaccine, correlates of immunity such as a serum-neutralizing antibody or virus-specific T-cell proliferative response were not found in protected animals. Differences in cytokine transcription profile, most notably in interferon gamma, were observed between the protected and unprotected groups. These data provide support for the importance of non-adaptive enhancement of the immune response in the prevention of CD4+ T-cell loss.

  13. An olive pollen protein with allergenic activity, Ole e 10, defines a novel family of carbohydrate-binding modules and is potentially implicated in pollen germination

    PubMed Central

    2005-01-01

    CBMs (carbohydrate-binding modules) are the most common non-catalytic modules associated with enzymes active in plant cell-wall hydrolysis. They have been frequently identified by amino acid sequence alignments, but only a few have been experimentally established to have a carbohydrate-binding activity. A small olive pollen protein, Ole e 10 (10 kDa), has been described as a major inducer of type I allergy in humans. In the present study, the ability of Ole e 10 to bind several polysaccharides has been analysed by affinity gel electrophoresis, which demonstrated that the protein bound 1,3-β-glucans preferentially. Analytical ultracentrifugation studies confirmed binding to laminarin, at a protein/ligand ratio of 1:1. The interaction of Ole e 10 with laminarin induced a conformational change in the protein, as detected by CD and fluorescence analyses, and an increase of 3.6 °C in the thermal denaturation temperature of Ole e 10 in the presence of the glycan. These results, and the absence of alignment of the sequence of Ole e 10 with that of any classified CBM, indicate that this pollen protein defines a novel family of CBMs, which we propose to name CBM43. Immunolocalization of Ole e 10 in mature and germinating pollen by transmission electron microscopy and confocal laser scanning microscopy demonstrated the co-localization of Ole e 10 and callose (1,3-β-glucan) in the growing pollen tube, suggesting a role for this protein in the metabolism of carbohydrates and in pollen tube wall re-formation during germination. PMID:15882149

  14. Novel utilization of the outer membrane proteins for the identification and differentiation of pathogenic versus nonpathogenic microbial strains using mass spectrometry-based proteomics approach

    NASA Astrophysics Data System (ADS)

    Jabbour, Rabih E.; Wade, Mary; Deshpande, Samir V.; McCubbin, Patrick; Snyder, A. Peter; Bevilacqua, Vicky

    2012-06-01

    Mass spectrometry based proteomic approaches are showing promising capabilities in addressing various biological and biochemical issues. Outer membrane proteins (OMPs) are often associated with virulence in gram-negative pathogens and could prove to be excellent model biomarkers for strain level differentiation among bacteria. Whole cells and OMP extracts were isolated from pathogenic and non-pathogenic strains of Francisella tularensis, Burkholderia thailandensis, and Burkholderia mallei. OMP extracts were compared for their ability to differentiate and delineate the correct database organism to an experimental sample and for the degree of dissimilarity to the nearest-neighbor database strains. This study addresses the comparative experimental proteome analyses of OMPs vs. whole cell lysates on the strain-level discrimination among gram negative pathogenic and non-pathogenic strains.

  15. Modified Primers for the Identification of Nonpathogenic Fusarium oxysporum Isolates That Have Biological Control Potential against Fusarium Wilt of Cucumber in Taiwan

    PubMed Central

    Wang, Chaojen; Lin, Yisheng; Lin, Yinghong; Chung, Wenhsin

    2013-01-01

    Previous investigations demonstrated that Fusarium oxysporum (Fo), which is not pathogenic to cucumbers, could serve as a biological control agent for managing Fusarium wilt of cucumber caused by Fo f. sp. cucumerinum (Foc) in Taiwan. However, thus far it has not been possible to separate the populations of pathogenic Fo from the nonpathogenic isolates that have biological control potential through their morphological characteristics. Although these two populations can be distinguished from one another using a bioassay, the work is laborious and time-consuming. In this study, a fragment of the intergenic spacer (IGS) region of ribosomal DNA from an Fo biological control agent, Fo366, was PCR-amplified with published general primers, FIGS11/FIGS12 and sequenced. A new primer, NPIGS-R, which was designed based on the IGS sequence, was paired with the FIGS11 primer. These primers were then evaluated for their specificity to amplify DNA from nonpathogenic Fo isolates that have biological control potential. The results showed that the modified primer pair, FIGS11/NPIGS-R, amplified a 500-bp DNA fragment from five of seven nonpathogenic Fo isolates. These five Fo isolates delayed symptom development of cucumber Fusarium wilt in greenhouse bioassay tests. Seventy-seven Fo isolates were obtained from the soil and plant tissues and then subjected to amplification using the modified primer pair; six samples showed positive amplification. These six isolates did not cause symptoms on cucumber seedlings when grown in peat moss infested with the isolates and delayed disease development when the same plants were subsequently inoculated with a virulent isolate of Foc. Therefore, the modified primer pair may prove useful for the identification of Fo isolates that are nonpathogenic to cucumber which can potentially act as biocontrol agents for Fusarium wilt of cucumber. PMID:23762289

  16. The role of cell wall-based defences in the early restriction of non-pathogenic hrp mutant bacteria in Arabidopsis.

    PubMed

    Mitchell, Kathy; Brown, Ian; Knox, Paul; Mansfield, John

    2015-04-01

    We have investigated the cause of the restricted multiplication of hrp mutant bacteria in leaves of Arabidopsis. Our focus was on early interactions leading to differentiation between virulent wild-type and non-pathogenic hrpA mutant strains of Pseudomonas syringae pv. tomato. An initial drop in recoverable bacteria detected 0-4 h after inoculation with either strain was dependent on a functional FLS2 receptor and H2O2 accumulation in challenged leaves. Wild-type bacteria subsequently multiplied rapidly whereas the hrpA mutant was restricted within 6 h. Despite the early restriction, the hrpA mutant was still viable several days after inoculation. Analysis of intercellular washing fluids (IWFs), showed that high levels of nutrients were readily available to bacteria in the apoplast and that no diffusible inhibitors were produced in response to bacterial challenge. Histochemical and immunocytochemical methods were used to detect changes in polysaccharides (callose, two forms of cellulose, and pectin), arabinogalactan proteins (AGPs), H2O2 and peroxidase. Quantitative analysis showed very similar changes in localisation of AGPs, cellulose epitopes and callose 2 and 4 h after inoculation with either strain. However from 6 to 12 h after inoculation papillae expanded only next to the hrp mutant. In contrast to the similar patterns of secretory activity recorded from mesophyll cells, accumulation of H2O2 and peroxidase was significantly greater around the hrpA mutant within the first 4h after inoculation. A striking differential accumulation of H2O2 was also found in chloroplasts in cells next to the mutant. Ascorbate levels were lower in the IWFs recovered from sites inoculated with the hrp mutant than with wild-type bacteria. The critical response, observed at the right time and place to explain the observed differential behaviour of wild-type and hrpA mutant bacteria was the accumulation of H2O2, probably generated through Type III peroxidase activity and in

  17. In vitro activity of telithromycin and quinupristin/dalfopristin against methicillin-resistant coagulase-negative staphylococci with defined resistance genotypes.

    PubMed

    Novotná, G; Spízek, J; Janata, J

    2007-01-01

    We determined the activities of new antibiotics telithromycin (ketolide) and quinupristin/dalfopristin (streptogramins) against 88 macrolide and/or lincosamide resistant coagulase-negative staphylococci (CoNS) isolates with defined resistance gene status. Telithromycin susceptibility was determined only in erythromycin-sensitive isolates (15) indicating the same mechanisms of resistance. In contrast, all erythromycin-resistant isolates (73) were either constitutively resistant to telithromycin (13 isolates with constitutive erm genes) or demonstrated telithromycin D-shaped zone (60 isolates with inducible msr(A) and/or erm). However, the level of inducible resistance conferred by msr(A) (35 isolates) was borderline even after induction by erythromycin. No quinupristin/dalfopristin resistant isolate was observed if tested by disk-diffusion method (DDM) but 18 isolates were intermediate (MIC = 1-3 mg/L) and two isolates resistant (MIC = 8 mg/L) if tested by E-test. All these isolates were resistant to streptogramin A and harbored vga(A) gene (1 isolate) or vga(A)LC gene (19 isolates). MICs for quinupristin/dalfopristin were higher for isolates with combination of streptogramin A resistance and constitutive MLSB resistance (MIC = 3-8 mg/L in 4 isolates) than for streptogramin A-resistant isolates susceptible to streptogramin B (MIC = 0.5-2 mg/L in 16 isolates). In addition to S. haemolyticus, vga(A)LC was newly identified in S. epidermidis and S. warnerii indicating its widespread occurrence in CoNS. Misidentification of low-level resistant isolates by DDM may contribute to dissemination of streptogramin A resistance. PMID:18450221

  18. Non-pathogenic Rhizobium radiobacter F4 deploys plant beneficial activity independent of its host Piriformospora indica.

    PubMed

    Glaeser, Stefanie P; Imani, Jafargholi; Alabid, Ibrahim; Guo, Huijuan; Kumar, Neelendra; Kämpfer, Peter; Hardt, Martin; Blom, Jochen; Goesmann, Alexander; Rothballer, Michael; Hartmann, Anton; Kogel, Karl-Heinz

    2016-04-01

    The Alphaproteobacterium Rhizobium radiobacter F4 (RrF4) was originally characterized as an endofungal bacterium in the beneficial endophytic Sebacinalean fungus Piriformospora indica. Although attempts to cure P. indica from RrF4 repeatedly failed, the bacterium can easily be grown in pure culture. Here, we report on RrF4's genome and the beneficial impact the free-living bacterium has on plants. In contrast to other endofungal bacteria, the genome size of RrF4 is not reduced. Instead, it shows a high degree of similarity to the plant pathogenic R. radiobacter (formerly: Agrobacterium tumefaciens) C58, except vibrant differences in both the tumor-inducing (pTi) and the accessor (pAt) plasmids, which can explain the loss of RrF4's pathogenicity. Similar to its fungal host, RrF4 colonizes plant roots without host preference and forms aggregates of attached cells and dense biofilms at the root surface of maturation zones. RrF4-colonized plants show increased biomass and enhanced resistance against bacterial leaf pathogens. Mutational analysis showed that, similar to P. indica, resistance mediated by RrF4 was dependent on the plant's jasmonate-based induced systemic resistance (ISR) pathway. Consistent with this, RrF4- and P. indica-induced pattern of defense gene expression were similar. In clear contrast to P. indica, but similar to plant growth-promoting rhizobacteria, RrF4 colonized not only the root outer cortex but also spread beyond the endodermis into the stele. On the basis of our findings, RrF4 is an efficient plant growth-promoting bacterium. PMID:26495996

  19. Yeast cell differentiation: Lessons from pathogenic and non-pathogenic yeasts.

    PubMed

    Palková, Zdena; Váchová, Libuše

    2016-09-01

    Yeasts, historically considered to be single-cell organisms, are able to activate different differentiation processes. Individual yeast cells can change their life-styles by processes of phenotypic switching such as the switch from yeast-shaped cells to filamentous cells (pseudohyphae or true hyphae) and the transition among opaque, white and gray cell-types. Yeasts can also create organized multicellular structures such as colonies and biofilms, and the latter are often observed as contaminants on surfaces in industry and medical care and are formed during infections of the human body. Multicellular structures are formed mostly of stationary-phase or slow-growing cells that diversify into specific cell subpopulations that have unique metabolic properties and can fulfill specific tasks. In addition to the development of multiple protective mechanisms, processes of metabolic reprogramming that reflect a changed environment help differentiated individual cells and/or community cell constituents to survive harmful environmental attacks and/or to escape the host immune system. This review aims to provide an overview of differentiation processes so far identified in individual yeast cells as well as in multicellular communities of yeast pathogens of the Candida and Cryptococcus spp. and the Candida albicans close relative, Saccharomyces cerevisiae. Molecular mechanisms and extracellular signals potentially involved in differentiation processes are also briefly mentioned. PMID:27084693

  20. Effect of bacterial monoassociation on brush-border enzyme activities in ex-germ-free piglets: comparison of commensal and pathogenic Escherichia coli strains.

    PubMed

    Kozakova, Hana; Kolinska, Jirina; Lojda, Zdenek; Rehakova, Zuzana; Sinkora, Jiri; Zakostelecka, Marie; Splichal, Igor; Tlaskalova-Hogenova, Helena

    2006-09-01

    This study was designed to investigate the effect of monoassociation of germ-free piglets with Escherichia coli strains on the development of intestinal brush-border enzyme activities. Piglets were delivered by hysterectomy, reared for seven days under germ-free conditions and fed milk formula diet. One group was maintained germ-free, the other four groups were monoassociated on day eight with one of four E. coli strains: non-pathogenic O86 or O83 and G58-1, or pathogenic 933D. The development of brush-border digestive enzyme functions in the small intestine was evaluated after 15 days. Germ-free controls exhibited slower developmental declines of lactase, gamma-glutamyltranspeptidase and alkaline phosphatase, and delayed increases of sucrase and glucoamylase compared to conventionally grown animals. Association of germ-free piglets with the non-pathogenic E. coli strains O86 and O83 resulted in increased enterocyte differentiation along the length of the small intestine, accompanied by declining activities of lactase, gamma-glutamyltranspeptidase and alkaline phosphatase, and elevated activities of maturational markers such as sucrase and glucoamylase. Maturational changes also occurred along the villus-crypt axis, as revealed by histochemical localization of aminopeptidase N on the villi tips in piglets colonized with E. coli O83. Interestingly, colonization with the pathogenic E. coli strain 933D stimulated changes in the main differentiation enzyme markers lactase, sucrase and glucoamylase to an extent comparable with those produced by the non-pathogenic and probiotic E. coli strains. In conclusion, germ-free piglets represent a valuable tool to study the consequences of colonization of the immature sterile gut with defined strains of bacteria. PMID:16949322

  1. Defense Responses in Two Ecotypes of Lotus japonicus against Non-Pathogenic Pseudomonas syringae

    PubMed Central

    Bordenave, Cesar D.; Escaray, Francisco J.; Menendez, Ana B.; Serna, Eva; Carrasco, Pedro; Ruiz, Oscar A.; Gárriz, Andrés

    2013-01-01

    Lotus japonicus is a model legume broadly used to study many important processes as nitrogen fixing nodule formation and adaptation to salt stress. However, no studies on the defense responses occurring in this species against invading microorganisms have been carried out at the present. Understanding how this model plant protects itself against pathogens will certainly help to develop more tolerant cultivars in economically important Lotus species as well as in other legumes. In order to uncover the most important defense mechanisms activated upon bacterial attack, we explored in this work the main responses occurring in the phenotypically contrasting ecotypes MG-20 and Gifu B-129 of L. japonicus after inoculation with Pseudomonas syringae DC3000 pv. tomato. Our analysis demonstrated that this bacterial strain is unable to cause disease in these accessions, even though the defense mechanisms triggered in these ecotypes might differ. Thus, disease tolerance in MG-20 was characterized by bacterial multiplication, chlorosis and desiccation at the infiltrated tissues. In turn, Gifu B-129 plants did not show any symptom at all and were completely successful in restricting bacterial growth. We performed a microarray based analysis of these responses and determined the regulation of several genes that could play important roles in plant defense. Interestingly, we were also able to identify a set of defense genes with a relative high expression in Gifu B-129 plants under non-stress conditions, what could explain its higher tolerance. The participation of these genes in plant defense is discussed. Our results position the L. japonicus-P. syringae interaction as a interesting model to study defense mechanisms in legume species. PMID:24349460

  2. Mutation of the Erwinia amylovora argD gene causes arginine auxotrophy, nonpathogenicity in apples, and reduced virulence in pears.

    PubMed

    Ramos, Laura S; Lehman, Brian L; Peter, Kari A; McNellis, Timothy W

    2014-11-01

    Fire blight is caused by Erwinia amylovora and is the most destructive bacterial disease of apples and pears worldwide. In this study, we found that E. amylovora argD(1000)::Tn5, an argD Tn5 transposon mutant that has the Tn5 transposon inserted after nucleotide 999 in the argD gene-coding region, was an arginine auxotroph that did not cause fire blight in apple and had reduced virulence in immature pear fruits. The E. amylovora argD gene encodes a predicted N-acetylornithine aminotransferase enzyme, which is involved in the production of the amino acid arginine. A plasmid-borne copy of the wild-type argD gene complemented both the nonpathogenic and the arginine auxotrophic phenotypes of the argD(1000)::Tn5 mutant. However, even when mixed with virulent E. amylovora cells and inoculated onto immature apple fruit, the argD(1000)::Tn5 mutant still failed to grow, while the virulent strain grew and caused disease. Furthermore, the pCR2.1-argD complementation plasmid was stably maintained in the argD(1000)::Tn5 mutant growing in host tissues without any antibiotic selection. Therefore, the pCR2.1-argD complementation plasmid could be useful for the expression of genes, markers, and reporters in E. amylovora growing in planta, without concern about losing the plasmid over time. The ArgD protein cannot be considered an E. amylovora virulence factor because the argD(1000)::Tn5 mutant was auxotrophic and had a primary metabolism defect. Nevertheless, these results are informative about the parasitic nature of the fire blight disease interaction, since they indicate that E. amylovora cannot obtain sufficient arginine from apple and pear fruit tissues or from apple vegetative tissues, either at the beginning of the infection process or after the infection has progressed to an advanced state. PMID:25172854

  3. Distribution and diversity of the haemoglobin–haptoglobin iron-acquisition systems in pathogenic and non-pathogenic Neisseria

    PubMed Central

    Harrison, Odile B.; Bennett, Julia S.; Derrick, Jeremy P.; Bayliss, Christopher D.

    2013-01-01

    A new generation of vaccines containing multiple protein components that aim to provide broad protection against serogroup B meningococci has been developed. One candidate, 4CMenB (4 Component MenB), has been approved by the European Medicines Agency, but is predicted to provide at most 70–80 % strain coverage; hence there is a need for second-generation vaccines that achieve higher levels of coverage. Prior knowledge of the diversity of potential protein vaccine components is a key step in vaccine design. A number of iron import systems have been targeted in meningococcal vaccine development, including the HmbR and HpuAB outer-membrane proteins, which mediate the utilization of haemoglobin or haemoglobin–haptoglobin complexes as iron sources. While the genetic diversity of HmbR has been described, little is known of the diversity of HpuAB. Using whole genome sequences deposited in a Bacterial Isolate Genome Sequence Database (BIGSDB), the prevalence and diversity of HpuAB among Neisseria were investigated. HpuAB was widely present in a range of Neisseria species whereas HmbR was mainly limited to the pathogenic species Neisseria meningitidis and Neisseria gonorrhoeae. Patterns of sequence variation in sequences from HpuAB proteins were suggestive of recombination and diversifying selection consistent with strong immune selection. HpuAB was subject to repeat-mediated phase variation in pathogenic Neisseria and the closely related non-pathogenic Neisseria species Neisseria lactamica and Neisseria polysaccharea but not in the majority of other commensal Neisseria species. These findings are consistent with HpuAB being subject to frequent genetic transfer potentially limiting the efficacy of this receptor as a vaccine candidate. PMID:23813677

  4. Enhanced Protective Efficacy of Nonpathogenic Recombinant Leishmania tarentolae Expressing Cysteine Proteinases Combined with a Sand Fly Salivary Antigen

    PubMed Central

    Taheri, Tahereh; Taslimi, Yasaman; Doustdari, Fatemeh; Seyed, Negar; Torkashvand, Fatemeh; Meneses, Claudio; Papadopoulou, Barbara; Kamhawi, Shaden; Valenzuela, Jesus G.; Rafati, Sima

    2014-01-01

    Background Novel vaccination approaches are needed to prevent leishmaniasis. Live attenuated vaccines are the gold standard for protection against intracellular pathogens such as Leishmania and there have been new developments in this field. The nonpathogenic to humans lizard protozoan parasite, Leishmania (L) tarentolae, has been used effectively as a vaccine platform against visceral leishmaniasis in experimental animal models. Correspondingly, pre-exposure to sand fly saliva or immunization with a salivary protein has been shown to protect mice against cutaneous leishmaniasis. Methodology/Principal Findings Here, we tested the efficacy of a novel combination of established protective parasite antigens expressed by L. tarentolae together with a sand fly salivary antigen as a vaccine strategy against L. major infection. The immunogenicity and protective efficacy of different DNA/Live and Live/Live prime-boost vaccination modalities with live recombinant L. tarentolae stably expressing cysteine proteinases (type I and II, CPA/CPB) and PpSP15, an immunogenic salivary protein from Phlebotomus papatasi, a natural vector of L. major, were tested both in susceptible BALB/c and resistant C57BL/6 mice. Both humoral and cellular immune responses were assessed before challenge and at 3 and 10 weeks after Leishmania infection. In both strains of mice, the strongest protective effect was observed when priming with PpSP15 DNA and boosting with PpSP15 DNA and live recombinant L. tarentolae stably expressing cysteine proteinase genes. Conclusion/Significance The present study is the first to use a combination of recombinant L. tarentolae with a sand fly salivary antigen (PpSP15) and represents a novel promising vaccination approach against leishmaniasis. PMID:24675711

  5. Ability of Nonpathogenic Fusarium oxysporum Strain Fo47 To Induce Resistance against Pythium ultimum Infection in Cucumber

    PubMed Central

    Benhamou, Nicole; Garand, Chantal; Goulet, Alain

    2002-01-01

    The influence exerted by nonpathogenic Fusarium oxysporum strain Fo47 in triggering cucumber protection against infection by Pythium ultimum was investigated ultrastructurally. Macroscopic and microscopic observations of the pathogen colony in dual cultures revealed that reduction of Pythium growth was associated with marked disorders, including generalized disorganization of the host cytoplasm, retraction of the plasmalemma, and complete loss of the protoplasm. Cytochemical labeling of cellulose with an exoglucanase-gold complex showed that the cellulose component of the host cell walls was structurally preserved at a time when the host cytoplasm had undergone complete disorganization. A similar antagonistic process was observed at the root cell surface. Most striking and interesting was the finding that mycoparasitism, as evidenced by the frequent occurrence of Fo47 hyphae within nearly empty cells of the pathogen, occurred not only at the root surface but also within the invaded root tissues. The specific labeling pattern obtained with the exoglucanase-gold complex confirmed that Fo47 successfully penetrated cells of the pathogen, both in the rhizosphere and inside the root tissues. Pythium cells that could evade the first defensive line in the rhizosphere could penetrate the root epidermis, but their growth was restricted to the outermost tissues. Positive correlations between Fo47 treatment and induced resistance to infection by P. ultimum in cucumber were confirmed by (i) the reduction of pathogen viability; (ii) the elaboration of newly formed barriers, a phenomenon which was not seen in Fo47-free plants, where the pathogen proliferated in all root tissues within a few days; and (iii) the occlusion of intercellular spaces with a dense material likely enriched in phenolics. Taken together, our observations provide the first convincing evidence that Fo47 exerts a direct inhibitory effect on P. ultimum through a combination of antibiosis and mycoparasitism, in

  6. Defining the Anthropocene

    NASA Astrophysics Data System (ADS)

    Lewis, Simon; Maslin, Mark

    2016-04-01

    Time is divided by geologists according to marked shifts in Earth's state. Recent global environmental changes suggest that Earth may have entered a new human-dominated geological epoch, the Anthropocene. Should the Anthropocene - the idea that human activity is a force acting upon the Earth system in ways that mean that Earth will be altered for millions of years - be defined as a geological time-unit at the level of an Epoch? Here we appraise the data to assess such claims, first in terms of changes to the Earth system, with particular focus on very long-lived impacts, as Epochs typically last millions of years. Can Earth really be said to be in transition from one state to another? Secondly, we then consider the formal criteria used to define geological time-units and move forward through time examining whether currently available evidence passes typical geological time-unit evidence thresholds. We suggest two time periods likely fit the criteria (1) the aftermath of the interlinking of the Old and New Worlds, which moved species across continents and ocean basins worldwide, a geologically unprecedented and permanent change, which is also the globally synchronous coolest part of the Little Ice Age (in Earth system terms), and the beginning of global trade and a new socio-economic "world system" (in historical terms), marked as a golden spike by a temporary drop in atmospheric CO2, centred on 1610 CE; and (2) the aftermath of the Second World War, when many global environmental changes accelerated and novel long-lived materials were increasingly manufactured, known as the Great Acceleration (in Earth system terms) and the beginning of the Cold War (in historical terms), marked as a golden spike by the peak in radionuclide fallout in 1964. We finish by noting that the Anthropocene debate is politically loaded, thus transparency in the presentation of evidence is essential if a formal definition of the Anthropocene is to avoid becoming a debate about bias. The

  7. Defining an emerging disease.

    PubMed

    Moutou, F; Pastoret, P-P

    2015-04-01

    Defining an emerging disease is not straightforward, as there are several different types of disease emergence. For example, there can be a 'real' emergence of a brand new disease, such as the emergence of bovine spongiform encephalopathy in the 1980s, or a geographic emergence in an area not previously affected, such as the emergence of bluetongue in northern Europe in 2006. In addition, disease can emerge in species formerly not considered affected, e.g. the emergence of bovine tuberculosis in wildlife species since 2000 in France. There can also be an unexpected increase of disease incidence in a known area and a known species, or there may simply be an increase in our knowledge or awareness of a particular disease. What all these emerging diseases have in common is that human activity frequently has a role to play in their emergence. For example, bovine spongiform encephalopathy very probably emerged as a result of changes in the manufacturing of meat-and-bone meal, bluetongue was able to spread to cooler climes as a result of uncontrolled trade in animals, and a relaxation of screening and surveillance for bovine tuberculosis enabled the disease to re-emerge in areas that had been able to drastically reduce the number of cases. Globalisation and population growth will continue to affect the epidemiology of diseases in years to come and ecosystems will continue to evolve. Furthermore, new technologies such as metagenomics and high-throughput sequencing are identifying new microorganisms all the time. Change is the one constant, and diseases will continue to emerge, and we must consider the causes and different types of emergence as we deal with these diseases in the future. PMID:26470448

  8. Interpolation and Definability

    NASA Astrophysics Data System (ADS)

    Gabbay, Dov M.; Maksimova, Larisa L.

    This chapter is on interpolation and definability. This notion is not only central in pure logic, but has significant meaning and applicability in all areas where logic itself is applied, especially in computer science, artificial intelligence, logic programming, philosophy of science and natural language. The notion may sometimes appear to the reader as too technical/mathematical but it does also have a general meaning in terms of expressibility and definability.

  9. Infection and establishment of latency in the dog brain after direct inoculation of a nonpathogenic strain of herpes simplex virus-1.

    PubMed

    Springer, S L; Vite, C H; Polesky, A C; Kesari, S; Fraser, N W; Wolfe, J H

    2001-04-01

    A number of diseases affecting the CNS occur in the dog and can be used as models for gene therapy in a large brain. HSV-1 has several potential advantages as a vector to transfer genes into the CNS. However, the ability of HSV-1 to infect CNS cells varies among species and no information was available for the dog. When the nonpathogenic 1716 strain of HSV-1 was injected into the brains of normal dogs it established a latent infection without signs of pathology. Thus, it appears to be suitable as a vector for therapeutic, or marker genes, in this species. PMID:11517387

  10. Defining Effective Teaching

    ERIC Educational Resources Information Center

    Layne, L.

    2012-01-01

    The author looks at the meaning of specific terminology commonly used in student surveys: "effective teaching." The research seeks to determine if there is a difference in how "effective teaching" is defined by those taking student surveys and those interpreting the results. To investigate this difference, a sample group of professors and students…

  11. Defining Equality in Education

    ERIC Educational Resources Information Center

    Benson, Ronald E.

    1977-01-01

    Defines equality of education in three areas: 1) by the degree of integration of school systems; 2) by a comparison of material resources and assets in education; and 3) by the effects of schooling as measured by the mean scores of groups on standardized tests. Available from: College of Education, 107 Quadrangle, Iowa State University, Ames, Iowa…

  12. Defining Supports Geometry

    ERIC Educational Resources Information Center

    Stephan, Michelle L.; McManus, George E.; Dickey, Ashley L.; Arb, Maxwell S.

    2012-01-01

    The process of developing definitions is underemphasized in most mathematics instruction. Investing time in constructing meaning is well worth the return in terms of the knowledge it imparts. In this article, the authors present a third approach to "defining," called "constructive." It involves modifying students' previous understanding of a term…

  13. On Defining Mass

    ERIC Educational Resources Information Center

    Hecht, Eugene

    2011-01-01

    Though central to any pedagogical development of physics, the concept of mass is still not well understood. Properly defining mass has proven to be far more daunting than contemporary textbooks would have us believe. And yet today the origin of mass is one of the most aggressively pursued areas of research in all of physics. Much of the excitement…

  14. Defining Faculty Work.

    ERIC Educational Resources Information Center

    Gray, Peter J.; Diamond, Robert M.

    1994-01-01

    A process of planned change is proposed for redefining college faculty work. Legitimate faculty work is defined in broad terms, and information sources and methods for collecting information to support redefinition are identified. The final step in the redefinition process is the development of new mission statements for the institution and its…

  15. Defined by Limitations

    ERIC Educational Resources Information Center

    Arriola, Sonya; Murphy, Katy

    2010-01-01

    Undocumented students are a population defined by limitations. Their lack of legal residency and any supporting paperwork (e.g., Social Security number, government issued identification) renders them essentially invisible to the American and state governments. They cannot legally work. In many states, they cannot legally drive. After the age of…

  16. Defining structural limit zones

    NASA Technical Reports Server (NTRS)

    Merchant, D. H.

    1978-01-01

    Method for defining limit loads uses probability distribution of largest load occurring during given time intervals. Method is compatible with both deterministic and probabilistic structural design criteria. It also rationally accounts for fact that longer structure is exposed to random loading environment, greater is possibility that it will experience extreme load.

  17. Defining Airflow Obstruction

    PubMed Central

    Eschenbacher, William L.

    2016-01-01

    Airflow obstruction has been defined using spirometric test results when the forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio is below a fixed cutoff (<70%) or lower limits of normal (LLN) from reference equations that are based on values from a normal population. However, similar to other positive or abnormal diagnostic test results that are used to identify the presence of disease, perhaps airflow obstruction should be defined based on the values of FEV1/FVC for a population of individuals with known disease such as chronic obstructive pulmonary disease (COPD). Unfortunately, we do not know such a distribution of values of FEV1/FVC for patients with COPD since there is no gold standard for this syndrome or condition. Yet, we have used this physiologic definition of airflow obstruction based on a normal population to identify patients with COPD. In addition, we have defined airflow obstruction as either being present or absent. Instead, we should use a different approach to define airflow obstruction based on the probability or likelihood that the airflow obstruction is present which in turn would give us the probability or likelihood of a disease state such as COPD. PMID:27239557

  18. Differential induction of CCL5 by pathogenic and non-pathogenic strains of West Nile virus in brain endothelial cells and astrocytes

    PubMed Central

    Hussmann, Katherine L.

