Science.gov

Sample records for arenaviruses provide broad

  1. Arenavirus Budding

    PubMed Central

    Urata, Shuzo; de la Torre, Juan Carlos

    2011-01-01

    Several arenaviruses cause hemorrhagic fever disease in humans and pose a significant public health concern in their endemic regions. On the other hand, the prototypic arenavirus LCMV is a superb workhorse for the investigation of virus-host interactions and associated disease. The arenavirus small RING finger protein called Z has been shown to be the main driving force of virus budding. The budding activity of Z is mediated by late (L) domain motifs, PT/SAP, and PPXY, located at the C-terminus of Z. This paper will present the current knowledge on arenavirus budding including the diversity of L domain motifs used by different arenaviruses. We will also discuss how improved knowledge of arenavirus budding may facilitate the development of novel antiviral strategies to combat human pathogenic arenaviruses. PMID:22312335

  2. Pathogenesis of arenavirus hemorrhagic fevers.

    PubMed

    Moraz, Marie-Laurence; Kunz, Stefan

    2011-01-01

    Viral hemorrhagic fevers (VHFs) caused by arenaviruses belong to the most devastating emerging human diseases and represent serious public health problems. Arenavirus VHFs in humans are acute diseases characterized by fever and, in severe cases, different degrees of hemorrhages associated with a shock syndrome in the terminal stage. Over the past years, much has been learned about the pathogenesis of arenaviruses at the cellular level, in particular their ability to subvert the host cell's innate antiviral defenses. Clinical studies and novel animal models have provided important new information about the interaction of hemorrhagic arenaviruses with the host's adaptive immune system, in particular virus-induced immunosuppression, and have provided the first hints towards an understanding of the terminal hemorrhagic shock syndrome. The scope of this article is to review our current knowledge on arenavirus VHF pathogenesis with an emphasis on recent developments. PMID:21171877

  3. Reverse Genetics Approaches to Control Arenavirus.

    PubMed

    Martínez-Sobrido, Luis; Cheng, Benson Yee Hin; de la Torre, Juan Carlos

    2016-01-01

    Several arenavirus cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. To date, no licensed vaccines are available to combat human arenavirus infections, and anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetics approaches provides investigators with a novel and powerful approach for the investigation of the arenavirus molecular and cell biology. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription and the identification of novel anti-arenaviral drug targets without requiring the use of live forms of arenaviruses. Likewise, it is now feasible to rescue infectious arenaviruses entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify anti-arenaviral drugs and development of novel live-attenuated arenavirus vaccines. Recently, reverse genetics have also allowed the generation of tri-segmented arenaviruses expressing foreign genes, facilitating virus detection and opening the possibility of implementing live-attenuated arenavirus-based vaccine vector approaches. Likewise, the development of single-cycle infectious, reporter-expressing, arenaviruses has provided a new experimental method to study some aspects of the biology of highly pathogenic arenaviruses without the requirement of high-security biocontainment required to study HF-causing arenaviruses. In this chapter we summarize the current knowledge on arenavirus reverse genetics and the implementation of plasmid-based reverse genetics techniques for the development of arenavirus vaccines and vaccine vectors. PMID:27076139

  4. Reporter-Expressing, Replicating-Competent Recombinant Arenaviruses.

    PubMed

    Martínez-Sobrido, Luis; de la Torre, Juan Carlos

    2016-01-01

    Several arenaviruses cause hemorrhagic fever (HF) disease in humans and pose an important public health problem in their endemic regions. To date, no Food and Drug Administration (FDA)-licensed vaccines are available to combat human arenavirus infections, and current anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetic approaches has provided investigators with a novel and powerful approach for the study of arenavirus biology including virus-host interactions underlying arenavirus induced disease. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription, as well as particle assembly and budding. Likewise, it is now feasible to rescue infectious arenaviruses containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis. The use of reverse genetics approaches has also allowed the generation of recombinant arenaviruses expressing additional genes of interest. These advances in arenavirus molecular genetics have also facilitated the implementation of novel screens to identify anti-arenaviral drugs, and the development of novel strategies for the generation of arenavirus live-attenuated vaccines. In this review, we will summarize the current knowledge on reporter-expressing, replicating-competent arenaviruses harboring reporter genes in different locations of the viral genome and their use for studying and understanding arenavirus biology and the identification of anti-arenaviral drugs to combat these important human pathogens. PMID:27447662

  5. Reporter-Expressing, Replicating-Competent Recombinant Arenaviruses

    PubMed Central

    Martínez-Sobrido, Luis; de la Torre, Juan Carlos

    2016-01-01

    Several arenaviruses cause hemorrhagic fever (HF) disease in humans and pose an important public health problem in their endemic regions. To date, no Food and Drug Administration (FDA)-licensed vaccines are available to combat human arenavirus infections, and current anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetic approaches has provided investigators with a novel and powerful approach for the study of arenavirus biology including virus–host interactions underlying arenavirus induced disease. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription, as well as particle assembly and budding. Likewise, it is now feasible to rescue infectious arenaviruses containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis. The use of reverse genetics approaches has also allowed the generation of recombinant arenaviruses expressing additional genes of interest. These advances in arenavirus molecular genetics have also facilitated the implementation of novel screens to identify anti-arenaviral drugs, and the development of novel strategies for the generation of arenavirus live-attenuated vaccines. In this review, we will summarize the current knowledge on reporter-expressing, replicating-competent arenaviruses harboring reporter genes in different locations of the viral genome and their use for studying and understanding arenavirus biology and the identification of anti-arenaviral drugs to combat these important human pathogens. PMID:27447662

  6. Generation of Recombinant Arenavirus for Vaccine Development in FDA-Approved Vero Cells

    PubMed Central

    de la Torre, Juan Carlos; Martínez-Sobrido, Luis

    2013-01-01

    The development and implementation of arenavirus reverse genetics represents a significant breakthrough in the arenavirus field 4. The use of cell-based arenavirus minigenome systems together with the ability to generate recombinant infectious arenaviruses with predetermined mutations in their genomes has facilitated the investigation of the contribution of viral determinants to the different steps of the arenavirus life cycle, as well as virus-host interactions and mechanisms of arenavirus pathogenesis 1, 3, 11 . In addition, the development of trisegmented arenaviruses has permitted the use of the arenavirus genome to express additional foreign genes of interest, thus opening the possibility of arenavirus-based vaccine vector applications 5 . Likewise, the development of single-cycle infectious arenaviruses capable of expressing reporter genes provides a new experimental tool to improve the safety of research involving highly pathogenic human arenaviruses 16 . The generation of recombinant arenaviruses using plasmid-based reverse genetics techniques has so far relied on the use of rodent cell lines 7,19 , which poses some barriers for the development of Food and Drug Administration (FDA)-licensed vaccine or vaccine vectors. To overcome this obstacle, we describe here the efficient generation of recombinant arenaviruses in FDA-approved Vero cells. PMID:23928556

  7. Highly Pathogenic New World and Old World Human Arenaviruses Induce Distinct Interferon Responses in Human Cells

    PubMed Central

    Huang, Cheng; Kolokoltsova, Olga A.; Yun, Nadezhda E.; Seregin, Alexey V.; Ronca, Shannon; Koma, Takaaki

    2015-01-01

    cytokines in severe and fatal cases. Arenaviruses initially target macrophages and dendritic cells, which are potent IFN/cytokine-producers. In human macrophages, JUNV reportedly does not trigger IFN responses. We here demonstrated that JUNV activated IFN responses in human dendritic cells. MACV, another highly pathogenic NW arenavirus, also activated IFN responses. LASV did not induce detectable IFN responses, in spite of higher replication levels, and blocked the MACV-triggered IFN response in a coinfection assay. Although these viruses are highly pathogenic to humans, our study highlights distinct innate immune responses to infections with the NW arenaviruses JUNV and MACV and to infection with the OW arenavirus LASV and provides important insights into the virus-host interaction and pathogenesis. PMID:25926656

  8. A Multivalent and Cross-Protective Vaccine Strategy against Arenaviruses Associated with Human Disease

    PubMed Central

    Kotturi, Maya F.; Botten, Jason; Sidney, John; Bui, Huynh-Hoa; Giancola, Lori; Maybeno, Matt; Babin, Josie; Oseroff, Carla; Pasquetto, Valerie; Greenbaum, Jason A.; Peters, Bjoern; Ting, Joey; Do, Danh; Vang, Lo; Alexander, Jeff; Grey, Howard; Buchmeier, Michael J.; Sette, Alessandro

    2009-01-01

    Arenaviruses are the causative pathogens of severe hemorrhagic fever and aseptic meningitis in humans, for which no licensed vaccines are currently available. Pathogen heterogeneity within the Arenaviridae family poses a significant challenge for vaccine development. The main hypothesis we tested in the present study was whether it is possible to design a universal vaccine strategy capable of inducing simultaneous HLA-restricted CD8+ T cell responses against 7 pathogenic arenaviruses (including the lymphocytic choriomeningitis, Lassa, Guanarito, Junin, Machupo, Sabia, and Whitewater Arroyo viruses), either through the identification of widely conserved epitopes, or by the identification of a collection of epitopes derived from multiple arenavirus species. By inoculating HLA transgenic mice with a panel of recombinant vaccinia viruses (rVACVs) expressing the different arenavirus proteins, we identified 10 HLA-A02 and 10 HLA-A03-restricted epitopes that are naturally processed in human antigen-presenting cells. For some of these epitopes we were able to demonstrate cross-reactive CD8+ T cell responses, further increasing the coverage afforded by the epitope set against each different arenavirus species. Importantly, we showed that immunization of HLA transgenic mice with an epitope cocktail generated simultaneous CD8+ T cell responses against all 7 arenaviruses, and protected mice against challenge with rVACVs expressing either Old or New World arenavirus glycoproteins. In conclusion, the set of identified epitopes allows broad, non-ethnically biased coverage of all 7 viral species targeted by our studies. PMID:20019801

  9. Arenavirus Genome Rearrangement for the Development of Live Attenuated Vaccines

    PubMed Central

    Cheng, Benson Yee Hin; Ortiz-Riaño, Emilio

    2015-01-01

    antiarenaviral therapy is limited to the off-label use of ribavirin, which is only partially effective and associated with side effects. Here we describe, for the first time, the generation of a recombinant LCMV where the viral protein products encoded by the S RNA segment (NP and GPC) were swapped to generate rLCMV/TransS. rLCMV/TransS exhibited reduced viral multiplication in cultured cells and was highly attenuated in vivo while conferring protection, upon a single immunization dose, against a lethal challenge with wild-type LCMV. Our studies provide a proof of concept for the rational development of safe and protective live attenuated vaccine candidates based on genome reorganization for the treatment of pathogenic arenavirus infections in humans. PMID:25972555

  10. Enhanced Methanol Production in Plants Provides Broad Spectrum Insect Resistance

    PubMed Central

    Dixit, Sameer; Upadhyay, Santosh Kumar; Singh, Harpal; Sidhu, Om Prakash; Verma, Praveen Chandra; K, Chandrashekar

    2013-01-01

    Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR) and spectra showed up to 16 fold higher methanol as compared to control wild type (WT) plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid) and Bemisia tabaci (whitefly), respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants. PMID:24223989

  11. Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections

    PubMed Central

    Stenglein, Mark D.; Jacobson, Elliott R.; Chang, Li-Wen; Sanders, Chris; Hawkins, Michelle G.; Guzman, David S-M.; Drazenovich, Tracy; Dunker, Freeland; Kamaka, Elizabeth K.; Fisher, Debbie; Reavill, Drury R.; Meola, Linda F.; Levens, Gregory; DeRisi, Joseph L.

    2015-01-01

    Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology

  12. Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections.

    PubMed

    Stenglein, Mark D; Jacobson, Elliott R; Chang, Li-Wen; Sanders, Chris; Hawkins, Michelle G; Guzman, David S-M; Drazenovich, Tracy; Dunker, Freeland; Kamaka, Elizabeth K; Fisher, Debbie; Reavill, Drury R; Meola, Linda F; Levens, Gregory; DeRisi, Joseph L

    2015-05-01

    Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology

  13. Morphology and morphogenesis of arenaviruses*

    PubMed Central

    Murphy, Frederick A.; Whitfield, Sylvia G.

    1975-01-01

    Arenaviruses have unique structural characteristics; they are pleomorphic, have a mean diameter of 110-130 nm, and consist of a membranous envelope with surface projections surrounding an interior containing ribosomes and filaments. Virus particles bud from plasma membranes of infected cells and in many cases large intracytoplasmic inclusion bodies are formed. These characteristics allow generic identification, but not differentiation of individual viruses. Ultrastructural identification of virus particles and pathological processes in infected tissues of man and experimental animals is important in understanding the nature of arenaviral pathogenesis Such identification also contributes to our understanding of the mechanisms of viral shedding and transmission in reservoir host species. ImagesFig. 3Fig. 4Fig. 5Fig. 11Fig. 12Fig. 13Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 1Fig. 2Fig. 14Fig. 15Fig. 16Fig. 17 PMID:182396

  14. Novel Arenavirus Isolates from Namaqua Rock Mice, Namibia, Southern Africa

    PubMed Central

    Kallies, René; Hoveka, Julia; Auste, Brita; Ithete, Ndapewa L.; Šoltys, Katarína; Szemes, Tomáš; Drosten, Christian; Preiser, Wolfgang; Klempa, Boris; Mfune, John K.E.; Kruger, Detlev H.

    2015-01-01

    Arenaviruses are feared as agents that cause viral hemorrhagic fevers. We report the identification, isolation, and genetic characterization of 2 novel arenaviruses from Namaqua rock mice in Namibia. These findings extend knowledge of the distribution and diversity of arenaviruses in Africa. PMID:26079174

  15. The New World arenavirus Tacaribe virus induces caspase-dependent apoptosis in infected cells.

    PubMed

    Wolff, Svenja; Groseth, Allison; Meyer, Bjoern; Jackson, David; Strecker, Thomas; Kaufmann, Andreas; Becker, Stephan

    2016-04-01

    The Arenaviridae is a diverse and growing family of viruses that already includes more than 25 distinct species. While some of these viruses have a significant impact on public health, others appear to be non-pathogenic. At present little is known about the host cell responses to infection with different arenaviruses, particularly those found in the New World; however, apoptosis is known to play an important role in controlling infection of many viruses. Here we show that infection with Tacaribe virus (TCRV), which is widely considered the prototype for non-pathogenic arenaviruses, leads to stronger induction of apoptosis than does infection with its human-pathogenic relative Junín virus. TCRV-induced apoptosis occurred in several cell types during late stages of infection and was shown to be caspase-dependent, involving the activation of caspases 3, 7, 8 and 9. Further, UV-inactivated TCRV did not induce apoptosis, indicating that the activation of this process is dependent on active viral replication/transcription. Interestingly, when apoptosis was inhibited, growth of TCRV was not enhanced, indicating that apoptosis does not have a direct negative effect on TCRV infection in vitro. Taken together, our data identify and characterize an important virus-host cell interaction of the prototypic, non-pathogenic arenavirus TCRV, which provides important insight into the growing field of arenavirus research aimed at better understanding the diversity in responses to different arenavirus infections and their functional consequences. PMID:26769540

  16. Investigation of type-I interferon dysregulation by arenaviruses : a multidisciplinary approach.

    SciTech Connect

    Kozina, Carol L.; Moorman, Matthew Wallace; Branda, Catherine; Wu, Meiye; Manginell, Ronald Paul; Ricken, James Bryce; James, Conrad D.; Negrete, Oscar A.; Misra, Milind; Carson, Bryan D.

    2011-09-01

    This report provides a detailed overview of the work performed for project number 130781, 'A Systems Biology Approach to Understanding Viral Hemorrhagic Fever Pathogenesis.' We report progress in five key areas: single cell isolation devices and control systems, fluorescent cytokine and transcription factor reporters, on-chip viral infection assays, molecular virology analysis of Arenavirus nucleoprotein structure-function, and development of computational tools to predict virus-host protein interactions. Although a great deal of work remains from that begun here, we have developed several novel single cell analysis tools and knowledge of Arenavirus biology that will facilitate and inform future publications and funding proposals.

  17. Identification and Mechanism of Action of a Novel Small-Molecule Inhibitor of Arenavirus Multiplication

    PubMed Central

    Ngo, Nhi; Cubitt, Beatrice; Iwasaki, Masaharu

    2015-01-01

    antiarenaviral therapy being limited to the off-label use of ribavirin that is only partially effective. Here we describe a novel recombinant LCMV and its use to develop a cell-based assay suitable for HTS to rapidly identify inhibitors arenavirus multiplication. The concepts and experimental strategies we describe in this work provide the bases for the rapid identification and characterization of novel anti-HFA therapeutics. PMID:26292327

  18. Identification, Characterization, and In Vitro Culture of Highly Divergent Arenaviruses from Boa Constrictors and Annulated Tree Boas: Candidate Etiological Agents for Snake Inclusion Body Disease

    PubMed Central

    Stenglein, Mark D.; Sanders, Chris; Kistler, Amy L.; Ruby, J. Graham; Franco, Jessica Y.; Reavill, Drury R.; Dunker, Freeland; DeRisi, Joseph L.

    2012-01-01

    ABSTRACT Inclusion body disease (IBD) is an infectious fatal disease of snakes typified by behavioral abnormalities, wasting, and secondary infections. At a histopathological level, the disease is identified by the presence of large eosinophilic cytoplasmic inclusions in multiple tissues. To date, no virus or other pathogen has been definitively characterized or associated with the disease. Using a metagenomic approach to search for candidate etiologic agents in snakes with confirmed IBD, we identified and de novo assembled the complete genomic sequences of two viruses related to arenaviruses, and a third arenavirus-like sequence was discovered by screening an additional set of samples. A continuous boa constrictor cell line was established and used to propagate and isolate one of the viruses in culture. Viral nucleoprotein was localized and concentrated within large cytoplasmic inclusions in infected cells in culture and tissues from diseased snakes. In total, viral RNA was detected in 6/8 confirmed IBD cases and 0/18 controls. These viruses have a typical arenavirus genome organization but are highly divergent, belonging to a lineage separate from that of the Old and New World arenaviruses. Furthermore, these viruses encode envelope glycoproteins that are more similar to those of filoviruses than to those of other arenaviruses. These findings implicate these viruses as candidate etiologic agents of IBD. The presence of arenaviruses outside mammals reveals that these viruses infect an unexpectedly broad range of species and represent a new reservoir of potential human pathogens. PMID:22893382

  19. A Specific Interaction of Small Molecule Entry Inhibitors with the Envelope Glycoprotein Complex of the Junín Hemorrhagic Fever Arenavirus*

    PubMed Central

    Thomas, Celestine J.; Casquilho-Gray, Hedi E.; York, Joanne; DeCamp, Dianne L.; Dai, Dongcheng; Petrilli, Erin B.; Boger, Dale L.; Slayden, Richard A.; Amberg, Sean M.; Sprang, Stephen R.; Nunberg, Jack H.

    2011-01-01

    Arenaviruses are responsible for acute hemorrhagic fevers worldwide and are recognized to pose significant threats to public health and biodefense. Small molecule compounds have recently been discovered that inhibit arenavirus entry and protect against lethal infection in animal models. These chemically distinct inhibitors act on the tripartite envelope glycoprotein (GPC) through its unusual stable signal peptide subunit to stabilize the complex against pH-induced activation of membrane fusion in the endosome. Here, we report the production and characterization of the intact transmembrane GPC complex of Junín arenavirus and its interaction with these inhibitors. The solubilized GPC is antigenically indistinguishable from the native protein and forms a homogeneous trimer in solution. When reconstituted into a lipid bilayer, the purified complex interacts specifically with its cell-surface receptor transferrin receptor-1. We show that small molecule entry inhibitors specific to New World or Old World arenaviruses bind to the membrane-associated GPC complex in accordance with their respective species selectivities and with dissociation constants comparable with concentrations that inhibit GPC-mediated membrane fusion. Furthermore, competitive binding studies reveal that these chemically distinct inhibitors share a common binding pocket on GPC. In conjunction with previous genetic studies, these findings identify the pH-sensing interface of GPC as a highly vulnerable target for antiviral intervention. This work expands our mechanistic understanding of arenavirus entry and provides a foundation to guide the development of small molecule compounds for the treatment of arenavirus hemorrhagic fevers. PMID:21159779

  20. Replication of Boid Inclusion Body Disease-Associated Arenaviruses Is Temperature Sensitive in both Boid and Mammalian Cells

    PubMed Central

    Kipar, Anja; Korzyukov, Yegor; Bell-Sakyi, Lesley; Vapalahti, Olli; Hetzel, Udo

    2014-01-01

    ABSTRACT Boid inclusion body disease (BIDB) is a fatal disease of boid snakes, the etiology of which has only recently been revealed following the identification of several novel arenaviruses in diseased snakes. BIBD-associated arenaviruses (BIBDAV) are genetically divergent from the classical Old and New World arenaviruses and also differ substantially from each other. Even though there is convincing evidence that BIBDAV are indeed the etiological agent of BIBD, the BIBDAV reservoir hosts—if any exist besides boid snakes themselves—are not yet known. In this report, we use University of Helsinki virus (UHV; a virus that we isolated from a Boa constrictor with BIBD) to show that BIBDAV can also replicate effectively in mammalian cells, including human cells, provided they are cultured at 30°C. The infection induces the formation of cytoplasmic inclusion bodies (IB), comprised mainly of viral nucleoprotein (NP), similar to those observed in BIBD and in boid cell cultures. Transferring infected cells from 30°C to 37°C ambient temperature resulted in progressive declines in IB formation and in the amounts of viral NP and RNA, suggesting that BIBDAV growth is limited at 37°C. These observations indirectly indicate that IB formation is linked to viral replication. In addition to mammalian and reptilian cells, UHV infected arthropod (tick) cells when grown at 30°C. Even though our findings suggest that BIBDAV have a high potential to cross the species barrier, their inefficient growth at mammalian body temperatures indicates that the reservoir hosts of BIBDAV are likely species with a lower body temperature, such as snakes. IMPORTANCE The newly discovered boid inclusion body disease-associated arenaviruses (BIBDAV) of reptiles have drastically altered the phylogeny of the family Arenavirus. Prior to their discovery, known arenaviruses were considered mainly rodent-borne viruses, with each arenavirus species having its own reservoir host. BIBDAV have so far been

  1. Broad-scale phylogenomics provides insights into retrovirus–host evolution

    PubMed Central

    Hayward, Alexander; Grabherr, Manfred; Jern, Patric

    2013-01-01

    Genomic data provide an excellent resource to improve understanding of retrovirus evolution and the complex relationships among viruses and their hosts. In conjunction with broad-scale in silico screening of vertebrate genomes, this resource offers an opportunity to complement data on the evolution and frequency of past retroviral spread and so evaluate future risks and limitations for horizontal transmission between different host species. Here, we develop a methodology for extracting phylogenetic signal from large endogenous retrovirus (ERV) datasets by collapsing information to facilitate broad-scale phylogenomics across a wide sample of hosts. Starting with nearly 90,000 ERVs from 60 vertebrate host genomes, we construct phylogenetic hypotheses and draw inferences regarding the designation, host distribution, origin, and transmission of the Gammaretrovirus genus and associated class I ERVs. Our results uncover remarkable depths in retroviral sequence diversity, supported within a phylogenetic context. This finding suggests that current infectious exogenous retrovirus diversity may be underestimated, adding credence to the possibility that many additional exogenous retroviruses may remain to be discovered in vertebrate taxa. We demonstrate a history of frequent horizontal interorder transmissions from a rodent reservoir and suggest that rats may have acted as important overlooked facilitators of gammaretrovirus spread across diverse mammalian hosts. Together, these results demonstrate the promise of the methodology used here to analyze large ERV datasets and improve understanding of retroviral evolution and diversity for utilization in wider applications. PMID:24277832

  2. Arenavirus Variations Due to Host-Specific Adaptation

    PubMed Central

    Zapata, Juan C.; Salvato, Maria S.

    2013-01-01

    Arenavirus particles are enveloped and contain two single-strand RNA genomic segments with ambisense coding. Genetic plasticity of the arenaviruses comes from transcription errors, segment reassortment, and permissive genomic packaging, and results in their remarkable ability, as a group, to infect a wide variety of hosts. In this review, we discuss some in vitro studies of virus genetic and phenotypic variation after exposure to selective pressures such as high viral dose, mutagens and antivirals. Additionally, we discuss the variation in vivo of selected isolates of Old World arenaviruses, particularly after infection of different animal species. We also discuss the recent emergence of new arenaviruses in the context of our observations of sequence variations that appear to be host-specific. PMID:23344562

  3. Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

    PubMed Central

    Golden, Joseph W.; Hammerbeck, Christopher D.; Mucker, Eric M.; Brocato, Rebecca L.

    2015-01-01

    Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF) and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM) to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs. PMID:26266264

  4. Symbionts Commonly Provide Broad Spectrum Resistance to Viruses in Insects: A Comparative Analysis of Wolbachia Strains

    PubMed Central

    Martinez, Julien; Longdon, Ben; Bauer, Simone; Chan, Yuk-Sang; Miller, Wolfgang J.; Bourtzis, Kostas; Teixeira, Luis; Jiggins, Francis M.

    2014-01-01

    In the last decade, bacterial symbionts have been shown to play an important role in protecting hosts against pathogens. Wolbachia, a widespread symbiont in arthropods, can protect Drosophila and mosquito species against viral infections. We have investigated antiviral protection in 19 Wolbachia strains originating from 16 Drosophila species after transfer into the same genotype of Drosophila simulans. We found that approximately half of the strains protected against two RNA viruses. Given that 40% of terrestrial arthropod species are estimated to harbour Wolbachia, as many as a fifth of all arthropods species may benefit from Wolbachia-mediated protection. The level of protection against two distantly related RNA viruses – DCV and FHV – was strongly genetically correlated, which suggests that there is a single mechanism of protection with broad specificity. Furthermore, Wolbachia is making flies resistant to viruses, as increases in survival can be largely explained by reductions in viral titer. Variation in the level of antiviral protection provided by different Wolbachia strains is strongly genetically correlated to the density of the bacteria strains in host tissues. We found no support for two previously proposed mechanisms of Wolbachia-mediated protection — activation of the immune system and upregulation of the methyltransferase Dnmt2. The large variation in Wolbachia's antiviral properties highlights the need to carefully select Wolbachia strains introduced into mosquito populations to prevent the transmission of arboviruses. PMID:25233341

  5. A diffraction-limited scanning system providing broad spectral range for laser scanning microscopy

    NASA Astrophysics Data System (ADS)

    Yu, Jiun-Yann; Liao, Chien-Sheng; Zhuo, Zong-Yan; Huang, Chen-Han; Chui, Hsiang-Chen; Chu, Shi-Wei

    2009-11-01

    Diversified research interests in scanning laser microscopy nowadays require broadband capability of the optical system. Although an all-mirror-based optical design with a suitable metallic coating is appropriate for broad-spectrum applications from ultraviolet to terahertz, most researchers prefer lens-based scanning systems despite the drawbacks of a limited spectral range, ghost reflection, and chromatic aberration. One of the main concerns is that the geometrical aberration induced by off-axis incidence on spherical mirrors significantly deteriorates image resolution. Here, we demonstrate a novel geometrical design of a spherical-mirror-based scanning system in which off-axis aberrations, both astigmatism and coma, are compensated to reach diffraction-limited performance. We have numerically simulated and experimentally verified that this scanning system meets the Marechà l condition and provides high Strehl ratio within a 3°×3° scanning area. Moreover, we demonstrate second-harmonic-generation imaging from starch with our new design. A greatly improved resolution compared to the conventional mirror-based system is confirmed. This scanning system will be ideal for high-resolution linear/nonlinear laser scanning microscopy, ophthalmoscopic applications, and precision fabrications.

  6. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection

    PubMed Central

    Malinge, Pauline; Magistrelli, Giovanni; Fischer, Nicolas; Sahin, Mehmet; Bergthaler, Andreas; Igonet, Sebastien; ter Meulen, Jan; Rigo, Dorothée; Meda, Paolo; Rabah, Nadia; Coutard, Bruno; Bowden, Thomas A.; Lambert, Paul-Henri; Siegrist, Claire-Anne; Pinschewer, Daniel D.

    2015-01-01

    Arenaviruses such as Lassa virus (LASV) can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb) responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein’s globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy. PMID:26587982

  7. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection.

    PubMed

    Sommerstein, Rami; Flatz, Lukas; Remy, Melissa M; Malinge, Pauline; Magistrelli, Giovanni; Fischer, Nicolas; Sahin, Mehmet; Bergthaler, Andreas; Igonet, Sebastien; Ter Meulen, Jan; Rigo, Dorothée; Meda, Paolo; Rabah, Nadia; Coutard, Bruno; Bowden, Thomas A; Lambert, Paul-Henri; Siegrist, Claire-Anne; Pinschewer, Daniel D

    2015-11-01

    Arenaviruses such as Lassa virus (LASV) can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb) responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein's globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy. PMID:26587982

  8. Computational and Functional Analysis of the Virus-Receptor Interface Reveals Host Range Trade-Offs in New World Arenaviruses

    PubMed Central

    Kerr, Scott A.; Jackson, Eleisha L.; Lungu, Oana I.; Meyer, Austin G.; Demogines, Ann; Ellington, Andrew D.; Georgiou, George

    2015-01-01

    ABSTRACT Animal viruses frequently cause zoonotic disease in humans. As these viruses are highly diverse, evaluating the threat that they pose remains a major challenge, and efficient approaches are needed to rapidly predict virus-host compatibility. Here, we develop a combined computational and experimental approach to assess the compatibility of New World arenaviruses, endemic in rodents, with the host TfR1 entry receptors of different potential new host species. Using signatures of positive selection, we identify a small motif on rodent TfR1 that conveys species specificity to the entry of viruses into cells. However, we show that mutations in this region affect the entry of each arenavirus differently. For example, a human single nucleotide polymorphism (SNP) in this region, L212V, makes human TfR1 a weaker receptor for one arenavirus, Machupo virus, but a stronger receptor for two other arenaviruses, Junin and Sabia viruses. Collectively, these findings set the stage for potential evolutionary trade-offs, where natural selection for resistance to one virus may make humans or rodents susceptible to other arenavirus species. Given the complexity of this host-virus interplay, we propose a computational method to predict these interactions, based on homology modeling and computational docking of the virus-receptor protein-protein interaction. We demonstrate the utility of this model for Machupo virus, for which a suitable cocrystal structural template exists. Our model effectively predicts whether the TfR1 receptors of different species will be functional receptors for Machupo virus entry. Approaches such at this could provide a first step toward computationally predicting the “host jumping” potential of a virus into a new host species. IMPORTANCE We demonstrate how evolutionary trade-offs may exist in the dynamic evolutionary interplay between viruses and their hosts, where natural selection for resistance to one virus could make humans or rodents susceptible

  9. Human and Host Species Transferrin Receptor 1 Use by North American Arenaviruses

    PubMed Central

    Zong, Min; Fofana, Isabel

    2014-01-01

    ABSTRACT At least five New World (NW) arenaviruses cause hemorrhagic fevers in South America. These pathogenic clade B viruses, as well as nonpathogenic arenaviruses of the same clade, use transferrin receptor 1 (TfR1) of their host species to enter cells. Pathogenic viruses are distinguished from closely related nonpathogenic ones by their additional ability to utilize human TfR1 (hTfR1). Here, we investigate the receptor usage of North American arenaviruses, whose entry proteins share greatest similarity with those of the clade B viruses. We show that all six North American arenaviruses investigated utilize host species TfR1 orthologs and present evidence consistent with arenavirus-mediated selection pressure on the TfR1 of the North American arenavirus host species. Notably, one of these viruses, AV96010151, closely related to the prototype Whitewater Arroyo virus (WWAV), entered cells using hTfR1, consistent with a role for a WWAV-like virus in three fatal human infections whose causative agent has not been identified. In addition, modest changes were sufficient to convert hTfR1 into a functional receptor for most of these viruses, suggesting that a minor alteration in virus entry protein may allow these viruses to use hTfR1. Our data establish TfR1 as a cellular receptor for North American arenaviruses, highlight an “arms race” between these viruses and their host species, support the association of North American arenavirus with fatal human infections, and suggest that these viruses have a higher potential to emerge and cause human diseases than has previously been appreciated. IMPORTANCE hTfR1 use is a key determinant for a NW arenavirus to cause hemorrhagic fevers in humans. All known pathogenic NW arenaviruses are transmitted in South America by their host rodents. North American arenaviruses are generally considered nonpathogenic, but some of these viruses have been tentatively implicated in human fatalities. We show that these North American

  10. Arenavirus Infection Induces Discrete Cytosolic Structures for RNA Replication

    PubMed Central

    Baird, Nicholas L.; York, Joanne

    2012-01-01

    Arenaviruses are responsible for acute hemorrhagic fevers with high mortality and pose significant threats to public health and biodefense. These enveloped negative-sense RNA viruses replicate in the cell cytoplasm and express four proteins. To better understand how these proteins insinuate themselves into cellular processes to orchestrate productive viral replication, we have identified and characterized novel cytosolic structures involved in arenavirus replication and transcription. In cells infected with the nonpathogenic Tacaribe virus or the attenuated Candid#1 strain of Junín virus, we find that newly synthesized viral RNAs localize to cytosolic puncta containing the nucleoprotein (N) of the virus. Density gradient centrifugation studies reveal that these replication-transcription complexes (RTCs) are associated with cellular membranes and contain full-length genomic- and antigenomic-sense RNAs. Viral mRNAs segregate at a higher buoyant density and are likewise scant in immunopurified RTCs, consistent with their translation on bulk cellular ribosomes. In addition, confocal microscopy analysis reveals that RTCs contain the lipid phosphatidylinositol-4-phosphate and proteins involved in cellular mRNA metabolism, including the large and small ribosomal subunit proteins L10a and S6, the stress granule protein G3BP1, and a subset of translation initiation factors. Elucidating the structure and function of RTCs will enhance our understanding of virus-cell interactions that promote arenavirus replication and mitigate against host cell immunity. This knowledge may lead to novel intervention strategies to limit viral virulence and pathogenesis. PMID:22875974

  11. Highly Sensitive Assay for Measurement of Arenavirus-cell Attachment.

    PubMed

    Klaus, Joseph P; Botten, Jason

    2016-01-01

    Arenaviruses are a family of enveloped RNA viruses that cause severe human disease. The first step in the arenavirus life cycle is attachment of viral particles to host cells. While virus-cell attachment can be measured through the use of virions labeled with biotin, radioactive isotopes, or fluorescent dyes, these approaches typically require high multiplicities of infection (MOI) to enable detection of bound virus. We describe a quantitative (q)RT-PCR-based assay that measures Junin virus strain Candid 1 attachment via quantitation of virion-packaged viral genomic RNA. This assay has several advantages including its extreme sensitivity and ability to measure attachment over a large dynamic range of MOIs without the need to purify or label input virus. Importantly, this approach can be easily tailored for use with other viruses through the use of virus-specific qRT-PCR reagents. Further, this assay can be modified to permit measurement of particle endocytosis and genome uncoating. In conclusion, we describe a simple, yet robust assay for highly sensitive measurement of arenavirus-cell attachment. PMID:26966937

  12. Isolation and characterization of a novel arenavirus harbored by Rodents and Shrews in Zhejiang province, China

    SciTech Connect

    Li, Kun; Lin, Xian-Dan; Wang, Wen; Shi, Mang; Guo, Wen-Ping; Zhang, Xiao-He; Xing, Jian-Guang; and others

    2015-02-15

    To determine the biodiversity of arenaviruses in China, we captured and screened rodents and shrews in Wenzhou city, Zhejiang province, a locality where hemorrhagic fever diseases are endemic in humans. Accordingly, arenaviruses were detected in 42 of 351 rodents from eight species, and in 12 of 272 Asian house shrews (Suncus murinus), by RT-PCR targeting the L segment. From these, a single arenavirus was successfully isolated in cell culture. The virion particles exhibited a typical arenavirus morphology under transmission electron microscopy. Comparison of the S and L segment sequences revealed high levels of nucleotide (>32.2% and >39.6%) and amino acid (>28.8% and >43.8%) sequence differences from known arenaviruses, suggesting that it represents a novel arenavirus, which we designated Wenzhou virus (WENV). Phylogenetic analysis revealed that all WENV strains harbored by both rodents and Asian house shrews formed a distinct lineage most closely related to Old World arenaviruses. - Highlights: • A novel arenavirus (Wenzhou virus) was identified in Zhejiang province, China. • The virus is highly circulating in five species of rats and one species of shrews • More efforts are needed to infer whether it is pathogenic to humans or not.