    2014-01-01

    The neuroinflammatory response to West Nile virus (WNV) infection can be either protective or pathological depending on the context. Although several studies have examined chemokine profiles within brains of WNV-infected mice, little is known about how various cell types within the central nervous system (CNS) contribute to chemokine expression. Here, we assessed chemokine expression in brain microvascular endothelial cells and astrocytes, which comprise the major components of the blood–brain barrier (BBB), in response to a non-pathogenic (WNV-MAD78) and a highly pathogenic (WNV-NY) strain of WNV. Higher levels of the chemokine CCL5 were detected in WNV-MAD78-infected brain endothelial monolayers compared with WNV-NY-infected cells. However, the opposite profile was observed in WNV-infected astrocytes, indicating that pathogenic and non-pathogenic strains of WNV provoke different CCL5 profiles at the BBB. Thus, cells comprising the BBB may contribute to a dynamic pro-inflammatory response within the CNS that evolves as WNV infection progresses. PMID:24413421

  19. Coculture of Escherichia coli O157:H7 with a Nonpathogenic E. coli Strain Increases Toxin Production and Virulence in a Germfree Mouse Model

    PubMed Central

    Goswami, Kakolie; Chen, Chun; Xiaoli, Lingzi; Eaton, Kathryn A.

    2015-01-01

    Escherichia coli O157:H7 is a notorious foodborne pathogen due to its low infectious dose and the disease symptoms it causes, which include bloody diarrhea and severe abdominal cramps. In some cases, the disease progresses to hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS), due to the expression of one or more Shiga toxins (Stx). Isoforms of Stx, including Stx2a, are encoded within temperate prophages. In the presence of certain antibiotics, phage induction occurs, which also increases the expression of toxin genes. Additionally, increased Stx2 accumulation has been reported when O157:H7 was cocultured with phage-susceptible nonpathogenic E. coli. This study characterized an E. coli O157:H7 strain, designated PA2, that belongs to the hypervirulent clade 8 cluster. Stx2a levels after ciprofloxacin induction were lower for PA2 than for the prototypical outbreak strains Sakai and EDL933. However, during coculture with the nonpathogenic strain E. coli C600, PA2 produced Stx2a levels that were 2- to 12-fold higher than those observed during coculture with EDL933 and Sakai, respectively. Germfree mice cocolonized by PA2 and C600 showed greater kidney damage, increased Stx2a accumulation in feces, and more visible signs of disease than mice given PA2 or C600 alone. These data suggest one mechanism by which microorganisms associated with the colonic microbiota could enhance the virulence of E. coli O157:H7, particularly a subset of clade 8 strains. PMID:26259815

  20. Coculture of Escherichia coli O157:H7 with a Nonpathogenic E. coli Strain Increases Toxin Production and Virulence in a Germfree Mouse Model.

    PubMed

    Goswami, Kakolie; Chen, Chun; Xiaoli, Lingzi; Eaton, Kathryn A; Dudley, Edward G

    2015-11-01

    Escherichia coli O157:H7 is a notorious foodborne pathogen due to its low infectious dose and the disease symptoms it causes, which include bloody diarrhea and severe abdominal cramps. In some cases, the disease progresses to hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS), due to the expression of one or more Shiga toxins (Stx). Isoforms of Stx, including Stx2a, are encoded within temperate prophages. In the presence of certain antibiotics, phage induction occurs, which also increases the expression of toxin genes. Additionally, increased Stx2 accumulation has been reported when O157:H7 was cocultured with phage-susceptible nonpathogenic E. coli. This study characterized an E. coli O157:H7 strain, designated PA2, that belongs to the hypervirulent clade 8 cluster. Stx2a levels after ciprofloxacin induction were lower for PA2 than for the prototypical outbreak strains Sakai and EDL933. However, during coculture with the nonpathogenic strain E. coli C600, PA2 produced Stx2a levels that were 2- to 12-fold higher than those observed during coculture with EDL933 and Sakai, respectively. Germfree mice cocolonized by PA2 and C600 showed greater kidney damage, increased Stx2a accumulation in feces, and more visible signs of disease than mice given PA2 or C600 alone. These data suggest one mechanism by which microorganisms associated with the colonic microbiota could enhance the virulence of E. coli O157:H7, particularly a subset of clade 8 strains. PMID:26259815

  1. Identification of two catalytic residues in RAG1 that define a single active site within the RAG1/RAG2 protein complex.

    PubMed

    Fugmann, S D; Villey, I J; Ptaszek, L M; Schatz, D G

    2000-01-01

    During V(D)J recombination, the RAG1 and RAG2 proteins cooperate to catalyze a series of DNA bond breakage and strand transfer reactions. The structure, location, and number of active sites involved in RAG-mediated catalysis have as yet not been determined. Using protein secondary structure prediction algorithms, we have identified a region of RAG1 with possible structural similarities to the active site regions of transposases and retroviral integrases. Based on this information, we have identified two aspartic acid residues in RAG1 (D600 and D708) that function specifically in catalysis. The results support a model in which RAG1 contains a single, divalent metal ion binding active site structurally related to the active sites of transposases/integrases and responsible for all catalytic functions of the RAG protein complex. PMID:10678172

  2. Defining the level of human immunodeficiency virus type 1 (HIV-1) protease activity required for HIV-1 particle maturation and infectivity.

    PubMed Central

    Rosé, J R; Babé, L M; Craik, C S

    1995-01-01

    The human immunodeficiency virus type 1 (HIV-1) protease is the enzyme required for processing of the Gag and Gag-Pol polyproteins to yield mature, infectious virions. Although the complete absence of proteolytic activity prevents maturation, the level of activity sufficient for maturation and subsequent infectivity has not been determined. Amino acid substitutions that reduce catalytic activity without affecting substrate recognition have been engineered into the active site of the HIV-1 protease. The catalytic efficiency (kcat) of the HIV-1 protease is decreased 4-fold when threonine 26 is replaced by serine (T26S) and approximately 50-fold when alanine 28 is replaced by serine (A28S). Genes containing these mutations were cloned into a proviral vector for analysis of their effects on virion maturation and infectivity. The results show that virions containing the T26S protease variant, in which only 25% of the protease is active, are very similar to wild-type virions, although slight reductions in infectivity are observed. Virions containing the A28S protease variant are not infectious, even though a limited amount of polyprotein processing does occur. There appears to be a linear correlation between the level of protease activity and particle infectivity. Our observations suggest that a threshold of protease activity exists between a 4-fold and 50-fold reduction, below which processing is insufficient to yield infectious particles. Our data also suggest that a reduction of protease activity by 50-fold or greater is sufficient to prevent the formation of infectious particles. PMID:7535864

  3. The p16(INK4A)/pRb pathway and telomerase activity define a subgroup of Ph+ adult Acute Lymphoblastic Leukemia associated with inferior outcome.

    PubMed

    Chien, Wei W; Catallo, Régine; Chebel, Amel; Baranger, Laurence; Thomas, Xavier; Béné, Marie-Christine; Gerland, Luc M; Schmidt, Aline; Beldjord, Kheira; Klein, Nathalie; Escoffre-Barbe, Martine; Leguay, Thibaut; Huguet, Françoise; Larosa, Fabrice; Hayette, Sandrine; Plesa, Adriana; Ifrah, Norbert; Dombret, Hervé; Salles, Gilles; Chassevent, Agnès; Ffrench, Martine

    2015-04-01

    Adult Acute Lymphoblastic Leukemia (ALL) therapies have been improved by pediatric-like approaches. However, treatment failures and relapses are common and new markers are needed to identify patients with poor prognosis in prospective trials. The p16(INK4A)/CDK4-6/pRb pathway and telomerase activity, which are implicated in cell activation and aging, were analyzed to identify new prognostic markers. Proteins of the p16(INK4A)/CDK4-6/pRb pathway and telomerase activity were analyzed in 123 adult B-cell precursor (BCP) ALL cases included in the GRAALL/GRAAPH trials. We found a significantly increased expression of p16(INK4A) in BCP-ALLs with MLL rearrangement. Telomerase activity was significantly lower in Philadelphia chromosome-negative/IKAROS-deleted (BCR-ABL1(-)/IKAROS(del)) cases compared to Philadelphia chromosome-positive (BCR-ABL1+) BCP-ALLs. In BCR-ABL1+ ALLs, high CDK4 expression, phosphorylated pRb (p-pRb) and telomerase activity were significantly associated with a shorter disease-free survival (DFS) and event-free survival (EFS). Enhanced p16(INK4A) expression was only related to a significantly shorter DFS. In vitro analyses of normal stimulated lymphocytes after short- and long-term cultures demonstrated that the observed protein variations of poor prognosis in BCR-ABL1+ ALLs may be related to cell activation but not to cell aging. For these patients, our findings argue for the development of therapeutic strategies including the addition of new lymphocyte activation inhibitors to current treatments. PMID:25675863

  4. Defining Dynamic Route Structure

    NASA Technical Reports Server (NTRS)

    Zelinski, Shannon; Jastrzebski, Michael

    2011-01-01

    This poster describes a method for defining route structure from flight tracks. Dynamically generated route structures could be useful in guiding dynamic airspace configuration and helping controllers retain situational awareness under dynamically changing traffic conditions. Individual merge and diverge intersections between pairs of flights are identified, clustered, and grouped into nodes of a route structure network. Links are placed between nodes to represent major traffic flows. A parametric analysis determined the algorithm input parameters producing route structures of current day flight plans that are closest to todays airway structure. These parameters are then used to define and analyze the dynamic route structure over the course of a day for current day flight paths. Route structures are also compared between current day flight paths and more user preferred paths such as great circle and weather avoidance routing.

  5. Activating Mutations in PIK3CB Confer Resistance to PI3K Inhibition and Define a Novel Oncogenic Role for p110β.

    PubMed

    Nakanishi, Yoshito; Walter, Kimberly; Spoerke, Jill M; O'Brien, Carol; Huw, Ling Y; Hampton, Garret M; Lackner, Mark R

    2016-03-01

    Activation of the PI3K pathway occurs commonly in a wide variety of cancers. Experience with other successful targeted agents suggests that clinical resistance is likely to arise and may reduce the durability of clinical benefit. Here, we sought to understand mechanisms underlying resistance to PI3K inhibition in PTEN-deficient cancers. We generated cell lines resistant to the pan-PI3K inhibitor GDC-0941 from parental PTEN-null breast cancer cell lines and identified a novel PIK3CB D1067Y mutation in both cell lines that was recurrent in cancer patients. Stable expression of mutant PIK3CB variants conferred resistance to PI3K inhibition that could be overcome by downstream AKT or mTORC1/2 inhibitors. Furthermore, we show that the p110β D1067Y mutant was highly activated and induced PIP3 levels at the cell membrane, subsequently promoting the localization and activation of AKT and PDK1 at the membrane and driving PI3K signaling to a level that could withstand treatment with proximal inhibitors. Finally, we demonstrate that the PIK3CB D1067Y mutant behaved as an oncogene and transformed normal cells, an activity that was enhanced by PTEN depletion. Collectively, these novel preclinical and clinical findings implicate the acquisition of activating PIK3CB D1067 mutations as an important event underlying the resistance of cancer cells to selective PI3K inhibitors. PMID:26759240

  6. Defining the Structural Parameters that Confer Anticonvulsant Activity by the Site-by-Site Modification of (R)-N′-Benzyl 2- Amino-3-methylbutanamide

    PubMed Central

    King, Amber; De Ryck, Marc; Kaminski, Rafal; Valade, Anne; Stables, James P.; Kohn, Harold

    2011-01-01

    Primary Amino Acid Derivatives (PAADs) (N′-benzyl 2-substituted 2-amino acetamides) are structurally related to Functionalized Amino Acids (FAAs) (N′-benzyl 2- substituted 2-acetamido acetamides) but differ by the absence of the terminal N-acetyl group. Both classes exhibit potent anticonvulsant activities in the maximal electroshock seizure animal model and the reported structure-activity relationships (SARs) of PAADs and FAAs differ in significant ways. Recently, we documented that PAAD efficacy was associated with a hydrocarbon moiety at the C(2)-carbon, while in the FAAs, a substituted heteroatom one atom removed from the C(2)-center was optimal. Previously in this issue, we showed that PAAD activity was dependent upon the electronic properties of the 4′-N′-benzylamide substituent, while FAA activity was insensitive to electronic changes at this site. In this study, we prepared analogs of (R)-N′-benzyl 2-amino-3-methylbutanamide to identify the structural components for maximal anticonvulsant activity. We demonstrated that the SAR of PAADs and FAAs diverged at the terminal amide site and that PAADs had considerably more structural latitude in the types of units that could be incorporated at this position, suggesting that these compounds function according to different mechanism(s). PMID:21861466

  7. Quantification of pulmonary thallium-201 activity after upright exercise in normal persons: importance of peak heart rate and propranolol usage in defining normal values

    SciTech Connect

    Brown, K.A.; Boucher, C.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

    1984-06-01

    Fifty-nine normal patients (34 angiographically normal and 25 clinically normal by Bayesian analysis) underwent thallium-201 imaging after maximal upright exercise. Lung activity was quantitated relative to myocardial activity and a lung/myocardial activity ratio was determined for each patient. Stepwise regression analysis was then used to examine the influence of patient clinical characteristics and exercise variables on the lung/myocardium ratio. Peak heart rate during exercise and propranolol usage both showed significant negative regression coefficients (p less than 0.001). No other patient data showed a significant relation. Using the regression equation and the estimated variance, a 95% confidence level upper limit of normal could be determined for a give peak heart rate and propranolol status. Sixty-one other patients were studied to validate the predicted upper limits of normal based on this model. None of the 27 patients without coronary artery disease had an elevated lung/myocardial ratio, compared with 1 of 8 with 1-vessel disease (difference not significant), 6 of 14 with 2-vessel disease (p less than 0.005), and 6 of 12 with 3-vessel disease (p less than 0.0001). Thus, lung activity on upright exercise thallium-201 studies can be quantitated relative to myocardial activity, and is inversely related to peak heart rate and propranolol use. Use of a regression analysis allows determination of a 95% confidence upper limit of normal to be anticipated in an individual patient.

  8. Electron beam lithographically-defined scanning electrochemical-atomic force microscopy probes: fabrication method and application to high resolution imaging on heterogeneously active surfaces.

    PubMed

    Dobson, Phillip S; Weaver, John M R; Burt, David P; Holder, Mark N; Wilson, Neil R; Unwin, Patrick R; Macpherson, Julie V

    2006-09-01

    This paper describes in detail the use of electron beam lithography (EBL) to successfully batch microfabricate combined scanning electrochemical-atomic force microscopy (SECM-AFM) probes. At present, the process produces sixty probes at a time, on a 1/4 of a three-inch wafer. Using EBL, gold triangular-shaped electrodes can be defined at the tip apex, with plasma enhanced chemical vapor deposited silicon nitride serving as an effective insulating layer, at a thickness of 75 nm. The key features of the fabrication technique and the critical steps are discussed. The capability of these probes for SECM-AFM imaging in both tapping and constant distance mode is illustrated with dual topographical-electrochemical scans over an array of closely-spaced 1 microm diameter Pt disc electrodes, held at a suitable potential to generate an electroactive species at a transport-limited rate. As highlighted herein, understanding diffusion to heterogeneous electrode surfaces, including array electrodes, is currently topical and we present preliminary data highlighting the use of SECM-AFM as a valuable tool for the investigation of diffusion and reactivity at high spatial resolution. PMID:19817052

  9. Use of a promiscuous, constitutively-active bacterial enhancer-binding protein to define the Sigma54 (RpoN) regulon of Salmonella Typhimurium LT2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Sigma54, or RpoN, is an alternative s factor found widely in eubacteria. A significant complication in analysis of the global sigma54 regulon in a bacterium is that the sigma54 RNA polymerase holoenzyme requires interaction with an active bacterial enhancer-binding protein (bEBP) to init...

  10. Bioactivity and Bioavailability of Ginsenosides Are Dependent on the Glycosidase Activities of the A/J Mouse Intestinal Microbiome Defined by Pyrosequencing

    PubMed Central

    Niu, Tao; Smith, Diane; Yang, Zhen; Gao, Song; Yin, Taijun; Jiang, Zhi-Hong; You, Ming; Gibbs, Richard A.; Petrosino, Joseph F.; Hu, Ming

    2015-01-01

    Purpose The ability of bacteria in the intestinal microbiome to convert naturally occurring primary ginsenosides in red ginseng extract or RGE to active secondary ginsenosides was investigated. Methods The anti-proliferative activity of ginsenosides was tested using the mouse lung cancer LM1 cells. Their permeabilities were evaluated in Caco-2 cell monolayers. Systemic exposure of secondary ginsenosides was determined in A/J mice. 16S rRNA gene pyrosequencing was used to determine membership and abundance of bacteria in the intestinal microbiome. Results Secondary ginsenoside C-K exhibited higher anti-proliferative activity and permeability than primary ginsenosides, and significant amounts of secondary ginsenosides (F2 and C-K) were found in the blood of A/J mice following oral administration of the primary ginsenoside Rb1. Because mammalian cells did not hydrolyze ginsenoside, we determined the ability of bacteria to hydrolyze ginsenosides and found that the primary ginsenoside Rb1 underwent stepwise hydrolysis to Rd, F2, and then C-K. Formation of F2 from Rd was the rate-limiting step in the biotransformation of Rb1 to C-K. Conclusion This is the first study to characterize the A/J mouse intestinal microbiome and reveal the presence of certain bacterial families capable of efficiently converting inactive primary ginsenosides to active secondary ginsenosides in vivo. PMID:23254888

  11. Young black women: defining health.

    PubMed

    Hargrove, H J; Keller, C

    1993-01-01

    The purpose of this study was to elicit a definition of health as described by young Black women and to characterize the factors related to their definitions of health. The research questions were: (a) How do young Black women define health and (b) what factors are related to their definition of health? Using interviews and open-ended questions, an exploratory descriptive design examined the factors which contribute to the definition of health. Twenty-two young Black women between the ages of 21 and 40 comprised the sample. A wide range of incomes, occupations, educational levels, marital status, and family sizes were represented. The informants defined health as comprising those characteristics, behaviors, and/or activities which include: (a) having or avoiding a disease, (b) the presence or absence of obesity, (c) experiencing and reducing stress, (d) good and bad health habits, (e) eating good and bad foods, and (f) engaging (or not) in exercise. PMID:8106873

  12. Defining functional dyspepsia.

    PubMed

    Mearin, Fermín; Calleja, José Luis

    2011-12-01

    Dyspepsia and functional dyspepsia represent a highly significant public health issue. A good definition of dyspepsia is key for helping us to better approach symptoms, decision making, and therapy indications.During the last few years many attempts were made at establishing a definition of dyspepsia. Results were little successful on most occasions, and clear discrepancies arose on whether symptoms should be associated with digestion, which types of symptoms were to be included, which anatomic location should symptoms have, etc.The Rome III Committee defined dyspepsia as "a symptom or set of symptoms that most physicians consider to originate from the gastroduodenal area", including the following: postprandial heaviness, early satiety, and epigastric pain or burning. Two new entities were defined: a) food-induced dyspeptic symptoms (postprandial distress syndrome); and b) epigastric pain (epigastric pain syndrome). These and other definitions have shown both strengths and weaknesses. At times they have been much too complex, at times much too simple; furthermore, they have commonly erred on the side of being inaccurate and impractical. On the other hand, some (the most recent ones) are difficult to translate into the Spanish language. In a meeting of gastroenterologists with a special interest in digestive functional disorders, the various aspects of dyspepsia definition were discussed and put to the vote, and the following conclusions were arrived at: dyspepsia is defined as a set of symptoms, either related or unrelated to food ingestion, localized on the upper half of the abdomen. They include: a) epigastric discomfort (as a category of severity) or pain; b) postprandial heaviness; and c) early satiety. Associated complaints include: nausea, belching, bloating, and epigastric burn (heartburn). All these must be scored according to severity and frequency. Furthermore, psychological factors may be involved in the origin of functional dyspepsia. On the other hand

  13. Highly Active Subnanometer Au Particles Supported on TiO2 for Photocatalytic Hydrogen Evolution from a Well-Defined Organogold Precursor, [Au5(mesityl)5].

    PubMed

    Siddiqi, Georges; Mougel, Victor; Copéret, Christophe

    2016-04-18

    A highly efficient H2 evolution photocatalyst based on TiO2 supported subnanometer Au particles was developed on the basis of the reaction of a gold(I) molecular precursor [Au5Mes5] (Mes = 2,4,6-trimethylphenyl), with titanium dioxide partially dehydroxylated at 120 °C. IR, UV-vis, elemental analysis, XANES, and STEM-EDX show that the deposition of [Au5Mes5] onto TiO2 leads to the formation of both subnanometer Au particles and chemisorbed [Au5Mes5]. The remaining organic ligands are removed via a mild treatment under H2, yielding subnanometer gold(0) particles. A range of Au loadings (0.3, 0.9, 2.4 wt %) with similar particle sizes (<1 nm) on TiO2 are obtained and tested in methanol-assisted photocatalytic hydrogen production under UV light. These catalysts display significantly higher activity than a commercial reference Au-TiO2 catalyst. The presence of chemisorbed [Au5Mes5] in the as-synthesized catalyst further improved activity, albeit at the expense of stability. This work demonstrates a simple synthetic route to obtain subnanometer Au particles on TiO2 that display exceptional activity in photocatalysis. PMID:27064051

  14. Defining periodontal health

    PubMed Central

    2015-01-01

    Assessment of the periodontium has relied exclusively on a variety of physical measurements (e.g., attachment level, probing depth, bone loss, mobility, recession, degree of inflammation, etc.) in relation to various case definitions of periodontal disease. Periodontal health was often an afterthought and was simply defined as the absence of the signs and symptoms of a periodontal disease. Accordingly, these strict and sometimes disparate definitions of periodontal disease have resulted in an idealistic requirement of a pristine periodontium for periodontal health, which makes us all diseased in one way or another. Furthermore, the consequence of not having a realistic definition of health has resulted in potentially questionable recommendations. The aim of this manuscript was to assess the biological, environmental, sociological, economic, educational and psychological relationships that are germane to constructing a paradigm that defines periodontal health using a modified wellness model. The paradigm includes four cardinal characteristics, i.e., 1) a functional dentition, 2) the painless function of a dentition, 3) the stability of the periodontal attachment apparatus, and 4) the psychological and social well-being of the individual. Finally, strategies and policies that advocate periodontal health were appraised. I'm not sick but I'm not well, and it's a sin to live so well. Flagpole Sitta, Harvey Danger PMID:26390888

  15. Suppressors of a cold-sensitive mutation in yeast U4 RNA define five domains in the splicing factor Prp8 that influence spliceosome activation.

    PubMed Central

    Kuhn, A N; Brow, D A

    2000-01-01

    The highly conserved splicing factor Prp8 has been implicated in multiple stages of the splicing reaction. However, assignment of a specific function to any part of the 280-kD U5 snRNP protein has been difficult, in part because Prp8 lacks recognizable functional or structural motifs. We have used a large-scale screen for Saccharomyces cerevisiae PRP8 alleles that suppress the cold sensitivity caused by U4-cs1, a mutant U4 RNA that blocks U4/U6 unwinding, to identify with high resolution five distinct regions of PRP8 involved in the control of spliceosome activation. Genetic interactions between two of these regions reveal a potential long-range intramolecular fold. Identification of a yeast two-hybrid interaction, together with previously reported results, implicates two other regions in direct and indirect contacts to the U1 snRNP. In contrast to the suppressor mutations in PRP8, loss-of-function mutations in the genes for two other splicing factors implicated in U4/U6 unwinding, Prp44 (Brr2/Rss1/Slt22/Snu246) and Prp24, show synthetic enhancement with U4-cs1. On the basis of these results we propose a model in which allosteric changes in Prp8 initiate spliceosome activation by (1) disrupting contacts between the U1 snRNP and the U4/U6-U5 tri-snRNP and (2) orchestrating the activities of Prp44 and Prp24. PMID:10924465

  16. Allosteric Activation of E2-RING Finger-Mediated Ubiquitylation by a Structurally Defined Specific E2-Binding Region of gp78

    SciTech Connect

    Das, Ranabir; Mariano, Jennifer; Tsai, Yien Che; Kalathur, Ravi C.; Kostova, Zlatka; Li, Jess; Tarasov, Sergey G.; McFeeters, Robert L.; Altieri, Amanda S.; Ji, Xinhua; Byrd, R. Andrew; Weissman, Allan M.

    2010-11-12

    The activity of RING finger ubiquitin ligases (E3) is dependent on their ability to facilitate transfer of ubiquitin from ubiquitin-conjugating enzymes (E2) to substrates. The G2BR domain within the E3 gp78 binds selectively and with high affinity to the E2 Ube2g2. Through structural and functional analyses, we determine that this occurs on a region of Ube2g2 distinct from binding sites for ubiquitin-activating enzyme (E1) and RING fingers. Binding to the G2BR results in conformational changes in Ube2g2 that affect ubiquitin loading. The Ube2g2:G2BR interaction also causes an 50-fold increase in affinity between the E2 and RING finger. This results in markedly increased ubiquitylation by Ube2g2 and the gp78 RING finger. The significance of this G2BR effect is underscored by enhanced ubiquitylation observed when Ube2g2 is paired with other RING finger E3s. These findings uncover a mechanism whereby allosteric effects on an E2 enhance E2-RING finger interactions and, consequently, ubiquitylation.

  17. Defining the role of a FYVE domain in the localization and activity of a cAMP phosphodiesterase implicated in osmoregulation in Trypanosoma cruzi.

    PubMed

    Schoijet, Alejandra C; Miranda, Kildare; Medeiros, Lia Carolina Soares; de Souza, Wanderley; Flawiá, Mirtha M; Torres, Héctor N; Pignataro, Omar P; Docampo, Roberto; Alonso, Guillermo D

    2011-01-01

    Intracellular levels of cyclic nucleotide second messengers are regulated predominantly by a large superfamily of phosphodiesterases (PDEs). Trypanosoma cruzi, the causative agent of Chagas disease, encodes four different PDE families. One of these PDEs, T. cruzi PDE C2 (TcrPDEC2) has been characterized as a FYVE domain containing protein. Here, we report a novel role for TcrPDEC2 in osmoregulation in T. cruzi and reveal the relevance of its FYVE domain. Our data show that treatment of epimastigotes with TcrPDEC2 inhibitors improves their regulatory volume decrease, whereas cells overexpressing this enzyme are unaffected by the same inhibitors. Consistent with these results, TcrPDEC2 localizes to the contractile vacuole complex, showing strong labelling in the region corresponding to the spongiome. Furthermore, transgenic parasites overexpressing a truncated version of TcrPDEC2 without the FYVE domain show a failure in its targeting to the contractile vacuole complex and a marked decrease in PDE activity, supporting the importance of this domain to the localization and activity of TcrPDEC2. Taking together, the results here presented are consistent with the importance of the cyclic AMP signalling pathway in regulatory volume decrease and implicate TcrPDEC2 as a specifically localized PDE involved in osmoregulation in T. cruzi. PMID:21166893

  18. Delineating and Defining the Boundaries of an Active Landslide in the Rainforest of Puerto Rico Using a Combination of Airborne and Terrestrial LIDAR Data

    NASA Astrophysics Data System (ADS)

    Wang, G.; Joyce, J.; Phillips, D. A.; Shrestha, R. L.; Carter, W. E.

    2013-05-01

    Light detection and ranging (LIDAR) is a remote sensing technique that uses light, often using pulses from a laser to measure the distance to a target. Both terrestrial and airborne based LIDAR techniques have been frequently used to map landslides. Airborne LIDAR has the advantage of identifying large scarps of landslides covered by tree canopies and is widely applied in identifying historical and current active landslides hidden in forested areas. However, because landslides naturally have relatively small vertical surface deformation in the foot area, it is practically difficult to identify the margins of landslide foot area with the limited spatial resolution (few decimeters) of airborne LIDAR. Alternatively, ground-based LIDAR can achieve resolution of several centimeters and also has the advantages of being portable, repeatable, and less costly. Thus ground based LIDAR can be used to identify small deformations in landslide foot areas by differencing repeated Terrestrial Laser Scanning (TLS) surveys. This study demonstrates a method of identifying the superficial boundaries as well as the bottom boundary (sliding plane) of an active landslide in National Rainforest Park, Puerto Rico, USA, using the combination of ground based and airborne LIDAR data. The method of combining terrestrial and airborne LIDAR data can be used to study landslides in other regions. This study indicates that intensity and density of laser point clouds are remarkably useful in identifying superficial boundaries of landslides.

  19. TAPERED DEFINING SLOT

    DOEpatents

    Pressey, F.W.

    1959-09-01

    An improvement is reported in the shape and formation of the slot or opening in the collimating slot member which forms part of an ion source of the type wherein a vapor of the material to be ionized is bombarded by electrons in a magnetic field to strike an arc-producing ionization. The defining slot is formed so as to have a substantial taper away from the cathode, causing the electron bombardment from the cathode to be dispersed over a greater area reducing its temperature and at the same time bringing the principal concentration of heat from the electron bombardment nearer the anode side of the slot, thus reducing deterioration and prolonging the life of the slot member during operation.

  20. Phylogenetic Analysis and Polyphasic Characterization of Clavibacter michiganensis Strains Isolated from Tomato Seeds Reveal that Nonpathogenic Strains Are Distinct from C. michiganensis subsp. michiganensis

    PubMed Central

    Durand, Karine; Orgeur, Geoffrey; Balidas, Samuel; Fricot, Céline; Bonneau, Sophie; Quillévéré, Anne; Audusseau, Corinne; Olivier, Valérie; Grimault, Valérie; Mathis, René

    2012-01-01

    The genus Clavibacter comprises one species and five subspecies of plant-pathogenic bacteria, four of which are classified as quarantine organisms due to the high economic threat they pose. Clavibacter michiganensis subsp. michiganensis is one of the most important pathogens of tomato, but the recommended diagnostic tools are not satisfactory due to false-negative and/or -positive results. To provide a robust analysis of the genetic relatedness among a worldwide collection of C. michiganensis subsp. michiganensis strains, relatives (strains from the four other C. michiganensis subspecies), and nonpathogenic Clavibacter-like strains isolated from tomato, we performed multilocus sequence-based analysis and typing (MLSA and MLST) based on six housekeeping genes (atpD, dnaK, gyrB, ppK, recA, and rpoB). We compared this “framework” with phenotypic and genotypic characteristics such as pathogenicity on tomato, reaction to two antisera by immunofluorescence and to five PCR identification tests, and the presence of four genes encoding the main C. michiganensis subsp. michiganensis pathogenicity determinants. We showed that C. michiganensis subsp. michiganensis is monophyletic and is distinct from its closest taxonomic neighbors. The nonpathogenic Clavibacter-like strains were identified as C. michiganensis using 16S rRNA gene sequencing. These strains, while cross-reacting with C. michiganensis subsp. michiganensis identification tools, are phylogenetically distinct from the pathogenic strains but belong to the C. michiganensis clade. C. michiganensis subsp. michiganensis clonal complexes linked strains from highly diverse geographical origins and also strains isolated over long periods of time in the same location. This illustrates the importance of seed transmission in the worldwide dispersion of this pathogen and its survival and adaptation abilities in a new environment once introduced. PMID:23001675

  1. Autoantibodies define a family of proteins with conserved double-stranded RNA-binding domains as well as DNA binding activity.