  13. Isolation, Identification, and Characterization of Novel Arenaviruses, the Etiological Agents of Boid Inclusion Body Disease

    PubMed Central

    Hetzel, Udo; Sironen, Tarja; Laurinmäki, Pasi; Liljeroos, Lassi; Patjas, Aino; Henttonen, Heikki; Vaheri, Antti; Artelt, Annette; Kipar, Anja; Butcher, Sarah J.; Vapalahti, Olli

    2013-01-01

    Boid inclusion body disease (BIBD) is a progressive, usually fatal disease of constrictor snakes, characterized by cytoplasmic inclusion bodies (IB) in a wide range of cell types. To identify the causative agent of the disease, we established cell cultures from BIBD-positive and -negative boa constrictors. The IB phenotype was maintained in cultured cells of affected animals, and supernatants from these cultures caused the phenotype in cultures originating from BIBD-negative snakes. Viruses were purified from the supernatants by ultracentrifugation and subsequently identified as arenaviruses. Purified virus also induced the IB phenotype in naive cells, which fulfilled Koch's postulates in vitro. One isolate, tentatively designated University of Helsinki virus (UHV), was studied in depth. Sequencing confirmed that UHV is a novel arenavirus species that is distinct from other known arenaviruses including those recently identified in snakes with BIBD. The morphology of UHV was established by cryoelectron tomography and subtomographic averaging, revealing the trimeric arenavirus spike structure at 3.2-nm resolution. Immunofluorescence, immunohistochemistry, and immunoblotting with a polyclonal rabbit antiserum against UHV and reverse transcription-PCR (RT-PCR) revealed the presence of genetically diverse arenaviruses in a large cohort of snakes with BIBD, confirming the causative role of arenaviruses. Some snakes were also found to carry arenavirus antibodies. Furthermore, mammalian cells (Vero E6) were productively infected with UHV, demonstrating the potential of arenaviruses to cross species barriers. In conclusion, we propose the newly identified lineage of arenaviruses associated with BIBD as a novel taxonomic entity, boid inclusion body disease-associated arenaviruses (BIBDAV), in the family Arenaviridae. PMID:23926354

  14. Isolation, identification, and characterization of novel arenaviruses, the etiological agents of boid inclusion body disease.

    PubMed

    Hetzel, Udo; Sironen, Tarja; Laurinmäki, Pasi; Liljeroos, Lassi; Patjas, Aino; Henttonen, Heikki; Vaheri, Antti; Artelt, Annette; Kipar, Anja; Butcher, Sarah J; Vapalahti, Olli; Hepojoki, Jussi

    2013-10-01

    Boid inclusion body disease (BIBD) is a progressive, usually fatal disease of constrictor snakes, characterized by cytoplasmic inclusion bodies (IB) in a wide range of cell types. To identify the causative agent of the disease, we established cell cultures from BIBD-positive and -negative boa constrictors. The IB phenotype was maintained in cultured cells of affected animals, and supernatants from these cultures caused the phenotype in cultures originating from BIBD-negative snakes. Viruses were purified from the supernatants by ultracentrifugation and subsequently identified as arenaviruses. Purified virus also induced the IB phenotype in naive cells, which fulfilled Koch's postulates in vitro. One isolate, tentatively designated University of Helsinki virus (UHV), was studied in depth. Sequencing confirmed that UHV is a novel arenavirus species that is distinct from other known arenaviruses including those recently identified in snakes with BIBD. The morphology of UHV was established by cryoelectron tomography and subtomographic averaging, revealing the trimeric arenavirus spike structure at 3.2-nm resolution. Immunofluorescence, immunohistochemistry, and immunoblotting with a polyclonal rabbit antiserum against UHV and reverse transcription-PCR (RT-PCR) revealed the presence of genetically diverse arenaviruses in a large cohort of snakes with BIBD, confirming the causative role of arenaviruses. Some snakes were also found to carry arenavirus antibodies. Furthermore, mammalian cells (Vero E6) were productively infected with UHV, demonstrating the potential of arenaviruses to cross species barriers. In conclusion, we propose the newly identified lineage of arenaviruses associated with BIBD as a novel taxonomic entity, boid inclusion body disease-associated arenaviruses (BIBDAV), in the family Arenaviridae. PMID:23926354

  15. Novel Arenavirus Entry Inhibitors Discovered by Using a Minigenome Rescue System for High-Throughput Drug Screening

    PubMed Central

    Rathbun, Jessica Y.; Droniou, Magali E.; Damoiseaux, Robert; Haworth, Kevin G.; Henley, Jill E.; Exline, Colin M.; Choe, Hyeryun

    2015-01-01

    ABSTRACT Certain members of the Arenaviridae family are category A agents capable of causing severe hemorrhagic fevers in humans. Specific antiviral treatments do not exist, and the only commonly used drug, ribavirin, has limited efficacy and can cause severe side effects. The discovery and development of new antivirals are inhibited by the biohazardous nature of the viruses, making them a relatively poorly understood group of human pathogens. We therefore adapted a reverse-genetics minigenome (MG) rescue system based on Junin virus, the causative agent of Argentine hemorrhagic fever, for high-throughput screening (HTS). The MG rescue system recapitulates all stages of the virus life cycle and enables screening of small-molecule libraries under biosafety containment level 2 (BSL2) conditions. The HTS resulted in the identification of four candidate compounds with potent activity against a broad panel of arenaviruses, three of which were completely novel. The target for all 4 compounds was the stage of viral entry, which positions the compounds as potentially important leads for future development. IMPORTANCE The arenavirus family includes several members that are highly pathogenic, causing acute viral hemorrhagic fevers with high mortality rates. No specific effective treatments exist, and although a vaccine is available for Junin virus, the causative agent of Argentine hemorrhagic fever, it is licensed for use only in areas where Argentine hemorrhagic fever is endemic. For these reasons, it is important to identify specific compounds that could be developed as antivirals against these deadly viruses. PMID:26041296

  16. Pathological and virological features of arenavirus disease in guinea pigs. Comparison of two Pichinde virus strains.

    PubMed Central

    Aronson, J. F.; Herzog, N. K.; Jerrells, T. R.

    1994-01-01

    A guinea pig passage-adapted strain of the arena-virus Pichinde (adPIC) is highly virulent in inbred guinea pigs, whereas the related strain PIC3739 is attenuated. Both viruses were macrophage tropic and infected peritoneal, splenic, liver, and alveolar macrophages during experimental Pichinde virus infection. Infection with the virulent strain was associated with unlimited viral replication in the face of exaggerated delayed-type hypersensitivity response, manifested by the macrophage disappearance reaction. Histopathological lesions unique to adPIC-infected guinea pigs included intestinal villus blunting with mucosal infiltration by pyknotic debris-laden macrophages and apoptosis of crypt epithelial cells. Splenic red pulp necrosis was also significantly associated with adPIC infection but not PIC3739 infection. These findings may provide clues to the pathogenesis of a group of poorly understood human viral hemorrhagic fevers. Images Figure 6 Figure 7 PMID:8030751

  17. Construction of the recombinant broad-host-range plasmids providing their bacterial hosts arsenic resistance and arsenite oxidation ability.

    PubMed

    Drewniak, Lukasz; Ciezkowska, Martyna; Radlinska, Monika; Sklodowska, Aleksandra

    2015-02-20

    The plasmid pSinA of Sinorhizobium sp. M14 was used as a source of functional phenotypic modules, encoding proteins involved in arsenite oxidation and arsenic resistance, to obtain recombinant broad-host-range plasmids providing their bacterial hosts arsenic resistance and arsenite oxidative ability. An arsenite oxidation module was cloned into pBBR1MCS-2 vector yielding plasmid vector pAIO1, while an arsenic resistance module was cloned into pCM62 vector yielding plasmid pARS1. Both plasmid constructs were introduced (separately and together) into the cells of phylogenetically distant (representing Alpha-, Beta-, and Gammaproteobacteria) and physiologically diversified (unable to oxidize arsenite and susceptible/resistant to arsenite and arsenate) bacteria. Functional analysis of the modified strains showed that: (i) the plasmid pARS1 can be used for the construction of strains with an increased resistance to arsenite [up to 20mM of As(III), (ii) the presence of the plasmid pAIO1 in bacteria previously unable to oxidize As(III) to As(V), contributes to the acquisition of arsenite oxidation abilities by these cells, (iii) the highest arsenite utilization rate are observed in the culture of strains harbouring both the plasmids pAIO1 and pARS1, (iv) the strains harbouring the plasmid pAIO1 were able to grow on arsenic-contaminated mine waters (∼ 3.0 mg As L(-1)) without any supplementation. PMID:25617684

  18. Virion RNA species of the arenaviruses Pichinde, Tacaribe, and Tamiami.

    PubMed Central

    Vezza, A C; Clewley, J P; Gard, G P; Abraham, N Z; Compans, R W; Bishop, D H

    1978-01-01

    The principal RNA species isolated from labeled preparations of the arenavirus Pichinde usually include a large viral RNA species L (apparent molecular weight = 3.2 X 10(6)), and a smaller viral RNA species S (apparent molecular weight = 1.6 X 10(6)). In addition, either little or considerable quantities of 28S rRNA as well as 18S rRNA can also be obtained in virus extracts, depending on the virus stock and growth conditions used to generate virus preparations. Similar RNA species have been identified in RNA extracted from Tacaribe and Tamiami arenavirus preparations. Oligonucleotide fingerprint analyses have confirmed the host ribosomal origin of the 28S and 18S species. Such analyses have also indicated that the Pichinde viral L and S RNA species each contain unique nucleotide sequences. Viral RNA preparations isolated by conventional phenol-sodium dodecyl sulfate extraction often have much of their L and S RNA species in the form of aggregates as visualized by either electron microscopy or oligonucleotide fingerprinting of material recovered from the top of gels (run by using undenatured RNA preparations). Circular and linear RNA forms have also been seen in electron micrographs of undenatured RNA preparations, although denatured viral RNA preparations have yielded mostly linear RNA species with few RNA aggregates or circular forms. Images PMID:660722

  19. Arenavirus Coinfections Are Common in Snakes with Boid Inclusion Body Disease.

    PubMed

    Hepojoki, J; Salmenperä, P; Sironen, T; Hetzel, U; Korzyukov, Y; Kipar, A; Vapalahti, O

    2015-08-01

    Recently, novel arenaviruses were found in snakes with boid inclusion body disease (BIBD); these form the new genus Reptarenavirus within the family Arenaviridae. We used next-generation sequencing and de novo sequence assembly to investigate reptarenavirus isolates from our previous study. Four of the six isolates and all of the samples from snakes with BIBD contained at least two reptarenavirus species. The viruses sequenced comprise four novel reptarenavirus species and a representative of a new arenavirus genus. PMID:26041290

  20. Arenavirus Coinfections Are Common in Snakes with Boid Inclusion Body Disease

    PubMed Central

    Salmenperä, P.; Sironen, T.; Hetzel, U.; Korzyukov, Y.; Kipar, A.; Vapalahti, O.

    2015-01-01

    Recently, novel arenaviruses were found in snakes with boid inclusion body disease (BIBD); these form the new genus Reptarenavirus within the family Arenaviridae. We used next-generation sequencing and de novo sequence assembly to investigate reptarenavirus isolates from our previous study. Four of the six isolates and all of the samples from snakes with BIBD contained at least two reptarenavirus species. The viruses sequenced comprise four novel reptarenavirus species and a representative of a new arenavirus genus. PMID:26041290

  1. Serological assays based on recombinant viral proteins for the diagnosis of arenavirus hemorrhagic fevers.

    PubMed

    Fukushi, Shuetsu; Tani, Hideki; Yoshikawa, Tomoki; Saijo, Masayuki; Morikawa, Shigeru

    2012-10-01

    The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World (OW) and New World (NW) complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever (VHF) in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques for these virus infections in institutes without BSL-4 facilities. To overcome these difficulties, antibody detection systems in the form of an enzyme-linked immunosorbent assay (ELISA) and an indirect immunofluorescence assay were developed using recombinant nucleoproteins (rNPs) derived from these viruses. Furthermore, several antigen-detection assays were developed. For example, novel monoclonal antibodies (mAbs) to the rNPs of Lassa and Junin viruses were generated. Sandwich antigen-capture (Ag-capture) ELISAs using these mAbs as capture antibodies were developed and confirmed to be sensitive and specific for detecting the respective arenavirus NPs. These rNP-based assays were proposed to be useful not only for an etiological diagnosis of VHFs, but also for seroepidemiological studies on VHFs. We recently developed arenavirus neutralization assays using vesicular stomatitis virus (VSV)-based pseudotypes bearing arenavirus recombinant glycoproteins. The goal of this article is to review the recent advances in developing laboratory diagnostic assays based on recombinant viral proteins for the diagnosis of VHFs and epidemiological studies on the VHFs caused by arenaviruses. PMID:23202455

  2. Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding

    PubMed Central

    Panico, Maria; Bouché, Laura; Binet, Daniel; O’Connor, Michael-John; Rahman, Dinah; Pang, Poh-Choo; Canis, Kevin; North, Simon J.; Desrosiers, Ronald C.; Chertova, Elena; Keele, Brandon F.; Bess, Julian W.; Lifson, Jeffrey D.; Haslam, Stuart M.; Dell, Anne; Morris, Howard R.

    2016-01-01

    The surface envelope glycoprotein (SU) of Human immunodeficiency virus type 1 (HIV-1), gp120SU plays an essential role in virus binding to target CD4+ T-cells and is a major vaccine target. Gp120 has remarkably high levels of N-linked glycosylation and there is considerable evidence that this “glycan shield” can help protect the virus from antibody-mediated neutralization. In recent years, however, it has become clear that gp120 glycosylation can also be included in the targets of recognition by some of the most potent broadly neutralizing antibodies. Knowing the site-specific glycosylation of gp120 can facilitate the rational design of glycopeptide antigens for HIV vaccine development. While most prior studies have focused on glycan analysis of recombinant forms of gp120, here we report the first systematic glycosylation site analysis of gp120 derived from virions produced by infected T lymphoid cells and show that a single site is exclusively substituted with complex glycans. These results should help guide the design of vaccine immunogens. PMID:27604319

  3. Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding.

    PubMed

    Panico, Maria; Bouché, Laura; Binet, Daniel; O'Connor, Michael-John; Rahman, Dinah; Pang, Poh-Choo; Canis, Kevin; North, Simon J; Desrosiers, Ronald C; Chertova, Elena; Keele, Brandon F; Bess, Julian W; Lifson, Jeffrey D; Haslam, Stuart M; Dell, Anne; Morris, Howard R

    2016-01-01

    The surface envelope glycoprotein (SU) of Human immunodeficiency virus type 1 (HIV-1), gp120(SU) plays an essential role in virus binding to target CD4+ T-cells and is a major vaccine target. Gp120 has remarkably high levels of N-linked glycosylation and there is considerable evidence that this "glycan shield" can help protect the virus from antibody-mediated neutralization. In recent years, however, it has become clear that gp120 glycosylation can also be included in the targets of recognition by some of the most potent broadly neutralizing antibodies. Knowing the site-specific glycosylation of gp120 can facilitate the rational design of glycopeptide antigens for HIV vaccine development. While most prior studies have focused on glycan analysis of recombinant forms of gp120, here we report the first systematic glycosylation site analysis of gp120 derived from virions produced by infected T lymphoid cells and show that a single site is exclusively substituted with complex glycans. These results should help guide the design of vaccine immunogens. PMID:27604319

  4. Novel Arenavirus Sequences in Hylomyscus sp. and Mus (Nannomys) setulosus from Côte d'Ivoire: Implications for Evolution of Arenaviruses in Africa

    PubMed Central

    Kouassi, Stéphane K.; Fichet-Calvet, Elisabeth; Becker-Ziaja, Beate; Rieger, Toni; Ölschläger, Stephan; Dosso, Hernri; Denys, Christiane; ter Meulen, Jan; Akoua-Koffi, Chantal; Günther, Stephan

    2011-01-01

    This study aimed to identify new arenaviruses and gather insights in the evolution of arenaviruses in Africa. During 2003 through 2005, 1,228 small mammals representing 14 different genera were trapped in 9 villages in south, east, and middle west of Côte d'Ivoire. Specimens were screened by pan-Old World arenavirus RT-PCRs targeting S and L RNA segments as well as immunofluorescence assay. Sequences of two novel tentative species of the family Arenaviridae, Menekre and Gbagroube virus, were detected in Hylomyscus sp. and Mus (Nannomys) setulosus, respectively. Arenavirus infection of Mus (Nannomys) setulosus was also demonstrated by serological testing. Lassa virus was not found, although 60% of the captured animals were Mastomys natalensis. Complete S RNA and partial L RNA sequences of the novel viruses were recovered from the rodent specimens and subjected to phylogenetic analysis. Gbagroube virus is a closely related sister taxon of Lassa virus, while Menekre virus clusters with the Ippy/Mobala/Mopeia virus complex. Reconstruction of possible virus–host co-phylogeny scenarios suggests that, within the African continent, signatures of co-evolution might have been obliterated by multiple host-switching events. PMID:21695269

  5. Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses

    SciTech Connect

    Abraham, Jonathan; Corbett, Kevin D.; Farzan, Michael; Choe, Hyeryun; Harrison, Stephen C.

    2010-08-18

    New World hemorrhagic fever arenaviruses are rodent-borne agents that cause severe human disease. The GP1 subunit of the surface glycoprotein mediates cell attachment through transferrin receptor 1 (TfR1). We report the structure of Machupo virus (MACV) GP1 bound with human TfR1. Atomic details of the GP1-TfR1 interface clarify the importance of TfR1 residues implicated in New World arenavirus host specificity. Analysis of sequence variation among New World arenavirus GP1s and their host-species receptors, in light of the molecular structure, indicates determinants of viral zoonotic transmission. Infectivities of pseudoviruses in cells expressing mutated TfR1 confirm that contacts at the tip of the TfR1 apical domain determine the capacity of human TfR1 to mediate infection by particular New World arenaviruses. We propose that New World arenaviruses that are pathogenic to humans fortuitously acquired affinity for human TfR1 during adaptation to TfR1 of their natural hosts.

  6. Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses.

    PubMed

    Meyer, Bjoern; Ly, Hinh

    2016-04-01

    Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options. PMID:26865707

  7. Bilaterian phylogeny: a broad sampling of 13 nuclear genes provides a new Lophotrochozoa phylogeny and supports a paraphyletic basal acoelomorpha.

    PubMed

    Paps, Jordi; Baguñà, Jaume; Riutort, Marta

    2009-10-01

    During the past decade, great progress has been made in clarifying the relationships among bilaterian animals. Studies based on a limited number of markers established new hypotheses such as the existence of three superclades (Deuterostomia, Ecdysozoa, and Lophotrochozoa) but left major questions unresolved. The data sets used to the present either bear few characters for many taxa (i.e., the ribosomal genes) or present many characters but lack many phyla (such as recent phylogenomic approaches) failing to provide definitive answers for all the regions of the bilaterian tree. We performed phylogenetic analyses using a molecular matrix with a high number of characters and bilaterian phyla. This data set is built from 13 genes (8,880 bp) belonging to 90 taxa from 27 bilaterian phyla. Probabilistic analyses robustly support the three superclades, the monophyly of Chordata, a spiralian clade including Brachiozoa, the basal position of a paraphyletic Acoelomorpha, and point to an ecdysozoan affiliation for Chaetognatha. This new phylogeny not only agrees with most classical molecular results but also provides new insights into the relationships between lophotrochozoans and challenges the results obtained using high-throughput strategies, highlighting the problems associated with the current trend to increase gene number rather than taxa. PMID:19602542

  8. Genomic and phylogenetic characterization of Merino Walk virus, a novel arenavirus isolated in South Africa

    PubMed Central

    Palacios, Gustavo; Savji, Nazir; Hui, Jeffrey; Travassos da Rosa, Amelia; Popov, Vsevolod; Briese, Thomas; Tesh, Robert; Lipkin, W. Ian

    2010-01-01

    Merino Walk virus (MWV), a proposed novel tentative species of the family Arenaviridae, was isolated from a rodent, Myotomys unisulcatus, collected at Merino Walk, Eastern Cape, South Africa, in 1985. Full-length genomic sequence confirmed MWV as an arenavirus related distantly to Mobala, Mopeia and Ippy viruses, all members of the Old World arenavirus complex. We propose MWV as a tentative novel species in the Lassa–lymphocytic choriomeningitis virus complex, based on its isolation from a novel rodent species and its genetic and serological characteristics. PMID:20071489

  9. Old world arenaviruses enter the host cell via the multivesicular body and depend on the endosomal sorting complex required for transport.

    PubMed

    Pasqual, Giulia; Rojek, Jillian M; Masin, Mark; Chatton, Jean-Yves; Kunz, Stefan

    2011-09-01

    The highly pathogenic Old World arenavirus Lassa virus (LASV) and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) use α-dystroglycan as a cellular receptor and enter the host cell by an unusual endocytotic pathway independent of clathrin, caveolin, dynamin, and actin. Upon internalization, the viruses are delivered to acidified endosomes in a Rab5-independent manner bypassing classical routes of incoming vesicular trafficking. Here we sought to identify cellular factors involved in the unusual and largely unknown entry pathway of LASV and LCMV. Cell entry of LASV and LCMV required microtubular transport to late endosomes, consistent with the low fusion pH of the viral envelope glycoproteins. Productive infection with recombinant LCMV expressing LASV envelope glycoprotein (rLCMV-LASVGP) and LCMV depended on phosphatidyl inositol 3-kinase (PI3K) as well as lysobisphosphatidic acid (LBPA), an unusual phospholipid that is involved in the formation of intraluminal vesicles (ILV) of the multivesicular body (MVB) of the late endosome. We provide evidence for a role of the endosomal sorting complex required for transport (ESCRT) in LASV and LCMV cell entry, in particular the ESCRT components Hrs, Tsg101, Vps22, and Vps24, as well as the ESCRT-associated ATPase Vps4 involved in fission of ILV. Productive infection with rLCMV-LASVGP and LCMV also critically depended on the ESCRT-associated protein Alix, which is implicated in membrane dynamics of the MVB/late endosomes. Our study identifies crucial cellular factors implicated in Old World arenavirus cell entry and indicates that LASV and LCMV invade the host cell passing via the MVB/late endosome. Our data further suggest that the virus-receptor complexes undergo sorting into ILV of the MVB mediated by the ESCRT, possibly using a pathway that may be linked to the cellular trafficking and degradation of the cellular receptor. PMID:21931550

  10. Old World Arenaviruses Enter the Host Cell via the Multivesicular Body and Depend on the Endosomal Sorting Complex Required for Transport

    PubMed Central

    Pasqual, Giulia; Rojek, Jillian M.; Masin, Mark; Chatton, Jean-Yves; Kunz, Stefan

    2011-01-01

    The highly pathogenic Old World arenavirus Lassa virus (LASV) and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) use α-dystroglycan as a cellular receptor and enter the host cell by an unusual endocytotic pathway independent of clathrin, caveolin, dynamin, and actin. Upon internalization, the viruses are delivered to acidified endosomes in a Rab5-independent manner bypassing classical routes of incoming vesicular trafficking. Here we sought to identify cellular factors involved in the unusual and largely unknown entry pathway of LASV and LCMV. Cell entry of LASV and LCMV required microtubular transport to late endosomes, consistent with the low fusion pH of the viral envelope glycoproteins. Productive infection with recombinant LCMV expressing LASV envelope glycoprotein (rLCMV-LASVGP) and LCMV depended on phosphatidyl inositol 3-kinase (PI3K) as well as lysobisphosphatidic acid (LBPA), an unusual phospholipid that is involved in the formation of intraluminal vesicles (ILV) of the multivesicular body (MVB) of the late endosome. We provide evidence for a role of the endosomal sorting complex required for transport (ESCRT) in LASV and LCMV cell entry, in particular the ESCRT components Hrs, Tsg101, Vps22, and Vps24, as well as the ESCRT-associated ATPase Vps4 involved in fission of ILV. Productive infection with rLCMV-LASVGP and LCMV also critically depended on the ESCRT-associated protein Alix, which is implicated in membrane dynamics of the MVB/late endosomes. Our study identifies crucial cellular factors implicated in Old World arenavirus cell entry and indicates that LASV and LCMV invade the host cell passing via the MVB/late endosome. Our data further suggest that the virus-receptor complexes undergo sorting into ILV of the MVB mediated by the ESCRT, possibly using a pathway that may be linked to the cellular trafficking and degradation of the cellular receptor. PMID:21931550

  11. Vaccination Strategies against Highly Pathogenic Arenaviruses: The Next Steps toward Clinical Trials

    PubMed Central

    Ölschläger, Stephan; Flatz, Lukas

    2013-01-01

    Vaccination is one of the most valuable weapons against infectious diseases and has led to a significant reduction in mortality and morbidity. However, for most viral hemorrhagic fevers caused by arenaviruses, no prophylactic vaccine is available. This is particularly problematic as these diseases are notoriously difficult to diagnose and treat. Lassa fever is globally the most important of the fevers caused by arenaviruses, potentially affecting millions of people living in endemic areas, particularly in Nigeria. Annually, an estimated 300,000 humans are infected and several thousands succumb to the disease. The successful development of the vaccine “Candid#1” against Junin virus, the causative agent of Argentine hemorrhagic fever, proved that an effective arenavirus vaccine can be developed. Although several promising studies toward the development of a Lassa fever vaccine have been published, no vaccine candidate has been tested in human volunteers or patients. This review summarizes the immunology and other aspects of existing experimental arenavirus vaccine studies, discusses the reasons for the lack of a vaccine, and proposes a plan for overcoming the final hurdles toward clinical trials. PMID:23592977

  12. Human Hemorrhagic Fever Causing Arenaviruses: Molecular Mechanisms Contributing to Virus Virulence and Disease Pathogenesis

    PubMed Central

    Shao, Junjie; Liang, Yuying; Ly, Hinh

    2015-01-01

    Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV) to highly virulent hemorrhagic fever (HF) causing viruses such as Lassa (LASV), Junin (JUNV), Machupo (MACV), Lujo (LUJV), Sabia (SABV), Guanarito (GTOV), and Chapare (CHPV), for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens. PMID:26011826

  13. Broad-spectrum sunscreens provide better protection from the suppression of the elicitation phase of delayed-type hypersensitivity response in humans.

    PubMed

    Moyal, D D; Fourtanier, A M

    2001-11-01

    ultraviolet B sunscreen failed to protect from solar- simulated radiation-induced immunosuppression. In contrast, the broad-spectrum sunscreen having the same sun protection factor but providing high protection in the ultraviolet A range significantly reduced local ultraviolet-induced immunosuppression and prevented the distal effects. In the outdoor study, as compared with delayed-type hypersensitivity responses obtained before sun exposure, no alteration of immune response was detected when the skin was protected by broad-spectrum sunscreen sun protection factor 25 and ultraviolet A-protection factor 14. Conversely, a broad-spectrum sunscreen sun protection factor 25 ultraviolet A-protection factor 6 failed to protect against the sun-impaired response. The above studies clearly demonstrate the role of ultraviolet A in the induction of photoimmunosuppression together with the need for sunscreen products providing efficient photoprotection throughout the entire ultraviolet spectrum. PMID:11710931

  14. Broad-Spectrum Antiviral Therapeutics

    PubMed Central

    Rider, Todd H.; Zook, Christina E.; Boettcher, Tara L.; Wick, Scott T.; Pancoast, Jennifer S.; Zusman, Benjamin D.

    2011-01-01

    Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza. DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered. PMID:21818340

  15. Comparative analysis of disease pathogenesis and molecular mechanisms of New World and Old World arenavirus infections

    PubMed Central

    McLay, Lisa; Liang, Yuying

    2014-01-01

    Arenaviruses can cause fatal human haemorrhagic fever (HF) diseases for which vaccines and therapies are extremely limited. Both the New World (NW) and Old World (OW) groups of arenaviruses contain HF-causing pathogens. Although these two groups share many similarities, important differences with regard to pathogenicity and molecular mechanisms of virus infection exist. These closely related pathogens share many characteristics, including genome structure, viral assembly, natural host selection and the ability to interfere with innate immune signalling. However, members of the NW and OW viruses appear to use different receptors for cellular entry, as well as different mechanisms of virus internalization. General differences in disease signs and symptoms and pathological lesions in patients infected with either NW or OW arenaviruses are also noted and discussed herein. Whilst both the OW Lassa virus (LASV) and the NW Junin virus (JUNV) can cause disruption of the vascular endothelium, which is an important pathological feature of HF, the immune responses to these related pathogens seem to be quite distinct. Whereas LASV infection results in an overall generalized immune suppression, patients infected with JUNV seem to develop a cytokine storm. Additionally, the type of immune response required for recovery and clearance of the virus is different between NW and OW infections. These differences may be important to allow the viruses to evade host immune detection. Understanding these differences will aid the development of new vaccines and treatment strategies against deadly HF viral infections. PMID:24068704

  16. Targeting of Arenavirus RNA Synthesis by a Carboxamide-Derivatized Aromatic Disulfide with Virucidal Activity

    PubMed Central

    Sepúlveda, Claudia S.; García, Cybele C.; Levingston Macleod, Jesica M.

    2013-01-01

    Several arenaviruses can cause severe hemorrhagic fever (HF) in humans, representing a public health threat in endemic areas of Africa and South America. The present study characterizes the potent virucidal activity of the carboxamide-derivatized aromatic disulfide NSC4492, an antiretroviral zinc finger-reactive compound, against Junín virus (JUNV), the causative agent of Argentine HF. The compound was able to inactivate JUNV in a time and temperature-dependent manner, producing more than 99 % reduction in virus titer upon incubation with virions at 37°C for 90 min. The ability of NSC4492-treated JUNV to go through different steps of the multiplication cycle was then evaluated. Inactivated virions were able to bind and enter into the host cell with similar efficiency as control infectious particles. In contrast, treatment with NSC4492 impaired the capacity of JUNV to drive viral RNA synthesis, as measured by quantitative RT-PCR, and blocked viral protein expression, as determined by indirect immunofluorescence. These results suggest that the disulfide NSC4492 targets on the arenavirus replication complex leading to impairment in viral RNA synthesis. Additionally, analysis of VLP produced in NSC4492-treated cells expressing JUNV matrix Z protein revealed that the compound may interact with Z resulting in an altered aggregation behavior of this protein, but without affecting its intrinsic self-budding properties. The potential perspectives of NSC4492 as an inactivating vaccinal compound for pathogenic arenaviruses are discussed. PMID:24278404

  17. Inhibition of mouse peritoneal macrophage DNA synthesis by infection with the arenavirus Pichinde.

    PubMed Central

    Friedlander, A M; Jahrling, P B; Merrill, P; Tobery, S

    1984-01-01

    Macrophage DNA synthesis and proliferation occur during the development of cell-mediated immunity and in the early nonspecific reaction to infection. Arenaviruses have a predilection for infection of cells of the reticuloendothelial system, and in this study we have examined the effect of the arenavirus Pichinde on macrophage DNA synthesis. We have found that infection of mouse peritoneal macrophages with Pichinde caused a profound dose-dependent inhibition of the DNA synthesis induced by macrophage growth factor-colony stimulating factor. At a multiplicity of inoculum of 5, there is a 75 to 95% inhibition of DNA synthesis. Viable virus is necessary for inhibition since Pichinde inactivated by heat or cobalt irradiation had no effect. Similarly, virus pretreated with an antiserum to Pichinde was without inhibitory effect. Inhibition was demonstrated by measuring DNA synthesis spectrofluorometrically as well as by [3H]thymidine incorporation. The inhibition of DNA synthesis was not associated with any cytopathology. There was no evidence that the inhibition was due to soluble factors, such as prostaglandins or interferon, released by infected cells. These studies demonstrate, for the first time in vitro, a significant alteration in macrophage function caused by infection with an arenavirus. It is possible that inhibition of macrophage proliferation represents a mechanism by which some microorganisms interfere with host resistance. PMID:6690404

  18. Differential Contributions of Tacaribe Arenavirus Nucleoprotein N-Terminal and C-Terminal Residues to Nucleocapsid Functional Activity

    PubMed Central

    D'Antuono, Alejandra; Loureiro, Maria Eugenia; Foscaldi, Sabrina; Marino-Buslje, Cristina

    2014-01-01

    ABSTRACT The arenavirus nucleoprotein (NP) is the main protein component of viral nucleocapsids and is strictly required for viral genome replication mediated by the L polymerase. Homo-oligomerization of NP is presumed to play an important role in nucleocapsid assembly, albeit the underlying mechanism and the relevance of NP-NP interaction in nucleocapsid activity are still poorly understood. Here, we evaluate the contribution of the New World Tacaribe virus (TCRV) NP self-interaction to nucleocapsid functional activity. We show that alanine substitution of N-terminal residues predicted to be available for NP-NP interaction strongly affected NP self-association, as determined by coimmunoprecipitation assays, produced a drastic inhibition of transcription and replication of a TCRV minigenome RNA, and impaired NP binding to RNA. Mutagenesis and functional analysis also revealed that, while dispensable for NP self-interaction, key amino acids at the C-terminal domain were essential for RNA synthesis. Furthermore, mutations at these C-terminal residues rendered NP unable to bind RNA both in vivo and in vitro but had no effect on the interaction with the L polymerase. In addition, while all oligomerization-defective variants tested exhibited unaltered capacities to sustain NP-L interaction, NP deletion mutants were fully incompetent to bind L, suggesting that, whereas NP self-association is dispensable, the integrity of both the N-terminal and C-terminal domains is required for binding the L polymerase. Overall, our results suggest that NP self-interaction mediated by the N-terminal domain may play a critical role in TCRV nucleocapsid assembly and activity and that the C-terminal domain of NP is implicated in RNA binding. IMPORTANCE The mechanism of arenavirus functional nucleocapsid assembly is still poorly understood. No detailed information is available on the nucleocapsid structure, and the regions of full-length NP involved in binding to viral RNA remain to be

  19. A Molecular Sensor To Characterize Arenavirus Envelope Glycoprotein Cleavage by Subtilisin Kexin Isozyme 1/Site 1 Protease

    PubMed Central

    Oppliger, Joel; da Palma, Joel Ramos; Burri, Dominique J.; Khatib, Abdel-Majid; Spiropoulou, Christina F.

    2015-01-01

    ABSTRACT Arenaviruses are emerging viruses including several causative agents of severe hemorrhagic fevers in humans. The advent of next-generation sequencing technology has greatly accelerated the discovery of novel arenavirus species. However, for many of these viruses, only genetic information is available, and their zoonotic disease potential remains unknown. During the arenavirus life cycle, processing of the viral envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P) is crucial for productive infection. The ability of newly emerging arenaviruses to hijack human SKI-1/S1P appears, therefore, to be a requirement for efficient zoonotic transmission and human disease potential. Here we implement a newly developed cell-based molecular sensor for SKI-1/S1P to characterize the processing of arenavirus GPC-derived target sequences by human SKI-1/S1P in a quantitative manner. We show that only nine amino acids flanking the putative cleavage site are necessary and sufficient to accurately recapitulate the efficiency and subcellular location of arenavirus GPC processing. In a proof of concept, our sensor correctly predicts efficient processing of the GPC of the newly emergent pathogenic Lujo virus by human SKI-1/S1P and defines the exact cleavage site. Lastly, we employed our sensor to show efficient GPC processing of a panel of pathogenic and nonpathogenic New World arenaviruses, suggesting that GPC cleavage represents no barrier for zoonotic transmission of these pathogens. Our SKI-1/S1P sensor thus represents a rapid and robust test system for assessment of the processing of putative cleavage sites derived from the GPCs of newly discovered arenavirus by the SKI-1/S1P of humans or any other species, based solely on sequence information. IMPORTANCE Arenaviruses are important emerging human pathogens that can cause severe hemorrhagic fevers with high mortality in humans. A crucial step in productive arenavirus

  20. Broad-spectrum sunscreens provide greater protection against ultraviolet-radiation-induced suppression of contact hypersensitivity to a recall antigen in humans.

    PubMed

    Damian, D L; Halliday, G M; Barnetson, R S

    1997-08-01

    This study investigates the extent to which sunscreens protect humans from ultraviolet (UV)-radiation-induced immunosuppression. In the presence of solar-simulated UV, three sunscreens with differing UVA transmission were assessed for their ability to protect the contact hypersensitivity (CHS) response to nickel of 16 nickel-allergic subjects. The sunscreens contained 2-ethylhexyl para-methoxycinnamate (cinnamate), cinnamate with oxybenzone, or cinnamate with zinc oxide, respectively. All had sun protection factors of 10 and hence inhibited UV erythema to similar extents. Volunteers were irradiated on their backs with suberythemal UV daily for 5 d after application of the sunscreens and their base lotion to different sites. Nickel-containing patches were then applied to both UV-treated sites and adjacent, unirradiated control sites. Erythema caused by nickel CHS at each site was quantitated 72 h later with a reflectance erythema meter. In comparison of the nickel reactions of irradiated and unirradiated skin, there was 35% mean immunosuppression in unprotected UV-treated skin. Significant immunosuppression also occurred at sites irradiated through the narrow-spectrum cinnamate-only sunscreen but was prevented by the two broad-spectrum sunscreens. To determine whether UV-induced suppression of the nickel response is specific for cell-mediated immunity or reflects suppression of nonspecific inflammation, a further 16 subjects were patch-tested with a skin irritant, sodium lauryl sulfate (SLS), following a sunscreen and irradiation protocol identical to that of the nickel volunteers. UV had no significant effect on SLS responses. We conclude that nickel patch testing is a valid means of assessing UV-induced immunosuppression in humans and that even with suberythemal UV, immune protection was provided only by sunscreens filtering both UVA and UVB. PMID:9242499

  1. Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever

    PubMed Central

    Mendenhall, Michelle; Russell, Andrew; Smee, Donald F.; Hall, Jeffery O.; Skirpstunas, Ramona; Furuta, Yousuke; Gowen, Brian B.

    2011-01-01

    Background Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed. Methodology/Principal Findings Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV) to further preclinical development of T-705 (Favipiravir), a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST) concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days) was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug's known toxicity. Conclusions/Significance Our findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based

  2. Isolation of Tacaribe Virus, a Caribbean Arenavirus, from Host-Seeking Amblyomma americanum Ticks in Florida

    PubMed Central

    Sayler, Katherine A.; Barbet, Anthony F.; Chamberlain, Casey; Clapp, William L.; Alleman, Rick; Loeb, Julia C.; Lednicky, John A.

    2014-01-01

    Arenaviridae are a family of single stranded RNA viruses of mammals and boid snakes. Twenty-nine distinct mammalian arenaviruses have been identified, many of which cause severe hemorrhagic disease in humans, particularly in parts of sub-Saharan Africa, and in Central and South America. Humans typically become infected with an arenavirus through contact with excreta from infected rodents. Tacaribe virus (TCRV) is an arenavirus that was first isolated from bats and mosquitoes during a rabies surveillance survey conducted in Trinidad from 1956 to 1958. Tacaribe virus is unusual because it has never been associated with a rodent host and since that one time isolation, the virus has not been isolated from any vertebrate or invertebrate hosts. We report the re-isolation of the virus from a pool of 100 host-seeking Amblyomma americanum (lone star ticks) collected in a Florida state park in 2012. TCRV was isolated in two cell lines and its complete genome was sequenced. The tick-derived isolate is nearly identical to the only remaining isolate from Trinidad (TRVL-11573), with 99.6% nucleotide identity across the genome. A quantitative RT-PCR assay was developed to test for viral RNA in host-seeking ticks collected from 3 Florida state parks. Virus RNA was detected in 56/500 (11.2%) of surveyed ticks. As this virus was isolated from ticks that parasitize humans, the ability of the tick to transmit the virus to people should be evaluated. Furthermore, reservoir hosts for the virus need to be identified in order to develop risk assessment models of human infection. PMID:25536075

  3. An Interferon Regulated MicroRNA Provides Broad Cell-Intrinsic Antiviral Immunity through Multihit Host-Directed Targeting of the Sterol Pathway

    PubMed Central

    Robertson, Kevin A.; Hsieh, Wei Yuan; Forster, Thorsten; Blanc, Mathieu; Lu, Hongjin; Crick, Peter J.; Yutuc, Eylan; Watterson, Steven; Martin, Kimberly; Griffiths, Samantha J.; Enright, Anton J.; Yamamoto, Mami; Pradeepa, Madapura M.; Lennox, Kimberly A.; Behlke, Mark A.; Talbot, Simon; Haas, Jürgen; Dölken, Lars; Griffiths, William J.; Wang, Yuqin; Angulo, Ana; Ghazal, Peter

    2016-01-01

    In invertebrates, small interfering RNAs are at the vanguard of cell-autonomous antiviral immunity. In contrast, antiviral mechanisms initiated by interferon (IFN) signaling predominate in mammals. Whilst mammalian IFN-induced miRNA are known to inhibit specific viruses, it is not known whether host-directed microRNAs, downstream of IFN-signaling, have a role in mediating broad antiviral resistance. By performing an integrative, systematic, global analysis of RNA turnover utilizing 4-thiouridine labeling of newly transcribed RNA and pri/pre-miRNA in IFN-activated macrophages, we identify a new post-transcriptional viral defense mechanism mediated by miR-342-5p. On the basis of ChIP and site-directed promoter mutagenesis experiments, we find the synthesis of miR-342-5p is coupled to the antiviral IFN response via the IFN-induced transcription factor, IRF1. Strikingly, we find miR-342-5p targets mevalonate-sterol biosynthesis using a multihit mechanism suppressing the pathway at different functional levels: transcriptionally via SREBF2, post-transcriptionally via miR-33, and enzymatically via IDI1 and SC4MOL. Mass spectrometry-based lipidomics and enzymatic assays demonstrate the targeting mechanisms reduce intermediate sterol pathway metabolites and total cholesterol in macrophages. These results reveal a previously unrecognized mechanism by which IFN regulates the sterol pathway. The sterol pathway is known to be an integral part of the macrophage IFN antiviral response, and we show that miR-342-5p exerts broad antiviral effects against multiple, unrelated pathogenic viruses such Cytomegalovirus and Influenza A (H1N1). Metabolic rescue experiments confirm the specificity of these effects and demonstrate that unrelated viruses have differential mevalonate and sterol pathway requirements for their replication. This study, therefore, advances the general concept of broad antiviral defense through multihit targeting of a single host pathway. PMID:26938778

  4. An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein

    SciTech Connect

    Garcia, C.C.; Topisirovic, I.; Djavani, M.; Borden, K.L.B.; Damonte, E.B.; Salvato, M.S.

    2010-03-19

    The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection.

  5. Targeting the proteolytic processing of the viral glycoprotein precursor is a promising novel antiviral strategy against arenaviruses.

    PubMed

    Rojek, Jillian M; Pasqual, Giulia; Sanchez, Ana B; Nguyen, Ngoc-Thao; de la Torre, Juan-Carlos; Kunz, Stefan

    2010-01-01

    A crucial step in the arenavirus life cycle is the biosynthesis of the viral envelope glycoprotein (GP) responsible for virus attachment and entry. Processing of the GP precursor (GPC) by the cellular proprotein convertase site 1 protease (S1P), also known as subtilisin-kexin-isozyme 1 (SKI-1), is crucial for cell-to-cell propagation of infection and production of infectious virus. Here, we sought to evaluate arenavirus GPC processing by S1P as a target for antiviral therapy using a recently developed peptide-based S1P inhibitor, decanoyl (dec)-RRLL-chloromethylketone (CMK), and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). To control for off-target effects of dec-RRLL-CMK, we employed arenavirus reverse genetics to introduce a furin recognition site into the GPC of LCMV. The rescued mutant virus grew to normal titers, and the processing of its GPC critically depended on cellular furin, but not S1P. Treatment with the S1P inhibitor dec-RRLL-CMK resulted in specific blocking of viral spread and virus production of LCMV. Combination of the protease inhibitor with ribavirin, currently used clinically for treatment of human arenavirus infections, resulted in additive drug effects. In cells deficient in S1P, the furin-dependent LCMV variant established persistent infection, whereas wild-type LCMV underwent extinction without the emergence of S1P-independent escape variants. Together, the potent antiviral activity of an inhibitor of S1P-dependent GPC cleavage, the additive antiviral effect with ribavirin, and the low probability of emergence of S1P-independent viral escape variants make S1P-mediated GPC processing by peptide-derived inhibitors a promising strategy for the development of novel antiarenaviral drugs. PMID:19846507

  6. The 2010 Broad Prize

    ERIC Educational Resources Information Center

    Education Digest: Essential Readings Condensed for Quick Review, 2011

    2011-01-01

    A new data analysis, based on data collected as part of The Broad Prize process, provides insights into which large urban school districts in the United States are doing the best job of educating traditionally disadvantaged groups: African-American, Hispanics, and low-income students. Since 2002, The Eli and Edythe Broad Foundation has awarded The…

  7. The good, the bad, and the ugly: the unnecessarily broad impact of qui tam civil False Claims Act cases on rural health care providers.

    PubMed

    Hyer, Andrew M

    2013-01-01

    The civil False Claims Act (FCA) imposes harsh penalties against parties who misappropriate federal funds. The statute's qui tam whistle-blower provisions create strong financial incentives for private individuals to bring and pursue FCA cases against health providers on the government's behalf--even where government attorneys decline to intervene. FCA cases where the government declined to intervene account for less than 2 percent of all recoveries in health care FCA cases. Yet the costs of defending such cases may be very high, especially for rural providers with small operating margins. Federal provider self-referral and anti-kickback laws carve out various exceptions to support the financial viability of rural providers. The FCA, however, contains no such exceptions. Although Department of Justice (DOJ) policy directs officials to take into account community access to care in pursuing FCA cases against rural providers, the ability for private whistleblowers to pursue cases where the government declines to intervene undermines the DOJ's ability to achieve that aim. This Article highlights the liability risks rural providers commonly face under the FCA and argues for amending the FCA to allow a whistleblower claim to proceed against providers serving designated underserved areas only where government authorities intervene in the case. PMID:24341079

  8. Arenavirus Stable Signal Peptide Is the Keystone Subunit for Glycoprotein Complex Organization

    PubMed Central

    Bederka, Lydia H.; Bonhomme, Cyrille J.; Ling, Emily L.

    2014-01-01

    ABSTRACT The rodent arenavirus glycoprotein complex encodes a stable signal peptide (SSP) that is an essential structural component of mature virions. The SSP, GP1, and GP2 subunits of the trimeric glycoprotein complex noncovalently interact to stud the surface of virions and initiate arenavirus infectivity. Nascent glycoprotein production undergoes two proteolytic cleavage events: first within the endoplasmic reticulum (ER) to cleave SSP from the remaining precursor GP1/2 (glycoprotein complex [GPC]) glycoprotein and second within the Golgi stacks by the cellular SKI-1/S1P for GP1/2 processing to yield GP1 and GP2 subunits. Cleaved SSP is not degraded but retained as an essential glycoprotein subunit. Here, we defined functions of the 58-amino-acid lymphocytic choriomeningitis virus (LCMV) SSP in regard to glycoprotein complex processing and maturation. Using molecular biology techniques, confocal microscopy, and flow cytometry, we detected SSP at the plasma membrane of transfected cells. Further, we identified a sorting signal (FLLL) near the carboxyl terminus of SSP that is required for glycoprotein maturation and trafficking. In the absence of SSP, the glycoprotein accumulated within the ER and was unable to undergo processing by SKI-1/S1P. Mutation of this highly conserved FLLL motif showed impaired glycoprotein processing and secretory pathway trafficking, as well as defective surface expression and pH-dependent membrane fusion. Immunoprecipitation of SSP confirmed an interaction between the signal peptide and the GP2 subunit; however, mutations within this FLLL motif disrupted the association of the GP1 subunit with the remaining glycoprotein complex. PMID:25352624

  9. Identification of two functional domains within the arenavirus nucleoprotein.

    PubMed

    Levingston Macleod, Jesica M; D'Antuono, Alejandra; Loureiro, Maria Eugenia; Casabona, Juan Cruz; Gomez, Guillermo A; Lopez, Nora

    2011-03-01

    Tacaribe virus (TCRV) belongs to the Arenaviridae family. Its bisegmented negative-stranded RNA genome encodes the nucleoprotein (N), the precursor of the envelope glycoproteins, the polymerase (L), and a RING finger matrix (Z) protein. The 570-amino-acid N protein binds to viral RNA, forming nucleocapsids, which are the template for transcription and replication by the viral polymerase. We have previously shown that the interaction between N and Z is required for assembly of infectious virus-like particles (VLPs) (J. C. Casabona et al., J. Virol. 83:7029-7039, 2009). Here, we examine the functional organization of TCRV N protein. A series of deletions and point mutations were introduced into the N-coding sequence, and the ability of the mutants to sustain heterotypic (N-Z) or homotypic (N-N) interactions was analyzed. We found that N protein displays two functional domains. By using coimmunoprecipitation studies, VLP incorporation assays, and double immunofluorescence staining, the carboxy-terminal region of N was found to be required for N-Z interaction and also necessary for incorporation of N protein into VLPs. Moreover, further analysis of this region showed that the integrity of a putative zinc-finger motif, as well as its amino-flanking sequence (residues 461 to 489), are critical for Z binding and N incorporation into VLPs. In addition, we provide evidence of an essential role of the amino-terminal region of N protein for N-N interaction. In this regard, using reciprocal coimmunoprecipitation analysis, we identified a 28-residue region predicted to form a coiled-coil domain (residues 92 to 119) as a newly recognized molecular determinant of N homotypic interactions. PMID:21159858

  10. Identification of Two Functional Domains within the Arenavirus Nucleoprotein▿

    PubMed Central

    Levingston Macleod, Jesica M.; D'Antuono, Alejandra; Loureiro, Maria Eugenia; Casabona, Juan Cruz; Gomez, Guillermo A.; Lopez, Nora

    2011-01-01

    Tacaribe virus (TCRV) belongs to the Arenaviridae family. Its bisegmented negative-stranded RNA genome encodes the nucleoprotein (N), the precursor of the envelope glycoproteins, the polymerase (L), and a RING finger matrix (Z) protein. The 570-amino-acid N protein binds to viral RNA, forming nucleocapsids, which are the template for transcription and replication by the viral polymerase. We have previously shown that the interaction between N and Z is required for assembly of infectious virus-like particles (VLPs) (J. C. Casabona et al., J. Virol. 83:7029-7039, 2009). Here, we examine the functional organization of TCRV N protein. A series of deletions and point mutations were introduced into the N-coding sequence, and the ability of the mutants to sustain heterotypic (N-Z) or homotypic (N-N) interactions was analyzed. We found that N protein displays two functional domains. By using coimmunoprecipitation studies, VLP incorporation assays, and double immunofluorescence staining, the carboxy-terminal region of N was found to be required for N-Z interaction and also necessary for incorporation of N protein into VLPs. Moreover, further analysis of this region showed that the integrity of a putative zinc-finger motif, as well as its amino-flanking sequence (residues 461 to 489), are critical for Z binding and N incorporation into VLPs. In addition, we provide evidence of an essential role of the amino-terminal region of N protein for N-N interaction. In this regard, using reciprocal coimmunoprecipitation analysis, we identified a 28-residue region predicted to form a coiled-coil domain (residues 92 to 119) as a newly recognized molecular determinant of N homotypic interactions. PMID:21159858

  11. The N-Terminal Domain of the Arenavirus L Protein Is an RNA Endonuclease Essential in mRNA Transcription

    PubMed Central

    Morin, Benjamin; Coutard, Bruno; Lelke, Michaela; Ferron, François; Kerber, Romy; Jamal, Saïd; Frangeul, Antoine; Baronti, Cécile; Charrel, Rémi; de Lamballerie, Xavier; Vonrhein, Clemens; Lescar, Julien; Bricogne, Gérard; Günther, Stephan; Canard, Bruno

    2010-01-01

    Arenaviridae synthesize viral mRNAs using short capped primers presumably acquired from cellular transcripts by a ‘cap-snatching’ mechanism. Here, we report the crystal structure and functional characterization of the N-terminal 196 residues (NL1) of the L protein from the prototypic arenavirus: lymphocytic choriomeningitis virus. The NL1 domain is able to bind and cleave RNA. The 2.13 Å resolution crystal structure of NL1 reveals a type II endonuclease α/β architecture similar to the N-terminal end of the influenza virus PA protein. Superimposition of both structures, mutagenesis and reverse genetics studies reveal a unique spatial arrangement of key active site residues related to the PD…(D/E)XK type II endonuclease signature sequence. We show that this endonuclease domain is conserved and active across the virus families Arenaviridae, Bunyaviridae and Orthomyxoviridae and propose that the arenavirus NL1 domain is the Arenaviridae cap-snatching endonuclease. PMID:20862324

  12. Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junin arenavirus envelope glycoprotein

    SciTech Connect

    York, Joanne . E-mail: joanne.york@umontana.edu; Agnihothram, Sudhakar S. . E-mail: sudhakar.agnihothram@umontana.edu; Romanowski, Victor . E-mail: victor@biol.unlp.edu.ar; Nunberg, Jack H. . E-mail: jack.nunberg@umontana.edu

    2005-12-20

    The G2 fusion subunit of the Junin virus envelope glycoprotein GP-C contains two hydrophobic heptad-repeat regions that are postulated to form a six-helix bundle structure required for the membrane fusion activity of Class I viral fusion proteins. We have investigated the role of these heptad-repeat regions and, specifically, the importance of the putative interhelical a and d position sidechains by using alanine-scanning mutagenesis. All the mutant glycoproteins were expressed and transported to the cell surface. Proteolytic maturation at the subtilisin kexin isozyme-1/site-1-protease (SKI-1/S1P) cleavage site was observed in all but two of the mutants. Among the adequately cleaved mutant glycoproteins, four positions in the N-terminal region (I333, L336, L347 and L350) and two positions in the C-terminal region (R392 and W395) were shown to be important determinants of cell-cell fusion. Taken together, our results indicate that {alpha}-helical coiled-coil structures are likely critical in promoting arenavirus membrane fusion. These findings support the inclusion of the arenavirus GP-C among the Class I viral fusion proteins and suggest pharmacologic and immunologic strategies for targeting arenavirus infection and hemorrhagic fever.

  13. Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds

    PubMed Central

    García, Cybele C.; Djavani, Mahmoud; Topisirovic, Ivan; Borden, Katherine L. B.; Salvato, María S.; Damonte, Elsa B.

    2008-01-01

    Several disulfide-based and azoic compounds have shown antiviral and virucidal properties against arenaviruses in virus yield-inhibition and inactivation assays, respectively. The most effective virucidal agent, the aromatic disulfide NSC20625, was able to inactivate two strains of the prototype arenavirus species Lymphocytic choriomeningitis virus (LCMV). Inactivated viral particles retained the biological functions of the virion envelope glycoproteins in virus binding and uptake, but were unable to perform viral RNA replication. Furthermore, in inactivated virions, the electrophoretic profile of the Z protein was altered when analysed under non-reducing conditions, whereas the patterns of the proteins NP and GP1 remained unaffected. Treatment of a recombinant LCMV Z protein with the virucidal agents induced unfolding and oligomerization of Z to high-molecular-mass aggregates, probably due to metal-ion ejection and the formation of intermolecular disulfide bonds through the cysteine residues of the Z RING finger. NSC20625 also exhibited antiviral properties in LCMV-infected cells without affecting other cellular RING-motif proteins, such as the promyelocytic leukaemia protein PML. Altogether, the investigations described here illustrate the potential of the Z protein as a promising target for therapy and the prospects of the Z-reactive compounds to prevent arenavirus dissemination. PMID:16603524

  14. Detection of arenavirus in a peripheral odontogenic fibromyxoma in a red tail boa (Boa constrictor constrictor) with inclusion body disease.

    PubMed

    Hellebuyck, Tom; Pasmans, Frank; Ducatelle, Richard; Saey, Veronique; Martel, An

    2015-03-01

    A captive bred red tail boa (Boa constrictor constrictor) was presented with a large intraoral mass originating from the buccal gingiva, attached to the right dentary teeth row. Based on the clinical features and histological examination, the diagnosis of a peripheral odontogenic fibromyxoma was made. Sections of liver biopsies and circulating lymphocytes contained relatively few eosinophilic intracytoplasmic inclusion bodies, indistinguishable from those observed in inclusion body disease-affected snakes. Inclusion bodies were not observed in cells comprising the neoplastic mass. Using reverse transcription polymerase chain reaction (RT-PCR), arenavirus was detected in the neoplastic tissue. Two years after surgical removal of the mass, recurrence of the neoplastic lesion was observed. Numerous large inclusion body disease inclusions were abundantly present in the neoplastic cells of the recurrent fibromyxoma. Sections of liver biopsies and circulating lymphocytes contained relatively few intracytoplasmic inclusions. The RT-PCR revealed the presence of arenavirus in blood, a liver biopsy, and neoplastic tissue. The present case describes the co-occurrence of an arenavirus infection and an odontogenic fibromyxoma in a red tail boa. PMID:25776548

  15. Dissection of the Role of the Stable Signal Peptide of the Arenavirus Envelope Glycoprotein in Membrane Fusion

    PubMed Central

    Messina, Emily L.; York, Joanne

    2012-01-01

    The arenavirus envelope glycoprotein (GPC) retains a stable signal peptide (SSP) as an essential subunit in the mature complex. The 58-amino-acid residue SSP comprises two membrane-spanning hydrophobic regions separated by a short ectodomain loop that interacts with the G2 fusion subunit to promote pH-dependent membrane fusion. Small-molecule compounds that target this unique SSP-G2 interaction prevent arenavirus entry and infection. The interaction between SSP and G2 is sensitive to the phylogenetic distance between New World (Junín) and Old World (Lassa) arenaviruses. For example, heterotypic GPC complexes are unable to support virion entry. In this report, we demonstrate that the hybrid GPC complexes are properly assembled, proteolytically cleaved, and transported to the cell surface but are specifically defective in their membrane fusion activity. Chimeric SSP constructs reveal that this incompatibility is localized to the first transmembrane segment of SSP (TM1). Genetic changes in TM1 also affect sensitivity to small-molecule fusion inhibitors, generating resistance in some cases and inhibitor dependence in others. Our studies suggest that interactions of SSP TM1 with the transmembrane domain of G2 may be important for GPC-mediated membrane fusion and its inhibition. PMID:22438561

  16. Uncovering Viral Protein-Protein Interactions and their Role in Arenavirus Life Cycle

    PubMed Central

    Loureiro, Maria Eugenia; D’Antuono, Alejandra; Levingston Macleod, Jesica M.; López, Nora

    2012-01-01

    The Arenaviridae family includes widely distributed pathogens that cause severe hemorrhagic fever in humans. Replication and packaging of their single-stranded RNA genome involve RNA recognition by viral proteins and a number of key protein-protein interactions. Viral RNA synthesis is directed by the virus-encoded RNA dependent-RNA polymerase (L protein) and requires viral RNA encapsidation by the Nucleoprotein. In addition to the role that the interaction between L and the Nucleoprotein may have in the replication process, polymerase activity appears to be modulated by the association between L and the small multifunctional Z protein. Z is also a structural component of the virions that plays an essential role in viral morphogenesis. Indeed, interaction of the Z protein with the Nucleoprotein is critical for genome packaging. Furthermore, current evidence suggests that binding between Z and the viral envelope glycoprotein complex is required for virion infectivity, and that Z homo-oligomerization is an essential step for particle assembly and budding. Efforts to understand the molecular basis of arenavirus life cycle have revealed important details on these viral protein-protein interactions that will be reviewed in this article. PMID:23170177

  17. Uncovering viral protein-protein interactions and their role in arenavirus life cycle.

    PubMed

    Loureiro, Maria Eugenia; D'Antuono, Alejandra; Levingston Macleod, Jesica M; López, Nora

    2012-09-01

    The Arenaviridae family includes widely distributed pathogens that cause severe hemorrhagic fever in humans. Replication and packaging of their single-stranded RNA genome involve RNA recognition by viral proteins and a number of key protein-protein interactions. Viral RNA synthesis is directed by the virus-encoded RNA dependent-RNA polymerase (L protein) and requires viral RNA encapsidation by the Nucleoprotein. In addition to the role that the interaction between L and the Nucleoprotein may have in the replication process, polymerase activity appears to be modulated by the association between L and the small multifunctional Z protein. Z is also a structural component of the virions that plays an essential role in viral morphogenesis. Indeed, interaction of the Z protein with the Nucleoprotein is critical for genome packaging. Furthermore, current evidence suggests that binding between Z and the viral envelope glycoprotein complex is required for virion infectivity, and that Z homo-oligomerization is an essential step for particle assembly and budding. Efforts to understand the molecular basis of arenavirus life cycle have revealed important details on these viral protein-protein interactions that will be reviewed in this article. PMID:23170177

  18. Comparative Structural and Functional Analysis of Bunyavirus and Arenavirus Cap-Snatching Endonucleases

    PubMed Central

    Reguera, Juan; Gerlach, Piotr; Rosenthal, Maria; Gaudon, Stephanie; Coscia, Francesca; Günther, Stephan; Cusack, Stephen

    2016-01-01

    Segmented negative strand RNA viruses of the arena-, bunya- and orthomyxovirus families uniquely carry out viral mRNA transcription by the cap-snatching mechanism. This involves cleavage of host mRNAs close to their capped 5′ end by an endonuclease (EN) domain located in the N-terminal region of the viral polymerase. We present the structure of the cap-snatching EN of Hantaan virus, a bunyavirus belonging to hantavirus genus. Hantaan EN has an active site configuration, including a metal co-ordinating histidine, and nuclease activity similar to the previously reported La Crosse virus and Influenza virus ENs (orthobunyavirus and orthomyxovirus respectively), but is more active in cleaving a double stranded RNA substrate. In contrast, Lassa arenavirus EN has only acidic metal co-ordinating residues. We present three high resolution structures of Lassa virus EN with different bound ion configurations and show in comparative biophysical and biochemical experiments with Hantaan, La Crosse and influenza ENs that the isolated Lassa EN is essentially inactive. The results are discussed in the light of EN activation mechanisms revealed by recent structures of full-length influenza virus polymerase. PMID:27304209

  19. Comparative Structural and Functional Analysis of Bunyavirus and Arenavirus Cap-Snatching Endonucleases.

    PubMed

    Reguera, Juan; Gerlach, Piotr; Rosenthal, Maria; Gaudon, Stephanie; Coscia, Francesca; Günther, Stephan; Cusack, Stephen

    2016-06-01

    Segmented negative strand RNA viruses of the arena-, bunya- and orthomyxovirus families uniquely carry out viral mRNA transcription by the cap-snatching mechanism. This involves cleavage of host mRNAs close to their capped 5' end by an endonuclease (EN) domain located in the N-terminal region of the viral polymerase. We present the structure of the cap-snatching EN of Hantaan virus, a bunyavirus belonging to hantavirus genus. Hantaan EN has an active site configuration, including a metal co-ordinating histidine, and nuclease activity similar to the previously reported La Crosse virus and Influenza virus ENs (orthobunyavirus and orthomyxovirus respectively), but is more active in cleaving a double stranded RNA substrate. In contrast, Lassa arenavirus EN has only acidic metal co-ordinating residues. We present three high resolution structures of Lassa virus EN with different bound ion configurations and show in comparative biophysical and biochemical experiments with Hantaan, La Crosse and influenza ENs that the isolated Lassa EN is essentially inactive. The results are discussed in the light of EN activation mechanisms revealed by recent structures of full-length influenza virus polymerase. PMID:27304209

  20. Molecular determinants of arenavirus Z protein homo-oligomerization and L polymerase binding.

    PubMed

    Loureiro, Maria Eugenia; Wilda, Maximiliano; Levingston Macleod, Jesica M; D'Antuono, Alejandra; Foscaldi, Sabrina; Marino Buslje, Cristina; Lopez, Nora

    2011-12-01

    The arenavirus Z is a zinc-binding RING protein that has been implicated in multiple functions during the viral life cycle. These roles of Z involve interactions with viral and cellular proteins that remain incompletely understood. In this regard, Z inhibits viral RNA transcription and replication through direct interaction with the viral L polymerase. Here, we defined the L-binding domain of Tacaribe virus (TCRV) Z protein and the structural requirements mediating Z homo-oligomerization. By using site-directed mutagenesis, coimmunoprecipitation, and functional assays, we showed that residues R37, N39, W44, L50, and Y57, located around the zinc coordination site I, play a critical role in the Z-L interaction. We also found that Z protein from either TCRV or the pathogenic Junin virus (JUNV) self-associates into oligomeric forms in mammalian cells. Importantly, mutation of the myristoylation site, the strictly conserved residue G at position 2, severely impaired the ability of both TCRV Z and JUNV Z to self-interact as well as their capacity to accumulate at the plasma membrane, strongly suggesting that Z homo-oligomerization is associated with its myristoylation and cell membrane targeting. In contrast, disruption of the RING structure or substitution of W44 or N39, which are critical for L protein recognition, did not affect Z self-binding. Overall, the data presented here indicate that homo-oligomerization is not a requirement for Z-L interaction or Z-mediated polymerase activity inhibition. PMID:21957305

  1. Molecular Determinants of Arenavirus Z Protein Homo-Oligomerization and L Polymerase Binding▿

    PubMed Central

    Loureiro, Maria Eugenia; Wilda, Maximiliano; Levingston Macleod, Jesica M.; D'Antuono, Alejandra; Foscaldi, Sabrina; Buslje, Cristina Marino; Lopez, Nora

    2011-01-01

    The arenavirus Z is a zinc-binding RING protein that has been implicated in multiple functions during the viral life cycle. These roles of Z involve interactions with viral and cellular proteins that remain incompletely understood. In this regard, Z inhibits viral RNA transcription and replication through direct interaction with the viral L polymerase. Here, we defined the L-binding domain of Tacaribe virus (TCRV) Z protein and the structural requirements mediating Z homo-oligomerization. By using site-directed mutagenesis, coimmunoprecipitation, and functional assays, we showed that residues R37, N39, W44, L50, and Y57, located around the zinc coordination site I, play a critical role in the Z-L interaction. We also found that Z protein from either TCRV or the pathogenic Junin virus (JUNV) self-associates into oligomeric forms in mammalian cells. Importantly, mutation of the myristoylation site, the strictly conserved residue G at position 2, severely impaired the ability of both TCRV Z and JUNV Z to self-interact as well as their capacity to accumulate at the plasma membrane, strongly suggesting that Z homo-oligomerization is associated with its myristoylation and cell membrane targeting. In contrast, disruption of the RING structure or substitution of W44 or N39, which are critical for L protein recognition, did not affect Z self-binding. Overall, the data presented here indicate that homo-oligomerization is not a requirement for Z-L interaction or Z-mediated polymerase activity inhibition. PMID:21957305

  2. Strand-Specific Quantitative Reverse Transcription-Polymerase Chain Reaction Assay for Measurement of Arenavirus Genomic and Antigenomic RNAs.

    PubMed

    Haist, Kelsey; Ziegler, Christopher; Botten, Jason

    2015-01-01

    Arenaviruses are bi-segmented, single-stranded RNA viruses that cause significant human disease. The manner in which they regulate the replication of their genome is not well-understood. This is partly due to the absence of a highly sensitive assay to measure individual species of arenavirus replicative RNAs. To overcome this obstacle, we designed a quantitative reverse transcription (RT)-PCR assay for selective quantitation of each of the lymphocytic choriomeningitis virus (LCMV) genomic or antigenomic RNAs. During the course of assay design, we identified a nonspecific priming phenomenon whereby, in the absence of an RT primer, cDNAs complementary to each of the LCMV replicative RNA species are generated during RT. We successfully circumvented this nonspecific priming event through the use of biotinylated primers in the RT reaction, which permitted affinity purification of primer-specific cDNAs using streptavidin-coated magnetic beads. As proof of principle, we used the assay to map the dynamics of LCMV replication at acute and persistent time points and to determine the quantities of genomic and antigenomic RNAs that are incorporated into LCMV particles. This assay can be adapted to measure total S or L segment-derived viral RNAs and therefore represents a highly sensitive diagnostic platform to screen for LCMV infection in rodent and human tissue samples and can also be used to quantify virus-cell attachment. PMID:25978311

  3. The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain

    SciTech Connect

    Burri, Dominique J.; Pasquato, Antonella; Ramos da Palma, Joel; Igonet, Sebastien; Oldstone, Michael B.A.; Kunz, Stefan

    2013-02-05

    Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

  4. The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain

    PubMed Central

    Burri, Dominique J.; Pasquato, Antonella; da Palma, Joel Ramos; Igonet, Sebastien; Oldstone, Michael B.A.; Kunz, Stefan

    2012-01-01

    Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC. PMID:23218200

  5. Inhibition of the Type I Interferon Response by the Nucleoprotein of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus

    PubMed Central

    Martínez-Sobrido, Luis; Zúñiga, Elina I.; Rosario, Debralee; García-Sastre, Adolfo; de la Torre, Juan Carlos

    2006-01-01

    The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a formidable battle horse for the study of viral immunology, as well as viral persistence and associated diseases. Investigations with LCMV have uncovered basic mechanisms by which viruses avoid elimination by the host adaptive immune response. In this study we show that LCMV also disables the host innate defense by interfering with beta interferon (IFN-β) production in response to different stimuli, including infection with Sendai virus and liposome-mediated DNA transfection. Inhibition of IFN production in LCMV-infected cells was caused by an early block in the IFN regulatory factor 3 (IRF-3) activation pathway. This defect was restored in cells cured of LCMV, indicating that one or more LCMV products are responsible for the inhibition of IRF-3 activation. Using expression plasmids encoding individual LCMV proteins, we found that expression of the LCMV nucleoprotein (NP) was sufficient to inhibit both IFN production and nuclear translocation of IRF-3. To our knowledge, this is the first evidence of an IFN-counteracting viral protein in the Arenaviridae family. Inhibition of IFN production by the arenavirus NP is likely to be a determinant of virulence in vivo. PMID:16940530

  6. Antibodies to Tacaribe Serocomplex Viruses (Family Arenaviridae, Genus Arenavirus) in Cricetid Rodents from New Mexico, Texas, and Mexico

    PubMed Central

    Milazzo, Mary L.; Barragán-Gomez, Artemio; Hanson, John Delton; Estrada-Franco, Jose G.; Arellano, Elizabeth; González-Cózatl, Francisco X.; Fernández-Salas, Ildefonso; Ramirez-Aguilar, Francisco; Rogers, Duke S.; Bradley, Robert D.