    PubMed

    Satoh, M; Shaheen, V M; Kao, P N; Okano, T; Shaw, M; Yoshida, H; Richards, H B; Reeves, W H

    1999-12-01

    Cellular responses to viral infection are signaled by double-stranded (ds) RNA, which is not found in substantial amounts in uninfected cells. Although cellular dsRNA-binding proteins have been described, their characterization is incomplete. We show that dsRNA-binding proteins are prominent autoantigens. Sera from B6 and B10.S mice with pristane-induced lupus and human autoimmune sera immunoprecipitated a novel set of 130-, 110-, 90-, 80-, and 45-kDa proteins. The proteins were all major cellular poly(IC)-binding factors. N-terminal amino acid sequences of p110 and p90 were identical and matched nuclear factor (NF) 90 and M phase phosphoprotein 4. p45 and p90 were identified as the NF45.NF90 complex, which binds the interleukin-2 promoter as well as certain highly structured viral RNAs. NF90.NF45 and M phase phosphoprotein 4 belong to a large group of proteins with conserved dsRNA-binding motifs. Besides binding dsRNA, NF90.NF45, p110, and p130 had single-stranded and dsDNA binding activity. Some sera contained autoantibodies whose binding was inhibited by poly(IC) but not single-stranded DNA or vice versa, suggesting that the DNA- and RNA-binding sites are different. These autoantibodies will be useful probes of the function of dsRNA-binding proteins. Their interaction with dsRNA, an immunological adjuvant, also could promote autoimmunity. PMID:10574923

  2. Real-Time Quantitative RT-PCR of Defense-Associated Gene Transcripts of Rhizoctonia solani-Infected Bean Seedlings in Response to Inoculation with a Nonpathogenic Binucleate Rhizoctonia Isolate.

    PubMed

    Wen, Kui; Seguin, Philippe; St-Arnaud, Marc; Jabaji-Hare, Suha

    2005-04-01

    ABSTRACT Certain isolates of nonpathogenic binucleate Rhizoctonia spp. (np-BNR) are effective biocontrol agents against seedling root rot and damping-off. Inoculation of bean seed with np-BNR strain 232-CG at sowing reduced disease symptoms in bean (Phaseolus vulgaris) seedlings caused by R. solani. Molecular analyses of the spatial expression of three defense-associated genes were carried out using real-time quantitative reverse transcription-polymerase chain reaction (QRT-PCR) assays. This method allowed accurate quantitative evaluation of transcript levels of pG101 encoding for 1,3-beta-D-glucanase, gPAL1 encoding for phenylalanine ammonia lyase, and CHS17 encoding for chalcone synthase in 1- and 2-week-old bean seedlings that were inoculated simultaneously with np-BNR and infected with R. solani, and in seedlings that were singly inoculated with either fungi or not inoculated. In the seedlings that were infected with R. solani only, results revealed that, following infection, activation of all defense-associated gene transcripts was achieved with significant increases ranging from 7- to 40-fold greater than the control, depending on the defense gene and tissue analyzed. Seedlings that were treated with np-BNR and infected with R. solani had expression similar to those that were treated with np-BNR only, but the levels were significantly down-regulated compared with those that were infected with R. solani only. These findings indicate that disease suppression by np-BNR isolate is not correlated to pG101, gPAL1, and CHS17 gene activation. PMID:18943035

  3. Monitoring and Modelling of Soil-Plant Interactions: the Joint Use of ERT, Sap Flow and Eddy Covariance to Define the Volume of Orange Tree Active Root Zones.

    NASA Astrophysics Data System (ADS)

    Cassiani, G.; Boaga, J.; Vanella, D.; Perri, M. T.; Consoli, S.

    2014-12-01

    Mass and energy exchanges between soil, plants and atmosphere are key factors controlling a number of environmental processes involving hydrology, biota and climate. The understanding of these exchanges also play a critical role for practical purposes such as precision agriculture. In this contribution we present a methodology based on coupling innovative data collection and models. In particular we propose the use of hydro-geophysical monitoring via 4D Electrical Resistivity Tomography (ERT) in conjunction with measurements of plant transpiration via sap flow and evapotranspiration from Eddy Correlation (EC). This abundance of data are to be fed in spatially distributed soil models in order to comprehend the distribution of active roots. We conducted experiments in an orange orchard in Eastern Sicily (Italy). We installed a 3D electrical tomography apparatus consisting of 4 instrumented micro boreholes placed at the corners of a square (about 1.3 m in side) surrounding an orange tree. During the monitoring, we collected repeated ERT and TDR soil moisture measurements, soil water sampling, sap flow measurements from the orange tree and EC data. Irrigation, precipitation, sap flow and ET data are available for a long period of time allowing knowledge of the long term forcing conditions on the system. This wealth of information was used to calibrate a 1D Richards' equation model representing the dynamics of the volume monitored via 3D ERT. Information on the soil hydraulic properties was collected from laboratory experiments as well as by time-lapse ERT monitoring of irrigation a few months after the main experiment, when the orange tree had been cut. The results of the calibrated modeling exercise allow the quantification of the soil volume interested by root water uptake. This volume is much smaller (an area less than 2 square meters, 40 cm thick) than generally believed and assumed in the design of classical drip irrigation schemes.

  4. A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model

    PubMed Central

    Saba, Corey; Paoloni, Melissa; Mazcko, Christina; Kisseberth, William; Burton, Jenna H.; Smith, Annette; Wilson-Robles, Heather; Allstadt, Sara; Vail, David; Henry, Carolyn; Lana, Susan; Ehrhart, E. J.; Charles, Brad; Kent, Michael; Lawrence, Jessica; Burgess, Kristine; Borgatti, Antonella; Suter, Steve; Woods, Paul; Gordon, Ira; Vrignaud, Patricia; Khanna, Chand; LeBlanc, Amy K.

    2016-01-01

    Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10–70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative

  5. A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model.

    PubMed

    Saba, Corey; Paoloni, Melissa; Mazcko, Christina; Kisseberth, William; Burton, Jenna H; Smith, Annette; Wilson-Robles, Heather; Allstadt, Sara; Vail, David; Henry, Carolyn; Lana, Susan; Ehrhart, E J; Charles, Brad; Kent, Michael; Lawrence, Jessica; Burgess, Kristine; Borgatti, Antonella; Suter, Steve; Woods, Paul; Gordon, Ira; Vrignaud, Patricia; Khanna, Chand; LeBlanc, Amy K

    2016-01-01

    Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative

  6. Collections Define Cataloging's Future

    ERIC Educational Resources Information Center

    Simpson, Betsy

    2007-01-01

    The role of catalogers within academic libraries is evolving to meet new demands and cultivating a broader understanding of cataloging--one that focuses on collections, not the catalog, and applies cataloger expertise across metadata activities. Working collaboratively as never before, catalogers are reinventing their place within the library.

  7. A Homozygous [Cys25]PTH(1-84) Mutation That Impairs PTH/PTHrP Receptor Activation Defines a Novel Form of Hypoparathyroidism.

    PubMed

    Lee, Sihoon; Mannstadt, Michael; Guo, Jun; Kim, Seul Min; Yi, Hyon-Seung; Khatri, Ashok; Dean, Thomas; Okazaki, Makoto; Gardella, Thomas J; Jüppner, Harald

    2015-10-01

    treatment of IHP patients with inappropriately high doses of active vitamin D and calcium can contribute to development of nephrocalcinosis and chronic kidney disease. PMID:25891861

  8. Defining Life: The Virus Viewpoint

    NASA Astrophysics Data System (ADS)

    Forterre, Patrick

    2010-04-01

    Are viruses alive? Until very recently, answering this question was often negative and viruses were not considered in discussions on the origin and definition of life. This situation is rapidly changing, following several discoveries that have modified our vision of viruses. It has been recognized that viruses have played (and still play) a major innovative role in the evolution of cellular organisms. New definitions of viruses have been proposed and their position in the universal tree of life is actively discussed. Viruses are no more confused with their virions, but can be viewed as complex living entities that transform the infected cell into a novel organism—the virus—producing virions. I suggest here to define life (an historical process) as the mode of existence of ribosome encoding organisms (cells) and capsid encoding organisms (viruses) and their ancestors. I propose to define an organism as an ensemble of integrated organs (molecular or cellular) producing individuals evolving through natural selection. The origin of life on our planet would correspond to the establishment of the first organism corresponding to this definition.

  9. Oligo-DNA Custom Macroarray for Monitoring Major Pathogenic and Non-Pathogenic Fungi and Bacteria in the Phyllosphere of Apple Trees

    PubMed Central

    He, Ying-Hong; Isono, Sayaka; Shibuya, Makoto; Tsuji, Masaharu; Adkar Purushothama, Charith-Raj; Tanaka, Kazuaki; Sano, Teruo

    2012-01-01

    Background To monitor the richness in microbial inhabitants in the phyllosphere of apple trees cultivated under various cultural and environmental conditions, we developed an oligo-DNA macroarray for major pathogenic and non-pathogenic fungi and bacteria inhabiting the phyllosphere of apple trees. Methods and Findings First, we isolated culturable fungi and bacteria from apple orchards by an agar-plate culture method, and detected 32 fungal and 34 bacterial species. Alternaria, Aureobasidium, Cladosporium, Rhodotorula, Cystofilobasidium, and Epicoccum genera were predominant among the fungi, and Bacillus, Pseudomonas, Sphingomonas, Methylobacterium, and Pantoea genera were predominant among the bacteria. Based on the data, we selected 29 major non-pathogenic and 12 phytopathogenic fungi and bacteria as the targets of macroarray. Forty-one species-specific 40-base pair long oligo-DNA sequences were selected from the nucleotide sequences of rDNA-internal transcribed spacer region for fungi and 16S rDNA for bacteria. The oligo-DNAs were fixed on nylon membrane and hybridized with digoxigenin-labeled cRNA probes prepared for each species. All arrays except those for Alternaria, Bacillus, and their related species, were specifically hybridized. The array was sensitive enough to detect 103 CFU for Aureobasidium pullulans and Bacillus cereus. Nucleotide sequencing of 100 each of independent fungal rDNA-ITS and bacterial 16S-rDNA sequences from apple tree was in agreement with the macroarray data obtained using the same sample. Finally, we analyzed the richness in the microbial inhabitants in the samples collected from apple trees in four orchards. Major apple pathogens that cause scab, Alternaria blotch, and Marssonina blotch were detected along with several non-phytopathogenic fungal and bacterial inhabitants. Conclusions The macroarray technique presented here is a strong tool to monitor the major microbial species and the community structures in the phyllosphere of

  10. Selection and identification of non-pathogenic bacteria isolated from fermented pickles with antagonistic properties against two shrimp pathogens

    PubMed Central

    Zokaeifar, Hadi; Luis Balcázar, José; Kamarudin, Mohd Salleh; Sijam, Kamaruzaman; Arshad, Aziz; Saad, Che Roos

    2012-01-01

    In this study, potential probiotic strains were isolated from fermented pickles based on antagonistic activity against two shrimp pathogens (Vibrio harveyi and Vibrio parahaemolyticus). Two strains L10 and G1 were identified by biochemical tests, followed by16S ribosomal RNA gene sequence analysis as Bacillus subtilis, and characterized by PCR amplification of repetitive bacterial DNA elements (Rep-PCR). Subsequently, B. subtilis L10 and G1 strains were tested for antibacterial activity under different physical conditions, including culture medium, salinity, pH and temperature using the agar well diffusion assay. Among the different culture media, LB broth was the most suitable medium for antibacterial production. Both strains showed the highest level of antibacterial activity against two pathogens at 30 °C and 1.0% NaCl. Under the pH conditions, strain G1 showed the greatest activity against V. harveyi at pH 7.3–8.0 and against V. parahaemolyticus at pH 6.0–8.0, whereas strain L10 showed the greatest activity against two pathogens at pH 7.3. The cell-free supernatants of both strains were treated with four different enzymes in order to characterize the antibacterial substances against V. harveyi. The result showed considerable reduction of antibacterial activity for both strains, indicating the proteinaceous nature of the antibacterial substances. A wide range of tolerance to NaCl, pH and temperature was also recorded for both strains. In addition, both strains showed no virulence effect in juvenile shrimp Litopenaeus vannamei. On the basis of these results and safety of strains to L. vannamei, they may be considered for future challenge experiments in shrimp as a very promising alternative to the use of antibiotics. PMID:22491136

  11. Selection and identification of non-pathogenic bacteria isolated from fermented pickles with antagonistic properties against two shrimp pathogens.

    PubMed

    Zokaeifar, Hadi; Balcázar, José Luis; Kamarudin, Mohd Salleh; Sijam, Kamaruzaman; Arshad, Aziz; Saad, Che Roos

    2012-06-01

    In this study, potential probiotic strains were isolated from fermented pickles based on antagonistic activity against two shrimp pathogens (Vibrio harveyi and Vibrio parahaemolyticus). Two strains L10 and G1 were identified by biochemical tests, followed by16S ribosomal RNA gene sequence analysis as Bacillus subtilis, and characterized by PCR amplification of repetitive bacterial DNA elements (Rep-PCR). Subsequently, B. subtilis L10 and G1 strains were tested for antibacterial activity under different physical conditions, including culture medium, salinity, pH and temperature using the agar well diffusion assay. Among the different culture media, LB broth was the most suitable medium for antibacterial production. Both strains showed the highest level of antibacterial activity against two pathogens at 30 °C and 1.0% NaCl. Under the pH conditions, strain G1 showed the greatest activity against V. harveyi at pH 7.3-8.0 and against V. parahaemolyticus at pH 6.0-8.0, whereas strain L10 showed the greatest activity against two pathogens at pH 7.3. The cell-free supernatants of both strains were treated with four different enzymes in order to characterize the antibacterial substances against V. harveyi. The result showed considerable reduction of antibacterial activity for both strains, indicating the proteinaceous nature of the antibacterial substances. A wide range of tolerance to NaCl, pH and temperature was also recorded for both strains. In addition, both strains showed no virulence effect in juvenile shrimp Litopenaeus vannamei. On the basis of these results and safety of strains to L. vannamei, they may be considered for future challenge experiments in shrimp as a very promising alternative to the use of antibiotics. PMID:22491136

  12. Miniature EVA Software Defined Radio

    NASA Technical Reports Server (NTRS)

    Pozhidaev, Aleksey

    2012-01-01

    As NASA embarks upon developing the Next-Generation Extra Vehicular Activity (EVA) Radio for deep space exploration, the demands on EVA battery life will substantially increase. The number of modes and frequency bands required will continue to grow in order to enable efficient and complex multi-mode operations including communications, navigation, and tracking applications. Whether conducting astronaut excursions, communicating to soldiers, or first responders responding to emergency hazards, NASA has developed an innovative, affordable, miniaturized, power-efficient software defined radio that offers unprecedented power-efficient flexibility. This lightweight, programmable, S-band, multi-service, frequency- agile EVA software defined radio (SDR) supports data, telemetry, voice, and both standard and high-definition video. Features include a modular design, an easily scalable architecture, and the EVA SDR allows for both stationary and mobile battery powered handheld operations. Currently, the radio is equipped with an S-band RF section. However, its scalable architecture can accommodate multiple RF sections simultaneously to cover multiple frequency bands. The EVA SDR also supports multiple network protocols. It currently implements a Hybrid Mesh Network based on the 802.11s open standard protocol. The radio targets RF channel data rates up to 20 Mbps and can be equipped with a real-time operating system (RTOS) that can be switched off for power-aware applications. The EVA SDR's modular design permits implementation of the same hardware at all Network Nodes concept. This approach assures the portability of the same software into any radio in the system. It also brings several benefits to the entire system including reducing system maintenance, system complexity, and development cost.

  13. Biodegradation of Selected Nigerian Fruit Peels by the use of a Non-pathogenic Rhizobium species CWP G34B.

    PubMed

    Esther Boboye, Bolatito; Ajayi, George Olarewaju

    2012-01-01

    This study was carried out to determine the ability of Rhizobium species CWP G34B to degrade the peels of selected Nigerian fruits. The potential of the bacterium to digest some carbon sources (lactose, maltose, sucrose and mannitol) and peels of some Nigerian fruits (pineapple, orange, plantain, banana, pawpaw and mango fruits) was investigated by growing the organism on the substances separately after which DNSA reagent method was used to quantify glucose released into the medium. The results showed that the bacterium was able to degrade all the carbohydrates with the highest and the lowest glucose concentrations of 5.52 mg/ml for lactose and 0.50 mg/ml for mannitol. The carbohydrate-catabolic-enzyme (CCE) activity ranged from 0.169 mg/ml to 1.346 mg/ml glucose per mg/ml protein. Mannitol exhibited the highest CCE activity while the lowest activity was observed in the presence of sucrose. The amount of extracellular protein synthesized was highest (9.803 mg/ml) in the presence of maltose and lowest (0.925 mg/ml) in mannitol. The mean polygalacturonase activity was 0.54 unit/ml when the bacterium was grown in pectin in contrast to 0.28 unit/ml when it was grown in mannitol. The bacterium showed ability to breakdown the peels of the Nigerian fruits with the highest capability in banana and pineapple (0.42 and 0.41 mg/ml glucose per mg/ml protein respectively). The fruit-peel-degrading enzyme activity was lowest in orange peel (0.75 unit/ml). PMID:23166567

  14. Field performance of cucurbit and tomato plants infected with a nonpathogenic mutant of Colletotrichum magna (teleomorph: Glomerella magna; Jekins and Winstead)

    USGS Publications Warehouse

    Redman, R.S.; Roossinck, M.J.; Maher, S.; Rodriguez, R.J.

    2002-01-01

    Path-1 is a UV-induced non-pathogenic mutant of a virulent Colletotrichum magna isolate that establishes mutualistic symbioses with cucurbit and tomato species. Under laboratory conditions, this mutualism results in plant growth enhancement, drought tolerance, and disease protection against fungal pathogens. This study focuses on the efficacy of this symbiosis and the symbiotic lifestyle expressed by path-1 under field conditions in the absence of disease stress. The effects of colonization by path-1 on fruit yields and growth was measured in field plots with four cucurbit species including four watermelon cultivars, and two tomato cultivars, over four growing seasons. The persistence of the symbiosis, extent of colonization, and path-1 transmission were also assessed. Yields from path-1 infected plants were equivalent to or greater than yields from non-inoculated control plants and path-1 systemically colonized plants throughout each growing season. Path-1 also increased the growth rates of tomato plants and was not transmitted to uncolonized plants. The results indicate that there are no metabolic costs of this symbiosis and the symbiosis is maintained under field conditions.

  15. Cytokine responses of intestinal epithelial-like Caco-2 cells to non-pathogenic and opportunistic pathogenic yeasts in the presence of butyric acid.

    PubMed

    Saegusa, Shizue; Totsuka, Mamoru; Kaminogawa, Shuichi; Hosoi, Tomohiro

    2007-10-01

    Candida albicans, Saccharomyces cerevisiae and their cell wall components, zymosan and glucan, have been shown to stimulate interleukin-8 (IL-8/CXCL-8) production by intestinal epithelial cell-like Caco-2 cells pre-cultured with 10 mM butyric acid. We examined in this study whether these yeasts also altered the production of other cytokines and cyclooxygenases (COXs) by Caco-2 cells. Culturing Caco-2 cells with 10 mM butyric acid and 15% FBS for 4 days enhanced the basal levels of mRNA encoding IL-6, IL-8, IL-18, monocyte chemoattractant protein (MCP)-1, stem cell factor, transforming growth factor (TGF)-beta1, TGF-beta3, tumor necrosis factor (TNF)-alpha, COX-1, and COX-2, but not of granulocyte-macrophage colony-stimulating factor (GM-CSF) and TGF-beta2. The inclusion of live S. cerevisiae or C. albicans further enhanced the production of IL-8, but not of the other cytokines and COXs. The non-pathogenic yeasts, C. kefyr, C. utilis, C. versatilis, Kluyveromyces lactis, K. marxianus, Schizosaccharomyces pombe and Zygosaccharomyces rouxii, used for the production of fermented foods and probiotics, and the opportunistic pathogens, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis, isolated from human tissue samples also enhanced IL-8 secretion by Caco-2 cells. PMID:17928716

  16. Bilateral single-site intracerebral injection of a nonpathogenic herpes simplex virus-1 vector decreases anxiogenic behavior in MPS VII mice

    PubMed Central

    Liu, Wenpei; Griffin, Gerald; Clarke, Trena; Parente, Michael K; Valentino, Rita J; Wolfe, John H; Fraser, Nigel W

    2015-01-01

    Genetic diseases of the brain usually have pathologic lesions distributed throughout, thus requiring global correction. Herpes simplex virus-1 (HSV-1) vectors may be especially useful for gene delivery in these disorders since they can spread trans-synaptically along neuronal pathways to distal sites from a localized injection. We have previously shown that a nonpathogenic HSV-1 (strain 1716), which is deleted in the ICP34.5 gene, and expressing the lysosomal enzyme β-glucuronidase (GUSB) from the latency-associated transcript (LAT) promoter, spreads within the brains of GUSB-deficient mucopolysaccharidosis VII mice to reverse the pathognomonic storage lesions throughout the diseased brain. In this study, we tested the ability of the 1716 LAT-GUSB vector to improve behavioral deficits. The treatment significantly decreased anxiogenic behaviors associated with the mutation, as indicated by open-field behavior and decreased neophobia in a novel object-recognition task. The treated mice also exhibited an improvement in cognitive function associated with the cerebral cortex in a familiar object test. The results indicate the functional therapeutic potential of the 1716 LAT-GUSB vector. PMID:26052529

  17. Comparative proteomic analysis of extracellular secreted proteins expressed by two pathogenic Acanthamoeba castellanii clinical isolates and a non-pathogenic ATCC strain.

    PubMed

    Huang, Jian-Ming; Lin, Wei-Chen; Li, Sung-Chou; Shih, Min-Hsiu; Chan, Wen-Ching; Shin, Jyh-Wei; Huang, Fu-Chin

    2016-07-01

    Acanthamoeba keratitis (AK) is a serious ocular disease caused by pathogenic Acanthamoeba gaining entry through wounds in the corneal injury; generally, patients at risk for contracting AK wear contact lenses, usually over a long period of time. Moreover, pathogenic Acanthamoeba causes serious consequences: it makes the cornea turbid and difficult to operate on, including procedures such as enucleation of the eyeball. At present, diagnosis of this disease is not straightforward, and treatment is very demanding. We have established the comparative transcriptome and extracellular secreted proteomic database according to the non-pathogenic strain ATCC 30010 and the pathogenic strains NCKU_B and NCKU_D. We identified 44 secreted proteins successfully, 10 consensus secreted proteins and 34 strain-specific secreted proteins. These proteins may provide targets for therapy and immuno-diagnosis of Acanthamoeba infections. This study shows a suitable approach to identify secreted proteins in Acanthamoeba and provides new perspectives for the study of molecules potentially involved in the AK. PMID:26995533

  18. The Tomato Wilt Fungus Fusarium oxysporum f. sp. lycopersici shares Common Ancestors with Nonpathogenic F. oxysporum isolated from Wild Tomatoes in the Peruvian Andes

    PubMed Central

    Inami, Keigo; Kashiwa, Takeshi; Kawabe, Masato; Onokubo-Okabe, Akiko; Ishikawa, Nobuko; Pérez, Enrique Rodríguez; Hozumi, Takuo; Caballero, Liliana Aragón; de Baldarrago, Fatima Cáceres; Roco, Mauricio Jiménez; Madadi, Khalid A.; Peever, Tobin L.; Teraoka, Tohru; Kodama, Motoichiro; Arie, Tsutomu

    2014-01-01

    Fusarium oxysporum is an ascomycetous fungus that is well-known as a soilborne plant pathogen. In addition, a large population of nonpathogenic F. oxysporum (NPF) inhabits various environmental niches, including the phytosphere. To obtain an insight into the origin of plant pathogenic F. oxysporum, we focused on the tomato (Solanum lycopersicum) and its pathogenic F. oxysporum f. sp. lycopersici (FOL). We collected F. oxysporum from wild and transition Solanum spp. and modern cultivars of tomato in Chile, Ecuador, Peru, Mexico, Afghanistan, Italy, and Japan, evaluated the fungal isolates for pathogenicity, VCG, mating type, and distribution of SIX genes related to the pathogenicity of FOL, and constructed phylogenies based on ribosomal DNA intergenic spacer sequences. All F. oxysporum isolates sampled were genetically more diverse than FOL. They were not pathogenic to the tomato and did not carry SIX genes. Certain NPF isolates including those from wild Solanum spp. in Peru were grouped in FOL clades, whereas most of the NPF isolates were not. Our results suggested that the population of NPF isolates in FOL clades gave rise to FOL by gaining pathogenicity. PMID:24909710

  19. Probability of Unmixed Young Groundwater (defined using chlorofluorocarbon-11 concentrations and tritium activities) in the Eagle River Watershed Valley-Fill Aquifer, Eagle County, North-Central Colorado, 2006-2007

    USGS Publications Warehouse

    Rupert, Michael G.; Plummer, L. Niel

    2009-01-01

    This raster data set delineates the predicted probability of unmixed young groundwater (defined using chlorofluorocarbon-11 concentrations and tritium activities) in groundwater in the Eagle River watershed valley-fill aquifer, Eagle County, North-Central Colorado, 2006-2007. This data set was developed by a cooperative project between the U.S. Geological Survey, Eagle County, the Eagle River Water and Sanitation District, the Town of Eagle, the Town of Gypsum, and the Upper Eagle Regional Water Authority. This project was designed to evaluate potential land-development effects on groundwater and surface-water resources so that informed land-use and water management decisions can be made. This groundwater probability map and its associated probability maps were developed as follows: (1) A point data set of wells with groundwater quality and groundwater age data was overlaid with thematic layers of anthropogenic (related to human activities) and hydrogeologic data by using a geographic information system to assign each well values for depth to groundwater, distance to major streams and canals, distance to gypsum beds, precipitation, soils, and well depth. These data then were downloaded to a statistical software package for analysis by logistic regression. (2) Statistical models predicting the probability of elevated nitrate concentrations, the probability of unmixed young water (using chlorofluorocarbon-11 concentrations and tritium activities), and the probability of elevated volatile organic compound concentrations were developed using logistic regression techniques. (3) The statistical models were entered into a GIS and the probability map was constructed.

  20. Chemically defined medium and Caenorhabditis elegans

    NASA Technical Reports Server (NTRS)

    Szewczyk, Nathaniel J.; Kozak, Elena; Conley, Catharine A.

    2003-01-01

    BACKGROUND: C. elegans has been established as a powerful genetic system. Use of a chemically defined medium (C. elegans Maintenance Medium (CeMM)) now allows standardization and systematic manipulation of the nutrients that animals receive. Liquid cultivation allows automated culturing and experimentation and should be of use in large-scale growth and screening of animals. RESULTS: We find that CeMM is versatile and culturing is simple. CeMM can be used in a solid or liquid state, it can be stored unused for at least a year, unattended actively growing cultures may be maintained longer than with standard techniques, and standard C. elegans protocols work well with animals grown in defined medium. We also find that there are caveats to using defined medium. Animals in defined medium grow more slowly than on standard medium, appear to display adaptation to the defined medium, and display altered growth rates as they change the composition of the defined medium. CONCLUSIONS: As was suggested with the introduction of C. elegans as a potential genetic system, use of defined medium with C. elegans should prove a powerful tool.

  1. Expression of the T-cell surface molecule CD2 and an epitope-loss CD2 mutant to define the role of lymphocyte function-associated antigen 3 (LFA-3) in T-cell activation.

    PubMed Central

    Bierer, B E; Peterson, A; Barbosa, J; Seed, B; Burakoff, S J

    1988-01-01

    To define the role of the CD2-lymphocyte function-associated antigen 3 (LFA-3) interaction in T-cell activation, we have expressed a cDNA encoding the human CD2 molecule in a murine antigen-specific T-cell hybridoma. Expression of the CD2 molecule greatly enhances T-cell responsiveness to antigen; this enhancement is inhibited by anti-CD2 and anti-LFA-3 monoclonal antibodies (mAbs). CD2+ hybridomas produce interleukin 2 in response to combinations of anti-CD2 mAbs 9.6 and 9-1 and, in the presence of mAb 9-1, to sheep erythrocytes or to the LFA-3 antigen. Furthermore, hybridomas expressing a mutant CD2 molecule that has lost mAb 9.6 binding do not exhibit the enhanced response to antigen or the ability to respond to LFA-3 plus mAb 9-1, but these hybridomas retain the ability to respond to combinations of anti-CD2 mAbs. The role of the CD2-LFA-3 interaction in T-cell activation and the potential for other physiologic ligands for CD2 are discussed. PMID:2448792

  2. Clarifying and Defining Library Services.

    ERIC Educational Resources Information Center

    Shubert, Joseph F., Ed.; Josey, E. J., Ed.

    1991-01-01

    This issue presents articles which, in some way, help to clarify and define library services. It is hoped that this clarification in library service will serve to secure the resources libraries need to serve the people of New York. The following articles are presented: (1) Introduction: "Clarifying and Defining Library Services" (Joseph F.…

  3. Crack-Defined Electronic Nanogaps.

    PubMed

    Dubois, Valentin; Niklaus, Frank; Stemme, Göran

    2016-03-01

    Achieving near-atomic-scale electronic nanogaps in a reliable and scalable manner will facilitate fundamental advances in molecular detection, plasmonics, and nanoelectronics. Here, a method is shown for realizing crack-defined nanogaps separating TiN electrodes, allowing parallel and scalable fabrication of arrays of sub-10 nm electronic nanogaps featuring individually defined gap widths. PMID:26784270

  4. Mannan-conjugated myelin peptides prime non-pathogenic Th1 and Th17 cells and ameliorate experimental autoimmune encephalomyelitis.