    2010-01-01

    Abstract Blood samples from 4893 cricetid rodents were tested for antibody (immunoglobulin G) to Whitewater Arroyo virus and Amaparí virus to extend our knowledge of the natural host range and geographical distribution of Tacaribe serocomplex viruses in North America. Antibodies to arenaviruses were found in northern pygmy mice (Baiomys taylori), woodrats (Neotoma spp.), northern grasshopper mice (Onychomys leucogaster), oryzomys (Oryzomys spp.), deermice (Megadontomys nelsoni and Peromyscus spp.), harvest mice (Reithrodontomys spp.), and cotton rats (Sigmodon spp.) captured in New Mexico, Texas, or Mexico. Comparison of endpoint antibody titers to Whitewater Arroyo virus and Amaparí virus in individual blood samples indicated that the Tacaribe complex viruses enzootic in Texas and Mexico are antigenically diverse. PMID:20795917

  7. Structural Characterization of the glycoprotein GP2 Core Domain from the CAS Virus, a Novel Arenavirus-like Species

    PubMed Central

    Koellhoffer, Jayne F.; Dai, Zhou; Malashkevich, Vladimir N.; Stenglein, Mark D.; Liu, Yanyun; Toro, Rafael; Harrison, Joseph; Chandran, Kartik; DeRisi, Joseph L.; Almo, Steven C.; Lai, Jonathan R.

    2014-01-01

    Fusion of the viral and host cell membranes is a necessary first step for infection by enveloped viruses, and is mediated by the envelope glycoprotein. The transmembrane subunits from the structurally defined “class I” glycoproteins adopt an α-helical “trimer- of-hairpins” conformation during the fusion pathway. Here we present our studies on the envelope glycoprotein transmembrane subunit, GP2, of the CAS virus (CASV). CASV was recently identified from annulated tree boas (Corallus annulatus) with inclusion body disease and is implicated in the disease etiology. We have generated and characterized two protein constructs consisting of the predicted CASV GP2 core domain. The crystal structure of the CASV GP2 post-fusion conformation indicates a trimeric α-helical bundle that is highly similar to those of Ebola Virus (EBOV) and Marburg Virus (MARV) GP2, despite CASV genome homology to arenaviruses. Denaturation studies demonstrate that the stability of CASV GP2 is pH-dependent with higher stability at lower pH; we propose that this behavior is due to a network of interactions among acidic residues that would destabilize the α-helical bundle under conditions where the side chains are deprotonated. The pH-dependent stability of the post-fusion structure has been observed in EBOV and MARV GP2, as well as other viruses that enter via the endosome. Infection experiments with CASV and the related Golden Gate Virus (GGV) support a mechanism of entry that requires endosomal acidification. Our results suggest that despite being primarily arenavirus-like, the transmembrane subunit of CASV is extremely similar to the filoviruses. PMID:24333483

  8. Infection of Type I Interferon Receptor-Deficient Mice with Various Old World Arenaviruses: A Model for Studying Virulence and Host Species Barriers

    PubMed Central

    Rieger, Toni; Merkler, Doron; Günther, Stephan

    2013-01-01

    Lassa virus causes hemorrhagic Lassa fever in humans, while the related Old World arenaviruses Mopeia, Morogoro, and Mobala are supposedly apathogenic to humans and cause only inapparent infection in non-human primates. Here, we studied whether the virulence of Old World arenaviruses in humans and non-human primates is reflected in type I interferon receptor deficient (IFNAR-/-) mice by testing several strains of Lassa virus vs. the apathogenic viruses Mopeia, Morogoro, and Mobala. All Lassa virus strains tested—Josiah, AV, BA366, and Nig04-10—replicated to high titers in blood, lung, kidney, heart, spleen, brain, and liver and caused disease as evidenced by weight loss and elevation of aspartate and alanine aminotransferase (AST and ALT) levels with a high AST/ALT ratio. Lassa fever-like pathology included acute hepatitis, interstitial pneumonia, and pronounced disturbance of splenic cytoarchitecture. Infiltrations of activated monocytes/macrophages expressing inducible nitric oxide synthase and T cells were found in liver and lung. In contrast, Mopeia, Morogoro, and Mobala virus replicated poorly in the animals and acute inflammatory alterations were not noted. Depletion of CD4+ and CD8+ T cells strongly enhanced susceptibility of IFNAR-/- mice to the apathogenic viruses. In conclusion, the virulence of Old World arenaviruses in IFNAR-/- mice correlates with their virulence in humans and non-human primates. In addition to the type I interferon system, T cells seem to regulate whether or not an arenavirus can productively infect non-host rodent species. The observation that Lassa virus overcomes the species barrier without artificial depletion of T cells suggests it is able to impair T cell functionality in a way that corresponds to depletion. PMID:23991083

  9. Novel approaches in anti-arenaviral drug development

    SciTech Connect

    Lee, Andrew M.; Pasquato, Antonella; Kunz, Stefan

    2011-03-15

    Hemorrhagic fevers caused by arenaviruses are among the most devastating emerging human diseases. Considering the number of individuals affected, the current lack of a licensed vaccine, and the limited therapeutic options, arenaviruses are arguably among the most neglected tropical pathogens and the development of efficacious anti-arenaviral drugs is of high priority. Over the past years significant efforts have been undertaken to identify novel potent inhibitors of arenavirus infection. High throughput screening of small molecule libraries employing pseudotype platforms led to the discovery of several potent and broadly active inhibitors of arenavirus cell entry that are effective against the major hemorrhagic arenaviruses. Mechanistic studies revealed that these novel entry inhibitors block arenavirus membrane fusion and provided novel insights into the unusual mechanism of this process. The success of these approaches highlights the power of small molecule screens in antiviral drug discovery and establishes arenavirus membrane fusion as a robust drug target. These broad screenings have been complemented by strategies targeting cellular factors involved in productive arenavirus infection. Approaches targeting the cellular protease implicated in maturation of the fusion-active viral envelope glycoprotein identified the proteolytic processing of the arenavirus glycoprotein precursor as a novel and promising target for anti-arenaviral strategies.

  10. The Broad Way

    ERIC Educational Resources Information Center

    Butler, Kevin

    2008-01-01

    In the world of corporate philanthropy, there are those who give to educational causes, and this article describes one such philanthropist, Eli Broad, who shares his take on schools in America. Broad is in a category unto himself not only because of the amount of money he has given--more than $280 million since 1999--but also for his unique…

  11. The Broad Foundations, 2006

    ERIC Educational Resources Information Center

    Broad Foundation, 2006

    2006-01-01

    The mission of the Broad Foundations is to transform K-12 urban public education through better governance, management, labor relations and competition; make significant contributions to advance major scientific and medical research; foster public appreciation of contemporary art by increasing access for audiences worldwide; and lead and…

  12. Broad Bandwidth Telecommunications Systems.

    ERIC Educational Resources Information Center

    Sodolski, John

    Broad bandwidth transmission systems have been around for years. They include microwave, assorted cable systems, and recently, satellites. With the exception of some privately owned systems, broadband services have been furnished by the common carriers. Recently, a new element has been added--Cable Antenna Television (CATV) distribution systems.…

  13. Broad-band beam buncher

    DOEpatents

    Goldberg, David A.; Flood, William S.; Arthur, Allan A.; Voelker, Ferdinand

    1986-01-01

    A broad-band beam buncher is disclosed, comprising an evacuated housing, an electron gun therein for producing an electron beam, a buncher cavity having entrance and exit openings through which the beam is directed, grids across such openings, a source providing a positive DC voltage between the cavity and the electron gun, a drift tube through which the electron beam travels in passing through such cavity, grids across the ends of such drift tube, gaps being provided between the drift tube grids and the entrance and exit grids, a modulator for supplying an ultrahigh frequency modulating signal to the drift tube for producing velocity modulation of the electrons in the beam, a drift space in the housing through which the velocity modulated electron beam travels and in which the beam is bunched, and a discharge opening from such drift tube and having a grid across such opening through which the bunched electron beam is discharged into an accelerator or the like. The buncher cavity and the drift tube may be arranged to constitute an extension of a coaxial transmission line which is employed to deliver the modulating signal from a signal source. The extended transmission line may be terminated in its characteristic impedance to afford a broad-band response and the device as a whole designed to effect broad-band beam coupling, so as to minimize variations of the output across the response band.

  14. Broad band waveguide spectrometer

    DOEpatents

    Goldman, Don S.

    1995-01-01

    A spectrometer for analyzing a sample of material utilizing a broad band source of electromagnetic radiation and a detector. The spectrometer employs a waveguide possessing an entry and an exit for the electromagnetic radiation emanating from the source. The waveguide further includes a surface between the entry and exit portions which permits interaction between the electromagnetic radiation passing through the wave guide and a sample material. A tapered portion forms a part of the entry of the wave guide and couples the electromagnetic radiation emanating from the source to the waveguide. The electromagnetic radiation passing from the exit of the waveguide is captured and directed to a detector for analysis.

  15. Mapping of the Tacaribe Arenavirus Z-Protein Binding Sites on the L Protein Identified both Amino Acids within the Putative Polymerase Domain and a Region at the N Terminus of L That Are Critically Involved in Binding▿

    PubMed Central

    Wilda, Maximiliano; Lopez, Nora; Casabona, Juan Cruz; Franze-Fernandez, Maria T.

    2008-01-01

    Tacaribe virus (TacV) is the prototype of the New World group of arenaviruses. The TacV genome encodes four proteins: the nucleoprotein (N), the glycoprotein precursor, the polymerase (L), and a RING finger protein (Z). Using a reverse genetics system, we demonstrated that TacV N and L are sufficient to drive transcription and replication mediated by TacV-like RNAs and that Z is a powerful inhibitor of these processes (Lopez et al., J. Virol. 65:12241-12251, 2001). More recently, we provided the first evidence of an interaction between Z and L and showed that Z's inhibitory activity was dependent on its ability to bind to L (Jácamo et al., J. Virol. 77:10383-10393, 2003). In the present study, we mapped the TacV Z-binding sites on the 2,210-amino-acid L polymerase. To that end, we performed deletion analysis and point mutations of L and studied the Z-L interaction by coimmunoprecipitation with specific sera. We found that the C-terminal region of L was not essential for the interaction and identified two noncontiguous regions that were critical for binding: one at the N-terminus of L between residues 156 and 292 and a second one in the polymerase domain (domain III). The importance of domain III in binding was revealed by substitutions in D1188 and H1189 within motif A and in each residue of the conserved SDD sequence (residues 1328, 1329, and 1330) within motif C. Our results showed that of the substituted residues, only H1189 and D1329 appeared to be critically involved in binding Z. PMID:18799569

  16. Broad spectrum bioactive sunscreens.

    PubMed

    Velasco, Maria Valéria Robles; Sarruf, Fernanda Daud; Salgado-Santos, Idalina Maria Nunes; Haroutiounian-Filho, Carlos Alberto; Kaneko, Telma Mary; Baby, André Rolim

    2008-11-01

    The development of sunscreens containing reduced concentration of chemical UV filters, even though, possessing broad spectrum effectiveness with the use of natural raw materials that improve and infer UV absorption is of great interest. Due to the structural similarities between polyphenolic compounds and organic UV filters, they might exert photoprotection activity. The objective of the present research work was to develop bioactive sunscreen delivery systems containing rutin, Passiflora incarnata L. and Plantago lanceolata extracts associated or not with organic and inorganic UV filters. UV transmission of the sunscreen delivery system films was performed by using diffuse transmittance measurements coupling to an integrating sphere. In vitro photoprotection efficacy was evaluated according to the following parameters: estimated sun protection factor (SPF); Boot's Star Rating category; UVA/UVB ratio; and critical wavelength (lambda(c)). Sunscreen delivery systems obtained SPF values ranging from 0.972+/-0.004 to 28.064+/-2.429 and bioactive compounds interacted with the UV filters positive and negatively. This behavior may be attributed to: the composition of the delivery system; the presence of inorganic UV filter and quantitative composition of the organic UV filters; and the phytochemical composition of the P. incarnata L. and P. lanceolata extracts. Among all associations of bioactive compounds and UV filters, we found that the broad spectrum sunscreen was accomplished when 1.68% (w/w) P. incarnata L. dry extract was in the presence of 7.0% (w/w) ethylhexyl methoxycinnamate, 2.0% (w/w) benzophenone-3 and 2.0% (w/w) TiO(2). It was demonstrated that this association generated estimated SPF of 20.072+/-0.906 and it has improved the protective defense against UVA radiation accompanying augmentation of the UVA/UVB ratio from 0.49 to 0.52 and lambda(c) from 364 to 368.6nm. PMID:18662760

  17. Broad-band beam buncher

    DOEpatents

    Goldberg, D.A.; Flood, W.S.; Arthur, A.A.; Voelker, F.

    1984-03-20

    A broad-band beam bunther is disclosed, comprising an evacuated housing, an electron gun therein for producing an electron beam, a buncher cavity having entrance and exit openings through which the beam is directed, grids across such openings, a source providing a positive DC voltage between the cavity and the electron gun, a drift tube through which the electron beam travels in passing through such cavity, grids across the ends of such drift tube, gaps being provided between the drift tube grids and the entrance and exit grids, a modulator for supplying an ultrahigh frequency modulating signal to the drift tube for producing velocity modulation of the electrons in the beam, a drift space in the housing through which the velocity modulated electron beam travels and in which the beam is bunched, and a discharge opening from such drift tube and having a grid across such opening through which the bunched electron beam is discharged into an accelerator or the like. The buncher cavity and the drift tube may be arranged to constitute an extension of a coaxial transmission line which is employed to deliver the modulating signal from a signal source. The extended transmission line may be terminated in its characteristic impedance to afford a broad-

  18. The Broad Foundations, 2008

    ERIC Educational Resources Information Center

    Broad Foundation, 2008

    2008-01-01

    This 2008 foundation report provides an opportunity to look back and ahead as the organization reviews what has been accomplished and identifies challenges to be tackled in the future in the areas of education, scientific and medical research, and the arts. Grant making from the perspective of grantees is presented in each area. [This document was…

  19. Broad spectrum solar cell

    DOEpatents

    Walukiewicz, Wladyslaw; Yu, Kin Man; Wu, Junqiao; Schaff, William J.

    2007-05-15

    An alloy having a large band gap range is used in a multijunction solar cell to enhance utilization of the solar energy spectrum. In one embodiment, the alloy is In.sub.1-xGa.sub.xN having an energy bandgap range of approximately 0.7 eV to 3.4 eV, providing a good match to the solar energy spectrum. Multiple junctions having different bandgaps are stacked to form a solar cell. Each junction may have different bandgaps (realized by varying the alloy composition), and therefore be responsive to different parts of the spectrum. The junctions are stacked in such a manner that some bands of light pass through upper junctions to lower junctions that are responsive to such bands.

  20. Broad-spectrum antiviral agents

    PubMed Central

    Zhu, Jun-Da; Meng, Wen; Wang, Xiao-Jia; Wang, Hwa-Chain R.

    2015-01-01

    Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents. PMID:26052325

  1. The RING Domain and the L79 Residue of Z Protein Are Involved in both the Rescue of Nucleocapsids and the Incorporation of Glycoproteins into Infectious Chimeric Arenavirus-Like Particles ▿

    PubMed Central

    Casabona, Juan Cruz; Levingston Macleod, Jesica M.; Loureiro, Maria Eugenia; Gomez, Guillermo A.; Lopez, Nora

    2009-01-01

    Arenaviruses, such as Tacaribe virus (TacV) and its closely related pathogenic Junin virus (JunV), are enveloped viruses with a bipartite negative-sense RNA genome that encodes the nucleocapsid protein (N), the precursor of the envelope glycoprotein complex (GP), the polymerase (L), and a RING finger protein (Z), which is the driving force of arenavirus budding. We have established a plasmid-based system which allowed the successful packaging of TacV-like nucleocapsids along with Z and GP of JunV into infectious virus-like particles (VLPs). By coexpressing different combinations of the system components, followed by biochemical analysis of the VLPs, the requirements for the assembly of both N and GP into particles were defined. We found that coexpression of N with Z protein in the absence of minigenome and other viral proteins was sufficient to recruit N within lipid-enveloped Z-containing VLPs. In addition, whereas GP was not required for the incorporation of N, coexpression of N substantially enhanced the ratio of GP to Z into VLPs. Disruption of the RING structure or mutation of residue L79 to alanine within Z protein, although it had no effect on Z self-budding, severely impaired VLP infectivity. These mutations drastically altered intracellular Z-N interactions and the incorporation of both N and GP into VLPs. Our results support the conclusion that the interaction between Z and N is required for assembly of both the nucleocapsids and the glycoproteins into infectious arenavirus budding particles. PMID:19420075

  2. The RING domain and the L79 residue of Z protein are involved in both the rescue of nucleocapsids and the incorporation of glycoproteins into infectious chimeric arenavirus-like particles.

    PubMed

    Casabona, Juan Cruz; Levingston Macleod, Jesica M; Loureiro, Maria Eugenia; Gomez, Guillermo A; Lopez, Nora

    2009-07-01

    Arenaviruses, such as Tacaribe virus (TacV) and its closely related pathogenic Junin virus (JunV), are enveloped viruses with a bipartite negative-sense RNA genome that encodes the nucleocapsid protein (N), the precursor of the envelope glycoprotein complex (GP), the polymerase (L), and a RING finger protein (Z), which is the driving force of arenavirus budding. We have established a plasmid-based system which allowed the successful packaging of TacV-like nucleocapsids along with Z and GP of JunV into infectious virus-like particles (VLPs). By coexpressing different combinations of the system components, followed by biochemical analysis of the VLPs, the requirements for the assembly of both N and GP into particles were defined. We found that coexpression of N with Z protein in the absence of minigenome and other viral proteins was sufficient to recruit N within lipid-enveloped Z-containing VLPs. In addition, whereas GP was not required for the incorporation of N, coexpression of N substantially enhanced the ratio of GP to Z into VLPs. Disruption of the RING structure or mutation of residue L79 to alanine within Z protein, although it had no effect on Z self-budding, severely impaired VLP infectivity. These mutations drastically altered intracellular Z-N interactions and the incorporation of both N and GP into VLPs. Our results support the conclusion that the interaction between Z and N is required for assembly of both the nucleocapsids and the glycoproteins into infectious arenavirus budding particles. PMID:19420075

  3. Cochlear microphonic broad tuning curves

    NASA Astrophysics Data System (ADS)

    Ayat, Mohammad; Teal, Paul D.; Searchfield, Grant D.; Razali, Najwani

    2015-12-01

    It is known that the cochlear microphonic voltage exhibits much broader tuning than does the basilar membrane motion. The most commonly used explanation for this is that when an electrode is inserted at a particular point inside the scala media, the microphonic potentials of neighbouring hair cells have different phases, leading to cancelation at the electrodes location. In situ recording of functioning outer hair cells (OHCs) for investigating this hypothesis is exceptionally difficult. Therefore, to investigate the discrepancy between the tuning curves of the basilar membrane and those of the cochlear microphonic, and the effect of phase cancellation of adjacent hair cells on the broadness of the cochlear microphonic tuning curves, we use an electromechanical model of the cochlea to devise an experiment. We explore the effect of adjacent hair cells (i.e., longitudinal phase cancellation) on the broadness of the cochlear microphonic tuning curves in different locations. The results of the experiment indicate that active longitudinal coupling (i.e., coupling with active adjacent outer hair cells) only slightly changes the broadness of the CM tuning curves. The results also demonstrate that there is a π phase difference between the potentials produced by the hair bundle and the soma near the place associated with the characteristic frequency based on place-frequency maps (i.e., the best place). We suggest that the transversal phase cancellation (caused by the phase difference between the hair bundle and the soma) plays a far more important role than longitudinal phase cancellation in the broadness of the cochlear microphonic tuning curves. Moreover, by increasing the modelled longitudinal resistance resulting the cochlear microphonic curves exhibiting sharper tuning. The results of the simulations suggest that the passive network of the organ of Corti determines the phase difference between the hair bundle and soma, and hence determines the sharpness of the

  4. Broad interband semiconductor laser diodes

    NASA Astrophysics Data System (ADS)

    Tan, Chee Loon

    A semiconductor laser is a diode device that emits light via stimulated emission. Conventionally, light emitted from a semiconductor laser is spatially coherent or narrowband. The fundamental mechanism of stimulated emission process in general leads only to a single wavelength emission. However, there are some lasers emit light with a broad spectrum or different distinct wavelength subjected to various operating conditions such as external grating configuration with semiconductor laser, diode-pumped self-Q-switch fiber laser, ultrashort pulse excitation, photonic crystal fiber, ultrabroadband solid-state lasers, semiconductor optical amplifier-based multiwavelength tunable fiber lasers, nonlinear crystal, broadband semiconductor laser etc. This type of broadband laser is vital in many practical applications such as optical telecommunications, spectroscopy measurement, imaging technology, etc. Recently, an ultra-broadband semiconductor laser that utilizes intersubband optical transitions via quantum cascade configuration has been realized. Laser action with a Fabry-Perot spectrum covering all wavelengths from 6 to 8 microm simultaneously is demonstrated with this approach. More recently, broadband emission results from interband optical transitions via quantum-dot/dash nanostructures have been demonstrated in a simple p-i-n laser diode structure. To date, this latest approach offers the simplest design by proper engineering of quantized energy states as well as utilizing the high inhomogeneity of the dot/dash nanostructures, which is inherent from self-assembled growth technology. In this dissertation, modeling of semiconductor InGaAs/GaAs quantum-dot broadband laser utilizing the properties of inhomogeneous and homogeneous broadening effects on lasing spectral will be discussed, followed by a detail analysis of another type of broad interband semiconductor laser, which is InAs/InGaAlAs quantum-dash broadband laser. Based on the device characterization results

  5. Broad-Application Test Reactor

    SciTech Connect

    Motloch, C.G.

    1992-05-01

    This report is about a new, safe, and operationally efficient DOE reactor of nuclear research and testing proposed for the early to mid- 21st Century. Dubbed the Broad-Application Test Reactor (BATR), the proposed facility incorporates a multiple-application, multiple-mission design to support DOE programs such as naval reactors and space power and propulsion, as well as research in medical, science, isotope, and electronics arenas. DOE research reactors are aging, and implementing major replacement projects requires long lead times. Primary design drivers include safety, low risk, minimum operation cost, mission flexibility, waste minimization, and long life. Scientists and engineers at the Idaho National Engineering Laboratory are evaluating possible fuel forms, structural materials, reactor geometries, coolants, and moderators.

  6. Interim Report on SNP analysis and forensic microarray probe design for South American hemorrhagic fever viruses, tick-borne encephalitis virus, henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever viruses, Rift Valley fever

    SciTech Connect

    Jaing, C; Gardner, S

    2012-06-05

    The goal of this project is to develop forensic genotyping assays for select agent viruses, enhancing the current capabilities for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the whole genome wide SNP analysis and microarray probe design for forensics characterization of South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.

  7. Broadly tunable picosecond ir source

    DOEpatents

    Campillo, A.J.; Hyer, R.C.; Shapiro, S.L.

    1980-04-23

    A picosecond traveling-wave parametric device capable of controlled spectral bandwidth and wavelength in the infrared is reported. Intense 1.064 ..mu..m picosecond pulses (1) pass through a 4.5 cm long LiNbO/sub 3/ optical parametric oscillator crystal (2) set at its degeneracy angle. A broad band emerges, and a simple grating (3) and mirror (4) arrangement is used to inject a selected narrow-band into a 2 cm long LiNbO/sub 3/ optical parametric amplifier crystal (5) along a second pump line. Typical input energies at 1.064 ..mu..m along both pump lines are 6 to 8 mJ for the oscillator and 10 mJ for the amplifier. This yields 1 mJ of tunable output in the range 1.98 to 2.38 ..mu..m which when down-converted in a 1 cm long CdSe crystal mixer (6) gives 2 ..mu..J of tunable radiation over the 14.8 to 18.5 ..mu..m region. The bandwidth and wavelength of both the 2 and 16 ..mu..m radiation output are controlled solely by the diffraction grating.

  8. Ghost imaging with broad distance

    NASA Astrophysics Data System (ADS)

    Duan, De-Yang; Zhang, Lu; Du, Shao-Jiang; Xia, Yun-Jie

    2015-10-01

    We present a scheme that is able to achieve the ghost imaging with broad distance. The physical nature of our scheme is that the different wavelength beams are separated in free space by an optical media according to the slow light or dispersion principle. Meanwhile, the equality of the optical distance of the two light arms is not violated. The photon correlation is achieved by the rotating ground glass plate (RGGP) and spatial light modulator (SLM), respectively. Our work shows that a monochromic ghost image can be obtained in the case of RGGP. More importantly, the position (or distance) of the object can be ascertained by the color of the image. Thus, the imaging and ranging processes are combined as one process for the first time to the best of our knowledge. In the case of SLM, we can obtain a colored image regardless of where the object is. Project supported by the National Natural Science Foundation of China (Grant Nos. 61178012, 11204156, 11304179, and 11247240), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant Nos. 20133705110001 and 20123705120002), the Scientific Research Foundation for Outstanding Young Scientists of Shandong Province, China (Grant No. BS2013DX034), and the Natural Science Foundation of Shandong Province, China (Grant No. ZR2012FQ024).

  9. Broadly tunable picosecond IR source

    DOEpatents

    Campillo, Anthony J.; Hyer, Ronald C.; Shapiro, Stanley J.

    1982-01-01

    A picosecond traveling-wave parametric device capable of controlled spectral bandwidth and wavelength in the infrared is reported. Intense 1.064 .mu.m picosecond pulses (1) pass through a 4.5 cm long LiNbO.sub.3 optical parametric oscillator crystal (2) set at its degeneracy angle. A broad band emerges, and a simple grating (3) and mirror (4) arrangement is used to inject a selected narrow-band into a 2 cm long LiNbO.sub.3 optical parametric amplifier crystal (5) along a second pump line. Typical input energies at 1.064 .mu.m along both pump lines are 6-8 mJ for the oscillator and 10 mJ for the amplifier. This yields 1 mJ of tunable output in the range 1.98 to 2.38 .mu.m which when down-converted in a 1 cm long CdSe crystal mixer (6) gives 2 .mu.J of tunable radiation over the 14.8 to 18.5 .mu.m region. The bandwidth and wavelength of both the 2 and 16 .mu.m radiation output are controlled solely by the diffraction grating.

  10. Providers issue brief: alternative providers.

    PubMed

    Rothouse, M

    1999-06-29

    Access by managed care plan enrollees, scope of practice issues and fee reimbursement by Medicaid and third parties such as insurance carriers is the engine that drives legislation recognizing alternative health care providers--chiropractors, acupuncturists, physical therapists, naturopaths, massage therapists, homeopaths, and dietitians and nutritionists. PMID:11073386

  11. The 2006 Broad Prize for Urban Education

    ERIC Educational Resources Information Center

    Broad Foundation, 2006

    2006-01-01

    The $1 million Broad Prize in Urban Education is the nation's largest award in K-12 public education. The Broad Prize is given annually by The Broad Foundation in the form of scholarships to urban school districts that demonstrate the greatest overall performance and improvement in student achievement while reducing achievement gaps among ethnic…

  12. 77 FR 50144 - Broad Stakeholder Survey

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-20

    ... SECURITY Broad Stakeholder Survey AGENCY: National Protection and Programs Directorate, DHS. ACTION: 60-day... comments concerning the Broad Stakeholder Survey. DATES: Comments are encouraged and will be accepted until... across the Nation. The Broad Stakeholder Survey is designed to gather stakeholder feedback on...

  13. 78 FR 20119 - Broad Stakeholder Survey

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-03

    ... SECURITY Broad Stakeholder Survey AGENCY: National Protection and Programs Directorate, DHS. ACTION: 30-day... soliciting comments concerning the Broad Stakeholder Survey. DHS previously published this ICR in the Federal... responders across the Nation. The Broad Stakeholder Survey is designed to gather stakeholder feedback on...

  14. Jupiter's Temperatures--Broad Latitude

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This is one of the highest resolution images ever recorded of Jupiter's temperature field. It was obtained by NASA's Galileo mission, with its Photopolarimeter-Radiometer (PPR) experiment, during the seventh of its 10 orbits around Jupiter to date. This map, shown in the left panel, indicates the forces powering Jovian winds, and differentiates between areas of strongest upwelling and downwelling winds in the upper part of the atmosphere. A Hubble Space Telescope Planetary Camera color composite of this same region, taken within 10 hours of the PPR map, is shown in the right panel for the same region, as a reference to the visual clouds. An outline of the region mapped by the PPR is also shown.

    This atmospheric observation covered a broad latitude region, and it shows that the visually dark regions generally have warmer temperatures than the visually light ones, indicating that they are regions of downwelling, dry air which clear out cloud condensate particles. The 'little red spot' at the northernmost part of this image is colder than its surroundings, consistent with it being a region of upwelling and cooling gas. The smaller spots to its southeast (lower right) and other lighter spots in the HST image are all colder than their surroundings, consistent with regions of upwelling and cooling gas. The northern half of the brightest band in the map is brighter than the southern half, and it reveals some detailed structure, down to the 1900- kilometer (1200-mile) resolution of the PPR, which is not always readily correlated with variations of the visual cloud field.

    One surprise of this temperature map involved temperatures near the dark blue-gray feature in the map, an area like the one into which the Probe descended. While large regions of downwelling wind heat the local area elsewhere in Jupiter, this region of vigorous downwelling appears close to being thermally neutral. The drying, downwelling winds may be deeper in the atmosphere than sensed by the PPR

  15. Oblique incidence for broad monoenergetic proton beams

    SciTech Connect

    Jette, David; Yuan Jiankui; Chen Weimin

    2010-11-15

    Purpose: The depth dose of a monoenergetic broad parallel proton beam has been modeled in a number of ways, but evidently not yet for oblique incidence. The purpose of this investigation is to find an accurate analytic formula for this case, which can then be used to model the depth dose of a broad beam with an initial Gaussian angular distribution. Methods: The Bortfeld model of depth dose in a broad normally incident proton beam has been extended to the case of oblique incidence. This extension uses an empirically determined Gaussian parameter {sigma}{sub x} which (roughly) characterizes the off-axis dose of a proton pencil beam. As with Bortfeld's work, the modeling is done in terms of parabolic cylinder functions. To obtain the depth dose for an initial angular distribution, the result is integrated over the angle of incidence, weighted by a Gaussian probability function. The predictions of the theory have been compared to MCNPX Monte Carlo calculations for four phantom materials (water, bone, aluminum, and copper) and for initial proton energies of 50, 100, 150, 200, and 250 MeV. Results: Comparisons of the depth dose predicted by this theory with Monte Carlo calculations have established that with very good accuracy, {sigma}{sub x} can be taken to be independent both of the depth and of the angle of incidence. As a function of initial proton range or of initial proton energy, {sigma}{sub x} has been found to obey a power law to very high accuracy. Good fits to Monte Carlo calculations have also been found for an initial Gaussian angular distribution. Conclusions: This investigation is the first step in the accurate modeling of a proton pencil beam with initial Gaussian angular distribution. It provides the longitudinal factor, with its Bragg peak buildup and sharp distal falloff. A transverse factor must still be incorporated into this theory and this will give the lateral penumbra of a collimated proton beam. Also, it will be necessary to model the dose of

  16. Development of broad-view camera unit for laparoscopic surgery.

    PubMed

    Kawahara, Tomohiro; Takaki, Takeshi; Ishii, Idaku; Okajima, Masazumi

    2009-01-01

    A disadvantage of laparoscopic surgery is the narrow operative field provided by the endoscope camera. This paper describes a newly developed broad-view camera unit for use with the Broad-View Camera System, which is capable of providing a wider view of the internal organs during laparoscopic surgery. The developed camera unit is composed of a miniature color CMOS camera, an indwelling needle, and an extra-thin connector. The specific design of the camera unit and the method for positioning it are shown. The performance of the camera unit has been confirmed through basic and animal experiments. PMID:19963983

  17. The 2007 Broad Prize for Urban Education

    ERIC Educational Resources Information Center

    Broad Foundation, 2007

    2007-01-01

    The $1 million Broad Prize in Urban Education, the nation's largest K-12 public education award given annually by The Broad Foundation, is awarded to urban school districts that demonstrate the greatest overall performance and improvement in student achievement while reducing income and ethnic achievement gaps. One hundred of the largest urban…

  18. Broad Prize: Do the Successes Spread?

    ERIC Educational Resources Information Center

    Samuels, Christina A.