    PubMed

    Tseveleki, Vivian; Tselios, Theodore; Kanistras, Ioannis; Koutsoni, Olga; Karamita, Maria; Vamvakas, Sotiris-Spyros; Apostolopoulos, Vasso; Dotsika, Eleni; Matsoukas, John; Lassmann, Hans; Probert, Lesley

    2015-05-01

    Antigen presenting cells (APC) are critical for regulating immune responses. We tested mannan-peptide conjugates for targeting myelin peptides to APC to induce T cell tolerance and resistance to experimental autoimmune encephalomyelitis (EAE). Myelin peptides conjugated to mannan in oxidized (OM) or reduced (RM) forms protected mice against EAE in prophylactic and therapeutic protocols, with OM-conjugated peptides giving best results. Protection was peptide-specific and associated with reduced antigen-specific T cell proliferation, but not alterations in Th1, Th17 and Treg cell differentiation or T cell apoptosis compared to EAE controls. Bone marrow-derived dendritic cells (DC) loaded with OM-MOG showed up-regulated expression of co-stimulatory molecules, reduced PD-L1 expression and enhanced CD40-inducible IL-12 and IL-23 production compared to MOG DC, features consistent with immunogenic DC. OM-MOG induced active T cell tolerance because i.d. administration or passive transfer of OM-MOG DC suppressed ongoing EAE, while OM-MOG-vaccinated mice did not reduce the proliferation of transferred MOG-specific T cells. As in vivo, MOG-specific T cells cultured with OM-MOG DC showed reduced proliferation and equal Th1 and Th17 cell differentiation compared to those with MOG DC, but surprisingly cytokine production was unresponsive to CD40 engagement. Impaired effector T cell function was further evidenced in spinal cord sections from OM-MOG-vaccinated EAE mice, where markedly reduced numbers of CD3(+) T cells were present, restricted to leptomeninges and exceptional parenchymal lesions. Our results show that mannan-conjugated myelin peptides protect mice against EAE through the expansion of antigen-specific Th1 and Th17 cells with impaired proliferation responses and APC-induced co-stimulatory signals that are required for licensing them to become fully pathogenic T cells. PMID:25447934

  5. Nucleotide sequence and genomic organization of Aleutian mink disease parvovirus (ADV): sequence comparisons between a nonpathogenic and a pathogenic strain of ADV.

    PubMed Central

    Bloom, M E; Alexandersen, S; Perryman, S; Lechner, D; Wolfinbarger, J B

    1988-01-01

    A DNA sequence of 4,592 nucleotides (nt) was derived for the nonpathogenic ADV-G strain of Aleutian mink disease parvovirus (ADV). The 3'(left) end of the virion strand contained a 117-nt palindrome that could assume a Y-shaped configuration similar to, but less stable than, that of other parvoviruses. The sequence obtained for the 5' end was incomplete and did not contain the 5' (right) hairpin structure but ended just after a 25-nt A + T-rich direct repeat. Features of ADV genomic organization are (i) major left (622 amino acids) and right (702 amino acids) open reading frames (ORFs) in different translational frames of the plus-sense strand, (ii) two short mid-ORFs, (iii) eight potential promoter motifs (TATA boxes), including ones at 3 and 36 map units, and (iv) six potential polyadenylation sites, including three clustered near the termination of the right ORF. Although the overall homology to other parvoviruses is less than 50%, there are short conserved amino acid regions in both major ORFs. However, two regions in the right ORF allegedly conserved among the parvoviruses were not present in ADV. At the DNA level, ADV-G is 97.5% related to the pathogenic ADV-Utah 1. A total of 22 amino acid changes were found in the right ORF; changes were found in both hydrophilic and hydrophobic regions and generally did not affect the theoretical hydropathy. However, there is a short heterogeneous region at 64 to 65 map units in which 8 out of 11 residues have diverged; this hypervariable segment may be analogous to short amino acid regions in other parvoviruses that determine host range and pathogenicity. These findings suggested that this region may harbor some of the determinants responsible for the differences in pathogenicity of ADV-G and ADV-Utah 1. PMID:2839709

  6. Highly Active Au/δ-MoC and Cu/δ-MoC Catalysts for the Conversion of CO2: The Metal/C Ratio as a Key Factor Defining Activity, Selectivity, and Stability.

    PubMed

    Posada-Pérez, Sergio; Ramírez, Pedro J; Evans, Jaime; Viñes, Francesc; Liu, Ping; Illas, Francesc; Rodriguez, José A

    2016-07-01

    The ever growing increase of CO2 concentration in the atmosphere is one of the main causes of global warming. Thus, CO2 activation and conversion toward valuable added compounds is a major scientific challenge. A new set of Au/δ-MoC and Cu/δ-MoC catalysts exhibits high activity, selectivity, and stability for the reduction of CO2 to CO with some subsequent selective hydrogenation toward methanol. Sophisticated experiments under controlled conditions and calculations based on density functional theory have been used to study the unique behavior of these systems. A detailed comparison of the behavior of Au/β-Mo2C and Au/δ-MoC catalysts provides evidence of the impact of the metal/carbon ratio in the carbide on the performance of the catalysts. The present results show that this ratio governs the chemical behavior of the carbide and the properties of the admetal, up to the point of being able to switch the rate and mechanism of the process for CO2 conversion. A control of the metal/carbon ratio paves the road for an efficient reutilization of this environmental harmful greenhouse gas. PMID:27308923

  7. Technical communication: Notes toward defining discipline

    NASA Technical Reports Server (NTRS)

    Rubens, P. M.

    1981-01-01

    In the field of technical communication, definitions posited in virtually any major text violate every major rule of definitions. The most popular method for defining the field is to state that technical writing is any writing that supports technology or technological activities. There is a need for a nice yardstick for measuring what "technology" is. Some ways in which the field can be defined in a tightly structured empirical way and some implications of technical communication for a humanistic education in a technological age are suggested.

  8. The Problem of Defining Intelligence.

    ERIC Educational Resources Information Center

    Lubar, David

    1981-01-01

    The major philosophical issues surrounding the concept of intelligence are reviewed with respect to the problems surrounding the process of defining and developing artificial intelligence (AI) in computers. Various current definitions and problems with these definitions are presented. (MP)

  9. Validation of Baking To Control Salmonella Serovars in Hamburger Bun Manufacturing, and Evaluation of Enterococcus faecium ATCC 8459 and Saccharomyces cerevisiae as Nonpathogenic Surrogate Indicators.

    PubMed

    Channaiah, Lakshmikantha H; Holmgren, Elizabeth S; Michael, Minto; Sevart, Nicholas J; Milke, Donka; Schwan, Carla L; Krug, Matthew; Wilder, Amanda; Phebus, Randall K; Thippareddi, Harshavardhan; Milliken, George

    2016-04-01

    This study was conducted to validate a simulated commercial baking process for hamburger buns to destroy Salmonella serovars and to determine the appropriateness of using nonpathogenic surrogates (Enterococcus faecium ATCC 8459 or Saccharomyces cerevisiae) for in-plant process validation studies. Wheat flour was inoculated (∼6 log CFU/g) with three Salmonella serovars (Typhimurium, Newport, or Senftenberg 775W) or with E. faecium. Dough was formed, proofed, and baked to mimic commercial manufacturing conditions. Buns were baked for up to 13 min in a conventional oven (218.3°C), with internal crumb temperature increasing to ∼100°C during the first 8 min of baking and remaining at this temperature until removal from the oven. Salmonella and E. faecium populations were undetectable by enrichment (>6-log CFU/g reductions) after 9.0 and 11.5 min of baking, respectively, and ≥5-log-cycle reductions were achieved by 6.0 and 7.75 min, respectively. D-values of Salmonella (three-serovar cocktail) and E. faecium 8459 in dough were 28.64 and 133.33, 7.61 and 55.67, and 3.14 and 14.72 min at 55, 58, and 61°C, respectively, whereas D-values of S. cerevisiae were 18.73, 5.67, and 1.03 min at 52, 55, and 58°C, respectivly. The z-values of Salmonella, E. faecium, and S. cerevisiae were 6.58, 6.25, and 4.74°C, respectively. A high level of thermal lethality was observed for baking of typical hamburger bun dough, resulting in rapid elimination of high levels of the three-strain Salmonella cocktail; however, the lethality and microbial destruction kinetics should not be extrapolated to other bakery products without further research. E. faecium demonstrated greater thermal resistance compared with Salmonella during bun baking and could serve as a conservative surrogate to validate thermal process lethality in commercial bun baking operations. Low thermal tolerance of S. cerevisiae relative to Salmonella serovars limits its usefulness as a surrogate for process validations

  10. Survival and Persistence of Nonpathogenic Escherichia coli and Attenuated Escherichia coli O157:H7 in Soils Amended with Animal Manure in a Greenhouse Environment.

    PubMed

    Sharma, Manan; Millner, Patricia D; Hashem, Fawzy; Camp, Mary; Whyte, Celia; Graham, Lorna; Cotton, Corrie P

    2016-06-01

    Animal manure provides benefits to agriculture but may contain pathogens that contaminate ready-to-eat produce. U.S. Food and Drug Administration standards include 90- or 120-day intervals between application of manure and harvest of crop to minimize risks of pathogen contamination of fresh produce. Data on factors affecting survival of Escherichia coli in soils under greenhouse conditions are needed. Three separate studies were conducted to evaluate survival of nonpathogenic E. coli (gEc) and attenuated E. coli O157:H7 (attO157) inoculated at either low (4 log CFU/ml) or high (6 log CFU/ml) populations over 56 days. Studies involved two pot sizes (small, 398 cm(3); large, 89 liters), three soil types (sandy loam, SL; clay loam, CL; silt loam, SIL), and four amendments (poultry litter, PL; dairy manure liquids, DML; horse manure, HM; unamended). Amendments were applied to the surface of the soil in either small or large containers. Study 1, conducted in regularly irrigated small containers, showed that populations of gEc and attO157 (2.84 to 2.88 log CFU/g) in PL-amended soils were significantly (P < 0.05) greater than those in DML-amended (0.29 to 0.32 log CFU/g [dry weight] [gdw]) or unamended (0.25 to 0.28 log CFU/gdw) soils; soil type did not affect E. coli survival. Results from study 2, in large pots with CL and SIL, showed that PL-amended soils supported significantly higher attO157 and gEc populations compared with HM-amended or unamended soils. Study 3 compared results from small and large containers that received high inoculum simultaneously. Overall, in both small and large containers, PLamended soils supported higher gEc and attO157 populations compared with HM-amended and unamended soils. Populations of attO157 were significantly greater in small containers (1.83 log CFU/gdw) than in large containers (0.65 log CFU/gdw) at week 8, perhaps because small containers received more regular irrigation than large pots. Regular irrigation of small pots may have

  11. Research misconduct oversight: defining case costs.

    PubMed

    Gammon, Elizabeth; Franzini, Luisa

    2013-01-01

    This study uses a sequential mixed method study design to define cost elements of research misconduct among faculty at academic medical centers. Using time driven activity based costing, the model estimates a per case cost for 17 cases of research misconduct reported by the Office of Research Integrity for the period of 2000-2005. Per case cost of research misconduct was found to range from $116,160 to $2,192,620. Research misconduct cost drivers are identified. PMID:24551963

  12. Defining Sex and Abstinence: Dialogue Is the Key

    ERIC Educational Resources Information Center

    Hamill, Shelley D.; Chepko, Stevie

    2005-01-01

    When does abstinence end and sexual activity begin? In previous generations, the continuum of sexual activity was well-defined in the old baseball analogy. Teens, parents, and teachers knew what going to first, second, or third base involved. For the current generation of young people, sex and abstinence are not so well-defined. As parents and…

  13. Defining "Folklore" in the Classroom.

    ERIC Educational Resources Information Center

    Falke, Anne

    Folklore, a body of traditional beliefs of a people conveyed orally or by means of custom, is very much alive, involves all people, and is not the study of popular culture. In studying folklore, the principal tasks of the folklorist have been defined as determining definition, classification, source (the folk), origin (who composed folklore),…

  14. Defined by Word and Space

    ERIC Educational Resources Information Center

    Brisco, Nicole D.

    2010-01-01

    In the author's art class, she found that many of her students in an intro art class have some technical skill, but lack the ability to think conceptually. Her goal was to create an innovative project that combined design, painting, and sculpture into a compact unit that asked students how they define themselves. In the process of answering this…

  15. Defining and managing sustainable yield.

    PubMed

    Maimone, Mark

    2004-01-01

    Ground water resource management programs are paying increasing attention to the integration of ground water and surface water in the planning process. Many plans, however, show a sophistication in approach and presentation that masks a fundamental weakness in the overall analysis. The plans usually discuss issues of demand and yield, yet never directly address a fundamental issue behind the plan--how to define sustainable yield of an aquifer system. This paper points out a number of considerations that must be addressed in defining sustainable yield in order to make the definition more useful in practical water resource planning studies. These include consideration for the spatial and temporal aspects of the problem, the development of a conceptual water balance, the influence of boundaries and changes in technology on the definition, the need to examine water demand as well as available supply, the need for stakeholder involvement, and the issue of uncertainty in our understanding of the components of the hydrologic system. PMID:15584295

  16. Defined DNA/nanoparticle conjugates.

    PubMed

    Ackerson, Christopher J; Sykes, Michael T; Kornberg, Roger D

    2005-09-20

    Glutathione monolayer-protected gold clusters were reacted by place exchange with 19- or 20-residue thiolated oligonucleotides. The resulting DNA/nanoparticle conjugates could be separated on the basis of the number of bound oligonucleotides by gel electrophoresis and assembled with one another by DNA-DNA hybridization. This approach overcomes previous limitations of DNA/nanoparticle synthesis and yields conjugates that are precisely defined with respect to both gold and nucleic acid content. PMID:16155122

  17. How do people define moderation?

    PubMed

    vanDellen, Michelle R; Isherwood, Jennifer C; Delose, Julie E

    2016-06-01

    Eating in moderation is considered to be sound and practical advice for weight maintenance or prevention of weight gain. However, the concept of moderation is ambiguous, and the effect of moderation messages on consumption has yet to be empirically examined. The present manuscript examines how people define moderate consumption. We expected that people would define moderate consumption in ways that justified their current or desired consumption rather than view moderation as an objective standard. In Studies 1 and 2, moderate consumption was perceived to involve greater quantities of an unhealthy food (chocolate chip cookies, gummy candies) than perceptions of how much one should consume. In Study 3, participants generally perceived themselves to eat in moderation and defined moderate consumption as greater than their personal consumption. Furthermore, definitions of moderate consumption were related to personal consumption behaviors. Results suggest that the endorsement of moderation messages allows for a wide range of interpretations of moderate consumption. Thus, we conclude that moderation messages are unlikely to be effective messages for helping people maintain or lose weight. PMID:26964691

  18. The Influence of Second-Hand Cigarette Smoke Exposure during Childhood and Active Cigarette Smoking on Crohn’s Disease Phenotype Defined by the Montreal Classification Scheme in a Western Cape Population, South Africa

    PubMed Central

    Chivese, Tawanda; Esterhuizen, Tonya M.; Basson, Abigail Raffner

    2015-01-01

    Background Smoking may worsen the disease outcomes in patients with Crohn’s disease (CD), however the effect of exposure to second-hand cigarette smoke during childhood is unclear. In South Africa, no such literature exists. The aim of this study was to investigate whether disease phenotype, at time of diagnosis of CD, was associated with exposure to second-hand cigarette during childhood and active cigarette smoking habits. Methods A cross sectional examination of all consecutive CD patients seen during the period September 2011-January 2013 at 2 large inflammatory bowel disease centers in the Western Cape, South Africa was performed. Data were collected via review of patient case notes, interviewer-administered questionnaire and clinical examination by the attending gastroenterologist. Disease phenotype (behavior and location) was evaluated at time of diagnosis, according to the Montreal Classification scheme. In addition, disease behavior was stratified as ‘complicated’ or ‘uncomplicated’, using predefined definitions. Passive cigarette smoke exposure was evaluated during 3 age intervals: 0–5, 6–10, and 11–18 years. Results One hundred and ninety four CD patients were identified. Cigarette smoking during the 6 months prior to, or at time of diagnosis was significantly associated with ileo-colonic (L3) disease (RRR = 3.63; 95%CI, 1.32–9.98, p = 0.012) and ileal (L1) disease (RRR = 3.54; 95%CI, 1.06–11.83, p = 0.040) compared with colonic disease. In smokers, childhood passive cigarette smoke exposure during the 0–5 years age interval was significantly associated with ileo-colonic CD location (RRR = 21.3; 95%CI, 1.16–391.55, p = 0.040). No significant association between smoking habits and disease behavior at diagnosis, whether defined by the Montreal scheme, or stratified as ‘complicated’ vs ‘uncomplicated’, was observed. Conclusion Smoking habits were associated with ileo-colonic (L3) and ileal (L1) disease at time of diagnosis in

  19. Impaired intracellular trafficking defines early Parkinson's disease

    PubMed Central

    Hunn, Benjamin H.M.; Cragg, Stephanie J.; Bolam, J. Paul; Spillantini, Maria-Grazia; Wade-Martins, Richard

    2015-01-01

    Parkinson's disease (PD) is an insidious and incurable neurodegenerative disease, and represents a significant cost to individuals, carers, and ageing societies. It is defined at post-mortem by the loss of dopamine neurons in the substantia nigra together with the presence of Lewy bodies and Lewy neurites. We examine here the role of α-synuclein and other cellular transport proteins implicated in PD and how their aberrant activity may be compounded by the unique anatomy of the dopaminergic neuron. This review uses multiple lines of evidence from genetic studies, human tissue, induced pluripotent stem cells, and refined animal models to argue that prodromal PD can be defined as a disease of impaired intracellular trafficking. Dysfunction of the dopaminergic synapse heralds trafficking impairment. PMID:25639775

  20. Defined DNA/nanoparticle conjugates

    NASA Astrophysics Data System (ADS)

    Ackerson, Christopher J.; Sykes, Michael T.; Kornberg, Roger D.

    2005-09-01

    Glutathione monolayer-protected gold clusters were reacted by place exchange with 19- or 20-residue thiolated oligonucleotides. The resulting DNA/nanoparticle conjugates could be separated on the basis of the number of bound oligonucleotides by gel electrophoresis and assembled with one another by DNA-DNA hybridization. This approach overcomes previous limitations of DNA/nanoparticle synthesis and yields conjugates that are precisely defined with respect to both gold and nucleic acid content. Freely available online through the PNAS open access option.

  1. Defining Life: Synthesis and Conclusions

    NASA Astrophysics Data System (ADS)

    Gayon, Jean

    2010-04-01

    The first part of the paper offers philosophical landmarks on the general issue of defining life. §1 defends that the recognition of “life” has always been and remains primarily an intuitive process, for the scientist as for the layperson. However we should not expect, then, to be able to draw a definition from this original experience, because our cognitive apparatus has not been primarily designed for this. §2 is about definitions in general. Two kinds of definition should be carefully distinguished: lexical definitions (based upon current uses of a word), and stipulative or legislative definitions, which deliberately assign a meaning to a word, for the purpose of clarifying scientific or philosophical arguments. The present volume provides examples of these two kinds of definitions. §3 examines three traditional philosophical definitions of life, all of which have been elaborated prior to the emergence of biology as a specific scientific discipline: life as animation (Aristotle), life as mechanism, and life as organization (Kant). All three concepts constitute a common heritage that structures in depth a good deal of our cultural intuitions and vocabulary any time we try to think about “life”. The present volume offers examples of these three concepts in contemporary scientific discourse. The second part of the paper proposes a synthesis of the major debates developed in this volume. Three major questions have been discussed. A first issue (§4) is whether we should define life or not, and why. Most authors are skeptical about the possibility of defining life in a strong way, although all admit that criteria are useful in contexts such as exobiology, artificial life and the origins of life. §5 examines the possible kinds of definitions of life presented in the volume. Those authors who have explicitly defended that a definition of life is needed, can be classified into two categories. The first category (or standard view) refers to two conditions

  2. Defining life: synthesis and conclusions.

    PubMed

    Gayon, Jean

    2010-04-01

    The first part of the paper offers philosophical landmarks on the general issue of defining life. Section 1 defends that the recognition of "life" has always been and remains primarily an intuitive process, for the scientist as for the layperson. However we should not expect, then, to be able to draw a definition from this original experience, because our cognitive apparatus has not been primarily designed for this. Section 2 is about definitions in general. Two kinds of definition should be carefully distinguished: lexical definitions (based upon current uses of a word), and stipulative or legislative definitions, which deliberately assign a meaning to a word, for the purpose of clarifying scientific or philosophical arguments. The present volume provides examples of these two kinds of definitions. Section 3 examines three traditional philosophical definitions of life, all of which have been elaborated prior to the emergence of biology as a specific scientific discipline: life as animation (Aristotle), life as mechanism, and life as organization (Kant). All three concepts constitute a common heritage that structures in depth a good deal of our cultural intuitions and vocabulary any time we try to think about "life". The present volume offers examples of these three concepts in contemporary scientific discourse. The second part of the paper proposes a synthesis of the major debates developed in this volume. Three major questions have been discussed. A first issue (Section 4) is whether we should define life or not, and why. Most authors are skeptical about the possibility of defining life in a strong way, although all admit that criteria are useful in contexts such as exobiology, artificial life and the origins of life. Section 5 examines the possible kinds of definitions of life presented in the volume. Those authors who have explicitly defended that a definition of life is needed, can be classified into two categories. The first category (or standard view) refers

  3. Defining biocultural approaches to conservation.

    PubMed

    Gavin, Michael C; McCarter, Joe; Mead, Aroha; Berkes, Fikret; Stepp, John Richard; Peterson, Debora; Tang, Ruifei

    2015-03-01

    We contend that biocultural approaches to conservation can achieve effective and just conservation outcomes while addressing erosion of both cultural and biological diversity. Here, we propose a set of guidelines for the adoption of biocultural approaches to conservation. First, we draw lessons from work on biocultural diversity and heritage, social-ecological systems theory, integrated conservation and development, co-management, and community-based conservation to define biocultural approaches to conservation. Second, we describe eight principles that characterize such approaches. Third, we discuss reasons for adopting biocultural approaches and challenges. If used well, biocultural approaches to conservation can be a powerful tool for reducing the global loss of both biological and cultural diversity. PMID:25622889

  4. 33 CFR 211.1 - Real estate defined.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Real estate defined. 211.1... DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.1 Real estate defined. The term real estate as used in this part includes...

  5. 33 CFR 211.1 - Real estate defined.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Real estate defined. 211.1... DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.1 Real estate defined. The term real estate as used in this part includes...

  6. 33 CFR 211.1 - Real estate defined.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Real estate defined. 211.1... DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.1 Real estate defined. The term real estate as used in this part includes...

  7. 20 CFR 212.2 - Military service defined.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Military service defined. 212.2 Section 212.2 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT MILITARY SERVICE § 212.2 Military service defined. Military service is the performance of active service by an...

  8. 20 CFR 212.2 - Military service defined.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Military service defined. 212.2 Section 212.2 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT MILITARY SERVICE § 212.2 Military service defined. Military service is the performance of active service by an...

  9. 20 CFR 212.2 - Military service defined.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Military service defined. 212.2 Section 212.2 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT MILITARY SERVICE § 212.2 Military service defined. Military service is the performance of active service by an...

  10. 20 CFR 212.2 - Military service defined.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Military service defined. 212.2 Section 212.2 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT MILITARY SERVICE § 212.2 Military service defined. Military service is the performance of active service by an...

  11. 20 CFR 212.2 - Military service defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Military service defined. 212.2 Section 212.2 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT MILITARY SERVICE § 212.2 Military service defined. Military service is the performance of active service by an...

  12. Defining Electron Backscatter Diffraction Resolution

    SciTech Connect

    El-Dasher, B S; Rollett, A D

    2005-02-07

    Automated electron backscatter diffraction (EBSD) mapping systems have existed for more than 10 years [1,2], and due to their versatility in characterizing multiple aspects of microstructure, they have become an important tool in microscale crystallographic studies. Their increasingly widespread use however raises questions about their accuracy in both determining crystallographic orientations, as well as ensuring that the orientation information is spatially correct. The issue of orientation accuracy (as defined by angular resolution) has been addressed previously [3-5]. While the resolution of EBSD systems is typically quoted to be on the order of 1{sup o}, it has been shown that by increasing the pattern quality via acquisition parameter adjustment, the angular resolution can be improved to sub-degree levels. Ultimately, the resolution is dependent on how it is identified. In some cases it can be identified as the orientation relative to a known absolute, in others as the misorientation between nearest neighbor points in a scan. Naturally, the resulting values can be significantly different. Therefore, a consistent and universal definition of resolution that can be applied to characterize any EBSD system is necessary, and is the focus of the current study. In this work, a Phillips (FEI) XL-40 FEGSEM coupled to a TexSEM Laboratories OIM system was used. The pattern capturing hardware consisted of both a 512 by 512 pixel SIT CCD camera and a 1300 by 1030 pixel Peltier cooled CCD camera. Automated scans of various sizes, each consisting of 2500 points, were performed on a commercial-grade single crystal silicon wafer used for angular resolution measurements. To adequately quantify angular resolution for all possible EBSD applications we define two angular values. The first is {omega}{sub center}, the mean of the misorientation angle distribution between all scan points and the scan point coincident to the calibration source (typically the scan center). The {omega

  13. Antimicrobial Efficacy of a Lactic Acid and Citric Acid Blend against Shiga Toxin-Producing Escherichia coli, Salmonella, and Nonpathogenic Escherichia coli Biotype I on Inoculated Prerigor Beef Carcass Surface Tissue.

    PubMed

    Scott, Brittney R; Yang, Xiang; Geornaras, Ifigenia; Delmore, Robert J; Woerner, Dale R; Adler, Jeremy M; Belk, Keith E

    2015-12-01

    Studies were conducted to (i) determine whether inoculants of nonpathogenic Escherichia coli biotype I effectively served as surrogates for E. coli O157:H7, non-O157 Shiga toxin-producing E. coli, and Salmonella when prerigor beef carcass tissue was treated with a commercially available blend of lactic acid and citric acid (LCA) at a range of industry conditions of concentration, temperature, and pressure; (ii) determine the antimicrobial efficacy of LCA; and (iii) investigate the use of surrogates to validate a hot water and LCA sequential treatment as a carcass spray intervention in a commercial beef harvest plant. In an initial laboratory study, beef brisket tissue samples were left uninoculated or were inoculated (∼6 log CFU/cm(2)) on the adipose side with E. coli O157:H7 (5-strain mixture), non-O157 Shiga toxin-producing E. coli (12-strain mixture), Salmonella (6-strain mixture), or nonpathogenic E. coli (5-strain mixture). Samples were left untreated (control) or were treated with LCA, in a spray cabinet, at one of eight combinations of solution concentration (1.9 and 2.5%), solution temperature (43 and 60°C), and application pressure (15 and 30 lb/in(2)). In a second study, the E. coli surrogates were inoculated (∼6 log CFU/cm(2)) on beef carcasses in a commercial facility to validate the use of a hot water treatment (92.2 to 92.8°C, 13 to 15 lb/in(2)) followed by an LCA treatment (1.9%, 50 to 51.7°C, 13 to 15 lb/in(2), 10 s). In the in vitro study, surrogate and pathogen bacteria did not differ in their response to the tested LCA treatments. Treatment with LCA reduced (P < 0.05) inoculated populations by 0.9 to 1.5 log CFU/cm(2), irrespective of inoculum type. The hot water and LCA sequential treatments evaluated in the commercial facility reduced (P < 0.05) the inoculated nonpathogenic E. coli surrogates on carcasses by 3.7 log CFU/cm(2). This study therefore provides the meat industry with data for this sequential multiple hurdle system for the

  14. Draft Genome Sequence of Bacillus subtilis ALBA01, a Strain with Antagonistic Activity against the Soilborne Fungal Pathogen of Onion Setophoma terrestris

    PubMed Central

    Tobares, Romina A.; Ducasse, Daniel A.; Smania, Andrea M.

    2016-01-01

    Bacillus subtilis is a nonpathogenic bacterium that lives in soil and has long been used as biological control agent in agriculture. Here, we report the genome sequence of a B. subtilis strain isolated from rhizosphere of onion that shows strong biological activity against the soilborne fungal pathogen Setophoma terrestris. PMID:27257193

  15. Draft Genome Sequence of Bacillus subtilis ALBA01, a Strain with Antagonistic Activity against the Soilborne Fungal Pathogen of Onion Setophoma terrestris.

    PubMed

    Albarracín Orio, Andrea G; Tobares, Romina A; Ducasse, Daniel A; Smania, Andrea M

    2016-01-01

    Bacillus subtilis is a nonpathogenic bacterium that lives in soil and has long been used as biological control agent in agriculture. Here, we report the genome sequence of a B. subtilis strain isolated from rhizosphere of onion that shows strong biological activity against the soilborne fungal pathogen Setophoma terrestris. PMID:27257193

  16. Defining the Stimulus - A Memoir

    PubMed Central

    Terrace, Herbert

    2010-01-01

    The eminent psychophysicist, S. S. Stevens, once remarked that, “the basic problem of psychology was the definition of the stimulus” (Stevens, 1951, p. 46). By expanding the traditional definition of the stimulus, the study of animal learning has metamorphosed into animal cognition. The main impetus for that change was the recognition that it is often necessary to postulate a representation between the traditional S and R of learning theory. Representations allow a subject to re-present a stimulus it learned previously that is currently absent. Thus, in delayed-matching-to-sample, one has to assume that a subject responds to a representation of the sample during test if it responds correctly. Other examples, to name but a few, include concept formation, spatial memory, serial memory, learning a numerical rule, imitation and metacognition. Whereas a representation used to be regarded as a mentalistic phenomenon that was unworthy of scientific inquiry, it can now be operationally defined. To accommodate representations, the traditional discriminative stimulus has to be expanded to allow for the role of representations. The resulting composite can account for a significantly larger portion of the variance of performance measures than the exteroceptive stimulus could by itself. PMID:19969047

  17. Endothelial progenitor cells: identity defined?

    PubMed Central

    Timmermans, Frank; Plum, Jean; Yöder, Mervin C; Ingram, David A; Vandekerckhove, Bart; Case, Jamie

    2009-01-01

    Abstract In the past decade, researchers have gained important insights on the role of bone marrow (BM)-derived cells in adult neovascularization. A subset of BM-derived cells, called endothelial progenitor cells (EPCs), has been of particular interest, as these cells were suggested to home to sites of neovascularization and neoendothelialization and differentiate into endothelial cells (ECs) in situ, a process referred to as postnatal vasculogenesis. Therefore, EPCs were proposed as a potential regenerative tool for treating human vascular disease and a possible target to restrict vessel growth in tumour pathology. However, conflicting results have been reported in the field, and the identification, characterization, and exact role of EPCs in vascular biology is still a subject of much discussion. The focus of this review is on the controversial issues in the field of EPCs which are related to the lack of a unique EPC marker, identification challenges related to the paucity of EPCs in the circulation, and the important phenotypical and functional overlap between EPCs, haematopoietic cells and mature ECs. We also discuss our recent findings on the origin of endothelial outgrowth cells (EOCs), showing that this in vitro defined EC population does not originate from circulating CD133+ cells or CD45+ haematopoietic cells. PMID:19067770

  18. Defining an Open Source Strategy for NASA

    NASA Astrophysics Data System (ADS)

    Mattmann, C. A.; Crichton, D. J.; Lindsay, F.; Berrick, S. W.; Marshall, J. J.; Downs, R. R.