    2011-01-01

    When the Broad Prize for Urban Education was created in 2002, billionaire philanthropist Eli Broad said he hoped the awards, in addition to rewarding high-performing school districts, would foster healthy competition; boost the prestige of urban education, long viewed as dysfunctional; and showcase best practices. Over the 10 years the prize has…

  19. Academic Ranking of World Universities by Broad Subject Fields

    ERIC Educational Resources Information Center

    Cheng, Ying; Liu, Nian Cai

    2007-01-01

    Upon numerous requests to provide ranking of world universities by broad subject fields/schools/colleges and by subject fields/programs/departments, the authors present the ranking methodologies and problems that arose from the research by the Institute of Higher Education, Shanghai Jiao Tong University on the Academic Ranking of World…

  20. Magnetohydrodynamic stability of broad line region clouds

    NASA Astrophysics Data System (ADS)

    Krause, Martin; Schartmann, Marc; Burkert, Andreas

    2012-10-01

    Hydrodynamic stability has been a longstanding issue for the cloud model of the broad line region in active galactic nuclei. We argue that the clouds may be gravitationally bound to the supermassive black hole. If true, stabilization by thermal pressure alone becomes even more difficult. We further argue that if magnetic fields are present in such clouds at a level that could affect the stability properties, they need to be strong enough to compete with the radiation pressure on the cloud. This would imply magnetic field values of a few gauss for a sample of active galactic nuclei we draw from the literature. We then investigate the effect of several magnetic configurations on cloud stability in axisymmetric magnetohydrodynamic simulations. For a purely azimuthal magnetic field which provides the dominant pressure support, the cloud first gets compressed by the opposing radiative and gravitational forces. The pressure inside the cloud then increases, and it expands vertically. Kelvin-Helmholtz and column density instabilities lead to a filamentary fragmentation of the cloud. This radiative dispersion continues until the cloud is shredded down to the resolution level. For a helical magnetic field configuration, a much more stable cloud core survives with a stationary density histogram which takes the form of a power law. Our simulated clouds develop sub-Alfvénic internal motions on the level of a few hundred km s-1.

  1. Can Broad Consent be Informed Consent?

    PubMed

    Sheehan, Mark

    2011-11-01

    In biobanks, a broader model of consent is often used and justified by a range of different strategies that make reference to the potential benefits brought by the research it will facilitate combined with the low level of risk involved (provided adequate measures are in place to protect privacy and confidentiality) or a questioning of the centrality of the notion of informed consent. Against this, it has been suggested that the lack of specific information about particular uses of the samples means that such consent cannot be fully autonomous and so is unethical. My answer to the title question is a definite 'yes'. Broad consent can be informed consent and is justified by appeal to the principle of respect for autonomy. Indeed, I will suggest that the distinction between the various kinds of consent is not a distinction between kinds of consent but between the kinds of choice a person makes. When an individual makes a choice (of any kind) it is important that they do so according to the standards of informed consent and consistent with the choice that they are making. PMID:22102849

  2. Influenza virus antigenicity and broadly neutralizing epitopes

    PubMed Central

    Air, Gillian M.

    2015-01-01

    A vaccine formulation that would be effective against all strains of influenza virus has long been a goal of vaccine developers, but antibodies after infection or vaccination were seen to be strain specific and there was little evidence of cross-reactive antibodies that neutralized across subtypes. Recently a number of broadly neutralizing monoclonal antibodies have been characterized. This review describes the different classes of broadly neutralizing antibodies and discusses the potential of their therapeutic use or for design of immunogens that induce a high proportion of broadly neutralizing antibodies. PMID:25846699

  3. Broad area search for regions and objects of interest

    SciTech Connect

    Skurikhin, Alexei N; Pope, Paul A

    2011-01-12

    A quad chart provides an overview on the on-going project 'Broad Area Search for Regions and Objects of Interest' funded by the DOE Office of Nonproliferation and Verification Research and Development. Specifically, the quad chart shows: (1) Project title 'Broad Area Search for Regions and Objects of Interest'; (2) PI and Co-investigators; (3) Concept Panel outlining the project's approach built upon front-end scale-space image analysis; (4) Technical Challenges posed by the project, such as robustness, non-conformities, disparate spatial configuration and weak correlation between presence of objects of interest and low-level description of the surrounding geospatial background; and (5) Planned Accomplishment.

  4. Broad Area Cooler Concepts for Cryogenic Propellant Tanks

    NASA Technical Reports Server (NTRS)

    Christie, R. J.; Tomsik, T. M.; Elchert, J. P.; Guzik, M. C.

    2011-01-01

    Numerous studies and ground tests have shown that broad area cooling (also known as distributed cooling) can reduce or eliminate cryogenic propellant boil-off and enable long duration storage in space. Various combinations of cryocoolers, circulators, heat exchangers and other hardware could be used to build the system. In this study, several configurations of broad area cooling systems were compared by weighing hardware combinations, input power requirements, component availability, and Technical Readiness Level (TRL). The preferred system has a high TRL and can be scaled up to provide cooling capacities on the order of 150W at 90K

  5. Formation of broad Balmer wings in symbiotic stars

    NASA Astrophysics Data System (ADS)

    Chang, Seok-Jun; Heo, Jeong-Eun; Hong, Chae-Lin; Lee, Hee-Won

    2016-07-01

    Symbiotic stars are binary systems composed of a hot white dwarf and a mass losing giant. In addition to many prominent emission lines symbiotic stars exhibit Raman scattered O VI features at 6825 and 7088 Å. Another notable feature present in the spectra of many symbiotics is the broad wings around Balmer lines. Astrophysical mechanisms that can produce broad wings include Thomson scattering by free electrons and Raman scattering of Ly,β and higher series by neutral hydrogen. In this poster presentation we produce broad wings around Hα and H,β adopting a Monte Carlo techinique in order to make a quantitative comparison of these two mechanisms. Thomson wings are characterized by the exponential cutoff given by the termal width whereas the Raman wings are dependent on the column density and continuum shape in the far UV region. A brief discussion is provided.

  6. OPLS3: A Force Field Providing Broad Coverage of Drug-like Small Molecules and Proteins.

    PubMed

    Harder, Edward; Damm, Wolfgang; Maple, Jon; Wu, Chuanjie; Reboul, Mark; Xiang, Jin Yu; Wang, Lingle; Lupyan, Dmitry; Dahlgren, Markus K; Knight, Jennifer L; Kaus, Joseph W; Cerutti, David S; Krilov, Goran; Jorgensen, William L; Abel, Robert; Friesner, Richard A

    2016-01-12

    The parametrization and validation of the OPLS3 force field for small molecules and proteins are reported. Enhancements with respect to the previous version (OPLS2.1) include the addition of off-atom charge sites to represent halogen bonding and aryl nitrogen lone pairs as well as a complete refit of peptide dihedral parameters to better model the native structure of proteins. To adequately cover medicinal chemical space, OPLS3 employs over an order of magnitude more reference data and associated parameter types relative to other commonly used small molecule force fields (e.g., MMFF and OPLS_2005). As a consequence, OPLS3 achieves a high level of accuracy across performance benchmarks that assess small molecule conformational propensities and solvation. The newly fitted peptide dihedrals lead to significant improvements in the representation of secondary structure elements in simulated peptides and native structure stability over a number of proteins. Together, the improvements made to both the small molecule and protein force field lead to a high level of accuracy in predicting protein-ligand binding measured over a wide range of targets and ligands (less than 1 kcal/mol RMS error) representing a 30% improvement over earlier variants of the OPLS force field. PMID:26584231

  7. Broad-Spectrum Solution-Processed Photovoltaics

    NASA Astrophysics Data System (ADS)

    Ip, Alexander Halley

    High global demand for energy coupled with dwindling fossil fuel supply has driven the development of sustainable energy sources such as solar photovoltaics. Emerging solar technologies aim for low-cost, solution-processable materials which would allow wide deployment. Colloidal quantum dots (CQDs) are such a materials system which exhibits the ability to absorb across the entire solar spectrum, including in the infrared where many technologies cannot harvest photons. However, due to their nanocrystalline nature, CQDs are susceptible to surface-associated electronic traps which greatly inhibit performance. In this thesis, surface engineering of CQDs is presented through a combined ligand approach which improves the passivation of surface trap states. A metal halide treatment is found to passivate quantum dot surfaces in solution, while bifunctional organic ligands produce a dense film in solid state. This approach reduced midgap trap states fivefold compared with conventional passivation strategies and led to solar cells with a record certified 7.0% power conversion efficiency. The effect of this process on the electronic structure is studied through photoelectron spectroscopy. It is found that while the halide provides deep trap passivation, the nature of the metal cation on the CQD surface affects the density of band tail states. This effect is explored further through a wide survey of materials, and it is found that the coordination ability of the metal cation is responsible for the suppression of shallow traps. With this understanding of CQD surface passivation, broad spectral usage is then explored through a study of visible-absorbing organolead halide perovskite materials as well as narrow-bandgap CQD solar cells. Control over growth conditions and modification of electrode interfaces resulted in efficient perovskite devices with effective usages of visible photons. For infrared-absorbing CQDs, it is found that, in addition to providing surface trap

  8. Silicon micromachined broad band light source

    NASA Technical Reports Server (NTRS)

    George, Thomas (Inventor); Jones, Eric (Inventor); Tuma, Margaret L. (Inventor); Eastwood, Michael (Inventor); Hansler, Richard (Inventor)

    2004-01-01

    A micro electromechanical system (MEMS) broad band incandescent light source includes three layers: a top transmission window layer; a middle filament mount layer; and a bottom reflector layer. A tungsten filament with a spiral geometry is positioned over a hole in the middle layer. A portion of the broad band light from the heated filament is reflective off the bottom layer. Light from the filament and the reflected light of the filament are transmitted through the transmission window. The light source may operate at temperatures of 2500 K or above. The light source may be incorporated into an on board calibrator (OBC) for a spectrometer.

  9. Teaching the Broad, Interdisciplinary Impact of Evolution

    ERIC Educational Resources Information Center

    Benson, David; Atlas, Pierre; Haberski, Raymond; Higgs, Jamie; Kiley, Patrick; Maxwell, Michael, Jr.; Mirola, William; Norton, Jamey

    2009-01-01

    As perhaps the most encompassing idea in biology, evolution has impacted not only science, but other academic disciplines as well. The broad, interdisciplinary impact of evolution was the theme of a course taught at Marian College, Indianapolis, Indiana in 2002, 2004, and 2006. Using a strategy that could be readily adopted at other institutions,…

  10. Education and Broad Concepts of Agency

    ERIC Educational Resources Information Center

    Winch, Christopher

    2014-01-01

    Drawing on recent debates about the relationship between propositional and practical knowledge, this article is concerned with broad concepts of agency. Specifically, it is concerned with agency that involves the forming and putting into effect of intentions over relatively extended periods, particularly in work contexts (called, for want of a…

  11. Giant Broad Line Regions in Dwarf Seyferts

    NASA Astrophysics Data System (ADS)

    Devereux, Nicholas A.

    2016-01-01

    High angular resolution spectroscopy obtained with the Hubble Space Telescope has revealed a remarkable population of galaxies hosting dwarf Seyfert nuclei with an unusually large broad-line region (BLR). These objects are remarkable for two reasons. Firstly, the size of the BLR can, in some cases, rival those seen in the most luminous quasars. Secondly, the size of the BLR is not correlated with the central continuum luminosity, an observation that distinguishes them from their reverberating counterparts. Collectively, these early results suggest that non-reverberating dwarf Seyferts are a heterogeneous group and not simply scaled versions of each other. Careful inspection reveals broad H Balmer emission lines with single peaks, double peaks, and a combination of the two, suggesting that the broad emission lines are produced in kinematically distinct regions centered on the black hole (BH). Because the gravitational field strength is already known for these objects, by virtue of knowing their BH mass, the relationship between velocity and radius may be established, given a kinematic model for the BLR gas. In this way, one can determine the inner and outer radii of the BLRs by modeling the shape of their broad emission line profiles. In the present contribution, high quality spectra obtained with the Space Telescope Imaging Spectrograph are used to constrain the size of the BLR in the dwarf Seyfert nuclei of M81, NGC 3998, NGC 4203, NGC 3227, NGC 4051, and NGC 3516.

  12. Giant Broad Line Regions in Dwarf Seyferts

    NASA Astrophysics Data System (ADS)

    Devereux, Nick

    2015-12-01

    High angular resolution spectroscopy obtained with the Hubble Space Telescope (HST) has revealed a remarkable population of galaxies hosting dwarf Seyfert nuclei with an unusually large broad-line region (BLR). These objects are remarkable for two reasons. Firstly, the size of the BLR can, in some cases, rival those seen in the most luminous quasars. Secondly, the size of the BLR is not correlated with the central continuum luminosity, an observation that distinguishes them from their reverberating counterparts. Collectively, these early results suggest that non-reverberating dwarf Seyferts are a heterogeneous group, and not simply scaled versions of each other. Careful inspection reveals broad H Balmer emission lines with single peaks, double peaks, and a combination of the two, suggesting that the broad emission lines are produced in kinematically distinct regions centered on the black hole (BH). Because the gravitational field strength is already known for these objects, by virtue of knowing their BH mass, the relationship between velocity and radius may be established, given a kinematic model for the BLR gas. In this way, one can determine the inner and outer radii of the BLRs by modeling the shape of their broad emission line profiles. In the present contribution, high quality spectra obtained with the Space Telescope Imaging Spectrograph (STIS) are used to constrain the size of the BLR in the dwarf Seyfert nuclei of M81, NGC 3998, NGC 4203, NGC 3227, NGC 4051 and NGC 3516.

  13. The GREGOR Broad-Band Imager

    NASA Astrophysics Data System (ADS)

    von der Lühe, O.; Volkmer, R.; Kentischer, T. J.; Geißler, R.

    2012-11-01

    The design and characteristics of the Broad-Band Imager (BBI) of GREGOR are described. BBI covers the visible spectral range with two cameras simultaneously for a large field and with critical sampling at 390 nm, and it includes a mode for observing the pupil in a Foucault configuration. Samples of first-light observations are shown.

  14. DIVA defense: Broad protection for salmonella suppression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A live, attenuated Salmonella enterica serovar Typhimurium vaccine was developed to confer broad protection against multiple Salmonella serovars to prevent disease and reduce pathogen colonization and shedding. Two vaccine trials were performed in swine to determine the protection afforded by the va...

  15. 21. Providence & Worchester RR: Freight house. Providence, Providence Co., ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. Providence & Worchester RR: Freight house. Providence, Providence Co., RI. Sec. 4119, mp 185.66 (See HAER no. RI-3 for further documentation on this site.) - Northeast Railroad Corridor, Amtrak route between CT & MA state lines, Providence, Providence County, RI

  16. Broad-spectrum antivirals against viral fusion

    PubMed Central

    Vigant, Frederic; Santos, Nuno C.; Lee, Benhur

    2015-01-01

    Effective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This ‘one bug–one drug’ approach to antiviral drug development can be successful, but it may be inadequate for responding to an increasing diversity of viruses that cause significant diseases in humans. The majority of viral pathogens that cause emerging and re-emerging infectious diseases are membrane-enveloped viruses, which require the fusion of viral and cell membranes for virus entry. Therefore, antivirals that target the membrane fusion process represent new paradigms for broad-spectrum antiviral discovery. In this Review, we discuss the mechanisms responsible for the fusion between virus and cell membranes and explore how broad-spectrum antivirals target this process to prevent virus entry. PMID:26075364

  17. A broad-band scalar vortex coronagraph

    NASA Astrophysics Data System (ADS)

    Errmann, R.; Minardi, S.; Pertsch, T.

    2013-10-01

    Broad-band coronagraphy with deep nulling and small inner working angle has the potential of delivering images and spectra of exoplanets and other faint objects. In recent years, many coronagraphic schemes have been proposed, the most promising being the optical vortex phase mask coronagraphs. In this paper, a new scheme of broad-band optical scalar vortex coronagraph is proposed and characterized experimentally in the laboratory. Our setup employs a pair of computer-generated phase gratings (one of them containing a singularity) to control the chromatic dispersion of phase plates and achieves a constant peak-to-peak attenuation below 1 × 10-3 over a bandwidth of 120 nm centred at 700 nm. An inner working angle of ˜λ/D is demonstrated along with a raw contrast of 11.5 mag at 2λ/D.

  18. Broad-band UHF dipole array

    NASA Technical Reports Server (NTRS)

    Bailey, M. C.

    1985-01-01

    A 6X6 array of fan-dipoles was designed to operate in the 510 to 660 MHz frequency range for aircraft flight test and evaluation of a UHF radiometer system. A broad-band dipole design operating near the first resonance is detailed. Measured VSWR and radiation patterns for the dipole array demonstrate achievable bandwidths in the 35 percent to 40 percent range.

  19. Relativistic redshifts in quasar broad lines

    SciTech Connect

    Tremaine, Scott; Shen, Yue; Liu, Xin; Loeb, Abraham E-mail: yshen@obs.carnegiescience.edu E-mail: aloeb@cfa.harvard.edu

    2014-10-10

    The broad emission lines commonly seen in quasar spectra have velocity widths of a few percent of the speed of light, so special- and general-relativistic effects have a significant influence on the line profile. We have determined the redshift of the broad Hβ line in the quasar rest frame (determined from the core component of the [O III] line) for over 20,000 quasars from the Sloan Digital Sky Survey Data Release 7 quasar catalog. The mean redshift as a function of line width is approximately consistent with the relativistic redshift that is expected if the line originates in a randomly oriented Keplerian disk that is obscured when the inclination of the disk to the line of sight exceeds ∼30°-45°, consistent with simple active galactic nucleus unification schemes. This result also implies that the net line-of-sight inflow/outflow velocities in the broad-line region are much less than the Keplerian velocity when averaged over a large sample of quasars with a given line width.

  20. 8. The entire south face of the Broad Street bridge ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. The entire south face of the Broad Street bridge as seen from the flood levy in front of Central High School. - Broad Street Bridge, Spanning Scioto River at U.S. Route 40 (Broad Street), Columbus, Franklin County, OH

  1. Broad-band acoustic Doppler current profiler

    USGS Publications Warehouse

    Cobb, E.D.

    1993-01-01

    The broad-band acoustic Doppler current profiler is an instrument that determines velocity based on the Doppler principle by reflecting acoustic signals off sediment particles in the water. The instrument is capable of measuring velocity magnitude and direction throughout a water column and of measuring water depth. It is also capable of bottom tracking and can, therefore, keep track of its own relative position as it is moved across a channel. Discharge measurements can be made quickly and, based on limited tests, accurately with this instrument. ?? 1993.

  2. Broad spectrum antibiotic compounds and use thereof

    DOEpatents

    Koglin, Alexander; Strieker, Matthias

    2016-07-05

    The discovery of a non-ribosomal peptide synthetase (NRPS) gene cluster in the genome of Clostridium thermocellum that produces a secondary metabolite that is assembled outside of the host membrane is described. Also described is the identification of homologous NRPS gene clusters from several additional microorganisms. The secondary metabolites produced by the NRPS gene clusters exhibit broad spectrum antibiotic activity. Thus, antibiotic compounds produced by the NRPS gene clusters, and analogs thereof, their use for inhibiting bacterial growth, and methods of making the antibiotic compounds are described.

  3. Broadly neutralizing antibodies against influenza viruses

    PubMed Central

    Laursen, Nick S.; Wilson, Ian A.

    2014-01-01

    Despite available antivirals and vaccines, influenza infections continue to be a major cause of mortality worldwide. Vaccination generally induces an effective, but strain-specific antibody response. As the virus continually evolves, new vaccines have to be administered almost annually when a novel strain becomes dominant. Furthermore, the sporadic emerging resistance to neuraminidase inhibitors among circulating strains suggests an urgent need for new therapeutic agents. Recently, several cross-reactive antibodies have been described, which neutralize an unprecedented spectrum of influenza viruses. These broadly neutralizing antibodies generally target conserved functional regions on the major influenza surface glycoprotein hemagglutinin (HA). The characterization of their neutralization breadth and epitopes on HA could stimulate the development of new antibody-based antivirals and broader influenza vaccines. PMID:23583287

  4. Broad specification fuels technology program, phase 1

    NASA Technical Reports Server (NTRS)

    Lohmann, R. P.; Jeroszko, R. A.

    1982-01-01

    An experimental evaluation was conducted to assess the impact of the use of broadened properties fuels on combustor design concepts. Emphasis was placed on establishing the viability of design modifications to current combustor concepts and the use of advanced technology concepts to facilitate operation on Experimental Referee Broad Specification (ERBS) fuel while meeting exhaust emissions and performance specifications and maintaining acceptable durability. Three different combustor concepts, representative of progressively more aggressive technology levels, were evaluated. When operated on ERBS rather than Jet A fuel, a single stage combustor typical of that in the most recent versions of the JT9D-7 engine was found to produce excess carbon monoxide emissions at idle and elevated liner temperatures at high power levels that were projected to reduced liner life by 13 percent. The introduction of improved component technology, such as refined fuel injectors and advanced liner cooling concepts were shown to have the potential of enhancing the fuel flexibility of the single stage combustor.

  5. Ptychography with broad-bandwidth radiation

    SciTech Connect

    Enders, B. Dierolf, M.; Stockmar, M.; Pfeiffer, F.; Cloetens, P.; Thibault, P.

    2014-04-28

    Ptychography, a scanning Coherent Diffractive Imaging (CDI) technique, has quickly gained momentum as a robust method to deliver quantitative images of extended specimens. A current conundrum for the development of X-ray CDI is the conflict between a need for higher flux to reach higher resolutions and the requirement to strongly filter the incident beam to satisfy the tight coherence prerequisite of the technique. Latest developments in algorithmic treatment of ptychographic data indicate that the technique is more robust than initially assumed, so that some experimental limitations can be substantially relaxed. Here, we demonstrate that ptychography can be conducted in conditions that were up to now considered insufficient, using a broad-bandwidth X-ray beam and an integrating scintillator-based detector. Our work shows the wide applicability of ptychography and paves the way to high-throughput, high-flux diffractive imaging.

  6. Broad Western Flows from Arsia Mons

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site]

    As we move futher away from the volcano, the western flows change in appearance. The flows are typically broad, and the surface texture is more subdued than the southern flows. At the bottom of the image a windstreak 'tail' has formed behind a crater. Other dark streaks indicate that strong westward blowing winds occur in this region.

    Image information: VIS instrument. Latitude -9.6, Longitude 227.6 East (132.4 West). 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  7. Broad-Band Activatable White-Opsin

    PubMed Central

    Batabyal, Subrata; Cervenka, Gregory; Ha, Ji Hee; Kim, Young-tae; Mohanty, Samarendra

    2015-01-01

    Currently, the use of optogenetic sensitization of retinal cells combined with activation/inhibition has the potential to be an alternative to retinal implants that would require electrodes inside every single neuron for high visual resolution. However, clinical translation of optogenetic activation for restoration of vision suffers from the drawback that the narrow spectral sensitivity of an opsin requires active stimulation by a blue laser or a light emitting diode with much higher intensities than ambient light. In order to allow an ambient light-based stimulation paradigm, we report the development of a ‘white-opsin’ that has broad spectral excitability in the visible spectrum. The cells sensitized with white-opsin showed excitability at an order of magnitude higher with white light compared to using only narrow-band light components. Further, cells sensitized with white-opsin produced a photocurrent that was five times higher than Channelrhodopsin-2 under similar photo-excitation conditions. The use of fast white-opsin may allow opsin-sensitized neurons in a degenerated retina to exhibit a higher sensitivity to ambient white light. This property, therefore, significantly lowers the activation threshold in contrast to conventional approaches that use intense narrow-band opsins and light to activate cellular stimulation. PMID:26360377

  8. Multimode Broad-Band Patch Antennas

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.

    2003-01-01

    Microstrip patch antennas of a proposed type would be tunable over broad wavelength ranges. These antennas would be attractive for use in a variety of microwave communication systems in which there are requirements for transmission and/or reception at multiple, widely separated frequencies. Prior efforts to construct tunable microstrip patch antennas have involved integration of microstrip circuitry with, variously, ferrite films with magneticfield tuning, solid-state electronic tuning devices, or piezoelectric tuning actuators. Those efforts have been somewhat successful, but have yielded tuning ranges of 20 percent and smaller much smaller than needed in typical practical cases. Like prior microstrip patch antennas (both tunable and non-tunable), the proposed antennas would have instantaneous bandwidths of about 1 percent of their nominal or resonance frequencies. However, these would be tunable over much broader frequency ranges as much as several octaves, depending on specific designs. They could be fabricated relatively simply and inexpensively by use of conventional photolithography, and without need for integration with solid-state electronic or piezoelectric control devices. An antenna as proposed (see figure) would include a microstrip patch radiating element on a thin ferroelectric film on a semiconductor substrate with a ground-plane conductor on the underside of the substrate. The ferroelectric film could be, for example, SrTiO3 with a thickness of the order of 1 or 2 micrometers.

  9. Broad Street elevation of the competition design for the New ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Broad Street elevation of the competition design for the New Masonic Temple, Philadelphia, by architects Collins and Authenrieth, 1867 - Masonic Temple, 1 North Broad Street, Philadelphia, Philadelphia County, PA

  10. Broad spectrum anthelmintic potential of Cassia plants

    PubMed Central

    Kundu, Suman; Roy, Saptarshi; Lyndem, Larisha Mawkhleing

    2014-01-01

    Objective To study the in vitro anthelmintic efficacy of Cassia alata (C. alata), Cassia angustifolia (C. angustifolia) and Cassia occidentalis (C. occidentalis). Methods Crude ethanol extract from leaves of the three plants were prepared in rotary evaporator and different concentrations (10, 20 and 40 mg/mL) of leaf extracts were used for treatment on different representatives of helminthes (Heterakis gallinarum, Raillietina tetragona and Catatropis sp.) from domestic fowl (Gallus gallus domesticus). Loss of motility and death were monitored frequently. Results C. alata showed early paralysis in all worms treated followed by C. angustifolia. C. occidentalis in combination with C. alata together caused early paralysis in all treated worms than the combination of C. alata with C. angustfolia. While Heterakis gallinarum in control survived for (81.33±2.07) h, treated worms lost their motility at (5.71±0.10) h, (6.60±0.86) h and (13.95±0.43) h with C. angustifolia, C. alata and C. occidentalis respectively at a concentration of 40 mg/mL which showed better efficacy than albendazole. Catatropis sp. survival period was (26.49±1.38) h in control, but with plant treatment, it lost its motility in just (0.57±0.08) h, (1.00±0.12) h and (1.47±0.40) h at 40 mg/mL concentration of C. alata, C. angustifolia and C. occidentalis respectively. Raillietina tetragona on the other hand became paralysed at (1.68±0.27) h, (2.95±0.29) h and (4.13±0.31) h with above concentrations treated with three plants respectively, however in control it survived up to (81.93±4.71) h. Conclusions This present study indicated broad spectrum vermifugal activity of all plants tested. PMID:25183125

  11. NATIONAL HEALTH PROVIDER INVENTORY

    EPA Science Inventory

    The National Health Provider Inventory provides data on services, location, staff, capacity, and other characteristics of selected health care providers in the United States. Information is collected via mail questionnaire with telephone follow up to all providers (100% census) o...

  12. MICROLENSING OF QUASAR BROAD EMISSION LINES: CONSTRAINTS ON BROAD LINE REGION SIZE

    SciTech Connect

    Guerras, E.; Mediavilla, E.; Kochanek, C. S.; Munoz, J. A.; Falco, E.; Motta, V.

    2013-02-20

    We measure the differential microlensing of the broad emission lines between 18 quasar image pairs in 16 gravitational lenses. We find that the broad emission lines are in general weakly microlensed. The results show, at a modest level of confidence (1.8{sigma}), that high ionization lines such as C IV are more strongly microlensed than low ionization lines such as H{beta}, indicating that the high ionization line emission regions are more compact. If we statistically model the distribution of microlensing magnifications, we obtain estimates for the broad line region size of r{sub s} = 24{sup +22} {sub -15} and r{sub s} = 55{sup +150} {sub -35} lt-day (90% confidence) for the high and low ionization lines, respectively. When the samples are divided into higher and lower luminosity quasars, we find that the line emission regions of more luminous quasars are larger, with a slope consistent with the expected scaling from photoionization models. Our estimates also agree well with the results from local reveberation mapping studies.

  13. Turbulent boundary layer flow over broad-banded roughness

    NASA Astrophysics Data System (ADS)

    Pawlak, Geno; Aghsaee, Payam; Mazrouei, Saeed; Leonardi, Stefano; Rajagopalan, Krishnakumar; Kobayashi, Marcelo

    2014-11-01

    The response of the boundary layer to a regular roughness is often parameterized in terms of the length scales defining the roughness. Difficulty arises in the case of broad-banded and highly irregular roughness distributions such as over coral reefs or urban canopies where the length scale that determines the response of the boundary layer is not clear. Here we use a spectral description for roughness to create idealized two-dimensional irregular roughness profiles, using square waves as a basis function. Laboratory experiments along with Direct Numerical Simulations (DNS) are used to examine the hydrodynamic response to the broad-banded roughness and flow characteristics are related to geometric characteristics of the boundary. The simulations and experiments show that the nature of the flow over two-dimensional irregular walls can be determined as a function of the hydrodynamic origin, which, in turn, can be determined as a function of a mean cavity shape. Results are interpreted in terms of the spectral characteristics of the roughness. The contribution of the various spectral components to the total drag is analyzed for each case. The roughness spectrum influences the flow through the shape of the cavities on the wall and can provide some guidance in predicting the nature of the flow.

  14. Automatic and controlled processing and the Broad Autism Phenotype.

    PubMed

    Camodeca, Amy; Voelker, Sylvia

    2016-01-30

    Research related to verbal fluency in the Broad Autism Phenotype (BAP) is limited and dated, but generally suggests intact abilities in the context of weaknesses in other areas of executive function (Hughes et al., 1999; Wong et al., 2006; Delorme et al., 2007). Controlled processing, the generation of search strategies after initial, automated responses are exhausted (Spat, 2013), has yet to be investigated in the BAP, and may be evidenced in verbal fluency tasks. One hundred twenty-nine participants completed the Delis-Kaplan Executive Function System Verbal Fluency test (D-KEFS; Delis et al., 2001) and the Broad Autism Phenotype Questionnaire (BAPQ; Hurley et al., 2007). The BAP group (n=53) produced significantly fewer total words during the 2nd 15" interval compared to the Non-BAP (n=76) group. Partial correlations indicated similar relations between verbal fluency variables for each group. Regression analyses predicting 2nd 15" interval scores suggested differentiation between controlled and automatic processing skills in both groups. Results suggest adequate automatic processing, but slowed development of controlled processing strategies in the BAP, and provide evidence for similar underlying cognitive constructs for both groups. Controlled processing was predictive of Block Design score for Non-BAP participants, and was predictive of Pragmatic Language score on the BAPQ for BAP participants. These results are similar to past research related to strengths and weaknesses in the BAP, respectively, and suggest that controlled processing strategy use may be required in instances of weak lower-level skills. PMID:26652842

  15. Absolute calibration for a broad range single shot electron spectrometer

    SciTech Connect

    Glinec, Y.; Faure, J.; Guemnie-Tafo, A.; Malka, V.; Monard, H.; Larbre, J. P.; De Waele, V.; Marignier, J. L.; Mostafavi, M.

    2006-10-15

    This article gives a detailed description of a single shot electron spectrometer which was used to characterize electron beams produced by laser-plasma interaction. Contrary to conventional electron sources, electron beams from laser-plasma accelerators can produce a broad range of energies. Therefore, diagnosing these electron spectra requires specific attention and experimental development. Here, we provide an absolute calibration of the Lanex Kodak Fine screen on a laser-triggered radio frequency picosecond electron accelerator. The efficiency of scintillating screens irradiated by electron beams has never been investigated so far. This absolute calibration is then compared to charge measurements from an integrating current transformer for quasimonoenergetic electron spectra from laser-plasma interaction.

  16. Effective Electron Beam Injection With Broad Energy Initial Beam

    SciTech Connect

    Cooley, J.H.; Hubbard, R.F.; Gordon, D.F.; Ting, A.; Sprangle, P.; Zigler, A.

    2004-12-07

    Laser Wakefield Accelerators (LWFA), in the resonant regime, require use of an injected electron beam. Several optical methods for generating electron bunches exist e.g., Laser Ionization and Ponderomotive Acceleration (LIPA) and Self-Modulated LWFA among others. Each of these schemes produces an electron bunch with a characteristic energy distribution. We examine the trapping characteristics in a resonant LWFA for an injection electron beam with a broad energy spread that can be characterized using a Boltzmann distribution with an 'effective temperature'. We present results of both analytic calculations and simulations which provide a methodology for optimizing the resulting accelerated electron bunch characteristics i.e., energy and energy spread, for a given LWFA configuration.

  17. Molecule formation in quasar broad-line cloud gas

    SciTech Connect

    Kallman, T.; Lepp, S.; Giovannoni, P.

    1987-10-01

    Models for the broad-line emitting clouds of quasars typically assume that the clouds have column densities of at most 10 to the 23rd/sq cm. The consequences of relaxing this assumption are examined, and it is shown that: (1) at slightly larger column densities the gas may cool to about 1000 K as a result of molecule formation; (2) in much of the molecule-forming region the temperature may have either of two values, about 1000 K or 6000-8000 K; (3) the strengths of most observable optical lines, including C II semiforbidden 2326-A lines and Fe II lines, are unaffected by such large column densities; and (4) lines from low-ionization species such as Na I are readily formed at large column densities. Observations of such lines provide evidence for large cloud column densities. 47 references.

  18. Method for detection and imaging over a broad spectral range

    DOEpatents

    Yefremenko, Volodymyr; Gordiyenko, Eduard; Pishko, legal representative, Olga; Novosad, Valentyn; Pishko, deceased; Vitalii

    2007-09-25

    A method of controlling the coordinate sensitivity in a superconducting microbolometer employs localized light, heating or magnetic field effects to form normal or mixed state regions on a superconducting film and to control the spatial location. Electron beam lithography and wet chemical etching were applied as pattern transfer processes in epitaxial Y--Ba--Cu--O films. Two different sensor designs were tested: (i) a 3 millimeter long and 40 micrometer wide stripe and (ii) a 1.25 millimeters long, and 50 micron wide meandering-like structure. Scanning the laser beam along the stripe leads to physical displacement of the sensitive area, and, therefore, may be used as a basis for imaging over a broad spectral range. Forming the superconducting film as a meandering structure provides the equivalent of a two-dimensional detector array. Advantages of this approach are simplicity of detector fabrication, and simplicity of the read-out process requiring only two electrical terminals.

  19. Broadly neutralizing antibodies abrogate established hepatitis C virus infection

    PubMed Central

    de Jong, Ype P.; Dorner, Marcus; Mommersteeg, Michiel C.; Xiao, Jing W.; Balazs, Alejandro B.; Robbins, Justin B.; Winer, Benjamin Y.; Gerges, Sherif; Vega, Kevin; Labitt, Rachael N.; Donovan, Bridget M.; Giang, Erick; Krishnan, Anuradha; Chiriboga, Luis; Charlton, Michael R.; Burton, Dennis R.; Baltimore, David; Law, Mansun; Rice, Charles M.; Ploss, Alexander

    2015-01-01

    Hepatitis C virus (HCV) establishes a chronic infection in the majority of exposed individuals and can cause cirrhosis and hepatocellular carcinoma. The role of antibodies directed against HCV in disease progression is poorly understood. Neutralizing antibodies (nAbs) can prevent HCV infection in vitro and in animal models. However, the effects of nAbs on an established HCV infection are unclear. Here, we demonstrate that three broadly nAbs, AR3A, AR3B and AR4A, delivered with adeno-associated viral (AAV) vectors can confer protection against viral challenge in humanized mice. Furthermore, we provide evidence that nAbs can abrogate an ongoing HCV infection in primary hepatocyte cultures and in a human liver chimeric mouse model. These results showcase a novel therapeutic approach to interfere with HCV infection exploiting a previously unappreciated need for HCV to continuously infect new hepatocytes in order to sustain chronicity. PMID:25232181

  20. Absolute calibration for a broad range single shot electron spectrometer

    NASA Astrophysics Data System (ADS)

    Glinec, Y.; Faure, J.; Guemnie-Tafo, A.; Malka, V.; Monard, H.; Larbre, J. P.; De Waele, V.; Marignier, J. L.; Mostafavi, M.

    2006-10-01

    This article gives a detailed description of a single shot electron spectrometer which was used to characterize electron beams produced by laser-plasma interaction. Contrary to conventional electron sources, electron beams from laser-plasma accelerators can produce a broad range of energies. Therefore, diagnosing these electron spectra requires specific attention and experimental development. Here, we provide an absolute calibration of the Lanex Kodak Fine screen on a laser-triggered radio frequency picosecond electron accelerator. The efficiency of scintillating screens irradiated by electron beams has never been investigated so far. This absolute calibration is then compared to charge measurements from an integrating current transformer for quasimonoenergetic electron spectra from laser-plasma interaction.

  1. Discovery of Potent Broad Spectrum Antivirals Derived from Marine Actinobacteria

    PubMed Central

    Raveh, Avi; Delekta, Phillip C.; Dobry, Craig J.; Peng, Weiping; Schultz, Pamela J.; Blakely, Pennelope K.; Tai, Andrew W.; Matainaho, Teatulohi; Irani, David N.; Sherman, David H.; Miller, David J.

    2013-01-01

    Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable target for the

  2. DISCOVERY OF THE TRANSITION OF A MINI-BROAD ABSORPTION LINE INTO A BROAD ABSORPTION LINE IN THE SDSS QUASAR J115122.14+020426.3

    SciTech Connect

    Hidalgo, Paola Rodriguez; Eracleous, Michael; Charlton, Jane; Hamann, Fred; Murphy, Michael T.; Nestor, Daniel

    2013-09-20

    We present the detection of a rare case of dramatic strengthening in the UV absorption profiles in the spectrum of the quasar J115122.14+020426.3 between observations {approx}2.86 yr apart in the quasar rest frame. A spectrum obtained in 2001 by the Sloan Digital Sky Survey shows a C IV ''mini-broad'' absorption line (FWHM = 1220 km s{sup -1}) with a maximum blueshift velocity of {approx}9520 km s{sup -1}, while a later spectrum from the Very Large Telescope shows a significantly broader and stronger absorption line, with a maximum blueshift velocity of {approx}12, 240 km s{sup -1} that qualifies as a broad absorption line. A similar variability pattern is observed in two additional systems at lower blueshifted velocities and in the Ly{alpha} and N V transitions as well. One of the absorption systems appears to be resolved and shows evidence for partial covering of the quasar continuum source (C{sub f} {approx} 0.65), indicating a transverse absorber size of, at least, {approx}6 Multiplication-Sign 10{sup 16} cm. In contrast, a cluster of narrower C IV lines appears to originate in gas that fully covers the continuum and broad emission line sources. There is no evidence for changes in the centroid velocity of the absorption troughs. This case suggests that at least some of the absorbers that produce ''mini-broad'' and broad absorption lines in quasar spectra do not belong to intrinsically separate classes. Here, the ''mini-broad'' absorption line is most likely interpreted as an intermediate phase before the appearance of a broad absorption line due to their similar velocities. While the current observations do not provide enough constraints to discern among the possible causes for this variability, future monitoring of multiple transitions at high resolution will help achieve this goal.

  3. Glycosylation modulates arenavirus glycoprotein expression and function

    SciTech Connect

    Bonhomme, Cyrille J. Capul, Althea A. Lauron, Elvin J. Bederka, Lydia H. Knopp, Kristeene A. Buchmeier, Michael J.

    2011-01-20

    The glycoprotein of lymphocytic choriomeningitis virus (LCMV) contains nine potential N-linked glycosylation sites. We investigated the function of these N-glycosylations by using alanine-scanning mutagenesis. All the available sites were occupied on GP1 and two of three on GP2. N-linked glycan mutations at positions 87 and 97 on GP1 resulted in reduction of expression and absence of cleavage and were necessary for downstream functions, as confirmed by the loss of GP-mediated fusion activity with T87A and S97A mutants. In contrast, T234A and E379N/A381T mutants impaired GP-mediated cell fusion without altered expression or processing. Infectivity via virus-like particles required glycans and a cleaved glycoprotein. Glycosylation at the first site within GP2, not normally utilized by LCMV, exhibited increased VLP infectivity. We also confirmed the role of the N-linked glycan at position 173 in the masking of the neutralizing epitope GP-1D. Taken together, our results indicated a strong relationship between fusion and infectivity.

  4. Provide, provide: the economics of aging.

    PubMed

    1998-06-26

    Most older persons face two potentially serious economic problems: (a) declining earning power and (b) declining health that can be partly offset by increased utilization of health care. The decline in earning power is largely attributable to physiological changes and to obsolescence of skills and knowledge. These adverse effects are exacerbated by public and private policies that reduce the incentives of older persons to continue work and increase the cost to employers of employing older workers. The problems of earnings replacement and health care payment are usually discussed separately, but there are several reasons why they should be considered together. First, there are often tradeoffs between the two. Money is money, and for most people there is never enough to go around. This is self-evident where private funds are concerned. Low-income elderly, for instance, frequently must choose between expensive prescription drugs and an adequate diet. For middle-income elderly, the choice may be between saving on medigap insurance or forgoing an airplane trip to a grandchild's graduation. Difficult choices are also inherent in the allocation of public funds. The same tax receipts that could be used to maintain or increase retirement benefits could be used to fund additional care, and vice versa. In discussing these tradeoffs, some analysts assert that people will gladly give up other goods and services for medical care that cures illness, relieves pain, or restores function. Others believe that some people would forgo some health insurance in order to maintain access to other goods and services. A second reason for looking at the two problems together is that they pose similar questions for public policy. How much should each generation provide for its own needs in old age, and how much should be provided by the generations that follow? How much provision should be voluntary, how much compulsory? How much intra-generational redistribution is appropriate after age 65

  5. Reproductive compensation in broad-nosed pipefish females.

    PubMed

    Goncalves, Ines Braga; Mobley, Kenyon B; Ahnesjö, Ingrid; Sagebakken, Gry; Jones, Adam G; Kvarnemo, Charlotta

    2010-05-22

    The differential allocation hypothesis assumes that animals should weigh costs and benefits of investing into reproduction with a current mate against the expected quality of future mates, and predicts that they should invest more into reproduction when pairing with a high-quality mate. In the broad-nosed pipefish (Syngnathus typhle), males care for the embryos in a brood pouch and females compete for access to male mating partners. Both sexes prefer mating with large partners. In the present study, we show that the same female provides both large and small mating partners with eggs of similar size, weight and lipid content when mated to two males in succession. Importantly, however, eggs provided to small males (less preferred) had higher egg protein content (11% more) than those provided to large males (preferred). Thus, contrary to the differential allocation hypothesis, eggs did not contain more resources when females mated with a larger male. Instead, the pattern observed in our results is consistent with a compensatory reproductive strategy. PMID:20106851

  6. Ultra-Broad-Band Optical Parametric Amplifier or Oscillator

    NASA Technical Reports Server (NTRS)

    Strekalov, Dmitry; Matsko, Andrey; Savchenkov, Anatolly; Maleki, Lute

    2009-01-01

    A concept for an ultra-broad-band optical parametric amplifier or oscillator has emerged as a by-product of a theoretical study in fundamental quantum optics. The study was originally intended to address the question of whether the two-photon temporal correlation function of light [in particular, light produced by spontaneous parametric down conversion (SPDC)] can be considerably narrower than the inverse of the spectral width (bandwidth) of the light. The answer to the question was found to be negative. More specifically, on the basis of the universal integral relations between the quantum two-photon temporal correlation and the classical spectrum of light, it was found that the lower limit of two-photon correlation time is set approximately by the inverse of the bandwidth. The mathematical solution for the minimum two-photon correlation time also provides the minimum relative frequency dispersion of the down-converted light components; in turn, the minimum relative frequency dispersion translates to the maximum bandwidth, which is important for the design of an ultra-broad-band optical parametric oscillator or amplifier. In the study, results of an analysis of the general integral relations were applied in the case of an optically nonlinear, frequency-dispersive crystal in which SPDC produces collinear photons. Equations were found for the crystal orientation and pump wavelength, specific for each parametric-down-converting crystal, that eliminate the relative frequency dispersion of collinear degenerate (equal-frequency) signal and idler components up to the fourth order in the frequency-detuning parameter

  7. 48 CFR 235.016 - Broad agency announcement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF DEFENSE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 235.016 Broad...), contracting officers shall— (1) Whenever practicable, reserve discrete or severable areas of research...

  8. Using New Media to Reach Broad Audiences

    NASA Astrophysics Data System (ADS)

    Gay, P. L.

    2008-06-01

    The International Year of Astronomy New Media Working Group (IYA NMWG) has a singular mission: To flood the Internet with ways to learn about astronomy, interact with astronomers and astronomy content, and socially network with astronomy. Within each of these areas, we seek to build lasting programs and partnerships that will continue beyond 2009. Our weapon of choice is New Media. It is often easiest to define New Media by what it is not. Television, radio, print and their online redistribution of content are not New Media. Many forms of New Media start as user provided content and content infrastructures that answer that individual's creative whim in a way that is adopted by a broader audience. Classic examples include Blogs and Podcasts. This media is typically distributed through content specific websites and RSS feeds, which allow syndication. RSS aggregators (iTunes has audio and video aggregation abilities) allow subscribers to have content delivered to their computers automatically when they connect to the Internet. RSS technology is also being used in such creative ways as allowing automatically updating Google-maps that show the location of someone with an intelligent GPS system, and in sharing 100 word microblogs from anyone (Twitters) through a single feed. In this poster, we outline how the IYA NMWG plans to use New Media to reach target primary audiences of astronomy enthusiasts, image lovers, and amateur astronomers, as well as secondary audiences, including: science fiction fans, online gamers, and skeptics.

  9. IYA: Using New Media to Reach Broad Audiences

    NASA Astrophysics Data System (ADS)

    Gay, Pamela L.; IYA New Media Working Group

    2007-12-01

    The International Year of Astronomy New Media Working Group (IYA NMWG) seeks to flood the Internet with ways to learn about astronomy and increase interaction among professionals, amateurs, and laypeople. Our primary audiences are amateur astronomers, astronomy and space enthusiasts, and image lovers, but secondary audiences include science fiction fans, online gamers, and skeptics. We aim to build lasting programs and partnerships that will continue beyond 2009. Our weapon of choice is New Media. New Media differ from traditional media (such as television, radio, and print) in their informality. Many forms of New Media start as user-provided content. New Media content-building infrastructures answer the content provider's creative whims, and New-Media content can be commented upon, shared, borrowed, adopted, edited, and re-posted by a broad audience. Classic examples of New Media include blogs and podcasts. This media is typically distributed through content-specific websites and RSS feeds, which allow individual Internet users to select preferred streams of media (including text, audio, and video) to be delivered to them automatically.

  10. Patients' Evaluations of Gynecologic Services Provided by Nurse Practitioners.

    ERIC Educational Resources Information Center

    Wagener, J. Mark; Carter, Glenna

    1978-01-01

    The development, operating principles, and users' evaluations of a broad based gynecologic program emphasizing effective birth control on a university campus are discussed. A major feature explored is the use of nurse practitioners as the primary service providers. (JMF)

  11. Techniques in molecular spectroscopy: from broad bandwidth to high resolution

    NASA Astrophysics Data System (ADS)

    Cossel, Kevin C.

    This thesis presents a range of different experiments all seeking to extended the capabilities of molecular spectroscopy and enable new applications. The new technique of cavity-enhanced direct frequency comb spectroscopy (CE-DFCS) provides a unique combination of broad bandwidth, high resolution, and high sensitivity that can be useful for a wide range of applications. Previous demonstrations of CE-DFCS were confined to the visible or near-infrared and operated over a limited bandwidth: for many applications it is desirable to increase the spectral coverage and to extend to the mid-infrared where strong, fundamental vibrational modes of molecules occur. There are several key requirements for CE-DFCS: a frequency comb source that provides broad bandwidth and high resolution, an optical cavity for high sensitivity, and a detection system capable of multiplex detection of the comb spectrum transmitted through the cavity. We first discuss comb sources with emphasis on the coherence properties of spectral broadening in nonlinear fiber and the development of a high-power frequency comb source in the mid-infrared based on an optical-parametric oscillator (OPO). To take advantage of this new mid-infrared comb source for spectroscopy, we also discuss the development of a rapid-scan Fourier-transform spectrometer (FTS). We then discuss the first demonstration of CE-DFCS with spectrally broadened light from a highly nonlinear fiber with the application to measurements of impurities in semiconductor manufacturing gases. We also cover our efforts towards extending CE-DFCS to the mid-infrared using the mid-infrared OPO and FTS to measure ppb levels of various gases important for breath analysis and atmospheric chemistry and highlight some future applications of this system. In addition to the study of neutral molecules, broad-bandwidth and high-resolution spectra of molecular ions are useful for astrochemistry where many of the observed molecules are ionic, for studying

  12. Assessing Eli Broad's Assault on Public School System Leadership

    ERIC Educational Resources Information Center

    English, Fenwick W.; Crowder, Zan

    2012-01-01

    Eli Broad's approach to reforming urban public education does not recognize his own self-interest in promoting changes within such educational systems, a classic problem of misrecognition. The Broad agenda is an assault on the notion of the mission of public education as a service instead of a for-profit enterprise concerned with making money for…

  13. Boot Camp for Education CEOs: The Broad Foundation Superintendents Academy

    ERIC Educational Resources Information Center

    Jehlen, Alain

    2012-01-01

    The Broad Foundation Superintendents Academy is the most prominent and most controversial training institute for school chiefs. The Academy is the flagship program of the Eli and Edythe Broad Foundation, the smallest of a triumvirate of corporate foundations that are at the heart of the billionaire campaign to remake public education in the image…

  14. Effects of General and Broad Cognitive Abilities on Mathematics Achievement

    ERIC Educational Resources Information Center

    Taub, Gordon E.; Keith, Timothy Z.; Floyd, Randy G.; Mcgrew, Kevin S.

    2008-01-01

    This study investigated the direct and indirect effects of general intelligence and 7 broad cognitive abilities on mathematics achievement. Structural equation modeling was used to investigate the simultaneous effects of both general and broad cognitive abilities on students' mathematics achievement. A hierarchical model of intelligence derived…

  15. 48 CFR 35.016 - Broad agency announcement.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Broad agency announcement. 35.016 Section 35.016 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 35.016 Broad agency announcement. (a) General. This paragraph prescribes...

  16. VIEW EASTACROSS SOUTH BROAD STREET LEFTBUILDING 28 BLACKSMITH SHOP (1885) ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW EAST-ACROSS SOUTH BROAD STREET LEFT-BUILDING 28 BLACKSMITH SHOP (1885) CENTER-REAR-BUILDING 40 WIRE WAREHOUSE (1915) RIGHT-BUILDING 32 MACHINE SHOP (1890) - John A. Roebling's Sons Company & American Steel & Wire Company, South Broad, Clark, Elmer, Mott & Hudson Streets, Trenton, Mercer County, NJ

  17. Social Cognition, Social Skill, and the Broad Autism Phenotype

    ERIC Educational Resources Information Center

    Sasson, Noah J.; Nowlin, Rachel B.; Pinkham, Amy E.

    2013-01-01

    Social-cognitive deficits differentiate parents with the "broad autism phenotype" from non-broad autism phenotype parents more robustly than other neuropsychological features of autism, suggesting that this domain may be particularly informative for identifying genetic and brain processes associated with the phenotype. The current study…

  18. Arizona's Application Service Provider.

    ERIC Educational Resources Information Center

    Jordan, Darla

    2002-01-01

    Describes the U.S.'s first statewide K-12 application service provider (ASP). The ASP, implemented by the Arizona School Facilities Board, provides access to productivity, communications, and education software programs from any Internet-enabled device, whether in the classroom or home. (EV)

  19. Provider 1997 corporate profiles.

    PubMed

    1997-05-01

    As the long term care industry seeks out new products, new solutions, and new ways of providing quality care, it is important for long term care providers to know more about the companies they do business with. The following corporate profiles showcase information about leading companies in the long term health care industry. Some of the areas highlighted include: mission of company, history, product lines, support services. We hope you will find this information useful when making purchasing decisions, and we're confident you'll keep this issue of Provider as a handy reference guide. The information in the following corporate profiles was supplied by the companies. Neither Provider magazine nor the American Health Care Association endorses the products and services listed in this section. Provider magazine and the American Health Care Association disclaim any and all liability related to or arising from the information contained in the profiles. PMID:10166888

  20. Combined PI3K/mTOR and MEK Inhibition Provides Broad Antitumor Activity in Faithful Murine Cancer Models

    PubMed Central

    Roberts, Patrick J.; Usary, Jerry E.; Darr, David B.; Dillon, Patrick M.; Pfefferle, Adam D.; Whittle, Martin C.; Duncan, James S.; Johnson, Soren M.; Combest, Austin J.; Jin, Jian; Zamboni, William C.; Johnson, Gary L.; Perou, Charles M.; Sharpless, Norman E.

    2013-01-01

    Purpose Anticancer drug development is inefficient, but genetically engineered murine models (GEMM) and orthotopic, syngeneic transplants (OST) of cancer may offer advantages to in vitro and xenograft systems. Experimental Design We assessed the activity of 16 treatment regimens in a RAS-driven, Ink4a/Arf-deficient melanoma GEMM. In addition, we tested a subset of treatment regimens in three breast cancer models representing distinct breast cancer subtypes: claudin-low (T11 OST), basal-like (C3-TAg GEMM), and luminal B (MMTV-Neu GEMM). Results Like human RAS-mutant melanoma, the melanoma GEMM was refractory to chemotherapy and single-agent small molecule therapies. Combined treatment with AZD6244 [mitogen-activated protein–extracellular signal-regulated kinase kinase (MEK) inhibitor] and BEZ235 [dual phosphoinositide-3 kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor] was the only treatment regimen to exhibit significant antitumor activity, showed by marked tumor regression and improved survival. Given the surprising activity of the "AZD/BEZ" combination in the melanoma GEMM, we next tested this regimen in the "claudin-low" breast cancer model that shares gene expression features with melanoma. The AZD/BEZ regimen also exhibited significant activity in this model, leading us to testing in even more diverse GEMMs of basal-like and luminal breast cancer. The AZD/BEZ combination was highly active in these distinct breast cancer models, showing equal or greater efficacy compared with any other regimen tested in studies of over 700 tumor-bearing mice. This regimen even exhibited activity in lapatinib-resistant HER2+ tumors. Conclusion These results show the use of credentialed murine models for large-scale efficacy testing of diverse anticancer regimens and predict that combinations of PI3K/mTOR and MEK inhibitors will show antitumor activity in a wide range of human malignancies. PMID:22872574

  1. Back to the Future: Implementing a Broad Economic, Inquiry-Based Approach to Accounting Education

    ERIC Educational Resources Information Center

    Frecka, Thomas J.; Morris, Michael H.; Ramanan, Ramachandran

    2004-01-01

    Motivated by concerns about the quality of accounting education and calls for a broader, more active approach to learning by numerous accounting educators and practitioners over the past 2 decades, the authors of this article sought to provide a framework and example materials to address those issues. The framework makes use of broad, economic…

  2. THE VIEWING ANGLES OF BROAD ABSORPTION LINE VERSUS UNABSORBED QUASARS

    SciTech Connect

    DiPompeo, M. A.; Brotherton, M. S.; De Breuck, C.

    2012-06-10

    It was recently shown that there is a significant difference in the radio spectral index distributions of broad absorption line (BAL) quasars and unabsorbed quasars, with an overabundance of BAL quasars with steeper radio spectra. This result suggests that source orientation does play into the presence or absence of BAL features. In this paper, we provide more quantitative analysis of this result based on Monte Carlo simulations. While the relationship between viewing angle and spectral index does indeed contain a lot of scatter, the spectral index distributions are different enough to overcome that intrinsic variation. Utilizing two different models of the relationship between spectral index and viewing angle, the simulations indicate that the difference in spectral index distributions can be explained by allowing BAL quasar viewing angles to extend about 10 Degree-Sign farther from the radio jet axis than non-BAL sources, though both can be seen at small angles. These results show that orientation cannot be the only factor determining whether BAL features are present, but it does play a role.

  3. Rainbow Vectors for Broad-Range Bacterial Fluorescence Labeling.

    PubMed

    Barbier, Mariette; Damron, F Heath

    2016-01-01

    Since their discovery, fluorescent proteins have been widely used to study protein function, localization or interaction, promoter activity and regulation, drug discovery or for non-invasive imaging. They have been extensively modified to improve brightness, stability, and oligomerization state. However, only a few studies have focused on understanding the dynamics of fluorescent proteins expression in bacteria. In this work, we developed a set plasmids encoding 12 fluorescent proteins for bacterial labeling to facilitate the study of pathogen-host interactions. These broad-spectrum plasmids can be used with a wide variety of Gram-negative microorganisms including Escherichia coli, Pseudomonas aeruginosa, Burkholderia cepacia, Bordetella bronchiseptica, Shigella flexneri or Klebsiella pneumoniae. For comparison, fluorescent protein expression and physical characteristics in Escherichia coli were analyzed using fluorescence microscopy, flow cytometry and in vivo imaging. Fluorescent proteins derived from the Aequorea Victoria family showed high photobleaching, while proteins form the Discosoma sp. and the Fungia coccina family were more photostable for microscopy applications. Only E2-Crimson, mCherry and mKeima were successfully detected for in vivo applications. Overall, E2-Crimson was the fastest maturing protein tested in E. coli with the best overall performance in the study parameters. This study provides a unified comparison and comprehensive characterization of fluorescent protein photostability, maturation and toxicity, and offers general recommendations on the optimal fluorescent proteins for in vitro and in vivo applications. PMID:26937640

  4. Broad activation of latent HIV-1 in vivo.

    PubMed

    Barton, Kirston; Hiener, Bonnie; Winckelmann, Anni; Rasmussen, Thomas Aagaard; Shao, Wei; Byth, Karen; Lanfear, Robert; Solomon, Ajantha; McMahon, James; Harrington, Sean; Buzon, Maria; Lichterfeld, Mathias; Denton, Paul W; Olesen, Rikke; Østergaard, Lars; Tolstrup, Martin; Lewin, Sharon R; Søgaard, Ole Schmeltz; Palmer, Sarah

    2016-01-01

    The 'shock and kill' approach to cure human immunodeficiency virus (HIV) includes transcriptional induction of latent HIV-1 proviruses using latency-reversing agents (LRAs) with targeted immunotherapy to purge infected cells. The administration of LRAs (panobinostat or vorinostat) to HIV-1-infected individuals on antiretroviral therapy induces a significant increase in cell-associated unspliced (CA-US) HIV-1 RNA from CD4(+) T cells. However, it is important to discern whether the increases in CA-US HIV-1 RNA are due to limited or broad activation of HIV-1 proviruses. Here we use single-genome sequencing to find that the RNA transcripts observed following LRA administration are genetically diverse, indicating activation of transcription from an extensive range of proviruses. Defective sequences are more frequently found in CA HIV-1 RNA than in HIV-1 DNA, which has implications for developing an accurate measure of HIV-1 reservoir size. Our findings provide insights into the effects of panobinostat and vorinostat as LRAs for latent HIV-1. PMID:27605062

  5. Improved PCR Amplification of Broad Spectrum GC DNA Templates

    PubMed Central

    Guido, Nicholas; Starostina, Elena; Leake, Devin; Saaem, Ishtiaq

    2016-01-01

    Many applications in molecular biology can benefit from improved PCR amplification of DNA segments containing a wide range of GC content. Conventional PCR amplification of DNA sequences with regions of GC less than 30%, or higher than 70%, is complex due to secondary structures that block the DNA polymerase as well as mispriming and mis-annealing of the DNA. This complexity will often generate incomplete or nonspecific products that hamper downstream applications. In this study, we address multiplexed PCR amplification of DNA segments containing a wide range of GC content. In order to mitigate amplification complications due to high or low GC regions, we tested a combination of different PCR cycling conditions and chemical additives. To assess the fate of specific oligonucleotide (oligo) species with varying GC content in a multiplexed PCR, we developed a novel method of sequence analysis. Here we show that subcycling during the amplification process significantly improved amplification of short template pools (~200 bp), particularly when the template contained a low percent of GC. Furthermore, the combination of subcycling and 7-deaza-dGTP achieved efficient amplification of short templates ranging from 10–90% GC composition. Moreover, we found that 7-deaza-dGTP improved the amplification of longer products (~1000 bp). These methods provide an updated approach for PCR amplification of DNA segments containing a broad range of GC content. PMID:27271574

  6. Robust linear regression with broad distributions of errors

    NASA Astrophysics Data System (ADS)

    Postnikov, Eugene B.; Sokolov, Igor M.

    2015-09-01

    We consider the problem of linear fitting of noisy data in the case of broad (say α-stable) distributions of random impacts ("noise"), which can lack even the first moment. This situation, common in statistical physics of small systems, in Earth sciences, in network science or in econophysics, does not allow for application of conventional Gaussian maximum-likelihood estimators resulting in usual least-squares fits. Such fits lead to large deviations of fitted parameters from their true values due to the presence of outliers. The approaches discussed here aim onto the minimization of the width of the distribution of residua. The corresponding width of the distribution can either be defined via the interquantile distance of the corresponding distributions or via the scale parameter in its characteristic function. The methods provide the robust regression even in the case of short samples with large outliers, and are equivalent to the normal least squares fit for the Gaussian noises. Our discussion is illustrated by numerical examples.

  7. Rainbow Vectors for Broad-Range Bacterial Fluorescence Labeling

    PubMed Central

    Barbier, Mariette; Damron, F. Heath

    2016-01-01

    Since their discovery, fluorescent proteins have been widely used to study protein function, localization or interaction, promoter activity and regulation, drug discovery or for non-invasive imaging. They have been extensively modified to improve brightness, stability, and oligomerization state. However, only a few studies have focused on understanding the dynamics of fluorescent proteins expression in bacteria. In this work, we developed a set plasmids encoding 12 fluorescent proteins for bacterial labeling to facilitate the study of pathogen-host interactions. These broad-spectrum plasmids can be used with a wide variety of Gram-negative microorganisms including Escherichia coli, Pseudomonas aeruginosa, Burkholderia cepacia, Bordetella bronchiseptica, Shigella flexneri or Klebsiella pneumoniae. For comparison, fluorescent protein expression and physical characteristics in Escherichia coli were analyzed using fluorescence microscopy, flow cytometry and in vivo imaging. Fluorescent proteins derived from the Aequorea Victoria family showed high photobleaching, while proteins form the Discosoma sp. and the Fungia coccina family were more photostable for microscopy applications. Only E2-Crimson, mCherry and mKeima were successfully detected for in vivo applications. Overall, E2-Crimson was the fastest maturing protein tested in E. coli with the best overall performance in the study parameters. This study provides a unified comparison and comprehensive characterization of fluorescent protein photostability, maturation and toxicity, and offers general recommendations on the optimal fluorescent proteins for in vitro and in vivo applications. PMID:26937640

  8. Broad Band Intra-Cavity Total Reflection Chemical Sensor

    DOEpatents

    Pipino, Andrew C. R.

    1998-11-10

    A broadband, ultrahigh-sensitivity chemical sensor is provided that allows etection through utilization of a small, extremely low-loss, monolithic optical cavity. The cavity is fabricated from highly transparent optical material in the shape of a regular polygon with one or more convex facets to form a stable resonator for ray trajectories sustained by total internal reflection. Optical radiation enters and exits the monolithic cavity by photon tunneling in which two totally reflecting surfaces are brought into close proximity. In the presence of absorbing material, the loss per pass is increased since the evanescent waves that exist exterior to the cavity at points where the circulating pulse is totally reflected, are absorbed. The decay rate of an injected pulse is determined by coupling out an infinitesimal fraction of the pulse to produce an intensity-versus-time decay curve. Since the change in the decay rate resulting from absorption is inversely proportional to the magnitude of absorption, a quantitative sensor of concentration or absorption cross-section with 1 part-per-million/pass or better sensitivity is obtained. The broadband nature of total internal reflection permits a single device to be used over a broad wavelength range. The absorption spectrum of the surrounding medium can thereby be obtained as a measurement of inverse decay time as a function of wavelength.

  9. Biodiversity inhibits parasites: Broad evidence for the dilution effect

    PubMed Central

    Civitello, David J.; Cohen, Jeremy; Fatima, Hiba; Halstead, Neal T.; Liriano, Josue; McMahon, Taegan A.; Ortega, C. Nicole; Sauer, Erin Louise; Sehgal, Tanya; Young, Suzanne; Rohr, Jason R.

    2015-01-01

    Infectious diseases of humans, wildlife, and domesticated species are increasing worldwide, driving the need to understand the mechanisms that shape outbreaks. Simultaneously, human activities are drastically reducing biodiversity. These concurrent patterns have prompted repeated suggestions that biodiversity and disease are linked. For example, the dilution effect hypothesis posits that these patterns are causally related; diverse host communities inhibit the spread of parasites via several mechanisms, such as by regulating populations of susceptible hosts or interfering with parasite transmission. However, the generality of the dilution effect hypothesis remains controversial, especially for zoonotic diseases of humans. Here we provide broad evidence that host diversity inhibits parasite abundance using a meta-analysis of 202 effect sizes on 61 parasite species. The magnitude of these effects was independent of host density, study design, and type and specialization of parasites, indicating that dilution was robust across all ecological contexts examined. However, the magnitude of dilution was more closely related to the frequency, rather than density, of focal host species. Importantly, observational studies overwhelmingly documented dilution effects, and there was also significant evidence for dilution effects of zoonotic parasites of humans. Thus, dilution effects occur commonly in nature, and they may modulate human disease risk. A second analysis identified similar effects of diversity in plant–herbivore systems. Thus, although there can be exceptions, our results indicate that biodiversity generally decreases parasitism and herbivory. Consequently, anthropogenic declines in biodiversity could increase human and wildlife diseases and decrease crop and forest production. PMID:26069208

  10. Phenomenology of Broad Emission Lines in Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Sulentic, J. W.; Marziani, P.; Dultzin-Hacyan, D.

    Broad emission lines hold fundamental clues about the kinematics and structure of the central regions in AGN. In this article we review the most robust line profile properties and correlations emerging from the best data available. We identify fundamental differences between the profiles of radio-quiet and radio-loud sources as well as differences between the high- and low-ionization lines, especially in the radio-quiet majority of AGN. An Eigenvector 1 correlation space involving FWHM Hβ, W(FeIIopt)/W(Hβ), and the soft X-ray spectral index provides optimal discrimination between all principal AGN types (from narrow-line Seyfert 1 to radio galaxies). Both optical and radio continuum luminosities appear to be uncorrelated with the E1 parameters. We identify two populations of radio-quiet AGN: Population A sources (with FWHM(Hβ) <~ 4000 km s-1, generally strong FeII emission and a soft X-ray excess) show almost no parameter space overlap with radio-loud sources. Population B shows optical properties largely indistinguishable from radio-loud sources, including usually weak FeII emission, FWHM(Hβ) >~ 4000 km s-1 and lack of a soft X-ray excess. There is growing evidence that a fundamental parameter underlying Eigenvector 1 may be the luminosity-to-mass ratio of the active nucleus (L/M), with source orientation playing a concomitant role.

  11. Broad targeting of resistance to apoptosis in cancer.

    PubMed

    Mohammad, Ramzi M; Muqbil, Irfana; Lowe, Leroy; Yedjou, Clement; Hsu, Hsue-Yin; Lin, Liang-Tzung; Siegelin, Markus David; Fimognari, Carmela; Kumar, Nagi B; Dou, Q Ping; Yang, Huanjie; Samadi, Abbas K; Russo, Gian Luigi; Spagnuolo, Carmela; Ray, Swapan K; Chakrabarti, Mrinmay; Morre, James D; Coley, Helen M; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S Salman; Helferich, William G; Yang, Xujuan; Boosani, Chandra S; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Mohammed, Sulma I; Keith, W Nicol; Bilsland, Alan; Halicka, Dorota; Nowsheen, Somaira; Azmi, Asfar S

    2015-12-01

    Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer. PMID:25936818

  12. Ultra-broad bandwidth parametric amplification at degeneracy.

    PubMed

    Limpert, J; Aguergaray, C; Montant, S; Manek-Hönninger, I; Petit, S; Descamps, D; Cormier, E; Salin, F

    2005-09-19

    We report on a novel approach of ultra-broad bandwidth parametric amplification around degeneracy. A bandwidth of up to 400 nm centered around 800 nm is amplified in a BBO crystal by using chirped pump pulses with a bandwitdth as broad as 10 nm. A supercontinuum signal is generated in a microstructured fiber, having to first order a quadratic chirp, which is necessary to ensure temporal overlap of the interacting waves over this broad bandwidth. Furthermore, we discuss the potential of this approach for an octave-spanning parametric amplification. PMID:19498762

  13. Microlensing of the broad line region in 17 lensed quasars

    NASA Astrophysics Data System (ADS)

    Sluse, D.; Hutsemékers, D.; Courbin, F.; Meylan, G.; Wambsganss, J.

    2012-08-01

    When an image of a strongly lensed quasar is microlensed, the different components of its spectrum are expected to be differentially magnified owing to the different sizes of the corresponding emitting region. Chromatic changes are expected to be observed in the continuum while the emission lines should be deformed as a function of the size, geometry and kinematics of the regions from which they originate. Microlensing of the emission lines has been reported only in a handful of systems so far. In this paper we search for microlensing deformations of the optical spectra of pairs of images in 17 lensed quasars with bolometric luminosities between 1044.7 - 47.4 erg/s and black hole masses 107.6 - 9.8 M⊙. This sample is composed of 13 pairs of previously unpublished spectra and four pairs of spectra from literature. Our analysis is based on a simple spectral decomposition technique which allows us to isolate the microlensed fraction of the flux independently of a detailed modeling of the quasar emission lines. Using this technique, we detect microlensing of the continuum in 85% of the systems. Among them, 80% show microlensing of the broad emission lines. Focusing on the most common emission lines in our spectra (C III] and Mg II) we detect microlensing of either the blue or the red wing, or of both wings with the same amplitude. This observation implies that the broad line region is not in general spherically symmetric. In addition, the frequent detection of microlensing of the blue and red wings independently but not simultaneously with a different amplitude, does not support existing microlensing simulations of a biconical outflow. Our analysis also provides the intrinsic flux ratio between the lensed images and the magnitude of the microlensing affecting the continuum. These two quantities are particularly relevant for the determination of the fraction of matter in clumpy form in galaxies and for the detection of dark matter substructures via the identification

  14. Testing Provides Crucial Information

    ERIC Educational Resources Information Center

    Morial, Marc H.

    2015-01-01

    The National Urban League president and CEO Marc H. Morial weighs in on what he sees as the need for continued annual assessments of students, rejecting the course of opting out that has taken hold in some places across America. Assessment data provides students with the opportunity to receive personalized supports and necessary interventions to…

  15. The Provident Principal.

    ERIC Educational Resources Information Center

    McCall, John R.