    2011-12-01

    Over the course of the past year, we have worked to help frame a strategy for NASA and open source software. This includes defining information processes to understand open source licensing, attribution, commerciality, redistribution, communities, architectures, and interactions within the agency. Specifically we held a training session at the NASA Earth Science Data Systems Working Group meeting in Open Source software as it relates to the NASA Earth Science data systems enterprise, including EOSDIS, the Distributed Active Archive Centers (DAACs), ACCESS proposals, and the MEASURES communities, and efforts to understand how open source software can be both consumed and produced within that ecosystem. In addition, we presented at the 1st NASA Open Source Summit (OSS) and helped to define an agency-level strategy, a set of recommendations and paths forward for how to identify healthy open source communities, how to deal with issues such as contributions originating from other agencies, and how to search out talent with the right skills to develop software for NASA in the modern age. This talk will review our current recommendations for open source at NASA, and will cover the set of thirteen recommendations output from the NASA Open Source Summit and discuss some of their implications for the agency.

  19. Defining the clinical course of multiple sclerosis

    PubMed Central

    Reingold, Stephen C.; Cohen, Jeffrey A.; Cutter, Gary R.; Sørensen, Per Soelberg; Thompson, Alan J.; Wolinsky, Jerry S.; Balcer, Laura J.; Banwell, Brenda; Barkhof, Frederik; Bebo, Bruce; Calabresi, Peter A.; Clanet, Michel; Comi, Giancarlo; Fox, Robert J.; Freedman, Mark S.; Goodman, Andrew D.; Inglese, Matilde; Kappos, Ludwig; Kieseier, Bernd C.; Lincoln, John A.; Lubetzki, Catherine; Miller, Aaron E.; Montalban, Xavier; O'Connor, Paul W.; Petkau, John; Pozzilli, Carlo; Rudick, Richard A.; Sormani, Maria Pia; Stüve, Olaf; Waubant, Emmanuelle; Polman, Chris H.

    2014-01-01

    Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined. PMID:24871874

  20. Characterization of Medicago truncatula (barrel medic) hydroperoxide lyase (CYP74C3), a water-soluble detergent-free cytochrome P450 monomer whose biological activity is defined by monomer–micelle association

    PubMed Central

    Hughes, Richard K.; Belfield, Eric J.; Muthusamay, Mylrajan; Khan, Anuja; Rowe, Arthur; Harding, Stephen E.; Fairhurst, Shirley A.; Bornemann, Stephen; Ashton, Ruth; Thorneley, Roger N. F.; Casey, Rod

    2006-01-01

    We describe the detailed biochemical characterization of CYP74C3 (cytochrome P450 subfamily 74C3), a recombinant plant cytochrome P450 enzyme with HPL (hydroperoxide lyase) activity from Medicago truncatula (barrel medic). Steady-state kinetic parameters, substrate and product specificities, RZ (Reinheitszahl or purity index), molar absorption coefficient, haem content, and new ligands for an HPL are reported. We show on the basis of gel filtration, sedimentation velocity (sedimentation coefficient distribution) and sedimentation equilibrium (molecular mass) analyses that CYP74C3 has low enzyme activity as a detergent-free, water-soluble, monomer. The enzyme activity can be completely restored by re-activation with detergent micelles, but not detergent monomers. Corresponding changes in the spin state equilibrium, and probably co-ordination of the haem iron, are novel for cytochrome P450 enzymes and suggest that detergent micelles have a subtle effect on protein conformation, rather than substrate presentation, which is sufficient to improve substrate binding and catalytic-centre activity by an order of magnitude. The kcat/Km of up to 1.6×108 M−1·s−1 is among the highest recorded, which is remarkable for an enzyme whose reaction mechanism involves the scission of a C–C bond. We carried out both kinetic and biophysical studies to demonstrate that this effect is a result of the formation of a complex between a protein monomer and a single detergent micelle. Association with a detergent micelle rather than oligomeric state represents a new mechanism of activation for membrane-associated cytochrome P450 enzymes. Highly concentrated and monodispersed samples of detergent-free CYP74C3 protein may be well suited for the purposes of crystallization and structural resolution of the first plant cytochrome P450 enzyme. PMID:16454766

  1. Defining nodes in complex brain networks

    PubMed Central

    Stanley, Matthew L.; Moussa, Malaak N.; Paolini, Brielle M.; Lyday, Robert G.; Burdette, Jonathan H.; Laurienti, Paul J.

    2013-01-01

    Network science holds great promise for expanding our understanding of the human brain in health, disease, development, and aging. Network analyses are quickly becoming the method of choice for analyzing functional MRI data. However, many technical issues have yet to be confronted in order to optimize results. One particular issue that remains controversial in functional brain network analyses is the definition of a network node. In functional brain networks a node represents some predefined collection of brain tissue, and an edge measures the functional connectivity between pairs of nodes. The characteristics of a node, chosen by the researcher, vary considerably in the literature. This manuscript reviews the current state of the art based on published manuscripts and highlights the strengths and weaknesses of three main methods for defining nodes. Voxel-wise networks are constructed by assigning a node to each, equally sized brain area (voxel). The fMRI time-series recorded from each voxel is then used to create the functional network. Anatomical methods utilize atlases to define the nodes based on brain structure. The fMRI time-series from all voxels within the anatomical area are averaged and subsequently used to generate the network. Functional activation methods rely on data from traditional fMRI activation studies, often from databases, to identify network nodes. Such methods identify the peaks or centers of mass from activation maps to determine the location of the nodes. Small (~10–20 millimeter diameter) spheres located at the coordinates of the activation foci are then applied to the data being used in the network analysis. The fMRI time-series from all voxels in the sphere are then averaged, and the resultant time series is used to generate the network. We attempt to clarify the discussion and move the study of complex brain networks forward. While the “correct” method to be used remains an open, possibly unsolvable question that deserves

  2. Defining moments in leadership character development.

    PubMed

    Bleich, Michael R

    2015-06-01

    Critical moments in life define one's character and clarify true values. Reflective leadership is espoused as an important practice for transformational leaders. Professional development educators can help surface and explore defining moments, strengthen leadership behavior with defining moments as a catalyst for change, and create safe spaces for leaders to expand their leadership capacity. PMID:26057159

  3. Defined contribution: a part of our future.

    PubMed Central

    Baugh, Reginald F.

    2003-01-01

    Rising employer health care costs and consumer backlash against managed care are trends fostering the development of defined contribution plans. Defined contribution plans limit employer responsibility to a fixed financial contribution rather than a benefit program and dramatically increase consumer responsibility for health care decision making. Possible outcomes of widespread adoption of defined contribution plans are presented. PMID:12934869

  4. 7 CFR 29.9201 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Terms defined. 29.9201 Section 29.9201 Agriculture... Tobacco Produced and Marketed in a Quota Area Definitions § 29.9201 Terms defined. As used in this subpart... hereinafter defined shall have the indicated meanings so assigned....

  5. 7 CFR 1206.200 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1206.200 Section 1206.200 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... INFORMATION Rules and Regulations § 1206.200 Terms defined. Unless otherwise defined in this subpart,...

  6. 7 CFR 1210.500 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1210.500 Section 1210.500 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Rules and Regulations Definitions § 1210.500 Terms defined. Unless otherwise defined in...

  7. 7 CFR 29.12 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Terms defined. 29.12 Section 29.12 Agriculture... INSPECTION Regulations Definitions § 29.12 Terms defined. As used in this subpart and in all instructions, forms, and documents in connection therewith, the words and phrases hereinafter defined shall have...

  8. 16 CFR 502.2 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Terms defined. 502.2 Section 502.2... FAIR PACKAGING AND LABELING ACT Definitions § 502.2 Terms defined. As used in this part, unless the... those terms are defined under part 500 of this chapter. (b) The term packager and labeler means...

  9. 20 CFR 725.703 - Physician defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Physician defined. 725.703 Section 725.703... defined. The term “physician” includes only doctors of medicine (MD) and osteopathic practitioners within the scope of their practices as defined by State law. No treatment or medical services performed...

  10. 29 CFR 779.107 - Goods defined.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Goods defined. 779.107 Section 779.107 Labor Regulations... Engaged in Commerce Or in the Production of Goods for Commerce § 779.107 Goods defined. The term goods is defined in section 3(i) of the Act and has a well established meaning under the Act since it has...

  11. 20 CFR 404.429 - Earnings; defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Earnings; defined. 404.429 Section 404.429...- ) Deductions; Reductions; and Nonpayments of Benefits § 404.429 Earnings; defined. (a) General. The term... purpose of the earnings test under this subpart: (i) If you reach full retirement age, as defined in §...

  12. 29 CFR 779.107 - Goods defined.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Goods defined. 779.107 Section 779.107 Labor Regulations... Engaged in Commerce Or in the Production of Goods for Commerce § 779.107 Goods defined. The term goods is defined in section 3(i) of the Act and has a well established meaning under the Act since it has...

  13. 20 CFR 725.703 - Physician defined.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Physician defined. 725.703 Section 725.703... AND HEALTH ACT, AS AMENDED Medical Benefits and Vocational Rehabilitation § 725.703 Physician defined... scope of their practices as defined by State law. No treatment or medical services performed by...

  14. Antimycobacterial activity of lichen metabolites in vitro.

    PubMed

    Ingólfsdóttir, K; Chung, G A; Skúlason, V G; Gissurarson, S R; Vilhelmsdóttir, M

    1998-04-01

    Several compounds, whose structures represent the most common chemical classes of lichen metabolites, were screened for in vitro activity against Mycobacterium aurum, a non-pathogenic organism with a similar sensitivity profile to M. tuberculosis. Of the compounds tested, usnic acid from Cladonia arbuscula exhibited the highest activity with an MIC value of 32 microg/ml. Atranorin and lobaric acid, both isolated from Stereocaulon alpinum, salazinic acid from Parmelia saxatilis and protolichesterinic acid from Cetraria islandica all showed MIC values >/=125 microg/ml. PMID:9795033

  15. Analysis of thymic stromal cell subpopulations grown in vitro on extracellular matrix in defined medium. III. Growth conditions of human thymic epithelial cells and immunomodulatory activities in their culture supernatant.

    PubMed Central

    Schreiber, L; Eshel, I; Meilin, A; Sharabi, Y; Shoham, J

    1991-01-01

    We report here on a new approach to the cultivation of human thymic epithelial (HTE) cells, which apparently allows more faithful preservation of cell function. This approach, previously developed by us for mouse thymic epithelial (MTE) cells, is based on the use of culture plates coated with extracellular matrix (ECM), and on the use of serum-free, growth factor-supplemented medium. The nutritional requirements of HTE and MTE are somewhat different. Although both are critically dependent on ECM and insulin, they differ in their dependency on other growth factors: selenium and transferrin are much more important for HTE cells, whereas epidermal growth factor and hydrocortisone play a more essential role in MTE cultures. The epithelial nature of the cultured cells is indicated by positive staining with anti-keratin antibodies and by the presence of desmosomes and tonofilaments. The ultrastructural appearance of the cells further suggests high metabolic and secretory activities, not usually found in corresponding cell lines. The culture supernatant (CS) of HTE cells exhibited a strong enhancing effect on thymocyte response to Con A stimulation, as measured by cell proliferation and lymphokine production. The effect was observed on both human and mouse thymocytes, but was much stronger in the homologous combination. Thymic factors tested in parallel did not have such a differential effect. The dose-effect relationships were in the form of a bell-shaped curve, with fivefold enhancement of response at the peak and a measurable effect even with 1:1000 dilution, when human thymocytes were used. The responding thymocytes were those which do not bind peanut agglutinin and are resistant to hydrocortisone. The culture system described here may have advantages for the in vitro study of thymic stromal cell function. Images Figure 1 Figure 3 Figure 4 PMID:1783421

  16. Modelling defined mixtures of environmental oestrogens found in domestic animal and sewage treatment effluents using an in vitro oestrogen-mediated transcriptional activation assay (T47D-KBluc).

    PubMed

    Bermudez, Dieldrich S; Gray, L Earl; Wilson, Vickie S

    2012-06-01

    There is growing concern of exposure of fish, wildlife and humans to water sources contaminated with oestrogens and the potential impact on reproductive health. Environmental oestrogens can come from various sources including concentrated animal feedlot operations (CAFO), municipal waste, agricultural and industrial effluents. US EPA's drinking water contaminant candidate list 3 (CCL3) includes several oestrogenic compounds. Although these contaminants are currently not subject to any proposed or promulgated national primary drinking water regulations, they are known or anticipated to occur in public water systems and may require future regulation under the Safe Drinking Water Act. Using an in vitro transcriptional activation assay, this study evaluated oestrogens from CCL3 both individually and as a seven oestrogen mixture (fixed ray design) over a broad range of concentrations, including environmentally relevant concentrations. Log EC(50) and Hillslope values for individual oestrogens were as follows: estrone, -11.92, 1.283; estradiol-17α, -9.61, 1.486; estradiol-17β, 11.77, 1.494; estriol, -11.14, 1.074; ethinyl estradiol-17α, -12.63, 1.562; Mestranol, -11.08, 0.809 and Equilin, -11.48, 0.946. In addition, mixtures that mirrored the primary oestrogens found in swine, poultry and dairy CAFO effluent (fixed-ratio ray design), and a ternary mixture (4 × 4 × 4 factorial design) of oestrogens found in hormone replacement therapy and/or oral contraceptives were tested. Mixtures were evaluated for additivity using both the concentration addition (CA) model and oestrogen equivalence (EEQ) model. For each of the mixture studies, a broad range of concentrations were tested, both above and below environmentally relevant concentrations. Results show that the observed data did not vary consistently from either the CA or EEQ predictions for any mixture. Therefore, either the CA or EEQ model should be useful predictors for modelling oestrogen mixtures. PMID:22612477

  17. Chemically Defined Medium and Caenorhabditis elegans: A Powerful Approach

    NASA Technical Reports Server (NTRS)

    Szewczyk, N. J.; Kozak, E.; Conley, C. A.

    2003-01-01

    C. elegans has been established as a powerful genetic system. Growth in a chemically defined medium (C. elegans Maintenance Medium (CeMM)) now allows standardization and systematic manipulation of the nutrients that animals receive. Liquid cultivation allows automated culturing and experimentation and should be of me in large-scale growth and screening of animals. Here we present our initial results from developing culture systems with CeMM. We find that CeMM is versatile and culturing is simple. CeMM can be used in a solid or liquid state, it can be stored unused for at least a year, unattended actively growing cultures may be maintained longer than with standard techniques, and standard C. elegans protocols work well with animals grown in defined medium. We also find that there are caveats of using defined medium. Animals in defined medium grow more slowly than on standard medium, appear to display adaptation to the defined medium, and display altered growth rates as they change defined medium composition. As was suggested with the introduction of C. elegans as a potential genetic system, use of defined medium with C. elegans should prove a powerful tool.

  18. Neotectonics and structure of the Himalayan deformation front in the Kashmir Himalaya, India: Implication in defining what controls a blind thrust front in an active fold-thrust belt

    NASA Astrophysics Data System (ADS)

    Gavillot, Y. G.; Meigs, A.; Yule, J. D.; Rittenour, T. M.; Malik, M. O. A.

    2014-12-01

    Active tectonics of a deformation front constrains the kinematic evolution and structural interaction between the fold-thrust belt and most-recently accreted foreland basin. In Kashmir, the Himalayan Frontal thrust (HFT) is blind, characterized by a broad fold, the Suruin-Mastargh anticline (SMA), and displays no emergent faults cutting either limb. A lack of knowledge of the rate of shortening and structural framework of the SMA hampers quantifying the earthquake potential for the deformation front. Our study utilized the geomorphic expression of dated deformed terraces on the Ujh River in Kashmir. Six terraces are recognized, and three yield OSL ages of 53 ka, 33 ka, and 0.4 ka. Vector fold restoration of long terrace profiles indicates a deformation pattern characterized by regional uplift across the anticlinal axis and back-limb, and by fold limb rotation on the forelimb. Differential uplift across the fold trace suggests localized deformation. Dip data and stratigraphic thicknesses suggest that a duplex structure is emplaced at depth along the basal décollement, folding the overlying roof thrust and Siwalik-Muree strata into a detachment-like fold. Localized faulting at the fold axis explains the asymmetrical fold geometry. Folding of the oldest dated terrace, suggest that rock uplift rates across the SMA range between 2.0-1.8 mm/yr. Assuming a 25° dipping ramp for the blind structure on the basis of dip data constraints, the shortening rate across the SMA ranges between 4.4-3.8 mm/yr since ~53 ka. Of that rate, ~1 mm/yr is likely absorbed by minor faulting in the near field of the fold axis. Given that Himalaya-India convergence is ~18.8-11 mm/yr, internal faults north of the deformation front, such as the Riasi thrust absorbs more of the Himalayan shortening than does the HFT in Kashmir. We attribute a non-emergent thrust at the deformation front to reflect deformation controlled by pre-existing basin architecture in Kashmir, in which the thick succession

  19. 47 CFR 2.908 - Identical defined.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Identical defined. 2.908 Section 2.908 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Equipment Authorization Procedures General Provisions § 2.908 Identical defined. As used in this subpart, the...

  20. 47 CFR 2.908 - Identical defined.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Identical defined. 2.908 Section 2.908 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Equipment Authorization Procedures General Provisions § 2.908 Identical defined. As used in this subpart, the...

  1. 47 CFR 2.908 - Identical defined.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Identical defined. 2.908 Section 2.908 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Equipment Authorization Procedures General Provisions § 2.908 Identical defined. As used in this subpart, the...

  2. 47 CFR 2.908 - Identical defined.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Identical defined. 2.908 Section 2.908 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Equipment Authorization Procedures General Provisions § 2.908 Identical defined. As used in this subpart, the...

  3. 47 CFR 2.908 - Identical defined.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Identical defined. 2.908 Section 2.908 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Equipment Authorization Procedures General Provisions § 2.908 Identical defined. As used in this subpart, the...

  4. 16 CFR 301.1 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Terms defined. 301.1 Section 301.1 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER FUR PRODUCTS LABELING ACT Regulations § 301.1 Terms defined. (a) As used in this part, unless the context otherwise specifically requires:...

  5. 20 CFR 702.404 - Physician defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... § 702.404 Physician defined. The term physician includes doctors of medicine (MD), surgeons, podiatrists, dentists, clinical psychologists, optometrists, chiropractors, and osteopathic practitioners within the... correct a subluxation shown by X-ray or clinical findings. Physicians defined in this part may...

  6. Dilution Confusion: Conventions for Defining a Dilution

    ERIC Educational Resources Information Center

    Fishel, Laurence A.

    2010-01-01

    Two conventions for preparing dilutions are used in clinical laboratories. The first convention defines an "a:b" dilution as "a" volumes of solution A plus "b" volumes of solution B. The second convention defines an "a:b" dilution as "a" volumes of solution A diluted into a final volume of "b". Use of the incorrect dilution convention could affect…

  7. 7 CFR 1280.401 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1280.401 Section 1280.401 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... INFORMATION ORDER Rules and Regulations § 1280.401 Terms defined. As used throughout this subpart, unless...

  8. 7 CFR 1260.301 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1260.301 Section 1260.301 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... and Regulations § 1260.301 Terms defined. As used throughout this subpart, unless the...

  9. 42 CFR 422.580 - Reconsideration defined.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Reconsideration defined. 422.580 Section 422.580 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 422.580 Reconsideration defined. A reconsideration consists of a review of an adverse...

  10. 16 CFR 1608.1 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Terms defined. 1608.1 Section 1608.1 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS GENERAL RULES AND REGULATIONS UNDER THE FLAMMABLE FABRICS ACT § 1608.1 Terms defined. As used in the rules and regulations...

  11. 16 CFR 304.1 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Terms defined. 304.1 Section 304.1 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER THE HOBBY PROTECTION ACT § 304.1 Terms defined. (a) Act means the Hobby Protection...

  12. 22 CFR 92.36 - Authentication defined.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication defined. 92.36 Section 92.36 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES NOTARIAL AND RELATED SERVICES Specific Notarial Acts § 92.36 Authentication defined. An authentication is a certification of the genuineness...

  13. 42 CFR 422.580 - Reconsideration defined.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Reconsideration defined. 422.580 Section 422.580 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 422.580 Reconsideration defined. A reconsideration consists of a review of an adverse...

  14. 45 CFR 504.1 - Claim defined.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Claim defined. 504.1 Section 504.1 Public Welfare Regulations Relating to Public Welfare (Continued) FOREIGN CLAIMS SETTLEMENT COMMISSION OF THE UNITED STATES... 1948, AS AMENDED FILING OF CLAIMS AND PROCEDURES THEREFOR § 504.1 Claim defined. (a) This subchapter...

  15. 9 CFR 592.2 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Terms defined. 592.2 Section 592.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS INSPECTION VOLUNTARY INSPECTION OF EGG PRODUCTS Definitions § 592.2 Terms defined. For the purpose of...

  16. 22 CFR 92.30 - Acknowledgment defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Acknowledgment defined. 92.30 Section 92.30 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES NOTARIAL AND RELATED SERVICES Specific Notarial Acts § 92.30 Acknowledgment defined. An acknowledgment is a proceeding by which a person who...

  17. 7 CFR 1215.100 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1215.100 Section 1215.100 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... CONSUMER INFORMATION Rules and Regulations Definitions § 1215.100 Terms defined. Unless otherwise...

  18. 7 CFR 1230.100 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1230.100 Section 1230.100 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... CONSUMER INFORMATION Rules and Regulations Definitions § 1230.100 Terms defined. As used throughout...

  19. 7 CFR 75.2 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Terms defined. 75.2 Section 75.2 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... AND CERTIFICATION OF QUALITY OF AGRICULTURAL AND VEGETABLE SEEDS Definitions § 75.2 Terms defined....

  20. 7 CFR 28.950 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Terms defined. 28.950 Section 28.950 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing..., TESTING, AND STANDARDS Cotton Fiber and Processing Tests Definitions § 28.950 Terms defined. As...

  1. 22 CFR 92.36 - Authentication defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Authentication defined. 92.36 Section 92.36 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES NOTARIAL AND RELATED SERVICES Specific Notarial Acts § 92.36 Authentication defined. An authentication is a certification of the genuineness...

  2. 7 CFR 1280.601 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1280.601 Section 1280.601 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.601 Terms defined. As used...

  3. 45 CFR 504.1 - Claim defined.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false Claim defined. 504.1 Section 504.1 Public Welfare Regulations Relating to Public Welfare (Continued) FOREIGN CLAIMS SETTLEMENT COMMISSION OF THE UNITED STATES... 1948, AS AMENDED FILING OF CLAIMS AND PROCEDURES THEREFOR § 504.1 Claim defined. (a) This subchapter...

  4. 16 CFR 1608.1 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Terms defined. 1608.1 Section 1608.1 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS GENERAL RULES AND REGULATIONS UNDER THE FLAMMABLE FABRICS ACT § 1608.1 Terms defined. As used in the rules and regulations...

  5. 7 CFR 160.3 - Rosin defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Rosin defined. 160.3 Section 160.3 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... STANDARDS FOR NAVAL STORES General § 160.3 Rosin defined. Except as provided in § 160.15, rosin is...

  6. 20 CFR 725.491 - Operator defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Operator defined. 725.491 Section 725.491 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR FEDERAL COAL MINE HEALTH... SAFETY AND HEALTH ACT, AS AMENDED Responsible Coal Mine Operators § 725.491 Operator defined. (a)...

  7. 22 CFR 92.30 - Acknowledgment defined.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Acknowledgment defined. 92.30 Section 92.30 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES NOTARIAL AND RELATED SERVICES Specific Notarial Acts § 92.30 Acknowledgment defined. An acknowledgment is a proceeding by which a person who...

  8. 20 CFR 401.25 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Terms defined. 401.25 Section 401.25... INFORMATION General § 401.25 Terms defined. Access means making a record available to a subject individual... means communication to an individual whether he is a subject individual. (Subject individual is...

  9. 7 CFR 1205.500 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... accordance with 7 CFR 713.55. (o) Importer means any person who enters, or withdraws from warehouse, cotton... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1205.500 Section 1205.500 Agriculture... Board Rules and Regulations Definitions § 1205.500 Terms defined. As used throughout this...

  10. 16 CFR 304.1 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Terms defined. 304.1 Section 304.1 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER THE HOBBY PROTECTION ACT § 304.1 Terms defined. (a) Act means the Hobby Protection...

  11. 38 CFR 17.31 - Duty periods defined.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Definitions and Active Duty § 17.31 Duty periods defined. Full-time duty as a member of the Women's Army Auxiliary Corps, Women's Reserve of the Navy and Marine Corps and Women's Reserve of the Coast Guard... Patient Rights...

  12. Live Attenuated Leishmania donovani p27 Gene Knockout Parasites Are Non-pathogenic and Elicit Long Term Protective Immunity in BALB/c Mice

    PubMed Central

    Dey, Ranadhir; Dagur, Pradeep K.; Selvapandiyan, Angamuthu; McCoy, J. Philip; Salotra, Poonam; Duncan, Robert; Nakhasi, Hira L.

    2013-01-01

    Leishmaniasis causes significant morbidity and mortality worldwide and there are no vaccines available against this disease. Previously, we had shown that the amastigote specific protein p27 (Ldp27) is a component of an active cytochrome c oxidase complex in L. donovani and upon deletion of its gene the parasite had reduced virulence in vivo. In this study, we have shown that Ldp27−/− parasites do not survive beyond 20 weeks in BALB/c mice, hence are safe as an immunogen. Upon virulent challenge, 12 weeks post-immunized mice showed significantly lower parasite burden in liver and spleen. When mice were challenged 20 weeks post immunization, there was still a significant reduction in parasite burden suggesting long term protection by Ldp27−/− immunization. Immunization with Ldp27−/− induced both pro- and anti- inflammatory cytokine responses and activated splenocytes for enhanced leishmaniacidal activity in association with NO production. Protection in both short and long term immunized mice after challenge with the wild type parasite correlated with the stimulation of multifunctional Th1 type CD4 and CD8 T cells. Adoptive transfer of T cells from long term immunized mice conferred protection against virulent challenge in naïve recipient mice suggesting involvement of memory T cell response in the protection against Leishmania infection. Immunization of mice with Ldp27−/− also demonstrated cross-protection against the Leishmania major and Leishmania braziliensis infection. Our data show that genetically modified live attenuated Ldp27−/− parasites are safe, induce protective immunity even in the absence of parasites and can provide protection against homologous and heterologous Leishmania species. PMID:23338240

  13. Bilayer graphene quantum dot defined by topgates

    SciTech Connect

    Müller, André; Kaestner, Bernd; Hohls, Frank; Weimann, Thomas; Pierz, Klaus; Schumacher, Hans W.

    2014-06-21

    We investigate the application of nanoscale topgates on exfoliated bilayer graphene to define quantum dot devices. At temperatures below 500 mK, the conductance underneath the grounded gates is suppressed, which we attribute to nearest neighbour hopping and strain-induced piezoelectric fields. The gate-layout can thus be used to define resistive regions by tuning into the corresponding temperature range. We use this method to define a quantum dot structure in bilayer graphene showing Coulomb blockade oscillations consistent with the gate layout.

  14. Characterization of a multimeric, eukaryotic prolyl aminopeptidase: an inducible and highly specific intracellular peptidase from the non-pathogenic fungus Talaromyces emersonii.

    PubMed

    Mahon, Cathal S; O'Donoghue, Anthony J; Goetz, David H; Murray, Patrick G; Craik, Charles S; Tuohy, Maria G

    2009-11-01

    Fungi are capable of degrading proteins in their environment by secreting peptidases. However, the link between extracellular digestion and intracellular proteolysis has scarcely been investigated. Mycelial lysates of the filamentous fungus Talaromyces emersonii were screened for intracellular peptidase production. Five distinct proteolytic activities with specificity for the p-nitroanilide (pNA) peptides Suc-AAPF-pNA, Suc-AAA-pNA, K-pNA, F-pNA and P-pNA were identified. The native enzyme responsible for the removal of N-terminal proline residues was purified to homogeneity by ammonium sulfate fractionation followed by five successive chromatographic steps. The enzyme, termed Talaromyces emersonii prolyl aminopeptidase (TePAP), displayed a 50-fold specificity for cleaving N-terminal Pro-X (k(cat)/K(m)=2.1 x 10(6) M(-1) s(-1)) compared with Ala-X or Val-X bonds. This intracellular aminopeptidase was optimally active at pH 7.4 and 50 degrees C. Peptide sequencing facilitated the design of degenerate oligonucleotides from homologous sequences encoding putative fungal proline aminopeptidases, enabling subsequent cloning of the gene. TePAP was shown to be relatively uninhibited by classical serine peptidase inhibitors and to be sensitive to selected cysteine- and histidine-modifying reagents, yet gene sequence analysis identified the protein as a serine peptidase with an alpha/beta hydrolase fold. Northern analysis indicated that Tepap mRNA levels were regulated by the composition of the growth medium. Highest Tepap transcript levels were observed when the fungus was grown in medium containing glucose and the protein hydrolysate casitone. Interestingly, both the induction profile and substrate preference of this enzyme suggest potential co-operativity between extracellular and intracellular proteolysis in this organism. Gel filtration chromatography suggested that the enzyme exists as a 270 kDa homo-hexamer, whereas most bacterial prolyl aminopeptidases (PAPs) are

  15. Characterization of a multimeric, eukaryotic prolyl aminopeptidase: an inducible and highly specific intracellular peptidase from the non-pathogenic fungus Talaromyces emersonii

    PubMed Central

    Mahon, Cathal S.; O'Donoghue, Anthony J.; Goetz, David H.; Murray, Patrick G.; Craik, Charles S.; Tuohy, Maria G.

    2009-01-01

    Fungi are capable of degrading proteins in their environment by secreting peptidases. However, the link between extracellular digestion and intracellular proteolysis has scarcely been investigated. Mycelial lysates of the filamentous fungus Talaromyces emersonii were screened for intracellular peptidase production. Five distinct proteolytic activities with specificity for the p-nitroanilide (pNA) peptides Suc-AAPF-pNA, Suc-AAA-pNA, K-pNA, F-pNA and P-pNA were identified. The native enzyme responsible for the removal of N-terminal proline residues was purified to homogeneity by ammonium sulfate fractionation followed by five successive chromatographic steps. The enzyme, termed Talaromyces emersonii prolyl aminopeptidase (TePAP), displayed a 50-fold specificity for cleaving N-terminal Pro–X (kcat/Km=2.1×106 M−1 s−1) compared with Ala–X or Val–X bonds. This intracellular aminopeptidase was optimally active at pH 7.4 and 50 °C. Peptide sequencing facilitated the design of degenerate oligonucleotides from homologous sequences encoding putative fungal proline aminopeptidases, enabling subsequent cloning of the gene. TePAP was shown to be relatively uninhibited by classical serine peptidase inhibitors and to be sensitive to selected cysteine- and histidine-modifying reagents, yet gene sequence analysis identified the protein as a serine peptidase with an α/β hydrolase fold. Northern analysis indicated that Tepap mRNA levels were regulated by the composition of the growth medium. Highest Tepap transcript levels were observed when the fungus was grown in medium containing glucose and the protein hydrolysate casitone. Interestingly, both the induction profile and substrate preference of this enzyme suggest potential co-operativity between extracellular and intracellular proteolysis in this organism. Gel filtration chromatography suggested that the enzyme exists as a 270 kDa homo-hexamer, whereas most bacterial prolyl aminopeptidases (PAPs) are

  16. Autism Spectrum Disorder: Defining Dimensions and Subgroups.

    PubMed

    Ousley, Opal; Cermak, Tracy

    2014-03-01

    Autism spectrum disorder (ASD) is a behaviorally defined neurodevelopmental disorder associated with the presence of social-communication deficits and restricted and repetitive behaviors. In the latest conceptualization of ASD, these two behavioral dimensions represent the core defining features of ASD, whereas associated dimensions, such as intellectual and language ability, provide a means for describing the ASD heterogeneity. In addition, the characterization of ASD subgroups, defined by the presence of known medical, genetic, or other psychiatric disorders, furthers our understanding of ASD heterogeneity. This paper reviews the history of autism, describes its core defining features, and provides an overview of the clinically and etiologically relevant subgroups that add to the complexity of this condition. PMID:25072016

  17. 20 CFR 702.404 - Physician defined.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... correct a subluxation shown by X-ray or clinical findings. Physicians defined in this part may interpret their own X-rays. All physicians in these categories are authorized by the Director to render...

  18. 20 CFR 702.404 - Physician defined.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... correct a subluxation shown by X-ray or clinical findings. Physicians defined in this part may interpret their own X-rays. All physicians in these categories are authorized by the Director to render...

  19. 20 CFR 702.404 - Physician defined.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... correct a subluxation shown by X-ray or clinical findings. Physicians defined in this part may interpret their own X-rays. All physicians in these categories are authorized by the Director to render...

  20. 20 CFR 702.404 - Physician defined.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... correct a subluxation shown by X-ray or clinical findings. Physicians defined in this part may interpret their own X-rays. All physicians in these categories are authorized by the Director to render...

  1. Application-Defined Decentralized Access Control.

    PubMed

    Xu, Yuanzhong; Dunn, Alan M; Hofmann, Owen S; Lee, Michael Z; Mehdi, Syed Akbar; Witchel, Emmett

    2014-01-01

    DCAC is a practical OS-level access control system that supports application-defined principals. It allows normal users to perform administrative operations within their privilege, enabling isolation and privilege separation for applications. It does not require centralized policy specification or management, giving applications freedom to manage their principals while the policies are still enforced by the OS. DCAC uses hierarchically-named attributes as a generic framework for user-defined policies such as groups defined by normal users. For both local and networked file systems, its execution time overhead is between 0%-9% on file system microbenchmarks, and under 1% on applications. This paper shows the design and implementation of DCAC, as well as several real-world use cases, including sandboxing applications, enforcing server applications' security policies, supporting NFS, and authenticating user-defined sub-principals in SSH, all with minimal code changes. PMID:25426493

  2. Autism Spectrum Disorder: Defining Dimensions and Subgroups

    PubMed Central

    Cermak, Tracy

    2014-01-01

    Autism spectrum disorder (ASD) is a behaviorally defined neurodevelopmental disorder associated with the presence of social-communication deficits and restricted and repetitive behaviors. In the latest conceptualization of ASD, these two behavioral dimensions represent the core defining features of ASD, whereas associated dimensions, such as intellectual and language ability, provide a means for describing the ASD heterogeneity. In addition, the characterization of ASD subgroups, defined by the presence of known medical, genetic, or other psychiatric disorders, furthers our understanding of ASD heterogeneity. This paper reviews the history of autism, describes its core defining features, and provides an overview of the clinically and etiologically relevant subgroups that add to the complexity of this condition. PMID:25072016

  3. Behaviourally Defined Objectives: A Critique. Part Two.

    ERIC Educational Resources Information Center

    Wesson, A. J.

    1983-01-01

    This is the concluding part of an article published in the August 1983 edition. A number of arguments are developed to demonstrate the inadequacy of behaviorally defined objectives as a basis for curriculum planning. (SSH)

  4. 16 CFR 1611.31 - Terms defined.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... FLAMMABILITY OF VINYL PLASTIC FILM Rules and Regulations § 1611.31 Terms defined. As used in this part, unless... pile, nap, or tufting. (i) The term film means any nonrigid, unsupported plastic, rubber or...

  5. Application-Defined Decentralized Access Control

    PubMed Central

    Xu, Yuanzhong; Dunn, Alan M.; Hofmann, Owen S.; Lee, Michael Z.; Mehdi, Syed Akbar; Witchel, Emmett

    2014-01-01

    DCAC is a practical OS-level access control system that supports application-defined principals. It allows normal users to perform administrative operations within their privilege, enabling isolation and privilege separation for applications. It does not require centralized policy specification or management, giving applications freedom to manage their principals while the policies are still enforced by the OS. DCAC uses hierarchically-named attributes as a generic framework for user-defined policies such as groups defined by normal users. For both local and networked file systems, its execution time overhead is between 0%–9% on file system microbenchmarks, and under 1% on applications. This paper shows the design and implementation of DCAC, as well as several real-world use cases, including sandboxing applications, enforcing server applications’ security policies, supporting NFS, and authenticating user-defined sub-principals in SSH, all with minimal code changes. PMID:25426493

  6. A Methodology to Define Flood Resilience

    NASA Astrophysics Data System (ADS)

    Tourbier, J.

    2012-04-01

    Flood resilience has become an internationally used term with an ever-increasing number of entries on the Internet. The SMARTeST Project is looking at approaches to flood resilience through case studies at cities in various countries, including Washington D.C. in the United States. In light of U.S. experiences a methodology is being proposed by the author that is intended to meet ecologic, spatial, structural, social, disaster relief and flood risk aspects. It concludes that: "Flood resilience combines (1) spatial, (2) structural, (3) social, and (4) risk management levels of flood preparedness." Flood resilience should incorporate all four levels, but not necessarily with equal emphasis. Stakeholders can assign priorities within different flood resilience levels and the considerations they contain, dividing 100% emphasis into four levels. This evaluation would be applied to planned and completed projects, considering existing conditions, goals and concepts. We have long known that the "road to market" for the implementation of flood resilience is linked to capacity building of stakeholders. It is a multidisciplinary enterprise, involving the integration of all the above aspects into the decision-making process. Traditional flood management has largely been influenced by what in the UK has been called "Silo Thinking", involving constituent organizations that are responsible for different elements, and are interested only in their defined part of the system. This barrier to innovation also has been called the "entrapment effect". Flood resilience is being defined as (1) SPATIAL FLOOD RESILIENCE implying the management of land by floodplain zoning, urban greening and management to reduce storm runoff through depression storage and by practicing Sustainable Urban Drainage (SUD's), Best Management Practices (BMP's, or Low Impact Development (LID). Ecologic processes and cultural elements are included. (2) STRUCTURAL FLOOD RESILIENCE referring to permanent flood defense

  7. Evaluation of the use of non-pathogenic porcine circovirus type 1 as a vaccine delivery virus vector to express antigenic epitopes of porcine reproductive and respiratory syndrome virus.

    PubMed

    Piñeyro, Pablo E; Kenney, Scott P; Giménez-Lirola, Luis G; Opriessnig, Tanja; Tian, Debin; Heffron, C Lynn; Meng, Xiang-Jin

    2016-02-01

    We previously demonstrated that the C-terminus of the capsid gene of porcine circovirus type 2 (PCV2) is an immune reactive epitope displayed on the surface of virions. Insertion of foreign epitope tags in the C-terminus produced infectious virions that elicited humoral immune responses against both PCV2 capsid and the inserted epitope tags, whereas mutation in the N terminus impaired viral replication. Since the non-pathogenic porcine circovirus type 1 (PCV1) shares similar genomic organization and significant sequence identity with pathogenic PCV2, in this study we evaluated whether PCV1 can serve as a vaccine delivery virus vector. Four different antigenic determinants of porcine reproductive and respiratory syndrome virus (PRRSV) were inserted in the C-terminus of the PCV1 capsid gene, the infectivity and immunogenicity of the resulting viruses are determined. We showed that an insertion of 12 (PRRSV-GP2 epitope II, PRRSV-GP3 epitope I, and PRRSV-GP5 epitope I), and 14 (PRRSV-GP5 epitope IV) amino acid residues did not affect PCV1 replication. We successfully rescued and characterized four chimeric PCV1 viruses expressing PRRSV linear antigenic determinants (GP2 epitope II: aa 40-51, ASPSHVGWWSFA; GP3 epitope I: aa 61-72, QAAAEAYEPGRS; GP5 epitope I: aa 35-46, SSSNLQLIYNLT; and GP5 epitope IV: aa 187-200, TPVTRVSAEQWGRP). We demonstrated that all chimeric viruses were stable and infectious in vitro and three chimeric viruses were infectious in vivo. An immunogenicity study in pigs revealed that PCV1-VR2385EPI chimeric viruses elicited neutralizing antibodies against PRRSV-VR2385. The results have important implications for further evaluating PCV1 as a potential vaccine delivery vector. PMID:26555162

  8. A global approach to defining flood seasons

    NASA Astrophysics Data System (ADS)

    Lee, D.; Ward, P.; Block, P.

    2015-04-01

    Globally, flood catastrophes lead all natural hazards in terms of impacts on society, causing billions of dollars of damages annually. While short-term flood warning systems are improving in number and sophistication, forecasting systems on the order of months to seasons are a rarity, yet may lead to further disaster preparedness. To lay the groundwork for prediction, dominant flood seasons must be adequately defined. A global approach is adopted here, using the PCR-GLOBWB model to define spatial and temporal characteristics of major flood seasons globally. The main flood season is identified using a volume-based threshold technique. In comparison with observations, 40% (50%) of locations at a station (sub-basin) scale have identical peak months and 81% (89%) are within 1 month, indicating strong agreement between model and observed flood seasons. Model defined flood seasons are additionally found to well represent actual flood records from the Dartmouth Flood Observatory, further substantiating the models ability to reproduce the appropriate flood season. Minor flood seasons are also defined for regions with bi-modal streamflow climatology. Properly defining flood seasons can lead to prediction through association of streamflow with local and large-scale hydroclimatic indicators, and eventual integration into early warning systems for informed advanced planning and management. This is especially attractive for regions with limited observations and/or little capacity to develop early warning flood systems.

  9. Defining human death: an intersection of bioethics and metaphysics.

    PubMed

    Manninen, Bertha Alvarez

    2009-01-01

    For many years now, bioethicists, physicians, and others in the medical field have disagreed concerning how to best define human death. Different theories range from the Harvard Criteria of Brain Death, which defines death as the cessation of all brain activity, to the Cognitive Criteria, which is based on the loss of almost all core mental properties, e.g., memory, self-consciousness, moral agency, and the capacity for reason. A middle ground is the Irreversibility Standard, which defines death as occurring when the capacity for consciousness is forever lost. Given all these different theories, how can we begin to approach solving the issue of how to define death? I propose that a necessary starting point is discussing an even more fundamental question that properly belongs in the philosophical field of metaphysics: we must first address the issue of diachronic identity over time, and the persistence conditions of personal identity. In this paper, I illustrate the interdependent relationship between this metaphysical question and questions concerning the definition of death. I also illustrate how it is necessary to antecedently attend to the metaphysical issue of defining death before addressing certain issues in medical ethics, e.g., whether it is morally permissible to euthanize patients in persistent vegetative states or procure organs from anencephalic infants. PMID:20157998

  10. Antinematode Activity of Violacein and the Role of the Insulin/IGF-1 Pathway in Controlling Violacein Sensitivity in Caenorhabditis elegans

    PubMed Central

    Ballestriero, Francesco; Daim, Malak; Penesyan, Anahit; Nappi, Jadranka; Schleheck, David; Bazzicalupo, Paolo; Di Schiavi, Elia; Egan, Suhelen

    2014-01-01

    The purple pigment violacein is well known for its numerous biological activities including antibacterial, antiviral, antiprotozoan, and antitumor effects. In the current study we identify violacein as the antinematode agent produced by the marine bacterium Microbulbifer sp. D250, thereby extending the target range of this small molecule. Heterologous expression of the violacein biosynthetic pathway in E. coli and experiments using pure violacein demonstrated that this secondary metabolite facilitates bacterial accumulation in the nematode intestine, which is accompanied by tissue damage and apoptosis. Nematodes such as Caenorhabditis elegans utilise a well-defined innate immune system to defend against pathogens. Using C. elegans as a model we demonstrate the DAF-2/DAF-16 insulin/IGF-1 signalling (IIS) component of the innate immune pathway modulates sensitivity to violacein-mediated killing. Further analysis shows that resistance to violacein can occur due to a loss of DAF-2 function and/or an increased function of DAF-16 controlled genes involved in antimicrobial production (spp-1) and detoxification (sod-3). These data suggest that violacein is a novel candidate antinematode agent and that the IIS pathway is also involved in the defence against metabolites from non-pathogenic bacteria. PMID:25295516

  11. What Defines a Separate Hydrothermal System

    SciTech Connect

    Lawless, J.V.; Bogie, I.; Bignall, G.

    1995-01-01

    Separate hydrothermal systems can be defined in a variety of ways. Criteria which have been applied include separation of heat source, upflow, economic resource and geophysical anomaly. Alternatively, connections have been defined by the effects of withdrawal of economically useful fluid and subsidence, effects of reinjection, changes in thermal features, or by a hydrological connection of groundwaters. It is proposed here that: ''A separate hydrothermal system is one that is fed by a separate convective upflow of fluid, at a depth above the brittle-ductile transition for the host rocks, while acknowledging that separate hydrothermal systems can be hydrologically interconnected at shallower levels''.

  12. Defining actionable mutations for oncology therapeutic development.

    PubMed

    Carr, T Hedley; McEwen, Robert; Dougherty, Brian; Johnson, Justin H; Dry, Jonathan R; Lai, Zhongwu; Ghazoui, Zara; Laing, Naomi M; Hodgson, Darren R; Cruzalegui, Francisco; Hollingsworth, Simon J; Barrett, J Carl

    2016-04-26

    Genomic profiling of tumours in patients in clinical trials enables rapid testing of multiple hypotheses to confirm which genomic events determine likely responder groups for targeted agents. A key challenge of this new capability is defining which specific genomic events should be classified as 'actionable' (that is, potentially responsive to a targeted therapy), especially when looking for early indications of patient subgroups likely to be responsive to new drugs. This Opinion article discusses some of the different approaches being taken in early clinical development to define actionable mutations, and describes our strategy to address this challenge in early-stage exploratory clinical trials. PMID:27112209

  13. Annotating user-defined abstractions for optimization

    SciTech Connect

    Quinlan, D; Schordan, M; Vuduc, R; Yi, Q

    2005-12-05

    This paper discusses the features of an annotation language that we believe to be essential for optimizing user-defined abstractions. These features should capture semantics of function, data, and object-oriented abstractions, express abstraction equivalence (e.g., a class represents an array abstraction), and permit extension of traditional compiler optimizations to user-defined abstractions. Our future work will include developing a comprehensive annotation language for describing the semantics of general object-oriented abstractions, as well as automatically verifying and inferring the annotated semantics.

  14. Software-defined Quantum Communication Systems

    SciTech Connect

    Humble, Travis S; Sadlier, Ronald J

    2013-01-01

    We show how to extend the paradigm of software-defined communication to include quantum communication systems. We introduce the decomposition of a quantum communication terminal into layers separating the concerns of the hardware, software, and middleware. We provide detailed descriptions of how each component operates and we include results of an implementation of the super-dense coding protocol. We argue that the versatility of software-defined quantum communication test beds can be useful for exploring new regimes in communication and rapidly prototyping new systems.

  15. Defining International Human Resource Development: A Proposal

    ERIC Educational Resources Information Center

    McLean, Gary N.; Wang, Xiaohui

    2007-01-01

    From the beginning of the use of the term, there have been struggles over the meaning of human resource development (HRD). In recent years, there has been increased attention to the field's definition. This paper moves this exploration one more step to an exploration of the dilemma of defining international and cross-national HRD. A beginning…

  16. 29 CFR 779.107 - Goods defined.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Goods defined. 779.107 Section 779.107 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS OF GENERAL POLICY OR INTERPRETATION NOT DIRECTLY RELATED TO REGULATIONS THE FAIR LABOR STANDARDS ACT AS APPLIED TO RETAILERS OF GOODS OR SERVICES Employment to...

  17. 9 CFR 351.2 - Terms defined.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Definitions § 351.2 Terms defined. When used in..., horses, mules and other equines. (k) Technical animal fat means animal fat eligible for exportation, or storage for exportation, in accordance with § 325.11 of this chapter. (l) Certified technical animal...

  18. 9 CFR 351.2 - Terms defined.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Definitions § 351.2 Terms defined. When used in..., horses, mules and other equines. (k) Technical animal fat means animal fat eligible for exportation, or storage for exportation, in accordance with § 325.11 of this chapter. (l) Certified technical animal...

  19. 9 CFR 351.2 - Terms defined.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Definitions § 351.2 Terms defined. When used in..., horses, mules and other equines. (k) Technical animal fat means animal fat eligible for exportation, or storage for exportation, in accordance with § 325.11 of this chapter. (l) Certified technical animal...

  20. 9 CFR 351.2 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Definitions § 351.2 Terms defined. When used in..., horses, mules and other equines. (k) Technical animal fat means animal fat eligible for exportation, or storage for exportation, in accordance with § 325.11 of this chapter. (l) Certified technical animal...

  1. 9 CFR 351.2 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Definitions § 351.2 Terms defined. When used in..., horses, mules and other equines. (k) Technical animal fat means animal fat eligible for exportation, or storage for exportation, in accordance with § 325.11 of this chapter. (l) Certified technical animal...

  2. Defining and Measuring Literacy: Facing the Reality

    ERIC Educational Resources Information Center

    Ahmed, Manzoor

    2011-01-01

    Increasing recognition of a broadened concept of literacy challenges policy-makers and practitioners to re-define literacy operationally, develop and apply appropriate methods of assessing literacy and consider and act upon the consequent policy implications. This task is given a new urgency by the call of the Belem Framework for Action to…

  3. Parallel Education and Defining the Fourth Sector.

    ERIC Educational Resources Information Center

    Chessell, Diana

    1996-01-01

    Parallel to the primary, secondary, postsecondary, and adult/community education sectors is education not associated with formal programs--learning in arts and cultural sites. The emergence of cultural and educational tourism is an opportunity for adult/community education to define itself by extending lifelong learning opportunities into parallel…

  4. Defining Grammatical Difficulty: A Student Teacher Perspective

    ERIC Educational Resources Information Center

    Graus, Johan; Coppen, Peter-Arno

    2015-01-01

    Numerous second language acquisition (SLA) researchers have tried to define grammatical difficulty in second and foreign language acquisition--often as part of an attempt to relate the efficacy of different types of instruction to the degree of difficulty of grammatical structures. The resulting proliferation of definitions and the lack of a…

  5. 7 CFR 1220.301 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Terms defined. 1220.301 Section 1220.301 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH,...

  6. 7 CFR 1220.301 - Terms defined.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Terms defined. 1220.301 Section 1220.301 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH,...

  7. 7 CFR 1220.301 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1220.301 Section 1220.301 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH,...

  8. 7 CFR 1220.301 - Terms defined.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Terms defined. 1220.301 Section 1220.301 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH,...

  9. 7 CFR 1220.301 - Terms defined.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Terms defined. 1220.301 Section 1220.301 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH,...

  10. Defining Student Success through Navajo Perspectives

    ERIC Educational Resources Information Center

    Bowman, Colleen Wilma

    2013-01-01

    The purpose of this qualitative study was to determine the definition of student success as defined by the Navajo people. The data collection method used was the focus group. The data were collected from two geographical settings from two public schools located within the boundaries of the Navajo Indian Reservation. The focus group participants…

  11. Defining the Devonian: 1979-89

    USGS Publications Warehouse

    Oliver, W.A., Jr.; Chlupac, I.

    1991-01-01

    Describes the work of the Subcommission on Devonian Stratigraphy which has attempted to achieve concensus on each of the Devonian boundaries, based mainly on biostratigraphic information. The base of the Devonian system and each of the Devonian stages are defined. -S.J.Stone

  12. Spaces defined by the Paley function

    SciTech Connect

    Astashkin, S V; Semenov, E M

    2013-07-31

    The paper is concerned with Haar and Rademacher series in symmetric spaces, and also with the properties of spaces defined by the Paley function. In particular, the symmetric hull of the space of functions with uniformly bounded Paley function is found. Bibliography: 27 titles.

  13. 50 CFR 260.6 - Terms defined.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 11 2012-10-01 2012-10-01 false Terms defined. 260.6 Section 260.6 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE PROCESSED FISHERY PRODUCTS, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS INSPECTION AND...

  14. 50 CFR 260.6 - Terms defined.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 11 2014-10-01 2014-10-01 false Terms defined. 260.6 Section 260.6 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE PROCESSED FISHERY PRODUCTS, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS INSPECTION AND...

  15. 50 CFR 260.6 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Terms defined. 260.6 Section 260.6 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE PROCESSED FISHERY PRODUCTS, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS INSPECTION AND...

  16. 7 CFR 160.3 - Rosin defined.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Rosin defined. 160.3 Section 160.3 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) NAVAL STORES REGULATIONS AND STANDARDS FOR NAVAL STORES General § 160.3...

  17. 7 CFR 1205.500 - Terms defined.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Terms defined. 1205.500 Section 1205.500 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE COTTON RESEARCH AND PROMOTION Cotton Board Rules and...

  18. 16 CFR 303.1 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS UNDER THE TEXTILE FIBER PRODUCTS IDENTIFICATION ACT § 303.1 Terms defined. As used in this part, unless the context otherwise specifically requires: (a) The term Act means the Textile Fiber Products... identification, or authorized substitute therefor, required to be on or affixed to textile fiber products by...

  19. 7 CFR 1221.200 - Terms defined.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Terms defined. 1221.200 Section 1221.200 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  20. 7 CFR 1221.200 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1221.200 Section 1221.200 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  1. 7 CFR 1221.200 - Terms defined.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Terms defined. 1221.200 Section 1221.200 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  2. 7 CFR 1221.200 - Terms defined.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Terms defined. 1221.200 Section 1221.200 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH,...

  3. On Defining Learning Disabilities: An Emerging Consensus.

    ERIC Educational Resources Information Center

    Hammill, Donald D.

    1990-01-01

    This article reviews the efforts made since 1962 to define learning disabilities, discusses 11 prominent definitions, identifies important conceptual elements on which the definitions differ, and calls for a consensual acceptance of the National Joint Committee on Learning Disabilities definition. (PB)

  4. Defining Distance Learning and Distance Education.

    ERIC Educational Resources Information Center

    King, Frederick B.; Young, Michael F.; Drivere-Richmond, Kelly; Schrader, P. G.

    2001-01-01

    This paper offers precise definitions of distance learning and distance education, and their interrelationship. First, a single definition of learning is proposed, and then the concept of learning is broken down into three subcategories: instruction, exploration, and serendipity. Each is defined and the concepts of distance learning and distance…

  5. 16 CFR 1611.31 - Terms defined.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... FLAMMABILITY OF VINYL PLASTIC FILM Rules and Regulations § 1611.31 Terms defined. As used in this part, unless... material subject to the act, except film and fabrics having a nitro-cellulose fiber, finish, or coating... pile, nap, or tufting. (i) The term film means any nonrigid, unsupported plastic, rubber or...

  6. 16 CFR 1611.31 - Terms defined.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... FLAMMABILITY OF VINYL PLASTIC FILM Rules and Regulations § 1611.31 Terms defined. As used in this part, unless... material subject to the act, except film and fabrics having a nitro-cellulose fiber, finish, or coating... pile, nap, or tufting. (i) The term film means any nonrigid, unsupported plastic, rubber or...

  7. 16 CFR 1611.31 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... FLAMMABILITY OF VINYL PLASTIC FILM Rules and Regulations § 1611.31 Terms defined. As used in this part, unless... material subject to the act, except film and fabrics having a nitro-cellulose fiber, finish, or coating... pile, nap, or tufting. (i) The term film means any nonrigid, unsupported plastic, rubber or...

  8. 16 CFR 1611.31 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FLAMMABILITY OF VINYL PLASTIC FILM Rules and Regulations § 1611.31 Terms defined. As used in this part, unless... material subject to the act, except film and fabrics having a nitro-cellulose fiber, finish, or coating... pile, nap, or tufting. (i) The term film means any nonrigid, unsupported plastic, rubber or...

  9. Defining Parental Involvement: Perception of School Administrators

    ERIC Educational Resources Information Center

    Young, Clara Y.; Austin, Sheila M.; Growe, Roslin

    2013-01-01

    There remains a plaguing question of how to get parents involved with their child's education. Many parents and educators have different perceptions of what parental involvement means. Miscommunication between the two groups often exists because of how parental involvement is conceptualized. While educators define parental involvement as…

  10. 16 CFR 301.1 - Terms defined.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER FUR PRODUCTS LABELING ACT Regulations § 301.1 Terms defined. (a) As used in this part, unless the context otherwise specifically requires: (1) The term act means the Fur Products Labeling...

  11. 16 CFR 301.1 - Terms defined.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER FUR PRODUCTS LABELING ACT Regulations § 301.1 Terms defined. (a) As used in this part, unless the context otherwise specifically requires: (1) The term act means the Fur Products Labeling...

  12. 16 CFR 301.1 - Terms defined.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER FUR PRODUCTS LABELING ACT Regulations § 301.1 Terms defined. (a) As used in this part, unless the context otherwise specifically requires: (1) The term act means the Fur Products Labeling...

  13. 7 CFR 205.2 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Terms defined. 205.2 Section 205.2 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) ORGANIC FOODS PRODUCTION ACT PROVISIONS NATIONAL ORGANIC PROGRAM Definitions §...

  14. 7 CFR 205.2 - Terms defined.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Terms defined. 205.2 Section 205.2 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) ORGANIC FOODS PRODUCTION ACT PROVISIONS NATIONAL ORGANIC PROGRAM Definitions §...

  15. 7 CFR 1206.200 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Terms defined. 1206.200 Section 1206.200 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH,...

  16. 7 CFR 1280.401 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Terms defined. 1280.401 Section 1280.401 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE LAMB PROMOTION, RESEARCH,...

  17. 7 CFR 1219.200 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Terms defined. 1219.200 Section 1219.200 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION,...

  18. 7 CFR 29.9201 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Terms defined. 29.9201 Section 29.9201 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS...

  19. 7 CFR 1215.100 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Terms defined. 1215.100 Section 1215.100 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH,...

  20. 7 CFR 1280.601 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Terms defined. 1280.601 Section 1280.601 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE LAMB PROMOTION, RESEARCH,...

  1. 7 CFR 1260.301 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Terms defined. 1260.301 Section 1260.301 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BEEF PROMOTION AND RESEARCH...

  2. 7 CFR 1210.500 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Terms defined. 1210.500 Section 1210.500 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND...

  3. 7 CFR 29.12 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Terms defined. 29.12 Section 29.12 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS...

  4. 7 CFR 160.3 - Rosin defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Rosin defined. 160.3 Section 160.3 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) NAVAL STORES REGULATIONS...

  5. 7 CFR 1230.100 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Terms defined. 1230.100 Section 1230.100 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH,...

  6. 16 CFR 1608.1 - Terms defined.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS GENERAL RULES AND REGULATIONS UNDER THE FLAMMABLE FABRICS ACT § 1608.1 Terms defined. As used in the rules and regulations in... Flammable Fabrics Act, sec. 1 et seq., 67 Stat. 111-115, as amended, 68 Stat. 770, 81 Stat. 568-74 (15...

  7. 16 CFR 1608.1 - Terms defined.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS GENERAL RULES AND REGULATIONS UNDER THE FLAMMABLE FABRICS ACT § 1608.1 Terms defined. As used in the rules and regulations in... Flammable Fabrics Act, sec. 1 et seq., 67 Stat. 111-115, as amended, 68 Stat. 770, 81 Stat. 568-74 (15...

  8. 16 CFR 1608.1 - Terms defined.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS GENERAL RULES AND REGULATIONS UNDER THE FLAMMABLE FABRICS ACT § 1608.1 Terms defined. As used in the rules and regulations in... Flammable Fabrics Act, sec. 1 et seq., 67 Stat. 111-115, as amended, 68 Stat. 770, 81 Stat. 568-74 (15...

  9. Defining Virtual Reality: Dimensions Determining Telepresence.

    ERIC Educational Resources Information Center

    Steuer, Jonathan

    1992-01-01

    Defines virtual reality as a particular type of experience (in terms of "presence" and "telepresence") rather than as a collection of hardware. Maintains that media technologies can be classified and studied in terms of vividness and interactivity, two attributes on which virtual reality ranks very high. (SR)

  10. Defining, constructing and assessing learning outcomes.

    PubMed

    Taylor, R M

    2009-08-01

    Learning outcomes define the veterinary curriculum and inform students about what they must be able to demonstrate to succeed. Stakeholder consultation during their development ensures that programme learning outcomes equip graduates to contribute to the veterinary profession. Effective learning outcomes form a hierarchy linking the programme, its courses and tasks. Clear outcomes direct students towards higher quality learning by indicating the achievements intended, but leave scope for emergent learning outcomes. Defined technical competencies fit within this overarching framework, complementing higher order learning. Mapping is used to align learning outcomes horizontally and vertically so students are systematically guided towards entry-level competence and professional independence. Constructively aligned learning and assessment tasks ensure learners spend the focused time required to sequentially develop programme outcomes. Assessment by staff, peers and other stakeholders certifies achievement of intended outcomes. Effective assessment also empowers students to define and achieve their own learning outcomes, so they develop the habits of autonomous life-long learning. Evaluation of the quality and consistency of achieved outcomes informs ongoing programme improvement. If we are going to achieve the objectives of this set of papers, i.e. to improve public health education globally (Rev. sci. tech. Off. int. Epiz. 28 [2] 2009), then it is essential that they be well defined in the learning outcomes statement of all veterinary schools. PMID:20128490

  11. Paleontological evidence for defining the Anthropocene

    NASA Astrophysics Data System (ADS)

    Barnosky, A. D.