    This monograph offers leadership approaches for school principals. Discussion applies the business leadership theory of Warren Bennis and Burt Nanus to the role of the principal. Each of the booklet's three parts concludes with discussion questions. Part 1, "Visions and Values for the Provident Principal," demonstrates the importance of…

  16. Providers get their due.

    PubMed

    Morrissey, J

    1994-11-01

    Providers are getting their due, but only after employing computer software programs to help sort through the complex managed-care contracts they've negotiated. More and more accounting departments are relying on contract management systems to ensure accurate billing. PMID:10138187

  17. What Drives the Outflows in Broad Absorption Line QSOs?

    NASA Technical Reports Server (NTRS)

    Begelman, Mitchell C.

    1997-01-01

    We have made progress in the areas related to the propulsion and confinement of gas responsible for broad absorption troughts in QSOs: Radiative Acceleration in BALQSOs; The "Ghost" of Lyman (alpha); and Magnetic Confinement of Absorbing Gas.

  18. 48 CFR 35.016 - Broad agency announcement.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    .... This paragraph prescribes procedures for the use of the broad agency announcement (BAA) with Peer or... the BAA shall be evaluated in accordance with evaluation criteria specified therein through a peer...

  19. 48 CFR 2035.71 - Broad agency announcements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 2035.71 Broad agency announcements. (a..., approaches, or concepts demonstrated by the proposal. (2) Overall scientific, technical, or economic merits... agency's scientific or engineering personnel and the principal investigator is permitted...

  20. 10. View to northeast from near siphon structure showing broad, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. View to northeast from near siphon structure showing broad, U-shaped earthen banked ditch - Natomas Ditch System, Blue Ravine Segment, Juncture of Blue Ravine & Green Valley Roads, Folsom, Sacramento County, CA

  1. Spectropolarimetric test of the relativistic disk model for the broad emission lines of active galactic nuclei

    NASA Technical Reports Server (NTRS)

    Chen, Kaiyou; Halpern, Jules P.

    1990-01-01

    Previously, it was claimed that the broad emission lines of the radio galaxy Arp 102B can be fitted by the line profile from a simple relativistic Keplerian thin disk. It was argued that the lines originating from the relativistic accretion disk could be polarized due to electron scattering, which is likely to be the dominant opacity in the line-emitting region of Arp 102B. In the present work, the expected polarization properties of these broad emission lines are calculated. The percentage of polarization depends strongly on the inclination angle. For some angles, the red peak of the polarized, double-peaked line profile can be higher than the blue peak. This is in contrast to the total line profile, in which the blue peak is always higher than the red one. Spectropolarimetric observations could, therefore, provide an independent test of the relativistic disk model for the broad emission lines of Arp 102B and other active galactic nuclei.

  2. Recent Results from Broad-Band Intensity Mapping Measurements of Cosmic Large Scale Structure

    NASA Astrophysics Data System (ADS)

    Zemcov, Michael B.; CIBER, Herschel-SPIRE

    2016-01-01

    Intensity mapping integrates the total emission in a given spectral band over the universe's history. Tomographic measurements of cosmic structure can be performed using specific line tracers observed in narrow bands, but a wealth of information is also available from broad-band observations performed by instruments capable of capturing high-fidelity, wide-angle images of extragalactic emission. Sensitive to the continuum emission from faint and diffuse sources, these broad-band measurements provide a view on cosmic structure traced by components not readily detected in point source surveys. After accounting for measurement effects and astrophysical foregrounds, the angular power spectra of such data can be compared to predictions from models to yield powerful insights into the history of cosmic structure formation. This talk will highlight some recent measurements of large scale structure performed using broad-band intensity mapping methods that have given new insights on faint, distant, and diffuse components in the extragalactic background light.

  3. SDSS 0956+5128: A BROAD-LINE QUASAR WITH EXTREME VELOCITY OFFSETS

    SciTech Connect

    Steinhardt, Charles L.; Schramm, Malte; Silverman, John D.; Alexandroff, Rachael; Pattarakijwanich, Petchara; Strauss, Michael A.; Capak, Peter; Civano, Francesca; Elvis, Martin; Masters, Dan; Mobasher, Bahram

    2012-11-01

    We report on the discovery of a Type 1 quasar, SDSS 0956+5128, with a surprising combination of extreme velocity offsets. SDSS 0956+5128 is a broad-lined quasar exhibiting emission lines at three substantially different redshifts: a systemic redshift of z {approx} 0.714 based on narrow emission lines, a broad Mg II emission line centered 1200 km s{sup -1} bluer than the systemic velocity, at z {approx} 0.707, and broad H{alpha} and H{beta} emission lines centered at z {approx} 0.690. The Balmer line peaks are 4100 km s{sup -1} bluer than the systemic redshift. There are no previously known objects with such an extreme difference between broad Mg II and broad Balmer emission. The two most promising explanations are either an extreme disk emitter or a high-velocity black hole recoil. However, neither explanation appears able to explain all of the observed features of SDSS 0956+5128, so the object may provide a challenge to our general understanding of quasar physics.

  4. Achieving Provider Engagement

    PubMed Central

    Greenfield, Geva; Pappas, Yannis; Car, Josip; Majeed, Azeem; Harris, Matthew

    2014-01-01

    The literature on integrated care is limited with respect to practical learning and experience. Although some attention has been paid to organizational processes and structures, not enough is paid to people, relationships, and the importance of these in bringing about integration. Little is known, for example, about provider engagement in the organizational change process, how to obtain and maintain it, and how it is demonstrated in the delivery of integrated care. Based on qualitative data from the evaluation of a large-scale integrated care initiative in London, United Kingdom, we explored the role of provider engagement in effective integration of services. Using thematic analysis, we identified an evolving engagement narrative with three distinct phases: enthusiasm, antipathy, and ambivalence, and argue that health care managers need to be aware of the impact of professional engagement to succeed in advancing the integrated care agenda. PMID:25212855

  5. Provider panel presentations.

    PubMed

    Buckelew, Larry C; Harvey, Deborah; Mello, Joe

    2003-08-01

    To wrap up the three big items--attracting talent, the professional nurse role, and our structural disadvantages--I would offer the following take-away thoughts: We ought to do what we can to get our disproportionate share of RNs out of the health care system to work in dialysis. If we work together, we have a shot at making that happen. As an industry, we must exploit our strengths. We have to exploit the pride that comes in the services and the care that we provide. We need to create in a very visual way that difference for nurses who are considering which area of specialty to go into and where to create their careers. We, as providers, have a huge opportunity to create the right environment for our nurses. That's something we own. We have to fix it. We have to create a better place to work for nurses than any place else. We must create a more enriching place for nurses than anywhere else. That's up to us. I know a lot of us on the provider side are doing tons of things to make that happen and we need to keep driving that. We need a level playing field. We've proven the fact that we can deliver clinical outcomes with the best. Now we need help from our biggest customer to make sure we can compete for the resources that are necessary to sustain and improve those clinical outcomes on an ongoing basis. PMID:14533522

  6. Why healthcare providers merge.

    PubMed

    Postma, Jeroen; Roos, Anne-Fleur

    2016-04-01

    In many OECD countries, healthcare sectors have become increasingly concentrated as a result of mergers. However, detailed empirical insight into why healthcare providers merge is lacking. Also, we know little about the influence of national healthcare policies on mergers. We fill this gap in the literature by conducting a survey study on mergers among 848 Dutch healthcare executives, of which 35% responded (resulting in a study sample of 239 executives). A total of 65% of the respondents was involved in at least one merger between 2005 and 2012. During this period, Dutch healthcare providers faced a number of policy changes, including increasing competition, more pressure from purchasers, growing financial risks, de-institutionalisation of long-term care and decentralisation of healthcare services to municipalities. Our empirical study shows that healthcare providers predominantly merge to improve the provision of healthcare services and to strengthen their market position. Also efficiency and financial reasons are important drivers of merger activity in healthcare. We find that motives for merger are related to changes in health policies, in particular to the increasing pressure from competitors, insurers and municipalities. PMID:26055501

  7. PROVIDING WOMEN, KEPT MEN

    PubMed Central

    Mojola, Sanyu A

    2014-01-01

    This paper draws on ethnographic and interview based fieldwork to explore accounts of intimate relationships between widowed women and poor young men that emerged in the wake of economic crisis and a devastating HIV epidemic among the Luo ethnic group in Western Kenya. I show how the cooptation of widow inheritance practices in the wake of an overwhelming number of widows as well as economic crisis resulted in widows becoming providing women and poor young men becoming kept men. I illustrate how widows in this setting, by performing a set of practices central to what it meant to be a man in this society – pursuing and providing for their partners - were effectively doing masculinity. I will also show how young men, rather than being feminized by being kept, deployed other sets of practices to prove their masculinity and live in a manner congruent with cultural ideals. I argue that ultimately, women’s practice of masculinity in large part seemed to serve patriarchal ends. It not only facilitated the fulfillment of patriarchal expectations of femininity – to being inherited – but also served, in the end, to provide a material base for young men’s deployment of legitimizing and culturally valued sets of masculine practice. PMID:25489121

  8. 45 CFR 156.235 - Essential community providers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... service area, in accordance with the Exchange's network adequacy standards. (c) Definition. Essential... providers, where available, to ensure reasonable and timely access to a broad range of such providers for... Exchange's network adequacy standards. (2) A QHP issuer that provides a majority of covered...

  9. Providing Contraception to Adolescents.

    PubMed

    Raidoo, Shandhini; Kaneshiro, Bliss

    2015-12-01

    Adolescents have high rates of unintended pregnancy and face unique reproductive health challenges. Providing confidential contraceptive services to adolescents is important in reducing the rate of unintended pregnancy. Long-acting contraception such as the intrauterine device and contraceptive implant are recommended as first-line contraceptives for adolescents because they are highly effective with few side effects. The use of barrier methods to prevent sexually transmitted infections should be encouraged. Adolescents have limited knowledge of reproductive health and contraceptive options, and their sources of information are often unreliable. Access to contraception is available through a variety of resources that continue to expand. PMID:26598305

  10. The Provident Sea

    NASA Astrophysics Data System (ADS)

    Cushing, David H.

    1988-09-01

    The Provident Sea describes the history of fish stock management (including whales and seals). The book traces, on the basis of the original scientific material, the history of the management of "the provident sea" up to recent times when problems of over-exploitation have had dramatic effects upon stocks. The need for management arose mainly from the increasing industrialization of capture. Hence the preindustrial fisheries are covered, in particular the old cod fishery on the Grand Bank and the herring fishery in the North Sea, as an essential background to current problems. The origins of fisheries and whaling science are described, as is the development up to 1965 of the science and institution in fisheries, whaling, and sealing. In the sixties and seventies, certain major fishing nations took a heavy harvest of fish stocks using sophisticated and efficient gathering methods. This in turn led to conflict and one consequence was the "Law of the Sea" conference set up to try and resolve these issues.

  11. Spatiotemporal exploratory models for broad-scale survey data.

    PubMed

    Fink, Daniel; Hochachka, Wesley M; Zuckerberg, Benjamin; Winkler, David W; Shaby, Ben; Munson, M Arthur; Hooker, Giles; Riedewald, Mirek; Sheldon, Daniel; Kelling, Steve

    2010-12-01

    The distributions of animal populations change and evolve through time. Migratory species exploit different habitats at different times of the year. Biotic and abiotic features that determine where a species lives vary due to natural and anthropogenic factors. This spatiotemporal variation needs to be accounted for in any modeling of species' distributions. In this paper we introduce a semiparametric model that provides a flexible framework for analyzing dynamic patterns of species occurrence and abundance from broad-scale survey data. The spatiotemporal exploratory model (STEM) adds essential spatiotemporal structure to existing techniques for developing species distribution models through a simple parametric structure without requiring a detailed understanding of the underlying dynamic processes. STEMs use a multi-scale strategy to differentiate between local and global-scale spatiotemporal structure. A user-specified species distribution model accounts for spatial and temporal patterning at the local level. These local patterns are then allowed to "scale up" via ensemble averaging to larger scales. This makes STEMs especially well suited for exploring distributional dynamics arising from a variety of processes. Using data from eBird, an online citizen science bird-monitoring project, we demonstrate that monthly changes in distribution of a migratory species, the Tree Swallow (Tachycineta bicolor), can be more accurately described with a STEM than a conventional bagged decision tree model in which spatiotemporal structure has not been imposed. We also demonstrate that there is no loss of model predictive power when a STEM is used to describe a spatiotemporal distribution with very little spatiotemporal variation; the distribution of a nonmigratory species, the Northern Cardinal (Cardinalis cardinalis). PMID:21265447

  12. Broadly tunable, longitudinally diode-pumped Alexandrite laser

    NASA Astrophysics Data System (ADS)

    Strotkamp, M.; Witte, U.; Munk, A.; Hartung, A.; Gausmann, S.; Hengesbach, S.; Traub, M.; Hoffmann, H.-D.; Hoeffner, J.; Jungbluth, B.

    2014-02-01

    We present design and first performance data of a broadly tunable Alexandrite laser longitudinally pumped by a newly developed high brightness single emitter diode laser module with output in the red spectral range. Replacing the flashlamps, which are usually used for pumping Alexandrite, will increase the efficiency and maintenance interval of the laser. The pump module is designed as an optical stack of seven single-emitter laser diodes. We selected an optomechanical concept for the tight overlay of the radiation using a minimal number of optical components for collimation, e.g. a FAC and a SAC lens, and focusing. The module provides optical output power of more than 14 W (peak pulse output in the focus) with a beam quality of M2 = 41 in the fast axis and M2 = 39 in the slow axis. The Alexandrite crystal is pumped from one end at a repetition rate of 35 Hz and 200μs long pump pulses. The temperature of the laser crystal can be tuned to between 30 °C and 190 °C using a thermostat. The diode-pumped Alexandrite laser reaches a maximum optical-optical efficiency of 20 % and a slope efficiency of more than 30 % in fundamental-mode operation (M2 < 1.10). When a Findlay-Clay analysis with four different output couplers is conducted, the round-trip loss of the cavity is determined to be around 1 %. The wavelength is tunable to between 755 and 788 nm via crystal temperature or between 745 and 805 nm via an additional Brewster prism.

  13. What HERA May Provide?

    SciTech Connect

    Jung, Hannes; De Roeck, Albert; Bartels, Jochen; Behnke, Olaf; Blumlein, Johannes; Brodsky, Stanley; Cooper-Sarkar, Amanda; Deak, Michal; Devenish, Robin; Diehl, Markus; Gehrmann, Thomas; Grindhammer, Guenter; Gustafson, Gosta; Khoze, Valery; Knutsson, Albert; Klein, Max; Krauss, Frank; Kutak, Krzysztof; Laenen, Eric; Lonnblad, Leif; Motyka, Leszek; /Hamburg U., Inst. Theor. Phys. II /Birmingham U. /Southern Methodist U. /DESY /Piemonte Orientale U., Novara /CERN /Paris, LPTHE /Hamburg U. /Penn State U.

    2011-11-10

    More than 100 people participated in a discussion session at the DIS08 workshop on the topic What HERA may provide. A summary of the discussion with a structured outlook and list of desirable measurements and theory calculations is given. The HERA accelerator and the HERA experiments H1, HERMES and ZEUS stopped running in the end of June 2007. This was after 15 years of very successful operation since the first collisions in 1992. A total luminosity of {approx} 500 pb{sup -1} has been accumulated by each of the collider experiments H1 and ZEUS. During the years the increasingly better understood and upgraded detectors and HERA accelerator have contributed significantly to this success. The physics program remains in full swing and plenty of new results were presented at DIS08 which are approaching the anticipated final precision, fulfilling and exceeding the physics plans and the previsions of the upgrade program. Most of the analyses presented at DIS08 were still based on the so called HERA I data sample, i.e. data taken until 2000, before the shutdown for the luminosity upgrade. This sample has an integrated luminosity of {approx} 100 pb{sup -1}, and the four times larger statistics sample from HERA II is still in the process of being analyzed.

  14. Ultrafast pulsed laser utilizing broad bandwidth laser glass

    DOEpatents

    Payne, Stephen A.; Hayden, Joseph S.

    1997-01-01

    An ultrafast laser uses a Nd-doped phosphate laser glass characterized by a particularly broad emission bandwidth to generate the shortest possible output pulses. The laser glass is composed primarily of P.sub.2 O.sub.5, Al.sub.2 O.sub.3 and MgO, and possesses physical and thermal properties that are compatible with standard melting and manufacturing methods. The broad bandwidth laser glass can be used in modelocked oscillators as well as in amplifier modules.

  15. Femtosecond soliton source with fast and broad spectral tunability.

    PubMed

    Masip, Martin E; Rieznik, A A; König, Pablo G; Grosz, Diego F; Bragas, Andrea V; Martinez, Oscar E

    2009-03-15

    We present a complete set of measurements and numerical simulations of a femtosecond soliton source with fast and broad spectral tunability and nearly constant pulse width and average power. Solitons generated in a photonic crystal fiber, at the low-power coupling regime, can be tuned in a broad range of wavelengths, from 850 to 1200 nm using the input power as the control parameter. These solitons keep almost constant time duration (approximately 40 fs) and spectral widths (approximately 20 nm) over the entire measured spectra regardless of input power. Our numerical simulations agree well with measurements and predict a wide working wavelength range and robustness to input parameters. PMID:19282951

  16. Analysis of fuel system technology for broad property fuels

    NASA Technical Reports Server (NTRS)

    Coffinberry, G. A.

    1984-01-01

    An analytical study was performed in order to assess relative performance and economic factors involved with alternative advanced fuel systems for future commercial aircraft operating with broad property fuels. Significant results, with emphasis on design practicality from the engine manufacturer' standpoint, are highlighted. Several advanced fuel systems were modeled to determine as accurately as possible the relative merits of each system from the standpoint of compatibility with broad property fuel. Freezing point, thermal stability, and lubricity were key property issues. A computer model was formulated to determine the investment incentive for each system. Results are given.

  17. Ultrafast pulsed laser utilizing broad bandwidth laser glass

    DOEpatents

    Payne, S.A.; Hayden, J.S.

    1997-09-02

    An ultrafast laser uses a Nd-doped phosphate laser glass characterized by a particularly broad emission bandwidth to generate the shortest possible output pulses. The laser glass is composed primarily of P{sub 2}O{sub 5}, Al{sub 2}O{sub 3} and MgO, and possesses physical and thermal properties that are compatible with standard melting and manufacturing methods. The broad bandwidth laser glass can be used in modelocked oscillators as well as in amplifier modules. 7 figs.

  18. Ultra high vacuum broad band high power microwave window

    DOEpatents

    Nguyen-Tuong, V.; Dylla, H.F. III

    1997-11-04

    An improved high vacuum microwave window has been developed that utilizes high density polyethylene coated on two sides with SiOx, SiNx, or a combination of the two. The resultant low dielectric and low loss tangent window creates a low outgassing, low permeation seal through which broad band, high power microwave energy may be passed. No matching device is necessary and the sealing technique is simple. The features of the window are broad band transmission, ultra-high vacuum compatibility with a simple sealing technique, low voltage standing wave ratio, high power transmission and low cost. 5 figs.

  19. Ultra high vacuum broad band high power microwave window

    DOEpatents

    Nguyen-Tuong, Viet; Dylla, III, Henry Frederick

    1997-01-01

    An improved high vacuum microwave window has been developed that utilizes high density polyethylene coated on two sides with SiOx, SiNx, or a combination of the two. The resultant low dielectric and low loss tangent window creates a low outgassing, low permeation seal through which broad band, high power microwave energy may be passed. No matching device is necessary and the sealing technique is simple. The features of the window are broad band transmission, ultra-high vacuum compatibility with a simple sealing technique, low voltage standing wave ratio, high power transmission and low cost.

  20. Antibody Response to Hypervariable Region 1 Interferes with Broadly Neutralizing Antibodies to Hepatitis C Virus

    PubMed Central

    Keck, Zhen-yong; Girard-Blanc, Christine; Wang, Wenyan; Lau, Patrick; Zuiani, Adam; Rey, Felix A.; Krey, Thomas; Diamond, Michael S.

    2015-01-01

    their epitopes. This study provides insight into a new immune antagonism mechanism by which the binding of antibodies to HVR1 blocks the binding and activity of broadly neutralizing antibodies to HCV. Immunization strategies that avoid the induction of HVR1 antibodies should increase the inhibitory activity of broadly neutralizing anti-HCV antibodies elicited by candidate vaccines. PMID:26739044

  1. Time Variable Broad Line Emission in NGC 4203: Evidence for Stellar Contrails

    NASA Astrophysics Data System (ADS)

    Devereux, Nicholas A.

    2012-01-01

    Dual epoch spectroscopy of the lenticular galaxy, NGC 4203, obtained with the Hubble Space Telescope has revealed that the double-peaked component of the broad Hα emission line is time variable, increasing by a factor of 2.2 in brightness between 1999 and 2010. Modeling the gas distribution responsible for the double-peaked profiles indicates that a ring is a more appropriate description than a disk and most likely represents the contrail of a red supergiant star that is being tidally disrupted at a distance of 1500 AU from the central black hole. There is also a bright core of broad Hα line emission that is not time variable and identified with a large scale inflow from an outer radius 1 pc. If the gas number density is ≥ 106 cm-3, as suggested by the absence of similarly broad [O I] and [O III] emission lines, then the steady state inflow rate is 2 × 10-2 M⊙/yr which exceeds the inflow requirement to explain the X-ray luminosity in terms of radiatively inefficient accretion by a factor of 6. The central AGN is unable to sustain ionization of the broad line region, the discrepancy is particularly acute in 2010 when the broad Hα emission line is dominated by the contrail of the in-falling supergiant star. However, ram pressure shock ionization produced by the interaction of the in-falling supergiant with the ambient interstellar medium may help alleviate the ionizing deficit by generating a mechanical source of ionization supplementing the photoionization provided by the AGN. Support for Program number HST AR-11752.01-A was provided by NASA through a grant from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, incorporated, under NASA contract NAS5-26555.

  2. The Content-Provider Paradox: Universities in the Information Ecosystem.

    ERIC Educational Resources Information Center

    Vaidhyanathan, Siva

    2002-01-01

    Asserts that universities' rush to abandon their role as "national parks" in the information ecosystem in favor of becoming profitable "content providers" has led to a paradox: to generate new knowledge, researchers and teachers need broad content freedom, but the role of content provider requires highly restrictive policies to create information…

  3. Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1

    PubMed Central

    McCoy, Laura E.; Rutten, Lucy; Frampton, Dan; Anderson, Ian; Granger, Luke; Bashford-Rogers, Rachael; Dekkers, Gillian; Strokappe, Nika M.; Seaman, Michael S.; Koh, Willie; Grippo, Vanina; Kliche, Alexander; Verrips, Theo; Kellam, Paul; Fassati, Ariberto; Weiss, Robin A.

    2014-01-01

    To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols. PMID:25522326

  4. Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1.

    PubMed

    McCoy, Laura E; Rutten, Lucy; Frampton, Dan; Anderson, Ian; Granger, Luke; Bashford-Rogers, Rachael; Dekkers, Gillian; Strokappe, Nika M; Seaman, Michael S; Koh, Willie; Grippo, Vanina; Kliche, Alexander; Verrips, Theo; Kellam, Paul; Fassati, Ariberto; Weiss, Robin A

    2014-12-01

    To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols. PMID:25522326

  5. Broad Hβ Emission-line Variability in a Sample of 102 Local Active Galaxies

    NASA Astrophysics Data System (ADS)

    Runco, Jordan N.; Cosens, Maren; Bennert, Vardha N.; Scott, Bryan; Komossa, S.; Malkan, Matthew A.; Lazarova, Mariana S.; Auger, Matthew W.; Treu, Tommaso; Park, Daeseong

    2016-04-01

    A sample of 102 local (0.02 ≤ z ≤ 0.1) Seyfert galaxies with black hole masses MBH > 107M⊙ was selected from the Sloan Digital Sky Survey (SDSS) and observed using the Keck 10 m telescope to study the scaling relations between MBH and host galaxy properties. We study profile changes of the broad Hβ emission line within the three to nine year time frame between the two sets of spectra. The variability of the broad Hβ emission line is of particular interest, not only because it is used to estimate MBH, but also because its strength and width are used to classify Seyfert galaxies into different types. At least some form of broad-line variability (in either width or flux) is observed in the majority (∼66%) of the objects, resulting in a Seyfert-type change for ∼38% of the objects, likely driven by variable accretion and/or obscuration. The broad Hβ line virtually disappears in 3/102 (∼3%) extreme cases. We discuss potential causes for these changing look active galactic nuclei. While similar dramatic transitions have previously been reported in the literature, either on a case-by-case basis or in larger samples focusing on quasars at higher redshifts, our study provides statistical information on the frequency of Hβ line variability in a sample of low-redshift Seyfert galaxies.

  6. Broad-Band Spectroscopy of Hercules X-1 with Suzaku

    NASA Technical Reports Server (NTRS)

    Asami, Fumi; Enoto, Teruaki; Iwakiri, Wataru; Yamada, Shin'ya; Tamagawa, Toru; Mihara, Tatehiro; Nagase, Fumiaki

    2014-01-01

    Hercules X-1 was observed with Suzaku in the main-on state from 2005 to 2010. The 0.4- 100 keV wide-band spectra obtained in four observations showed a broad hump around 4-9 keV in addition to narrow Fe lines at 6.4 and 6.7 keV. The hump was seen in all the four observations regardless of the selection of the continuum models. Thus it is considered a stable and intrinsic spectral feature in Her X-1. The broad hump lacked a sharp structure like an absorption edge. Thus it was represented by two different spectral models: an ionized partial covering or an additional broad line at 6.5 keV. The former required a persistently existing ionized absorber, whose origin was unclear. In the latter case, the Gaussian fitting of the 6.5-keV line needs a large width of sigma = 1.0-1.5 keV and a large equivalent width of 400-900 eV. If the broad line originates from Fe fluorescence of accreting matter, its large width may be explained by the Doppler broadening in the accretion flow. However, the large equivalent width may be inconsistent with a simple accretion geometry.

  7. CHICKEN COOP AND BROAD LEAF MAPLE, LOOKING NORTHEAST. Three chicken ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CHICKEN COOP AND BROAD LEAF MAPLE, LOOKING NORTHEAST. Three chicken coops on the farm were used by both chickens and turkeys. The yards around the buildings were once fenced in to give the poultry brooding space. - Kineth Farm, Chicken Coop, 19162 STATE ROUTE 20, Coupeville, Island County, WA

  8. Numerical Models of Broad Bandwidth Nanosecond Optical Parametric Oscillators

    SciTech Connect

    Bowers, M.S.; Gehr, R.J.; Smith, A.V.

    1998-10-14

    We describe results from three new methods of numerically modeling broad-bandwidth, nanosecond OPO's in the plane-wave approximate ion. They account for differences in group velocities among the three mixing waves, and also include a qutt~ttun noise model.

  9. Thinking Broadly: Financing Strategies for Comprehensive Child and Family Initiatives.

    ERIC Educational Resources Information Center

    Hayes, Cheryl D.

    In the current tight fiscal environment, it is critical for state and community leaders to think broadly and systematically about how to finance important education, family, and child services, and community development initiatives. This guide presents a conceptual framework for financing child and family services and community building and…

  10. Broad-Area Laser Diode With Fiber-Optic Injection

    NASA Technical Reports Server (NTRS)

    Hazel, Geoffrey; Mead, Patricia; Davis, Christopher; Cornwell, Donald

    1992-01-01

    Fiber-optic injection-locked broad-area laser diode features single-mode output via fiber-optic injection and serves as compact, rugged, high-power near-infrared source. Useful in free-space and fiber-optic communication links, as communication-receiver preamplifier, and pump source for solid-state lasers.

  11. It's Up to Us! Broad Form Deeds in Kentucky.

    ERIC Educational Resources Information Center

    Zuercher, Melanie A., Ed.

    This adult literacy curriculum best serves groups of students, but is also effective for one-on-one tutoring methods. The material covers the history of broad form deeds in Kentucky (instruments with which coal rights, but not the farmlands above the coal, were sold to mining companies) and includes four personal narratives of Kentucky residents…

  12. Model Invariance across Genders of the Broad Autism Phenotype Questionnaire

    ERIC Educational Resources Information Center

    Broderick, Neill; Wade, Jordan L.; Meyer, J. Patrick; Hull, Michael; Reeve, Ronald E.

    2015-01-01

    ASD is one of the most heritable neuropsychiatric disorders, though comprehensive genetic liability remains elusive. To facilitate genetic research, researchers employ the concept of the broad autism phenotype (BAP), a milder presentation of traits in undiagnosed relatives. Research suggests that the BAP Questionnaire (BAPQ) demonstrates…

  13. The Broad Autism Phenotype. Findings from an Epidemiological Survey

    ERIC Educational Resources Information Center

    Micali, N.; Chakrabarti, S.; Fombonne, E.

    2004-01-01

    This study aimed to determine if relatives of children with autism and less severe pervasive developmental disorders (PDDs) have higher rates of various components of the broad autistic phenotype. Psychiatric and medical disorders were investigated. Parents of children with PDDs were selected from an epidemiological survey and compared with…

  14. A planar broad-band flared microstrip slot antenna

    NASA Astrophysics Data System (ADS)

    Povinelli, Mark J.

    1987-08-01

    Experimental results have been obtained on a planar multioctave bandwidth flared microstrip slot. When crossed, the element is capable of horizontal, vertical, or circular polarization. A design was fabricated and measurements were taken to define the performance. The input impedance and radiation characteristics are shown to have a broad-band response when configured as a cavity-backed element.

  15. Broad Classification and the Provisional Nature of Science

    ERIC Educational Resources Information Center

    McCarthy, Susan; Sanders, Martie

    2007-01-01

    This paper proposes the use of a key biological concept--broad classification--to teach the provisional and contested nature of science in school biology curricula. It also examines existing curriculum-related factors which might pose obstacles to implementing such a change. An investigation in South Africa highlights the problems regarding…

  16. Optimizing technology investments: a broad mission model approach

    NASA Technical Reports Server (NTRS)

    Shishko, R.

    2003-01-01

    A long-standing problem in NASA is how to allocate scarce technology development resources across advanced technologies in order to best support a large set of future potential missions. Within NASA, two orthogonal paradigms have received attention in recent years: the real-options approach and the broad mission model approach. This paper focuses on the latter.

  17. Public Broadly Embraces the Need for Higher Standards, Rigorously Enforced.

    ERIC Educational Resources Information Center

    American Educator, 1996

    1996-01-01

    A series of focus group studies conducted by the Public Agenda Foundation explored public reactions to educational standards in 1993. This study revealed broad and spontaneous support for the idea that higher expectations will produce higher achievement. The strong endorsement of higher standards was also a manifestation of the public's concern…

  18. Self in Culture: Confusions of a Broad-Minded Constructivist.

    ERIC Educational Resources Information Center

    Kahn, Peter H., Jr.

    This essay emphasizes a need for broad-minded constructivism which posits that individuals have coherent ways of understanding their world and that these understandings are structured and hierarchically organized. The meaning behind the term "co-construction," used in psychology, anthropology, sociology, and other disciplines, is analyzed. Three…

  19. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor suppressor genes

    PubMed Central

    Chen, Kaifu; Chen, Zhong; Wu, Dayong; Zhang, Lili; Lin, Xueqiu; Su, Jianzhong; Rodriguez, Benjamin; Xi, Yuanxin; Xia, Zheng; Chen, Xi; Shi, Xiaobing; Wang, Qianben; Li, Wei

    2016-01-01

    Tumor suppressors are mostly defined by inactivating mutations in tumors, yet little is known about their epigenetic features in normal cells. Through integrative analysis of 1,134 genome-wide epigenetic profiles, mutations from >8,200 tumor-normal pairs, and our experimental data from clinical samples, we discovered broad H3K4me3 (wider than 4 kb) as the first epigenetic signature for tumor suppressors in normal cells. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity together leading to exceptionally high gene expression, and is distinct from other broad epigenetic features, such as super-enhancers. Broad H3K4me3 conserved across normal cells may represent pan-cancer tumor suppressors, such as P53 and PTEN, whereas cell-type-specific broad H3K4me3 may indicate cell-identity genes and cell-type-specific tumor suppressors. Furthermore, widespread shortening of broad H3K4me3 in cancers is associated with repression of tumor suppressors. Together, the broad H3K4me3 epigenetic signature provides mutation-independent information for the discovery and characterization of novel tumor suppressors. PMID:26301496

  20. Effects of broad frequency vibration on cultured osteoblasts

    NASA Technical Reports Server (NTRS)

    Tanaka, Shigeo M.; Li, Jiliang; Duncan, Randall L.; Yokota, Hiroki; Burr, David B.; Turner, Charles H.

    2003-01-01

    Bone is subjected in vivo to both high amplitude, low frequency strain, incurred by locomotion, and to low amplitude, broad frequency strain. The biological effects of low amplitude, broad frequency strain are poorly understood. To evaluate the effects of low amplitude strains ranging in frequency from 0 to 50 Hz on osteoblastic function, we seeded MC3T3-E1 cells into collagen gels and applied the following loading protocols for 3 min per day for either 3 or 7 days: (1) sinusoidal strain at 3 Hz, with 0-3000 microstrain peak-to-peak followed by 0.33 s resting time, (2) "broad frequency vibration" of low amplitude strain (standard deviation of 300 microstrain) including frequency components from 0 to 50 Hz, and (3) sinusoidal strain combined with broad frequency vibration (S + V). The cells were harvested on day 4 or 8. We found that the S + V stimulation significantly repressed cell proliferation by day 8. Osteocalcin mRNA was up-regulated 2.6-fold after 7 days of S + V stimulation, and MMP-9 mRNA was elevated 1.3-fold after 3 days of vibration alone. Sinusoidal stimulation alone did not affect the cell responses. No differences due to loading were observed in alkaline phosphatase activity and in mRNA levels of type I collagen, osteopontin, connexin 43, MMPs-1A, -3, -13. These results suggest that osteoblasts are more sensitive to low amplitude, broad frequency strain, and this kind of strain could sensitize osteoblasts to high amplitude, low frequency strain. This suggestion implies a potential contribution of stochastic resonance to the mechanical sensitivity of osteoblasts. Copyright 2002 Elsevier Science Ltd.

  1. The orientation and polarization of broad absorption line quasars

    NASA Astrophysics Data System (ADS)

    DiPompeo, M. A.; Brotherton, M. S.; De Breuck, C.

    2013-01-01

    We present new spectropolarimetric observations of eight radio-loud broad absorption line (BAL) quasars, and combine these new data with our previous spectropolarimetric atlases (of both radio-loud and radio-quiet objects; DiPompeo et al. 2010, DiPompeo et al. 2011a) in order to investigate the polarization properties of BAL quasars as a group. The total (radio-selected) sample includes 36 (26) high-ionization and 22 (15) low-ionization BAL quasars (HiBALs and LoBALs, respectively). On average, we confirm that broad emission lines are polarized at a level similar to or less than the continuum and broad absorption troughs are more highly polarized, but we note that these properties are not true for all individual objects. Of the whole sample, 18 (31 per cent) have high (>2 per cent) continuum polarization, including 45 per cent of the LoBALs and 22 per cent of the HiBALs. We identify a few correlations between polarization and other quasar properties, as well as some interesting non-correlations. In particular, continuum polarization does not correlate with radio spectral index, which suggests that the polarization is not due to a standard geometry and preferred viewing angle to BAL quasars. The polarization also does not correlate with the amount of intrinsic dust reddening, indicating that the polarization is not solely due to direct light attenuation either. Polarization does appear to depend on the minimum BAL outflow velocity, confirming the results of previous studies and it may correlate with the maximum outflow velocity. We also find that continuum polarization anticorrelates with the polarization in the C iv broad emission and broad absorption. These results suggest that the polarization of BAL quasars cannot be described by one simple model, and that the scatterer location and geometry can vary significantly from object to object.