    2012-12-01

    Paleontological criteria formed the basis for defining most of the geological eras, periods, epochs, and ages that are commonly recognized. By the same token, the Anthropocene can be defined by paleontological distinctiveness in accordance with commonly accepted biostratigraphic and biochronologic practice. Here I focus on the utility of defining the Anthropocene by the distinctive fossils (or potential fossils of the future) that have accumulated and are accumulating in the sedimentary record. I discuss what kinds of biostratrigraphic criteria would be of most use in recognizing the Anthropocene's base and temporal extent, including pros and cons of definitions based on range zones, interval zones, lineage zones, assemblage zones, and abundance zones, as well as implications for potential reference sections. Key paleontological criteria useful in formally defining the Anthropocene as a geological epoch include (1) anthropogenic trace fossils such as buildings, roads, plastics, etc; (2) abundance zones based on remains of domesticated species and humans; and (3) assemblage zones based on species transported around the globe by people. The magnitude of paleontologically-recognizable changes that have occurred since humans became the dominant species on Earth is at least as great as the paleontological differences that distinguish other Cenozoic epochs, and supports recognition of the Anthropocene as a formal stratigraphic unit.

  12. 16 CFR 500.2 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... INTERPRETATION AND EXEMPTIONS UNDER THE FAIR PACKAGING AND LABELING ACT REGULATIONS UNDER SECTION 4 OF THE FAIR PACKAGING AND LABELING ACT § 500.2 Terms defined. As used in this part, unless the context otherwise specifically requires: (a) The term Act means the “Fair Packaging and Labeling Act” (Pub. L. 89-755,...

  13. Defining and Operationalising L2 Complexity

    ERIC Educational Resources Information Center

    Bulte, Bram; Housen, Alex

    2012-01-01

    This chapter takes a critical look at complexity in L2 research. We demonstrate several problems in the L2 literature in terms of how complexity has been defined and operationalised as a construct. In the first part of the chapter we try to unravel its highly complex, multidimensional nature by presenting a taxonomic model that identifies major…

  14. 47 CFR 54.401 - Lifeline defined.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) UNIVERSAL SERVICE Universal Service Support for Low-Income Consumers § 54.401 Lifeline defined. (a) As used in this... qualifying low-income consumers at the time such consumers subscribe to Lifeline service. If the...

  15. 47 CFR 54.401 - Lifeline defined.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) UNIVERSAL SERVICE Universal Service Support for Low-Income Consumers § 54.401 Lifeline defined. (a) As used in this... qualifying low-income consumers at the time such consumers subscribe to Lifeline service. If the...

  16. A self-defining hierarchical data system

    NASA Technical Reports Server (NTRS)

    Bailey, J.

    1992-01-01

    The Self-Defining Data System (SDS) is a system which allows the creation of self-defining hierarchical data structures in a form which allows the data to be moved between different machine architectures. Because the structures are self-defining they can be used for communication between independent modules in a distributed system. Unlike disk-based hierarchical data systems such as Starlink's HDS, SDS works entirely in memory and is very fast. Data structures are created and manipulated as internal dynamic structures in memory managed by SDS itself. A structure may then be exported into a caller supplied memory buffer in a defined external format. This structure can be written as a file or sent as a message to another machine. It remains static in structure until it is reimported into SDS. SDS is written in portable C and has been run on a number of different machine architectures. Structures are portable between machines with SDS looking after conversion of byte order, floating point format, and alignment. A Fortran callable version is also available for some machines.

  17. Precise Interval Timer for Software Defined Radio

    NASA Technical Reports Server (NTRS)

    Pozhidaev, Aleksey (Inventor)

    2014-01-01

    A precise digital fractional interval timer for software defined radios which vary their waveform on a packet-by-packet basis. The timer allows for variable length in the preamble of the RF packet and allows to adjust boundaries of the TDMA (Time Division Multiple Access) Slots of the receiver of an SDR based on the reception of the RF packet of interest.

  18. 7 CFR 1250.500 - Terms defined.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Terms defined. 1250.500 Section 1250.500 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Rules and Regulations Definitions §...

  19. 7 CFR 1250.500 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1250.500 Section 1250.500 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Rules and Regulations Definitions §...

  20. reDefined contribution health care.

    PubMed

    Lair, Tamra

    2004-01-01

    To combat rising health care costs and a society increasingly unsatisfied with employer-sponsored health care services, reDefined Contribution Health Care suggests a process to create a more consumer-driven health care market. To create this value-sensitive market requires a planned, staged approach that will include immediate actions and work toward fundamental, long-term changes. PMID:15146751

  1. Defining the Worker-Client Relationship.

    ERIC Educational Resources Information Center

    Proctor, Enola K.

    1982-01-01

    Suggests that effective use of the relationship between worker and client requires defining the concept of relationship more specifically. This may be accomplished through a consideration of the context and purpose of the particular treatment situations, the outcomes desired and the responses that are necessary to achieve these goals. (Author)

  2. Tomato Plant Proteins Actively Responding to Fungal Applications and Their Role in Cell Physiology

    PubMed Central

    Bashir, Zoobia; Shafique, Sobiya; Ahmad, Aqeel; Shafique, Shazia; Yasin, Nasim A.; Ashraf, Yaseen; Ibrahim, Asma; Akram, Waheed; Noreen, Sibgha

    2016-01-01

    The pattern of protein induction in tomato plants has been investigated after the applications of pathogenic and non-pathogenic fungal species. Moreover, particular roles of the most active protein against biological applications were also determined using chromatographic techniques. Alternaria alternata and Penicillium oxalicum were applied as a pathogenic and non-pathogenic fungal species, respectively. Protein profile analysis revealed that a five protein species (i.e., protein 1, 6, 10, 12, and 13) possessed completely coupled interaction with non-pathogenic inducer application (P. oxalicum). However, three protein species (i.e., 10, 12, and 14) recorded a strong positive interaction with both fungal species. Protein 14 exhibited the maximum interaction with fungal applications, and its role in plant metabolism was studied after its identification as protein Q9M1W6. It was determined that protein Q1M1W6 was involved in guaiacyl lignin biosynthesis, and its inhibition increased the coumarin contents in tomato plants. Moreover, it was also observed that the protein Q9M1W6 takes significant part in the biosynthesis of jasmonic acid and Indole acetic acid contents, which are defense and growth factors of tomato plants. The study will help investigators to design fundamental rules of plant proteins affecting cell physiology under the influence of external fungal applications. PMID:27445848

  3. Nonpathogenicity of antiintestinal antibody in the rabbit.

    PubMed Central

    Rabin, B. S.; Rogers, S. J.

    1976-01-01

    Rabbits were immunized with intestinal extract prepared from rabbits, guinea pigs, and germ-free rats. The resultant serum antibody response to intestinal antigen was determined by gel precipitation and direct tissue immunofluorescence. Forty-eight hours prior to sacrifice of each immunized animal, a portion of the duodenum, ileum, and colon were traumatized to bring circulating antibody into contact with the tissue. Sections for histology and direct immunofluorescence were taken from the area of trauma, just adjacent to the area, and 10 cm from it. The humoral immune response, the presence of tissue bound immunoglobulin, and tissue histology were compared. The area of trauma in normal and immunized animals showed the same histologic changes. In each animal, tissue just adjacent to the area of trauma and 10 cm from it were histologically identical. The pathologic alterations in the immunized animals were similar to those associated with malabsorption in man. Direct immunofluorescence of the intestinal tissue revealed bound immunoglobulin in histologically normal and abnormal tissue. Precipitating antibody to intestine was present in the serum of rabbits with normal and abnormal histology. Thus, antiintestinal antibody as dected by precipitation in gel and direct tissue immunofluorescence does not appear to be a factor in the pathogenesis of this model of immunologically induced histologic changes in the intestine. Images Figure 5 Figure 6 Figure 7 Figure 8 Figure 1 Figure 2 Figure 3 Figure 4 PMID:1266943

  4. In vitro responses of chicken macrophage-like monocytes following exposure to pathogenic and non-pathogenic E. coli ghosts loaded with a rational design of conserved genetic materials of influenza and Newcastle disease viruses.

    PubMed

    Lagzian, Milad; Bassami, Mohammad Reza; Dehghani, Hesam

    2016-08-01

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two important viral diseases in the poultry industry. Therefore, new disease-fighting strategies, especially effective genetic vaccination, are in high demand. Bacterial Ghost (BG) is a promising platform for delivering genetic materials to macrophages, cells that are among the first to encounter these viruses. However, there is no investigation on the immune response of these macrophage-targeted treatments. Here, we investigated the effect of genetic materials of AIV and NDV on the gene expression profile of important pro-inflammatory cytokines, a chemokine, a transcription factor, major histocompatibility complexes, and the viability of the chicken macrophage-like monocyte cells (CMM). Our genetic construct contained the external domain of matrix protein 2 and nucleoprotein gene of AIV, and immunodominant epitopes of fusion and hemagglutinin-neuraminidase proteins of NDV (hereinafter referred to as pAIV-Vax), delivered via the pathogenic and non-pathogenic BGs (Escherichia coli O78K80 and E. coli TOP10 respectively). The results demonstrated that both types of BGs were able to efficiently deliver the construct to the CMM, although the pathogenic strain derived BG was a significantly better stimulant and delivery vehicle. Both BGs were safe regarding LPS toxicity and did not induce any cell death. Furthermore, the loaded BGs were more powerful in modulating the pro-inflammatory cytokines' responses and antigen presentation systems in comparison to the unloaded BGs. Nitric oxide production of the BG-stimulated cells was also comparable to those challenged by the live bacteria. According to the results, the combination of pAIV-Vax construct and E. coli O78K80 BG is promising in inducing a considerable innate and adaptive immune response against AIV-NDV and perhaps the pathogenic E. coli, provided that the current combination be a potential candidate for in vivo testing regarding the development of an

  5. Ammonium chloride, an inhibitor of phagosome-lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic mycobacterium and a nonpathogenic yeast.

    PubMed

    Hart, P D; Young, M R

    1991-10-01

    The weak base ammonium chloride has been previously reported to inhibit lysosomal movements and phagosome-lysosome (Ph-L) fusion in cultured mouse macrophages (M phi), thus reducing delivery, to an intraphagosomal infection, of endocytosed solutes that have concentrated in secondary lysosomes. We have now addressed the question, whether NH4Cl might affect any direct interaction (if it exists) between such infection phagosomes and earlier, nonlysosomal compartments of the endocytic pathway, i.e., solute-containing endosomes. The phagosomes studied were formed after ingestion of the mouse pathogen Mycobacterium microti and the nonpathogenic yeast Saccharomyces cerevisiae; and the endosomes were formed after nonreceptor-mediated endocytosis of electronopaque and fluorescent soluble markers. By electron microscopy, survey of the cell profiles of M phi that had been treated with 10 mM NH4Cl so that Ph-L fusion was prevented, and that displayed many ferritin-labeled endosomes, revealed numerous examples of the fusion of electronlucent endosomes, revealed numerous examples of the fusion of electronlucent vesicles with phagosomes, whether containing M. microti bacilli or S. cerevisiae yeasts. Fusion was recognized by transfer of label and by morphological evidence of fusion in progress. The fusing vesicles were classed as endosomes, not NH4Cl-lysosomes, by their appearance and provenance, and because lysosome participation was excluded by the concurrent, NH4Cl-caused block of Ph-L fusion and associated lysosomal stasis. No evidence of such phagosome-endosome (Ph-E) fusion was observed in profiles from M phi treated with chloroquine, nor in those from normal, untreated M phi. NH4Cl-treated living M phi that had ingested yeasts at 37 degrees C, followed by endocytosis of lucifer yellow at 17 degrees C (to accumulate labeled endosomes and postpone label passing to lysosomes), were then restored to 37 degrees C. Fluorescence microscopy showed that as many as half of the yeast

  6. Defining Life or Bringing Biology to Life

    NASA Astrophysics Data System (ADS)

    Ruiz-Mirazo, Kepa; Peretó, Juli; Moreno, Alvaro

    2010-04-01

    In the present, post-genomic times, systemic or holistic approaches to living phenomena are compulsory to overcome the limits of traditional strategies, such as the methodological reductionism of molecular biology. In this paper, we propose that theoretical and philosophical efforts to define life also contribute to those integrative approaches, providing a global theoretical framework that may help to deal with or interpret the huge amount of data being collected by current high-throughput technologies, in this so-called ‘omics’ revolution. We claim that two fundamental notions can capture the core of the living, (basic) autonomy and open-ended evolution, and that only the complementary combination of these two theoretical constructs offers an adequate solution to the problem of defining the nature of life in specific enough—but also encompassing enough—terms. This tentative solution should also illuminate, in its most elementary version, the leading steps towards living beings on Earth.

  7. Defining Tiger Parenting in Chinese Americans

    PubMed Central

    Kim, Su Yeong

    2016-01-01

    “Tiger” parenting, as described by Amy Chua [2011], has instigated scholarly discourse on this phenomenon and its possible effects on families. Our eight-year longitudinal study, published in the Asian American Journal of Psychology [Kim, Wang, Orozco-Lapray, Shen, & Murtuza, 2013b], demonstrates that tiger parenting is not a common parenting profile in a sample of 444 Chinese American families. Tiger parenting also does not relate to superior academic performance in children. In fact, the best developmental outcomes were found among children of supportive parents. We examine the complexities around defining tiger parenting by reviewing classical literature on parenting styles and scholarship on Asian American parenting, along with Amy Chua’s own description of her parenting method, to develop, define, and categorize variability in parenting in a sample of Chinese American families. We also provide evidence that supportive parenting is important for the optimal development of Chinese American adolescents. PMID:27182075

  8. Defining life or bringing biology to life.

    PubMed

    Ruiz-Mirazo, Kepa; Peretó, Juli; Moreno, Alvaro

    2010-04-01

    In the present, post-genomic times, systemic or holistic approaches to living phenomena are compulsory to overcome the limits of traditional strategies, such as the methodological reductionism of molecular biology. In this paper, we propose that theoretical and philosophical efforts to define life also contribute to those integrative approaches, providing a global theoretical framework that may help to deal with or interpret the huge amount of data being collected by current high-throughput technologies, in this so-called 'omics' revolution. We claim that two fundamental notions can capture the core of the living, (basic) autonomy and open-ended evolution, and that only the complementary combination of these two theoretical constructs offers an adequate solution to the problem of defining the nature of life in specific enough-but also encompassing enough-terms. This tentative solution should also illuminate, in its most elementary version, the leading steps towards living beings on Earth. PMID:20182798

  9. Defining professional nursing accountability: a literature review.

    PubMed

    Krautscheid, Lorretta C

    2014-01-01

    Professional nursing accountability is described by both professional nursing organizations and nursing education credentialing agencies as a core aspect that underpins professional nursing practice. Although accountability is foundational to professional practice, a review of the literature revealed no consistent language or definition regarding professional nursing accountability. Instead, the literature itself reveals that professional nursing accountability is challenging to both describe and define. The ambiguity surrounding how to define professional nursing accountability contributes to challenges associated with both teaching and evaluating student nurse accountability within nursing education curricula. This article provides a reliable and comprehensive definition of professional nursing accountability derived from a synthesis of the literature. Recommendations for nursing education practice and recommendations for nursing education research are proposed. PMID:24503314

  10. Observer models for statistically-defined backgrounds

    NASA Astrophysics Data System (ADS)

    Burgess, Arthur E.

    1994-04-01

    Investigation of human signal-detection performance for noise- limited tasks with statistically defined signal or image parameters represents a step towards clinical realism. However, the ideal observer procedure is then usually nonlinear, and analysis becomes mathematically intractable. Two linear but suboptimal observer models, the Hotelling observer and the non- prewhitening (NPW) matched filter, have been proposed for mathematical convenience. Experiments by Rolland and Barrett involving detection of signals in white noise superimposed on statistically defined backgrounds showed that the Hotelling model gave a good fit while the simple NPW matched filter gave a poor fit. It will be shown that the NPW model can be modified to fit their data by adding a spatial frequency filter of shape similar to the human contrast sensitivity function. The best fit is obtained using an eye filter model, E(f) equals f1.3 exp(-cf2) with c selected to give a peak at 4 cycles per degree.

  11. Software-defined Quantum Communication Systems

    SciTech Connect

    Humble, Travis S; Sadlier, Ronald J

    2014-01-01

    Quantum communication systems harness modern physics through state-of-the-art optical engineering to provide revolutionary capabilities. An important concern for quantum communication engineering is designing and prototyping these systems to prototype proposed capabilities. We apply the paradigm of software-defined communica- tion for engineering quantum communication systems to facilitate rapid prototyping and prototype comparisons. We detail how to decompose quantum communication terminals into functional layers defining hardware, software, and middleware concerns, and we describe how each layer behaves. Using the super-dense coding protocol as a test case, we describe implementations of both the transmitter and receiver, and we present results from numerical simulations of the behavior. We find that while the theoretical benefits of super dense coding are maintained, there is a classical overhead associated with the full implementation.

  12. Responsibility for proving and defining in abstract algebra class

    NASA Astrophysics Data System (ADS)

    Fukawa-Connelly, Timothy

    2016-07-01

    There is considerable variety in inquiry-oriented instruction, but what is common is that students assume roles in mathematical activity that in a traditional, lecture-based class are either assumed by the teacher (or text) or are not visible at all in traditional math classrooms. This paper is a case study of the teaching of an inquiry-based undergraduate abstract algebra course. In particular, gives a theoretical account of the defining and proving processes. The study examines the intellectual responsibility for the processes of defining and proving that the professor devolved to the students. While the professor wanted the students to engage in all aspects of defining and proving, he was only successful at devolving responsibility for certain aspects and much more successful at devolving responsibility for proving than conjecturing or defining. This study suggests that even a well-intentioned instructor may not be able to devolve responsibility to students for some aspects of mathematical practice without using a research-based curriculum or further professional development.

  13. HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies

    PubMed Central

    2009-01-01

    Objective To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. Design Observational cohort study. Methods Patients (23 437) were followed prospectively for 104 921 person-years. We used Poisson regression models to identify factors independently associated with deaths from ADM and nADM. Analyses of factors associated with mortality due to nADM were repeated after excluding nADM known to be associated with a specific risk factor. Results Three hundred five patients died due to a malignancy, 298 prior to the cutoff for this analysis (ADM: n=110; nADM: n=188). The mortality rate due to ADM decreased from 20.1/1000 person-years of follow-up [95% confidence interval (CI) 14.4, 25.9] when the most recent CD4 cell count was <50 cells/μl to 0.1 (0.03, 0.3)/1000 person-years of follow-up when the CD4 cell count was more than 500 cells/μl; the mortality rate from nADM decreased from 6.0 (95% CI 3.3, 10.1) to 0.6 (0.4, 0.8) per 1000 person-years of follow-up between these two CD4 cell count strata. In multivariable regression analyses, a two-fold higher latest CD4 cell count was associated with a halving of the risk of ADM mortality. Other predictors of an increased risk of ADM mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS diagnosis and earlier calendar years. Predictors of an increased risk of nADM mortality included lower CD4 cell count, older age, current/ex-smoking status, longer cumulative exposure to combination antiretroviral therapy, active hepatitis B infection and earlier calendar year. Conclusion The severity of immunosuppression is predictive of death from both ADM and nADM in HIV-infected populations. PMID:18832878

  14. Localization of functions defined on cantor group

    NASA Astrophysics Data System (ADS)

    Krivoshein, Aleksander V.; Lebedeva, Elena A.

    2013-10-01

    We introduce a notion of localization for dyadic functions, i. e. functions defined on Cantor group. Both non-periodic and periodic cases are discussed. Localization is characterized by functionals UCd and UCdp similar to the Heisenberg (the Breitenberger) uncertainty constants used for real-line (periodic) functions. We are looking for dyadic analogs of uncertainty principles. To justify definition we use some test functions including dyadic scaling and wavelet functions.

  15. Defining the space in a general spacetime

    NASA Astrophysics Data System (ADS)

    Arminjon, Mayeul

    2016-01-01

    A global vector field v on a “spacetime” differentiable manifold V, of dimension N + 1, defines a congruence of world lines: the maximal integral curves of v, or orbits. The associated global space Nv is the set of these orbits. A “v-adapted” chart on V is one for which the ℝN vector x ≡ (xj) (j = 1,…,N) of the “spatial” coordinates remains constant on any orbit l. We consider non-vanishing vector fields v that have non-periodic orbits, each of which is a closed set. We prove transversality theorems relevant to such vector fields. Due to these results, it can be considered plausible that, for such a vector field, there exists in the neighborhood of any point X ∈V a chart χ that is v-adapted and “nice”, i.e. such that the mapping χ¯ : l↦x is injective — unless v has some “pathological” character. This leads us to define a notion of “normal” vector field. For any such vector field, the mappings χ¯ build an atlas of charts, thus providing Nv with a canonical structure of differentiable manifold (when the topology defined on Nv is Hausdorff, for which we give a sufficient condition met in important physical situations). Previously, a local space manifold MF had been associated with any “reference frame” F, defined as an equivalence class of charts. We show that, if F is made of nice v-adapted charts, MF is naturally identified with an open subset of the global space manifold Nv.

  16. Defining and measuring sustainability: The biogeophysical foundations

    SciTech Connect

    Munasinghe, M.; Shearer, W.

    1995-10-01

    This volume is based on papers prepared for the International Conference on the Definition and Measurement of Sustainability: The Biophysical Foundations, which was convened at the World Bank in Washington, D.C. from June 22 to 25 1992. The conference was conceived as an exercise to advance thinking on the biogeophysical foundations for defining and measuring sustainability and to provide useful policy considerations for international development community.

  17. Smooth Pursuit of Flicker-Defined Motion

    NASA Technical Reports Server (NTRS)

    Mulligan, Jeffrey B.; Stevenson, Scott B.

    2014-01-01

    We examined the pursuit response to stimuli defined by space-variant flicker of a dense random dot carrier pattern. On each frame, every element of the pattern could change polarity, with a probability given by a two-dimensional Gaussian distribution. A normal distribution produces a circular region of twinkle, while inverting the distribution results in a spot of static texture in a twinkling surround. In this latter case, the carrier texture could be stationary, or could move with the twinkle modulator, thereby producing first-order motion in the region of the spot. While the twinkle-defined spot produces a strong sensation of motion, the complementary stimulus defined by the absence of twinkle does not, when viewed peripherally, it appears to move in steps even when the generating distribution moves smoothly. We examined pursuit responses to these stimuli using two techniques: 1) the eye movement correlogram, obtained by cross-correlating eye velocity with the velocity of a randomly-moving stimulus; and 2) delayed visual feedback, where transient stabilization of a target can produce spontaneous oscillations of the eye, with a period empirically observed to vary linearly with the applied delay. Both techniques provide an estimate of the internal processing time, which can be as short as 100 milliseconds for a first-order target. Assessed by the correlogram method, the response to flicker-defined motion is delayed by more than 100 milliseconds, and significantly weaker (especially in the vertical dimension). When initially presented in the delayed feedback condition, purely saccadic oscillation is observed. One subject eventually developed smooth oscillations (albeit with significant saccadic intrusions), showing a period-versus-delay slope similar to that observed for first-order targets. This result is somewhat surprising, given that we interpret the slope of the period-versus-delay-function as reflecting the balance between position- and velocity

  18. Speciation without Pre-Defined Fitness Functions

    PubMed Central

    Gras, Robin; Golestani, Abbas; Hendry, Andrew P.; Cristescu, Melania E.

    2015-01-01

    The forces promoting and constraining speciation are often studied in theoretical models because the process is hard to observe, replicate, and manipulate in real organisms. Most models analyzed to date include pre-defined functions influencing fitness, leaving open the question of how speciation might proceed without these built-in determinants. To consider the process of speciation without pre-defined functions, we employ the individual-based ecosystem simulation platform EcoSim. The environment is initially uniform across space, and an evolving behavioural model then determines how prey consume resources and how predators consume prey. Simulations including natural selection (i.e., an evolving behavioural model that influences survival and reproduction) frequently led to strong and distinct phenotypic/genotypic clusters between which hybridization was low. This speciation was the result of divergence between spatially-localized clusters in the behavioural model, an emergent property of evolving ecological interactions. By contrast, simulations without natural selection (i.e., behavioural model turned off) but with spatial isolation (i.e., limited dispersal) produced weaker and overlapping clusters. Simulations without natural selection or spatial isolation (i.e., behaviour model turned off and high dispersal) did not generate clusters. These results confirm the role of natural selection in speciation by showing its importance even in the absence of pre-defined fitness functions. PMID:26372462

  19. Software Defined Radio with Parallelized Software Architecture

    NASA Technical Reports Server (NTRS)

    Heckler, Greg

    2013-01-01

    This software implements software-defined radio procession over multicore, multi-CPU systems in a way that maximizes the use of CPU resources in the system. The software treats each processing step in either a communications or navigation modulator or demodulator system as an independent, threaded block. Each threaded block is defined with a programmable number of input or output buffers; these buffers are implemented using POSIX pipes. In addition, each threaded block is assigned a unique thread upon block installation. A modulator or demodulator system is built by assembly of the threaded blocks into a flow graph, which assembles the processing blocks to accomplish the desired signal processing. This software architecture allows the software to scale effortlessly between single CPU/single-core computers or multi-CPU/multi-core computers without recompilation. NASA spaceflight and ground communications systems currently rely exclusively on ASICs or FPGAs. This software allows low- and medium-bandwidth (100 bps to approx.50 Mbps) software defined radios to be designed and implemented solely in C/C++ software, while lowering development costs and facilitating reuse and extensibility.

  20. Software Defined Radio with Parallelized Software Architecture

    NASA Technical Reports Server (NTRS)

    Heckler, Greg

    2013-01-01

    This software implements software-defined radio procession over multi-core, multi-CPU systems in a way that maximizes the use of CPU resources in the system. The software treats each processing step in either a communications or navigation modulator or demodulator system as an independent, threaded block. Each threaded block is defined with a programmable number of input or output buffers; these buffers are implemented using POSIX pipes. In addition, each threaded block is assigned a unique thread upon block installation. A modulator or demodulator system is built by assembly of the threaded blocks into a flow graph, which assembles the processing blocks to accomplish the desired signal processing. This software architecture allows the software to scale effortlessly between single CPU/single-core computers or multi-CPU/multi-core computers without recompilation. NASA spaceflight and ground communications systems currently rely exclusively on ASICs or FPGAs. This software allows low- and medium-bandwidth (100 bps to .50 Mbps) software defined radios to be designed and implemented solely in C/C++ software, while lowering development costs and facilitating reuse and extensibility.

  1. 20 CFR 404.430 - Monthly and annual exempt amounts defined; excess earnings defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Monthly and annual exempt amounts defined; excess earnings defined. 404.430 Section 404.430 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Deductions; Reductions; and Nonpayments of Benefits § 404.430 Monthly and annual...

  2. Infant motion: detection (M:D) ratios for chromatically defined and luminance-defined moving stimuli.

    PubMed

    Dobkins, K R; Teller, D Y

    1996-10-01

    In order to assess the relative contributions of chromatic vs luminance information to motion processing in infants, we employed a motion:detection (M:D) paradigm. Stimuli consisted of 27 deg by 40 deg, 0.25 c/deg sinusoidal gratings moving at 22 deg/sec (5.6 Hz), and were either chromatically defined or luminance-defined. Contrast thresholds for direction-of-motion (M) were obtained using a directional eye movement technique. Contrast thresholds for detection (D) were obtained using forced-choice preferential looking. M:D threshold ratios were obtained for individual infant subjects, and results were compared to those of adults. As expected, adult M:D threshold ratios were near 1:1 for luminance-defined stimuli, but greater than 1:1 for chromatically defined stimuli. This suggests that, for adults, luminance-defined, but not chromatically defined, stimuli are detected by mechanisms labeled for direction of motion. By contrast, infant M:D ratios for chromatically and luminance-defined stimuli were approximately equal and close to 1:1, suggesting that, for infants, luminance- as well as chromatically defined stimuli are detected by mechanisms that are labeled for direction of motion. PMID:8944288

  3. Antibacterial Activity of and Resistance to Small Molecule Inhibitors of the ClpP Peptidase

    PubMed Central

    Compton, Corey L.; Schmitz, Karl R.; Sauer, Robert T.; Sello, Jason K.

    2014-01-01

    There is rapidly mounting evidence that intracellular proteases in bacteria are compelling targets for antibacterial drugs. Multiple reports suggest that the human pathogen Mycobacterium tuberculosis and other actinobacteria may be particularly sensitive to small molecules that perturb the activities of self-compartmentalized peptidases, which catalyze intracellular protein turnover as components of ATP-dependent proteolytic machines. Here, we report chemical syntheses and evaluations of structurally diverse β-lactones, which have a privileged structure for selective, suicide inhibition of the self-compartmentalized ClpP peptidase. β-lactones with certain substituents on the α- and β-carbons were found to be toxic to M. tuberculosis. Using an affinity-labeled analog of a bioactive β-lactone in a series of chemical proteomic experiments, we selectively captured the ClpP1P2 peptidase from live cultures of two different actinobacteria that are related to M. tuberculosis. Importantly, we found that the growth inhibitory β-lactones also inactivate the M. tuberculosis ClpP1P2 peptidase in vitro via formation of a covalent adduct at the ClpP2 catalytic serine. Given the potent antibacterial activity of these compounds and their medicinal potential, we sought to identify innate mechanisms of resistance. Using a genome mining strategy, we identified a genetic determinant of β-lactone resistance in Streptomyces coelicolor, a non-pathogenic relative of M. tuberculosis. Collectively, these findings validate the potential of ClpP inhibition as a strategy in antibacterial drug development and define a mechanism by which bacteria could resist the toxic effects of ClpP inhibitors. PMID:24047344

  4. Parallel scheduling of recursively defined arrays

    NASA Technical Reports Server (NTRS)

    Myers, T. J.; Gokhale, M. B.

    1986-01-01

    A new method of automatic generation of concurrent programs which constructs arrays defined by sets of recursive equations is described. It is assumed that the time of computation of an array element is a linear combination of its indices, and integer programming is used to seek a succession of hyperplanes along which array elements can be computed concurrently. The method can be used to schedule equations involving variable length dependency vectors and mutually recursive arrays. Portions of the work reported here have been implemented in the PS automatic program generation system.

  5. Software-defined reconfigurable microwave photonics processor.

    PubMed

    Pérez, Daniel; Gasulla, Ivana; Capmany, José

    2015-06-01

    We propose, for the first time to our knowledge, a software-defined reconfigurable microwave photonics signal processor architecture that can be integrated on a chip and is capable of performing all the main functionalities by suitable programming of its control signals. The basic configuration is presented and a thorough end-to-end design model derived that accounts for the performance of the overall processor taking into consideration the impact and interdependencies of both its photonic and RF parts. We demonstrate the model versatility by applying it to several relevant application examples. PMID:26072824

  6. Defining Requirements for Improved Photovoltaic System Reliability

    SciTech Connect

    Maish, A.B.

    1998-12-21

    Reliable systems are an essential ingredient of any technology progressing toward commercial maturity and large-scale deployment. This paper defines reliability as meeting system fictional requirements, and then develops a framework to understand and quantify photovoltaic system reliability based on initial and ongoing costs and system value. The core elements necessary to achieve reliable PV systems are reviewed. These include appropriate system design, satisfactory component reliability, and proper installation and servicing. Reliability status, key issues, and present needs in system reliability are summarized for four application sectors.

  7. Defining recovery in adult bulimia nervosa.

    PubMed

    Yu, Jessica; Agras, W Stewart; Bryson, Susan

    2013-01-01

    To examine how different definitions of recovery lead to varying rates of recovery, maintenance of recovery, and relapse in bulimia nervosa (BN), end-of-treatment (EOT) and follow-up data were obtained from 96 adults with BN. Combining behavioral, physical, and psychological criteria led to recovery rates between 15.5% and 34.4% at EOT, though relapse was approximately 50%. Combining these criteria and requiring abstinence from binge eating and purging when defining recovery may lead to lower recovery rates than those found in previous studies; however, a strength of this definition is that individuals who meet this criteria have no remaining disordered behaviors or symptoms. PMID:24044595

  8. Dynamically defined measures and equilibrium states

    NASA Astrophysics Data System (ADS)

    Werner, Ivan

    2011-12-01

    A technique of dynamically defined measures is developed and its relation to the theory of equilibrium states is shown. The technique uses Carathéodory's method and the outer measure introduced in a previous work by I. Werner [Math. Proc. Camb. Phil. Soc. 140(2), 333-347 (2006), 10.1017/S0305004105009072]. As an application, equilibrium states for contractive Markov systems [I. Werner, J. London Math. Soc. 71(1), 236-258 (2005), 10.1112/S0024610704006088] are obtained.

  9. Defining the criteria for identifying constitutional epimutations.

    PubMed

    Sloane, Mathew A; Ward, Robyn L; Hesson, Luke B

    2016-01-01

    In the January 2016 issue of Clinical Epigenetics, Quiñonez-Silva et al. (Clin Epigenetics 8:1, 2016) described a possible constitutional epimutation of the RB1 gene as a cause of hereditary predisposition to retinoblastoma. The term constitutional epimutation describes an epigenetic aberration in normal tissues that predisposes to disease. The data presented by Quiñonez-Silva et al. are interesting, but further analysis is required to demonstrate a constitutional epimutation in this family. Here, we define the criteria and describe the experimental approach necessary to identify an epigenetic aberration as a constitutional epimutation. PMID:27096027

  10. Healthcare Engineering Defined: A White Paper.

    PubMed

    Chyu, Ming-Chien; Austin, Tony; Calisir, Fethi; Chanjaplammootil, Samuel; Davis, Mark J; Favela, Jesus; Gan, Heng; Gefen, Amit; Haddas, Ram; Hahn-Goldberg, Shoshana; Hornero, Roberto; Huang, Yu-Li; Jensen, Øystein; Jiang, Zhongwei; Katsanis, J S; Lee, Jeong-A; Lewis, Gladius; Lovell, Nigel H; Luebbers, Heinz-Theo; Morales, George G; Matis, Timothy; Matthews, Judith T; Mazur, Lukasz; Ng, Eddie Yin-Kwee; Oommen, K J; Ormand, Kevin; Rohde, Tarald; Sánchez-Morillo, Daniel; Sanz-Calcedo, Justo García; Sawan, Mohamad; Shen, Chwan-Li; Shieh, Jiann-Shing; Su, Chao-Ton; Sun, Lilly; Sun, Mingui; Sun, Yi; Tewolde, Senay N; Williams, Eric A; Yan, Chongjun; Zhang, Jiajie; Zhang, Yuan-Ting

    2015-01-01

    Engineering has been playing an important role in serving and advancing healthcare. The term "Healthcare Engineering" has been used by professional societies, universities, scientific authors, and the healthcare industry for decades. However, the definition of "Healthcare Engineering" remains ambiguous. The purpose of this position paper is to present a definition of Healthcare Engineering as an academic discipline, an area of research, a field of specialty, and a profession. Healthcare Engineering is defined in terms of what it is, who performs it, where it is performed, and how it is performed, including its purpose, scope, topics, synergy, education/training, contributions, and prospects. PMID:27010831

  11. Induction of pluripotency by defined factors

    PubMed Central

    TANABE, Koji; TAKAHASHI, Kazutoshi; YAMANAKA, Shinya

    2014-01-01

    The “reversion of cell fate from differentiated states back into totipotent or pluripotent states” has been an interest of many scientists for a long time. With the help of knowledge accumulated by those scientists, we succeeded in converting somatic cells to a pluripotent cell lineage by the forced expression of defined factors. These established induced pluripotent stem (iPS) cells have similar features to embryonic stem (ES) cells, including pluripotency and immortality. The iPS cell technology provides unprecedented opportunities for regenerative medicine and drug discovery. PMID:24621955

  12. Evolutionary Conserved Positions Define Protein Conformational Diversity.

    PubMed

    Saldaño, Tadeo E; Monzon, Alexander M; Parisi, Gustavo; Fernandez-Alberti, Sebastian

    2016-03-01

    Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix. PMID:27008419

  13. Inducing cellular senescence using defined genetic elements.

    PubMed

    Nakagawa, Hiroshi; Opitz, Oliver G

    2007-01-01

    Cellular senescence is generally defined as an irreversible state of G1 cell cycle arrest in which cells are refractory to growth factor stimulation. Cellular senescence can be induced through several different mechanisms. Primary mammalian cells display a finite life span, suggesting a mechanism that counts cell divisions. Those cells initially proliferate but eventually enter a state of permanent growth arrest, called replicative senescence. Erosion of telomeric DNA has emerged as a key factor in replicative senescence, which is antagonized during cell immortalization. Nevertheless, besides telomere shortening, there are other mechanisms inducing a growth arrest similar to the replicative senescencent phenotype. Oncogenic or mitogenic signals as well as DNA damage can induce such a phenotype of cellular senescence. All forms of cellular senescence share common signaling pathways and morphological features. Thereby, p53 seems to be essential for the senescence response. Many of these senescence inducing mechanisms can be experimentally recapitulated by the introduction of defined genetic elements. Replicative senescence due to telomere shortening can, for example, be induced by a dominant negative version of telomerase, premature senescence by the overexpression of oncogenic ras, or p16. PMID:17634581

  14. Defining surfaces for skewed, highly variable data

    USGS Publications Warehouse

    Helsel, D.R.; Ryker, S.J.

    2002-01-01

    Skewness of environmental data is often caused by more than simply a handful of outliers in an otherwise normal distribution. Statistical procedures for such datasets must be sufficiently robust to deal with distributions that are strongly non-normal, containing both a large proportion of outliers and a skewed main body of data. In the field of water quality, skewness is commonly associated with large variation over short distances. Spatial analysis of such data generally requires either considerable effort at modeling or the use of robust procedures not strongly affected by skewness and local variability. Using a skewed dataset of 675 nitrate measurements in ground water, commonly used methods for defining a surface (least-squares regression and kriging) are compared to a more robust method (loess). Three choices are critical in defining a surface: (i) is the surface to be a central mean or median surface? (ii) is either a well-fitting transformation or a robust and scale-independent measure of center used? (iii) does local spatial autocorrelation assist in or detract from addressing objectives? Published in 2002 by John Wiley & Sons, Ltd.

  15. Defining and Measuring Vulnerability in Young People.

    PubMed

    Arora, Shilpa Khanna; Shah, Dheeraj; Chaturvedi, Sanjay; Gupta, Piyush

    2015-01-01

    Adolescents and youth, together addressed as "young people", form the future building blocks of any society. They being most energetic and dynamic, tend to get involved in high-risk behaviors making themselves susceptible to criminal offences, accidents, physical injuries, emotional trauma, and medical problems - some of them extremely serious like transmission of human immunodeficiency virus (HIV). The concept of vulnerability is applicable to all the people who are more exposed to risks than their peers like the young people. In order to deal with social evils like criminal offences, domestic violence, sexual abuse, HIV, etc. we need to define vulnerability and understand the factors that influence it. This review also attempts to summarize the indicators of vulnerability and the data currently available to estimate its burden in India. Measuring the magnitude of vulnerability by means of certain indicators/variables might help us in devising tools to assess this poorly defined entity. This may also evolve a conceptual framework on which targeted remedial interventions can be devised and implemented. PMID:26170545

  16. Membership of Defined Responses in Stimulus Classes

    PubMed Central

    Lionello-DeNolf, Karen M.; Braga-Kenyon, Paula

    2012-01-01

    Sidman (2000) has suggested that in addition to conditional and discriminative stimuli, class-consistent defined responses can also become part of an equivalence class. In the current study, this assertion was tested using a mixed-schedule procedure that allowed defined response patterns to be “presented” as samples in the absence of different occasioning stimuli. Four typically developing adults were first trained to make distinct response topographies to two visual color stimuli, and then were taught to match those color stimuli to two different form-sample stimuli in a matching task. Three separate tests were given in order to determine whether training had established two classes each comprised of a response, a color, and a form: a form-response test in which the forms were presented to test if the participants would make differential responses to them; and two response-matching tests to test if the participants would match visual stimulus comparisons to response-pattern samples. Three of the four participants showed class-consistent responding in the tests, although some participants needed additional training prior to passing the tests. In general, the data indicated that the different response patterns had entered into a class with the visual stimuli. These results add to a growing literature on the role of class-consistent responding in stimulus class formation, and provide support for the notion that differential responses themselves can become a part of an equivalence class. PMID:24778458

  17. Evolutionary Conserved Positions Define Protein Conformational Diversity

    PubMed Central

    Saldaño, Tadeo E.; Monzon, Alexander M.; Parisi, Gustavo; Fernandez-Alberti, Sebastian

    2016-01-01

    Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix. PMID:27008419

  18. Defining and Measuring Vulnerability in Young People

    PubMed Central

    Arora, Shilpa Khanna; Shah, Dheeraj; Chaturvedi, Sanjay; Gupta, Piyush

    2015-01-01

    Adolescents and youth, together addressed as “young people”, form the future building blocks of any society. They being most energetic and dynamic, tend to get involved in high-risk behaviors making themselves susceptible to criminal offences, accidents, physical injuries, emotional trauma, and medical problems — some of them extremely serious like transmission of human immunodeficiency virus (HIV). The concept of vulnerability is applicable to all the people who are more exposed to risks than their peers like the young people. In order to deal with social evils like criminal offences, domestic violence, sexual abuse, HIV, etc. we need to define vulnerability and understand the factors that influence it. This review also attempts to summarize the indicators of vulnerability and the data currently available to estimate its burden in India. Measuring the magnitude of vulnerability by means of certain indicators/variables might help us in devising tools to assess this poorly defined entity. This may also evolve a conceptual framework on which targeted remedial interventions can be devised and implemented. PMID:26170545

  19. Defining the genetic blueprint of kidney development.

    PubMed

    Potter, S Steven; Brunskill, Eric W; Patterson, Larry T

    2011-09-01

    Thousands of genes show differential expression patterns during kidney development, suggesting that the genetic program driving this process is complex. While great progress has been made in defining the outline of the genetic basis of nephrogenesis, it is clear that much remains to be learned. A global atlas of the gene expression profiles of the multiple elements of the developing kidney would allow the identification of novel growth factor-receptor interactions, identify additional molecular markers of distinct components, facilitate the generation of compartment specific GFP-CRE transgenic mouse tools, lend insights into the genetic regulatory circuits governing nephron formation, and fully characterize the waves of gene expression that impel nephrogenesis. Both microarrays and next generation deep sequencing of cDNA libraries can be used to define comprehensive, sensitive, and quantitative gene expression profiles. In addition, laser capture microdissection and transgenic GFP mice can be used to isolate specific compartments and pure cell types from the developing kidney. Advancing technologies are even allowing robust gene expression profiling of single cells. The final goal is the production of an exquisitely detailed atlas of the gene expression program that drives kidney development. PMID:21336810

  20. Defining a genetic ideotype for crop improvement.

    PubMed

    Trethowan, Richard M

    2014-01-01

    While plant breeders traditionally base selection on phenotype, the development of genetic ideotypes can help focus the selection process. This chapter provides a road map for the establishment of a refined genetic ideotype. The first step is an accurate definition of the target environment including the underlying constraints, their probability of occurrence, and impact on phenotype. Once the environmental constraints are established, the wealth of information on plant physiological responses to stresses, known gene information, and knowledge of genotype ×environment and gene × environment interaction help refine the target ideotype and form a basis for cross prediction.Once a genetic ideotype is defined the challenge remains to build the ideotype in a plant breeding program. A number of strategies including marker-assisted recurrent selection and genomic selection can be used that also provide valuable information for the optimization of genetic ideotype. However, the informatics required to underpin the realization of the genetic ideotype then becomes crucial. The reduced cost of genotyping and the need to combine pedigree, phenotypic, and genetic data in a structured way for analysis and interpretation often become the rate-limiting steps, thus reducing genetic gain. Systems for managing these data and an example of ideotype construction for a defined environment type are discussed. PMID:24816655

  1. Selecting objectively defined reference sites for stream bioassessment programs.

    PubMed

    Yates, Adam Gordon; Bailey, Robert C

    2010-11-01

    Our study develops and demonstrates an objective method for selecting reference sites for the assessment of ecological condition in freshwater ecosystems. The method uses widely available GIS data to group potential sites based on their natural environments. It then establishes the degree and types of human activities each site is exposed to prior to scoring the sites in each group by the relative amount of human activity present. Finally, the sites in each group with the least amount of human activity are categorized as reference sites, with the boundary between reference and test sites defined to maximize the distinctiveness of the two categories with respect to human activity. Application of this technique for the purpose of identifying headwater reference basins in rural areas of southwestern Ontario resulted in the classification of basins into six natural groups based on the dominant texture of the surface geology. Development of a human activity gradient indicated that basins varied according to the amount of exposure to agricultural activities with most basins having at least moderate exposure. Establishment of the reference test boundary indicated that the selected reference basins exhibited substantively lower extents of agricultural activity than test sites for most groups. Because this method uses only widely available GIS data, it enables rapid and cost-effective identification of candidate reference sites, even for large, remote, and understudied regions. PMID:19902368

  2. Synthetic lipids and their role in defining macromolecular assemblies.

    PubMed

    Parrill, Abby L

    2015-10-01

    Lipids have a variety of physiological roles, ranging from structural and biophysical contributions to membrane functions to signaling contributions in normal and abnormal physiology. This review highlights some of the contributions made by Robert Bittman to our understanding of lipid assemblies through the production of synthetic lipid analogs in the sterol, sphingolipid, and glycolipid classes. His contributions have included the development of a fluorescent cholesterol analog that shows strong functional analogies to cholesterol that has allowed live imaging of cholesterol distribution in living systems, to stereospecific synthetic approaches to both sphingolipid and glycolipid analogs crucial in defining the structure-activity relationships of lipid biological targets. PMID:26248325

  3. Continuous Culture of Ruminal Microorganisms in Chemically Defined Medium1

    PubMed Central

    Quinn, Loyd Y.; Burroughs, Wise; Christiansen, William C.

    1962-01-01

    Ruminal ciliates have been grown in continuous culture in chemically defined media and in the absence of viable bacteria. Oligotrichic ruminal ciliates seem to require insoluble carbohydrates for growth; the holotrichic ciliates require soluble carbohydrates, but at low concentrations. Both groups of ciliates utilize amino acids as their principal nitrogen source when these are supplied in micromolar concentrations; at millimolar concentrations, amino acids are toxic, possibly from excessive ammonia formation arising from ciliate deaminase activity. Holotrichic ruminal ciliates are destroyed by overdeposition of amylopectin when glucose is present above 0.1% concentration in the medium. Ecological requirements of ruminal ciliates are also described. Images FIG. 1 FIG. 2 PMID:13972780

  4. Locally adaptive method to define coordination shell.

    PubMed

    Higham, Jonathan; Henchman, Richard H

    2016-08-28

    An algorithm is presented to define a particle's coordination shell for any collection of particles. It requires only the particles' positions and no pre-existing knowledge or parameters beyond those already in the force field. A particle's shell is taken to be all particles that are not blocked by any other particle and not further away than a blocked particle. Because blocking is based on two distances and an angle for triplets of particles, it is called the relative angular distance (RAD) algorithm. RAD is applied to Lennard-Jones particles in molecular dynamics simulations of crystalline, liquid, and gaseous phases at various temperatures and densities. RAD coordination shells agree well with those from a cut-off in the radial distribution function for the crystals and liquids and are slightly higher for the gas. PMID:27586905

  5. Quantum computing. Defining and detecting quantum speedup.

    PubMed

    Rønnow, Troels F; Wang, Zhihui; Job, Joshua; Boixo, Sergio; Isakov, Sergei V; Wecker, David; Martinis, John M; Lidar, Daniel A; Troyer, Matthias

    2014-07-25

    The development of small-scale quantum devices raises the question of how to fairly assess and detect quantum speedup. Here, we show how to define and measure quantum speedup and how to avoid pitfalls that might mask or fake such a speedup. We illustrate our discussion with data from tests run on a D-Wave Two device with up to 503 qubits. By using random spin glass instances as a benchmark, we found no evidence of quantum speedup when the entire data set is considered and obtained inconclusive results when comparing subsets of instances on an instance-by-instance basis. Our results do not rule out the possibility of speedup for other classes of problems and illustrate the subtle nature of the quantum speedup question. PMID:25061205

  6. Recognizing and defining clinical nurse leaders.

    PubMed

    Stanley, David

    This article addresses the issue of clinical leadership and how it is defined. The concepts and definitions of clinical leadership are considered as well as the results of new research that suggests that clinical leaders can be seen as experts in their field, and because they are approachable and are effective communicators, are empowered to act as a role model, motivating others by matching their values and beliefs about nursing and care to their practice. This is supported by a new leadership theory, congruent leadership, proposed as the most appropriate leadership theory to support an understanding of clinical leadership. Congruent leaders (clinical nurse leaders) are followed because there is a match between the leader's values and beliefs and their actions. PMID:16493288

  7. Defining the ideal femtosecond laser capsulotomy

    PubMed Central

    Packer, Mark; Teuma, E Valas; Glasser, Adrian; Bott, Steven

    2015-01-01

    Purpose We define the ideal anterior capsulotomy through consideration of capsular histology and biomechanics. Desirable qualities include preventing posterior capsular opacification (PCO), maintaining effective lens position (ELP) and optimising capsular strength. Methods Laboratory study of capsular biomechanics and literature review of histology and published clinical results. Results Parameters of ideal capsulotomy construction include complete overlap of the intraocular lens to prevent PCO, centration on the clinical approximation of the optical axis of the lens to ensure concentricity with the capsule equator, and maximal capsular thickness at the capsulotomy edge to maintain integrity. Conclusions Constructing the capsulotomy centred on the clinical approximation of the optical axis of the lens with diameter 5.25 mm optimises prevention of PCO, consistency of ELP and capsular strength. PMID:25829488

  8. Defining and testing a granular continuum element

    SciTech Connect

    Rycroft, Chris H.; Kamrin, Ken; Bazant, Martin Z.

    2007-12-03

    Continuum mechanics relies on the fundamental notion of amesoscopic volume "element" in which properties averaged over discreteparticles obey deterministic relationships. Recent work on granularmaterials suggests a continuum law may be inapplicable, revealinginhomogeneities at the particle level, such as force chains and slow cagebreaking. Here, we analyze large-scale Discrete-Element Method (DEM)simulations of different granular flows and show that a "granularelement" can indeed be defined at the scale of dynamical correlations,roughly three to five particle diameters. Its rheology is rather subtle,combining liquid-like dependence on deformation rate and solid-likedependence on strain. Our results confirm some aspects of classicalplasticity theory (e.g., coaxiality of stress and deformation rate),while contradicting others (i.e., incipient yield), and can guide thedevelopment of more realistic continuum models.

  9. Reconfigurable, Cognitive Software-Defined Radio

    NASA Technical Reports Server (NTRS)

    Bhat, Arvind

    2015-01-01

    Software-defined radio (SDR) technology allows radios to be reconfigured to perform different communication functions without using multiple radios to accomplish each task. Intelligent Automation, Inc., has developed SDR platforms that switch adaptively between different operation modes. The innovation works by modifying both transmit waveforms and receiver signal processing tasks. In Phase I of the project, the company developed SDR cognitive capabilities, including adaptive modulation and coding (AMC), automatic modulation recognition (AMR), and spectrum sensing. In Phase II, these capabilities were integrated into SDR platforms. The reconfigurable transceiver design employs high-speed field-programmable gate arrays, enabling multimode operation and scalable architecture. Designs are based on commercial off-the-shelf (COTS) components and are modular in nature, making it easier to upgrade individual components rather than redesigning the entire SDR platform as technology advances.

  10. Defining and measuring pilot mental workload

    NASA Technical Reports Server (NTRS)

    Kantowitz, Barry H.

    1988-01-01

    A theory is sought that is general enough to help the researcher deal with a wide range of situations involving pilot mental stress. A limited capacity theory of attention forms the basis for the theory. Mental workload is then defined as an intervening variable, similar to attention, that modulates or indexes the tuning between the demands of the environment and the capacity of the organism. Two methods for measuring pilot mental workload are endorsed: (1) objective measures based on secondary tasks; and (2) psychophysiological measures, which have not yet been perfected but which will become more useful as theoretical models are refined. Secondary-task research is illustrated by simulator studies in which flying performance has been shown not to be adversely affected by adding a complex choice-reaction secondary task.

  11. Using archetypes for defining CDA templates.

    PubMed

    Moner, David; Moreno, Alberto; Maldonado, José A; Robles, Montserrat; Parra, Carlos

    2012-01-01

    While HL7 CDA is a widely adopted standard for the documentation of clinical information, the archetype approach proposed by CEN/ISO 13606 and openEHR is gaining recognition as a means of describing domain models and medical knowledge. This paper describes our efforts in combining both standards. Using archetypes as an alternative for defining CDA templates permit new possibilities all based on the formal nature of archetypes and their ability to merge into the same artifact medical knowledge and technical requirements for semantic interoperability of electronic health records. We describe the process followed for the normalization of existing legacy data in a hospital environment, from the importation of the HL7 CDA model into an archetype editor, the definition of CDA archetypes and the application of those archetypes to obtain normalized CDA data instances. PMID:22874151

  12. Multiphoton microscopy in defining liver function

    NASA Astrophysics Data System (ADS)

    Thorling, Camilla A.; Crawford, Darrell; Burczynski, Frank J.; Liu, Xin; Liau, Ian; Roberts, Michael S.

    2014-09-01

    Multiphoton microscopy is the preferred method when in vivo deep-tissue imaging is required. This review presents the application of multiphoton microscopy in defining liver function. In particular, multiphoton microscopy is useful in imaging intracellular events, such as mitochondrial depolarization and cellular metabolism in terms of NAD(P)H changes with fluorescence lifetime imaging microscopy. The morphology of hepatocytes can be visualized without exogenously administered fluorescent dyes by utilizing their autofluorescence and second harmonic generation signal of collagen, which is useful in diagnosing liver disease. More specific imaging, such as studying drug transport in normal and diseased livers are achievable, but require exogenously administered fluorescent dyes. If these techniques can be translated into clinical use to assess liver function, it would greatly improve early diagnosis of organ viability, fibrosis, and cancer.

  13. Activity.

    ERIC Educational Resources Information Center

    Clearing: Nature and Learning in the Pacific Northwest, 1984

    1984-01-01

    Presents three activities: (1) investigating succession in a schoolground; (2) investigating oak galls; and (3) making sun prints (photographs made without camera or darkroom). Each activity includes a list of materials needed and procedures used. (JN)

  14. 20 CFR 725.491 - Operator defined.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... awarding benefits against a corporation that has not secured its liability for benefits in accordance with... shall not be contingent upon the amount or percentage of its work or business related to activities...

  15. Defining Future Directions for Endometriosis Research

    PubMed Central

    D’Hooghe, Thomas M.; Fazleabas, Asgerally; Giudice, Linda C.; Montgomery, Grant W.; Petraglia, Felice; Taylor, Robert N.

    2013-01-01

    Endometriosis, defined as estrogen-dependent lesions containing endometrial glands and stroma outside the uterus, is a chronic and often painful gynecological condition that affects 6% to 10% of reproductive age women. Endometriosis has estimated annual costs of US $12 419 per woman (approximately €9579), comprising one-third of the direct health care costs with two-thirds attributed to loss of productivity. Decreased quality of life is the most important predictor of direct health care and total costs. It has been estimated that there is a mean delay of 6.7 years between onset of symptoms and a surgical diagnosis of endometriosis, and each affected woman loses on average 10.8 hours of work weekly, mainly owing to reduced effectiveness while working. To encourage and facilitate research into this debilitating disease, a consensus workshop to define future directions for endometriosis research was held as part of the 11th World Congress on Endometriosis in September 2011 in Montpellier, France. The objective of this workshop was to review and update the endometriosis research priorities consensus statement developed following the 10th World Congress on Endometriosis in 2008.1 A total of 56 recommendations for research have been developed, grouped under 6 subheadings: (1) diagnosis, (2) classification and prognosis, (3) clinical trials, treatment, and outcomes, (4) epidemiology, (5) pathophysiology, and (6) research policy. By producing this consensus international research priorities statement, it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis. PMID:23427182

  16. Multiplexed Dosing Assays by Digitally Definable Hydrogel Volumes.

    PubMed

    Faralli, Adele; Melander, Fredrik; Larsen, Esben Kjaer Unmack; Chernyy, Sergey; Andresen, Thomas L; Larsen, Niels B

    2016-01-21

    Stable and low-cost multiplexed drug sensitivity assays using small volumes of cells or tissue are in demand for personalized medicine, including patient-specific combination chemotherapy. Spatially defined projected light photopolymerization of hydrogels with embedded active compounds is introduced as a flexible and cost-efficient method for producing multiplexed dosing assays. The high spatial resolution of light projector technology defines multiple compound doses by the volume of individual compound-embedded hydrogel segments. Quantitative dosing of multiple proteins with a dynamic range of 1-2 orders of magnitude is demonstrated using fluorescently labeled albumins. The hydrogel matrix results from photopolymerization of low-cost poly(ethylene glycol) diacrylates (PEGDA), and tuning of the PEGDA composition enables fast complete dosing of all tested species. Dosing of hydrophilic and hydrophobic compounds is demonstrated using two first-line chemotherapy regimens combining oxaliplatin, SN-38, 5-fluorouracil, and folinic acid, with each compound being dosed from a separate light-defined hydrogel segment. Cytotoxicity studies using a colorectal cancer cell line show equivalent effects of dissolved and released compounds. Further control of the dosing process is demonstrated by liposomal encapsulation of oxaliplatin, stable embedding of the liposomes in hydrogels for more than 3 months, and heat-triggered complete release of the loaded oxaliplatin. PMID:26619161

  17. Differentiation of purified astrocytes in a chemically defined medium

    SciTech Connect

    Morrison, R.S.; de Vellis, J.

    1981-01-01

    Homogeneous cultures of astrocytes and oligodendrocytes provide an excellent model system for studying the regulation of glial structure and function. Recently, a chemically defined (CD) medium was developed for purified cultures of astrocytes, thus eliminating the requirement for serum and providing a controlled system for the study of astroglial properties. Due to the widespread use of astrocyte cultures and the potential benefits to be gained from using a defined medium, astrocyte cultures raised in CD medium were analyzed for purity as well as morphological and biochemical properties. Purity was assessed using immunocytochemical staining for glial fibrillary acidic protein (GFAP) and fibronectin. Astrocytes raised in CD medium are 95% pure using the expression of GFAP as a criterion. Fewer than 1% of the cells in CD medium stained positive for fibronectin eliminating the possibility that CD medium is selective for meningeal or endothelial cells. Astrocytes raised in CD medium exhibit a striking degree of morphological differentiation as seen in scanning electron micrographs. They also exhibit a high degree of biochemical differentiation illustrated by increases in the specific activity of S-100 protein and the induction of glutamine synthetase by glucocorticoids. A defined medium that supports the proliferation of rat astrocytes and enhances numerous morphological and biochemical properties should greatly facilitate the study of factors controlling glial proliferation and differentiation.

  18. Self-defining memories and self-defining future projections in hypomania-prone individuals.

    PubMed

    Lardi Robyn, Claudia; Ghisletta, Paolo; Van der Linden, Martial

    2012-06-01

    Mania and hypomania involve dysfunctional beliefs about the self, others, and the world, as well about affect regulation. The present study explored the impact of these beliefs on self-defining memories and self-defining future projections of individuals with a history of hypomanic symptoms. The main findings showed that a history of hypomanic symptoms was related to enhanced retrieval of memories describing positive relationships and to reduced future projections about relationships, suggesting both a need for social bonding and a striving for autonomy. Moreover, hypomania-prone individuals tended to describe more recent events and to produce self-defining memories with references to tension that were more integrated in their self-structure. All of these findings support the presence of conflicting dysfunctional beliefs and the importance of memories containing references to tension in hypomania. PMID:22405587

  19. Characterization and biological activity against Naegleria fowleri of amoebicins produced by Bacillus licheniformis D-13.

    PubMed Central

    Gálvez, A; Maqueda, M; Cordovilla, P; Martínez-Bueno, M; Lebbadi, M; Valdivia, E

    1994-01-01

    The strain Bacillus licheniformis D-13 produces three hydrophobic peptides (amoebicins d13-A, d13-B, and d13-C) that elicit antiamoebic activity against human-pathogenic and nonpathogenic species of Naegleria and have a broad spectrum of antibacterial activity. The three amoebicins have the same amino acid composition (three Asp, two Glu, two Val, and nine Leu residues) and molecular weight (1,870). Amoebicin d13-B causes lysis of amoebae through disorganization of the cell membrane. It also induces permeability to 86Rb and membrane disruption in asolectin vesicles. Images PMID:8092831

  20. Defining sleep disturbance after brain injury.

    PubMed

    Clinchot, D M; Bogner, J; Mysiw, W J; Fugate, L; Corrigan, J

    1998-01-01

    Sleep disorders are a relatively common occurrence after brain injury. Sleep disturbances often result in a poor daytime performance and a poor individual sense of well-being. Unfortunately, there has been minimal attention paid to this common and often disabling sequela of brain injury. This study attempts to define and to correlate the incidence and type of sleep disturbances that occur after brain injury. Consecutive admissions to a rehabilitation unit were used to create a longitudinal database designed to predict long-term outcomes for individuals who suffered a brain injury. Fifty percent of subjects had difficulty sleeping. Sixty-four percent described waking up too early, 25% described sleeping more than usual, and 45% described problems falling asleep. Eighty percent of subjects reporting sleep problems also reported problems with fatigue. Logistic regression analysis revealed the following: the more severe the brain injury the less likely the subject would be to have a sleep disturbance; subjects who had sleep disturbances were more likely to have problems with fatigue; females were more likely to have trouble with sleep. This study demonstrates the substantial prevalence of sleep disturbances after brain injury. It underscores the relationship between sleep disorders and perception of fatigue. It also underscores the need for clinicians to strive for interventional studies to look at the treatment of sleep and fatigue problems after brain injury. PMID:9715917