  2. TIME VARIABLE BROAD-LINE EMISSION IN NGC 4203: EVIDENCE FOR STELLAR CONTRAILS

    SciTech Connect

    Devereux, Nick

    2011-12-10

    Dual epoch spectroscopy of the lenticular galaxy, NGC 4203, obtained with the Hubble Space Telescope has revealed that the double-peaked component of the broad H{alpha} emission line is time variable, increasing by a factor of 2.2 in brightness between 1999 and 2010. Modeling the gas distribution responsible for the double-peaked profiles indicates that a ring is a more appropriate description than a disk and most likely represents the contrail of a red supergiant star that is being tidally disrupted at a distance of {approx}1500 AU from the central black hole. There is also a bright core of broad H{alpha} line emission that is not time variable and identified with a large-scale inflow from an outer radius of {approx}1 pc. If the gas number density is {>=}10{sup 6} cm{sup -3}, as suggested by the absence of similarly broad [O I] and [O III] emission lines, then the steady state inflow rate is {approx} 2 Multiplication-Sign 10{sup -2} M{sub Sun} yr{sup -1}, which exceeds the inflow requirement to explain the X-ray luminosity in terms of radiatively inefficient accretion by a factor of {approx}6. The central active galactic nucleus (AGN) is unable to sustain ionization of the broad-line region; the discrepancy is particularly acute in 2010 when the broad H{alpha} emission line is dominated by the contrail of the infalling supergiant star. However, ram pressure shock ionization produced by the interaction of the infalling supergiant with the ambient interstellar medium may help alleviate the ionizing deficit by generating a mechanical source of ionization supplementing the photoionization provided by the AGN.

  3. Comparison of PA imaging by narrow beam scanning and one-shot broad beam excitation

    NASA Astrophysics Data System (ADS)

    Xia, Jinjun; Wei, Chen-Wei; Huang, Lingyun; Pelivanov, I. M.; O'Donnell, Matthew

    2011-03-01

    Current systems designed for deep photoacoustic (PA) imaging typically use a low repetition rate, high power pulsed laser to provide a ns-scale pulse illuminating a large tissue volume. Acoustic signals recorded on each laser firing can be used to reconstruct a complete 2-D (3-D) image of sources of heat release within that region. Using broad-beam excitation, the maximum frame rate of the imaging system is restricted by the pulse repetition rate of the laser. An alternate illumination approach is proposed based on fast scanning by a low energy (~ 1 mJ) high repetition rate (up to a few kHz) narrow laser beam (~1 mm) along the tissue surface over a region of interest. A final PA image is produced from the summation of individual PA images reconstructed at each laser beam position. This concept can take advantage of high repetition rate fiber lasers to create PA images with much higher frame rates than current systems, enabling true real-time integration of photoacoustics with ultrasound imaging. As an initial proof of concept, we compare conventional broad beam illumination to a scanned beam approach in a simple model system. Two transparent teflon tubes with diameters of 1.6 mm and 0.8 mm were filled with ink having an absorption coefficient of 5 cm-1. These tubes were buried inside chicken breast tissue acting as an optical scattering medium. They were separated by 3 mm or 10 mm to test spatial and contrast resolution for the two scan formats. The excitation wavelength was 700 nm. The excitation source is a traditional OPO pumped by a Q-switched Nd:YAG laser with doubler. Photoacoustic images were reconstructed using signals from a small, scanned PVDF transducer acting as an acoustic array. Two different illumination schemes were compared: one was 15 mm x 10 mm in cross section and acted as the broad beam; the other was 5 mm x 2 mm in cross section (15 times smaller than the broad beam case) and was scanned over an area equivalent to broad beam illumination

  4. The precipitation synthesis of broad-spectrum UV absorber nanoceria

    SciTech Connect

    Nurhasanah, Iis; Sutanto, Heri; Puspaningrum, Nurul Wahyu

    2013-09-09

    In this paper the possibility of nanoceria as broad-spectrum UV absorber was evaluated. Nanoceria were synthesized by precipitation process from cerium nitrate solution and ammonium hydroxide as precipitant agent. Isopropanol was mixed with water as solvent to prevent hard agglomeration. The structure of resulting nanoceria was characterized by x-ray diffractometer (XRD). The transparency in the visible light and efficiency of protection in UV A region were studied using ultraviolet-visible (UV - Vis) spectrophotometer. The results show that nanoceria possess good tranparency in visible light and high UV light absorption. The critical absorption wavelenght of 368 nm was obtained which is desirable for excellent broad-spectrum protection absorbers. Moreover, analysis of photodegradation nanoceria to methylene blue solution shows poor photocatalytic activity. It indicates that nanoceria suitable for used as UV absorber in personal care products.

  5. Shaper-assisted phase optimization of a broad "holey" spectrum.

    PubMed

    Zhi, Miaochan; Wang, Kai; Hua, Xia; Strycker, Benjamin D; Sokolov, Alexei V

    2011-11-01

    We develop a technique for optimizing the phase of broad spectrally-separated frequency sidebands-a "holey" spectrum. We use a source of multiple-order coherent Raman sidebands, obtained by crossing femtosecond pump and Stokes beams in synthetic single-crystal diamond. We combine the sidebands into a single beam and show the phase coherence among the sidebands by investigating the interference between them in groups of three while varying one sideband phase by an acousto-optics pulse shaper. We then show how we optimize the broad "holey" spectrum by overcoming the limited temporal shaping window of the pulse shaper. We also explore how the resultant second harmonic/sum frequency generation of the full combined broadband spectrum varies as we vary different sideband phases. This step-by-step phase optimization of the "holey" spectrum can be applied to sidebands with similar structure to synthesize arbitrary optical waveforms. PMID:22109216

  6. Broad Consent For Research With Biological Samples: Workshop Conclusions

    PubMed Central

    Grady, Christine; Eckstein, Lisa; Berkman, Ben; Brock, Dan; Cook-Deegan, Robert; Fullerton, Stephanie M.; Greely, Hank; Hansson, Mats G.; Hull, Sara; Kim, Scott; Lo, Bernie; Pentz, Rebecca; Rodriguez, Laura; Weil, Carol; Wilfond, Benjamin S.; Wendler, David

    2016-01-01

    Different types of consent are used to obtain human biospecimens for future research. This variation has resulted in confusion regarding what research is permitted, inadvertent constraints on future research, and research proceeding without consent. The NIH Clinical Center’s Department of Bioethics held a workshop to consider the ethical acceptability of addressing these concerns by using broad consent for future research on stored biospecimens. Multiple bioethics scholars, who have written on these issues, discussed the reasons for consent, the range of consent strategies, gaps in our understanding, and concluded with a proposal for broad initial consent coupled with oversight and, when feasible, ongoing provision of information to donors. The manuscript describes areas of agreement as well as areas that need more research and dialogue. Given recent proposed changes to the Common Rule, and new guidance regarding storing and sharing data and samples, this is an important and timely topic. PMID:26305750

  7. Experimental evaluation of combustor concepts for burning broad property fuels

    NASA Technical Reports Server (NTRS)

    Kasper, J. M.; Ekstedt, E. E.; Dodds, W. J.; Shayeson, M. W.

    1980-01-01

    A baseline CF6-50 combustor and three advanced combustor designs were evaluated to determine the effects of combustor design on operational characteristics using broad property fuels. Three fuels were used in each test: Jet A, a broad property 13% hydrogen fuel, and a 12% hydrogen fuel blend. Testing was performed in a sector rig at true cruise and simulated takeoff conditions for the CF6-50 engine cycle. The advanced combustors (all double annular, lean dome designs) generally exhibited lower metal temperatures, exhaust emissions, and carbon buildup than the baseline CF6-50 combustor. The sensitivities of emissions and metal temperatures to fuel hydrogen content were also generally lower for the advanced designs. The most promising advanced design used premixing tubes in the main stage. This design was chosen for additional testing in which fuel/air ratio, reference velocity, and fuel flow split were varied.

  8. The precipitation synthesis of broad-spectrum UV absorber nanoceria

    NASA Astrophysics Data System (ADS)

    Nurhasanah, Iis; Sutanto, Heri; Puspaningrum, Nurul Wahyu

    2013-09-01

    In this paper the possibility of nanoceria as broad-spectrum UV absorber was evaluated. Nanoceria were synthesized by precipitation process from cerium nitrate solution and ammonium hydroxide as precipitant agent. Isopropanol was mixed with water as solvent to prevent hard agglomeration. The structure of resulting nanoceria was characterized by x-ray diffractometer (XRD). The transparency in the visible light and efficiency of protection in UV A region were studied using ultraviolet-visible (UV - Vis) spectrophotometer. The results show that nanoceria possess good tranparency in visible light and high UV light absorption. The critical absorption wavelenght of 368 nm was obtained which is desirable for excellent broad-spectrum protection absorbers. Moreover, analysis of photodegradation nanoceria to methylene blue solution shows poor photocatalytic activity. It indicates that nanoceria suitable for used as UV absorber in personal care products.

  9. Broad Feshbach resonances in collisions of Dy atoms

    NASA Astrophysics Data System (ADS)

    Julienne, P.; Jachymski, K.; Maier, T.; Ferrier-Barbut, I.; Karan, H.; Schmitt, M.; Wenzel, M.; Wink, C.; Pfau, T.

    2016-05-01

    RF spectroscopy of weakly bound dimers of ultra cold bosonic Dy atoms gives evidence for the emergence of a universal s-wave halo state in a background of chaotic background resonance states. The halo state is associated with a broad magnetic Feshbach resonance. Using a coupled channels theory taking into account the short ranged van dear Waals interaction and a correction due to the strong dipole moment of Dy, we are able to extract the scattering length as a function of magnetic field tuning near two such broad resonances. These results offer prospects for tuning the interactions of Dy atoms in a regime where three-body losses are not too strong. Supported in part by the DFG, the Foundation for Polish Science International Ph. D Projects Programme, and an AFOSR MURI.

  10. Broad Absorption Line Quasar catalogues with Supervised Neural Networks

    NASA Astrophysics Data System (ADS)

    Scaringi, Simone; Cottis, Christopher E.; Knigge, Christian; Goad, Michael R.

    2008-12-01

    We have applied a Learning Vector Quantization (LVQ) algorithm to SDSS DR5 quasar spectra in order to create a large catalogue of broad absorption line quasars (BALQSOs). We first discuss the problems with BALQSO catalogues constructed using the conventional balnicity and/or absorption indices (BI and AI), and then describe the supervised LVQ network we have trained to recognise BALQSOs. The resulting BALQSO catalogue should be substantially more robust and complete than BI-or AI-based ones.

  11. Broad Absorption Line Quasar catalogues with Supervised Neural Networks

    SciTech Connect

    Scaringi, Simone; Knigge, Christian; Cottis, Christopher E.; Goad, Michael R.

    2008-12-05

    We have applied a Learning Vector Quantization (LVQ) algorithm to SDSS DR5 quasar spectra in order to create a large catalogue of broad absorption line quasars (BALQSOs). We first discuss the problems with BALQSO catalogues constructed using the conventional balnicity and/or absorption indices (BI and AI), and then describe the supervised LVQ network we have trained to recognise BALQSOs. The resulting BALQSO catalogue should be substantially more robust and complete than BI-or AI-based ones.

  12. Broad Spectrum Antiangiogenic Treatment for Ocular Neovascular Diseases

    PubMed Central

    Benny, Ofra; Nakai, Kei; Yoshimura, Takeru; Bazinet, Lauren; Akula, James D.; Nakao, Shintaro; Hafezi-Moghadam, Ali; Panigrahy, Dipak; Pakneshan, Pouya; D'Amato, Robert J.

    2010-01-01

    Pathological neovascularization is a hallmark of late stage neovascular (wet) age-related macular degeneration (AMD) and the leading cause of blindness in people over the age of 50 in the western world. The treatments focus on suppression of choroidal neovascularization (CNV), while current approved therapies are limited to inhibiting vascular endothelial growth factor (VEGF) exclusively. However, this treatment does not address the underlying cause of AMD, and the loss of VEGF's neuroprotective can be a potential side effect. Therapy which targets the key processes in AMD, the pathological neovascularization, vessel leakage and inflammation could bring a major shift in the approach to disease treatment and prevention. In this study we have demonstrated the efficacy of such broad spectrum antiangiogenic therapy on mouse model of AMD. Methods and Findings Lodamin, a polymeric formulation of TNP-470, is a potent broad-spectrum antiangiogenic drug. Lodamin significantly reduced key processes involved in AMD progression as demonstrated in mice and rats. Its suppressive effects on angiogenesis, vascular leakage and inflammation were studied in a wide array of assays including; a Matrigel, delayed-type hypersensitivity (DTH), Miles assay, laser-induced CNV and corneal micropocket assay. Lodamin significantly suppressed the secretion of various pro-inflammatory cytokines in the CNV lesion including monocyte chemotactic protein-1 (MCP-1/Ccl2). Importantly, Lodamin was found to regress established CNV lesions, unlike soluble fms-like tyrosine kinase-1 (sFlk-1). The drug was found to be safe in mice and have little toxicity as demonstrated by electroretinography (ERG) assessing retinal and by histology. Conclusions Lodamin, a polymer formulation of TNP-470, was identified as a first in its class, broad-spectrum antiangiogenic drug that can be administered orally or locally to treat corneal and retinal neovascularization. Several unique properties make Lodamin especially

  13. 78 FR 67084 - Drawbridge Operation Regulation; Broad Creek, Laurel, DE

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ...The Coast Guard is proposing to change the regulation that governs the operation of the Poplar Street Bridge, mile 8.2, and the U.S. 13A Bridge over Broad Creek, mile 8.25, both at Laurel, DE. The proposed new rule would change the current regulation by requiring a forty-eight hour advance notice and by allowing the bridges to remain in the closed position for the passage of...

  14. Flow structure in front of the broad-crested weir

    NASA Astrophysics Data System (ADS)

    Zachoval, Zbyněk; Roušar, Ladislav

    2015-05-01

    The paper deals with research focused on description of flow structure in front of broad-crested weir. Based on experimental measurement, the flow structure in front of the weir (the recirculation zone of flow and tornado vortices) and flow structure on the weir crest has been described. The determined flow character has been simulated using numerical model and based on comparing results the suitable model of turbulence has been recommended.

  15. Development of broad beam ion sources at CSSAR

    NASA Astrophysics Data System (ADS)

    Feng, Y. C.; You, D. W.; Kuang, Y. Z.

    1994-04-01

    High-energy and intense beam current broad beam ion sources have been developed for ion implantation and dynamic recoil mixing at CSSAR. The sources can be operated over beam energy and current ranges of 3-120 keV and 5-70 mA, respectively. For sputter coating of thin films, a series of focusing beam ion sources with different structures has also been developed. The energy and current range from 1-10 keV and 100-350 mA for different applications. For some applications, low-energy (below 100 eV) ion beams are required. CSSAR has developed a 6-cm-diam broad beam ion source. The source can be operated at beam energy 10-70 eV, and the beam current 15-80 mA has been extracted. Typical structures and operational data are given for the sources mentioned above. Recently a new type of broad beam metal ion source (Electron Beam Evaporation Metal Ion Source EBE) is being studied. Ion beams of several kinds of materials such as C, W, Ta, Mo, Cr, Ti, B, Cu, etc. have been extracted from the source. Typical operation conditions and ion yields are given in this paper.

  16. Broad Halpha Wing Formation in the Planetary Nebula IC 4997.

    PubMed

    Lee; Hyung

    2000-02-10

    The young and compact planetary nebula IC 4997 is known to exhibit very broad wings with a width exceeding 5000 km s-1 around Halpha. We propose that the broad wings are formed through Rayleigh-Raman scattering that involves atomic hydrogen, by which Lybeta photons with a velocity width of a few 102 km s-1 are converted to optical photons and fill the Halpha broad wing region. The conversion efficiency reaches 0.6 near the line center, where the scattering optical depth is much larger than 1, and rapidly decreases in the far wings. Assuming that close to the central star there exists an unresolved inner compact core of high density, nH approximately 109-1010 cm-3, we use the photoionization code "CLOUDY" to show that sufficient Lybeta photons for scattering are produced. Using a top-hat-incident profile for the Lybeta flux and a scattering region with a H i column density NHi=2x1020 cm-2 and a substantial covering factor, we perform a profile-fitting analysis in order to obtain a satisfactory fit to the observed flux. We briefly discuss the astrophysical implications of the Rayleigh-Raman processes in planetary nebulae and other emission objects. PMID:10642203

  17. A broadly tuned mouse odorant receptor that detects nitrotoluenes

    PubMed Central

    Li, Jingyi; Haddad, Rafi; Chen, Sisi; Santos, Vanessa; Luetje, Charles W.

    2012-01-01

    Mammals employ large numbers of odorant receptors to sample and identify volatile chemicals in the environment. These receptors are thought to vary not only in specificity for particular odorants, but also in breadth of tuning. That is, some odorant receptors are narrowly focused on a few closely related structures, while other odorant receptors may be “broadly tuned”, responding to a wide variety of odorant structures. Here we have performed a detailed examination the mouse odorant receptor MOR256-17, demonstrating that this receptor is broadly tuned. This receptor responds to odorant structures that span a significant portion of a multi-dimensional odor space. However, we found that broad tuning was not a defining characteristic of other members the MOR256 subfamily. Two additional members of this odorant receptor subfamily (MOR256-8 and MOR256-22) were more narrowly focused on small sets of odorant structures. Interestingly, the receptive range of MOR256-17 encompassed a variety of nitrotoluenes, including various TNT synthesis intermediates, degradation products and TNT itself, suggesting the potential utility of odorant receptors in the development of sensing technologies for the detection of explosives and other forms of contraband. PMID:22443178

  18. Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1

    SciTech Connect

    Kong, Leopold; Giang, Erick; Robbins, Justin B.; Stanfield, Robyn L.; Burton, Dennis R.; Wilson, Ian A.; Law, Mansun

    2012-10-29

    Hepatitis C virus (HCV) infects more than 2% of the global population and is a leading cause of liver cirrhosis, hepatocellular carcinoma, and end-stage liver diseases. Circulating HCV is genetically diverse, and therefore a broadly effective vaccine must target conserved T- and B-cell epitopes of the virus. Human mAb HCV1 has broad neutralizing activity against HCV isolates from at least four major genotypes and protects in the chimpanzee model from primary HCV challenge. The antibody targets a conserved antigenic site (residues 412-423) on the virus E2 envelope glycoprotein. Two crystal structures of HCV1 Fab in complex with an epitope peptide at 1.8-{angstrom} resolution reveal that the epitope is a {beta}-hairpin displaying a hydrophilic face and a hydrophobic face on opposing sides of the hairpin. The antibody predominantly interacts with E2 residues Leu{sup 413} and Trp{sup 420} on the hydrophobic face of the epitope, thus providing an explanation for how HCV isolates bearing mutations at Asn{sup 415} on the same binding face escape neutralization by this antibody. The results provide structural information for a neutralizing epitope on the HCV E2 glycoprotein and should help guide rational design of HCV immunogens to elicit similar broadly neutralizing antibodies through vaccination.

  19. 27. Yards north of Branch Avenue Bridge. Providence, Providence Co., ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    27. Yards north of Branch Avenue Bridge. Providence, Providence Co., RI. Sec. 4116, mp 186.25. - Northeast Railroad Corridor, Amtrak route between CT & MA state lines, Providence, Providence County, RI

  20. 28. Yards north of Branch Avenue Bridge. Providence, Providence Co., ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. Yards north of Branch Avenue Bridge. Providence, Providence Co., RI. Sec. 4116, mp 186.25. - Northeast Railroad Corridor, Amtrak route between CT & MA state lines, Providence, Providence County, RI

  1. An evolutionary perspective on the broad antiviral specificity of MxA.

    PubMed

    Mitchell, Patrick S; Emerman, Michael; Malik, Harmit S

    2013-08-01

    Germ line encoded antiviral defenses in vertebrate cells tend to be either broadly acting factors that exploit general features of viral replication or effectors with strong pathogen preference by virtue of specific recognition of viral proteins. The Mx GTPases, however, are atypical since they have broad antiviral activity against a wide range of RNA and DNA viruses despite specifically targeting different proteins across virus families. This review presents recent advances in understanding the biochemical properties and evolution of the primate ortholog MxA, and discusses how this information begins to provide molecular insights into the mechanisms behind the intriguing conundrum of how MxA is able to engage a diversity of viral proteins yet elicit antiviral breadth. PMID:23725670

  2. Safety requirements, facility user needs, and reactor concepts for a new Broad Application Test Reactor

    SciTech Connect

    Ryskamp, J.M.; Liebenthal, J.L.; Denison, A.B.; Fletcher, C.D.

    1992-07-01

    This report describes the EG&G Laboratory Directed Research and Development Program (LDRD) Broad Application Test Reactor (BATR) Project that was conducted in fiscal year 1991. The scope of this project was divided into three phases: a project process definition phase, a requirements development phase, and a preconceptual reactor design and evaluation phase. Multidisciplinary teams of experts conducted each phase. This report presents the need for a new test reactor, the project process definition, a set of current and projected regulatory compliance and safety requirements, a set of facility user needs for a broad range of projected testing missions, and descriptions of reactor concepts capable of meeting these requirements. This information can be applied to strategic planning to provide the Department of Energy with management options.

  3. Safety requirements, facility user needs, and reactor concepts for a new Broad Application Test Reactor

    SciTech Connect

    Ryskamp, J.M.; Liebenthal, J.L.; Denison, A.B.; Fletcher, C.D.

    1992-07-01

    This report describes the EG G Laboratory Directed Research and Development Program (LDRD) Broad Application Test Reactor (BATR) Project that was conducted in fiscal year 1991. The scope of this project was divided into three phases: a project process definition phase, a requirements development phase, and a preconceptual reactor design and evaluation phase. Multidisciplinary teams of experts conducted each phase. This report presents the need for a new test reactor, the project process definition, a set of current and projected regulatory compliance and safety requirements, a set of facility user needs for a broad range of projected testing missions, and descriptions of reactor concepts capable of meeting these requirements. This information can be applied to strategic planning to provide the Department of Energy with management options.

  4. Intrinsic performance-limiting instabilities in two-level class-B broad-area lasers

    NASA Astrophysics Data System (ADS)

    Pakhomov, A. V.; Molevich, N. E.; Krents, A. A.; Anchikov, D. A.

    2016-08-01

    The present paper is concerned with the analytical and numerical investigation of the transverse spatio-temporal instabilities in two-level broad-area lasers for the specific class-B case. We show that the two-level class-B broad-area laser tends to naturally operate in the filamentary state. This is revealed to be provided with two causes. First of them is related with the homogeneous output profile being intrinsically unstable due to the traveling-wave instability, independently from the boundary conditions. Secondly, high sensitivity to the boundaries of the pumping region was found for the commonly used top-hat-like profile leading to boundaries-induced filamentary dynamics. Spatio-temporal properties of both instability mechanisms are studied and their effects on the resulting laser dynamical behavior are analyzed.

  5. Ground Based Test Results for Broad Band LIDAR

    NASA Astrophysics Data System (ADS)

    Heaps, W. S.; Georgieva, E.; Huang, W.; Baldauf, B.; McComb, T.

    2010-12-01

    a 1.57 μm superluminescent light emitting diode (SLED) amplified by an optical parametric amplifier (OPA). In 2008 NGAS, leveraging expertise in thulium (Tm) fiber laser systems and recognizing the merit of the broadband approach, suggested a partnership with GSFC to develop a broadband lidar operating at 2.05 μm. Such a system takes advantage of the broad Tm-fiber gain spectrum and the inherent mechanical robustness, compact size, simple power scalability, efficiency and high beam quality offered by fiber lasers. In early 2010 NGAS completed development of a laboratory level, highly efficient, Tm-fiber laser that produces a specially formatted pulsed broadband output around 2.05 μm, a spectral region where CO2 has strong atmospheric absorption features. NGAS has loaned this tunable 2.05 μm laser to GSFC which had concurrently developed a 2.05 μm lidar sensor/receiver. In May 2010 the two systems were tested together to provide proof of concept of 2.05 µm broadband detection of CO2. This presentation will present results of ground based testing of the 1.57 μm and the 2.05 μm systems and discuss their potential application as space borne sensors for the ASCENDS mission.

  6. Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes: A Nationwide Danish Cohort Study

    PubMed Central

    Bergholt, Thomas; Bouaziz, Olivier; Arpi, Magnus; Eriksson, Frank; Rasmussen, Steen; Keiding, Niels; Løkkegaard, Ellen C.

    2016-01-01

    Background Studies link antibiotic treatment and delivery by cesarean section with increased risk of chronic diseases through changes of the gut-microbiota. We aimed to evaluate the association of broad-spectrum antibiotic treatment during the first two years of life with subsequent onset of childhood type 1 diabetes and the potential effect-modification by mode of delivery. Materials and Methods A Danish nationwide cohort study including all singletons born during 1997–2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow-spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes. Results Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years of life (HR 1.13; 95% CI 1.02 to 1.25), however, the rate was modified by mode of delivery. Broad-spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by either intrapartum cesarean section (HR 1.70; 95% CI 1.15 to 2.51) or prelabor cesarean section (HR 1.63; 95% CI 1.11 to 2.39), but not in vaginally delivered children. Number needed to harm was 433 and 562, respectively. The association with broad-spectrum antibiotics was not modified by parity, genetic predisposition or maternal redemption of antibiotics during pregnancy or lactation. Conclusions Redemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section. PMID:27560963

  7. Earthquake response considerations of broad liquid storage tanks

    NASA Astrophysics Data System (ADS)

    Cambra, F. J.

    1982-11-01

    The influences of tank geometry and foundation stiffness variation on the simulated seismic structural response of a model broad tank are discussed. An empirical method for describing tank bottom plate uplift geometry is proposed which recognizes radial catenary force and foundation stiffness. Axial symmetric lift, static tilt and dynamic shaking table tests were performed in the University of California, Berkeley, earthquake simulator laboratory. A structural geometric survey of a 63 ft - 10 inches tall by 289 ft - 6 inches diameter crude oil storage tank was conducted to establish a comparative base by which to evaluate the model tank eccentricities.

  8. Broad-line region at the center of the Galaxy

    SciTech Connect

    Geballe, T.R.; Wade, R.; Krisciunas, K.; Gatley, I.; Bird, M.C.

    1987-09-01

    The high-velocity wings of the Br-alpha (405 micron) line at the Galactic center have been mapped with a 2.5 arcsec beam and at a velocity resolution of 400 km/s. The peak intensity of the high-velocity line emission is coincident with the position of the source IRS 16 Center. It is suggested that the broad-line emission either is from more than one compact wind source or is the result of an interaction between an ultrahigh velocity wind and slower moving ionized gas in the bar whose trajectory brings it close to the wind source. 31 references.

  9. Assessment of autonomic response by broad-band respiration

    NASA Technical Reports Server (NTRS)

    Berger, R. D.; Saul, J. P.; Cohen, R. J.

    1989-01-01

    We present a technique for introducing broad-band respiratory perturbations so that the response characteristics of the autonomic nervous system can be determined noninvasively over a wide range of physiologically relevant frequencies. A subject's respiratory bandwidth was broadened by breathing on cue to a sequence of audible tones spaced by Poisson intervals. The transfer function between the respiratory input and the resulting instantaneous heart rate was then computed using spectral analysis techniques. Results using this method are comparable to those found using traditional techniques, but are obtained with an economy of data collection.

  10. 4. Looking east towards the Broad Street Bridge at Fall ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Looking east towards the Broad Street Bridge at Fall No. 2. A dam extended from the rock abutment, visible on the left, to a point just above Monadnock Mill No. 1, the right border in the photo. Water entered a canal on the south side of the dam, an area under the 1 1/2 story wood structure, and then flowed into Mill No. 1 where it powered a breast wheel. The long 3-story building was the Cloth Room Building/Old Bleach House. - Claremont Village Industrial District, Between B, Claremont, Sullivan County, NH

  11. Novel approaches to increasing the brightness of broad area lasers

    NASA Astrophysics Data System (ADS)

    Crump, P.; Winterfeldt, M.; Decker, J.; Ekterai, M.; Fricke, J.; Knigge, S.; Maaßdorf, A.; Erbert, G.

    2016-03-01

    Progress in studies to increase the lateral brightness Blat of broad area lasers is reviewed. Blat=Pout/BPPlat is maximized by developing designs and technology for lowest lateral beam parameter product, BPPlat, at highest optical output power Pout. This can be achieved by limiting the number of guided lateral modes and by improving the beam quality of low-order lateral modes. Important effects to address include process and packaging induced wave-guiding, lateral carrier accumulation and the thermal lens profile. A careful selection of vertical design is also shown to be important, as are advanced techniques to filter out higher order modes.

  12. THE LICK AGN MONITORING PROJECT: ALTERNATE ROUTES TO A BROAD-LINE REGION RADIUS

    SciTech Connect

    Greene, Jenny E.; Hood, Carol E.; Barth, Aaron J.; Bentz, Misty C.; Walsh, Jonelle L.; Bennert, Vardha N.; Treu, Tommaso; Filippenko, Alexei V.; Gates, Elinor; Malkan, Matthew A.; Woo, Jong-Hak

    2010-11-01

    It is now possible to estimate black hole (BH) masses across cosmic time, using broad emission lines in active galaxies. This technique informs our views of how galaxies and their central BHs coevolve. Unfortunately, there are many outstanding uncertainties associated with these 'virial' mass estimates. One of these comes from using the accretion luminosity to infer a size for the broad-line region (BLR). Incorporating the new sample of low-luminosity active galaxies from our recent monitoring campaign at Lick Observatory, we recalibrate the radius-luminosity relation with tracers of the accretion luminosity other than the optical continuum. We find that the radius of the BLR scales as the square root of the X-ray and H{beta} luminosities, in agreement with recent optical studies. On the other hand, the scaling appears to be marginally steeper with narrow-line luminosities. This is consistent with a previously observed decrease in the ratio of narrow-line to X-ray luminosity with increasing total luminosity. The radius of the BLR correlates most tightly with H{beta} luminosity, while the X-ray and narrow-line relations both have comparable scatter of a factor of 2. These correlations provide useful alternative virial BH masses in objects with no detectable optical/UV continuum emission, such as high-redshift galaxies with broad emission lines, radio-loud objects, or local active galaxies with galaxy-dominated continua.

  13. Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

    SciTech Connect

    Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki; Oshita, Masatoshi; Ideno, Shoji; Yunoki, Mikihiro; Kuhara, Motoki; Yamamoto, Naomasa; Okuno, Yoshinobu; Ikuta, Kazuyoshi

    2009-09-11

    Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.

  14. Ray-based geoacoustic inversion for high frequency broad band data

    NASA Astrophysics Data System (ADS)

    Siderius, Martin; Hursky, Paul; Porter, Michael

    2003-04-01

    One of the difficulties in making reliable acoustic propagation predictions in shallow water is the lack of good information about the seabed type. In recent years, matched field processing- (MFP-) based geoacoustic inversion has been shown as a practical technique for estimating properties of the seabed. The MFP inversion method compares measured acoustic fields to those generated using an acoustic propagation model. Often, thousands of forward model calculations are required to find a set of seabed parameters that correlate well with the measured data. The large number of forward model calculations is computationally demanding and this is made worse when matching at higher frequencies or over broad band data. Ray-based propagation modeling relieves some of the computational burden since the calculation time is fairly insensitive to frequency and is inherently broad band. Further, the ray arrival amplitudes and delays are well suited for interpolation and this allows the seabed parameter search space to be explored using just a few ray trace calculations. The broad band nature of the modeled data provides flexibility in choosing correlation functions and this allows for more robust inversions. In this presentation, techniques using ray-based propagation modeling will be applied to the geoacoustic inversion problem.

  15. Baculovirus Displaying Hemagglutinin Elicits Broad Cross-Protection against Influenza in Mice

    PubMed Central

    Seong, Baik Lin; Nguyen, Huan Huu; Chang, Jun

    2016-01-01

    The widespread influenza virus infection further emphasizes the need for novel vaccine strategies that effectively reduce the impact of epidemic as well as pandemic influenza. Conventional influenza vaccines generally induce virus neutralizing antibody responses which are specific for a few antigenically related strains within the same subtype. However, antibodies directed against the conserved stalk domain of HA could neutralize multiple subtypes of influenza virus and thus provide broad-spectrum protection. In this study, we designed and constructed a recombinant baculovirus-based vaccine, rBac-HA virus, that expresses full-length HA of pandemic H1N1 influenza virus (A/California/04/09) on the viral envelope. We demonstrated that repeated intranasal immunizations with rBac-HA virus induced HA stalk-specific antibody responses and protective immunity against homologous as well as heterosubtypic virus challenge. The adoptive transfer experiment shows that the cross-protection is conferred by the immune sera which contain HA stalk-specific antibodies. These results warrant further development of rBac-HA virus as a broad-protective vaccine against influenza. The vaccine induced protection against infection with the same subtype as well as different subtype, promising a potential universal vaccine for broad protection against different subtypes to control influenza outbreaks including pandemic. PMID:27023684

  16. In-air broad beam ionoluminescence microscopy as a tool for rocks and stone artworks characterisation.

    PubMed

    Lo Giudice, Alessandro; Re, Alessandro; Angelici, Debora; Calusi, Silvia; Gelli, Nicla; Giuntini, Lorenzo; Massi, Mirko; Pratesi, Giovanni

    2012-07-01

    Broad beam ionoluminescence (IL) microscopy is a promising technique for the non-destructive characterisation of rocks and stone objects. Luminescence imaging by means of broad ion beams has been sporadically used by other authors but, to our knowledge, its potential has not yet been fully investigated, neither in geological science nor in other fields. The in-air broad beam IL microscope was developed and installed at the INFN-LABEC external microbeam in Florence. Similar to the cathodoluminescence (CL) microscope, the apparatus exploits a CCD colour camera collecting images (few square millimetres wide, with ~10-μm spatial resolution) of the luminescence emitted by the sample hit by a defocused megaelectron volt (MeV) proton beam. The main differences with the well-established and widespread CL are the possibility of working in air (no sampling or conductive coatings required) and the possibility of combining the analysis with microbeam analysis, such as, for example, μ-IL and μ-PIXE (particle-induced X-ray emission). To show the potential of the technique, IL images of thin sections of lapis lazuli are compared with those obtained by means of an in-vacuum cold CL. An application to the study of stone artworks is also reported. This technique and apparatus will provide a valuable help for interdisciplinary applications, e.g. in geological sciences and in the cultural heritage field. PMID:22644153

  17. Interpreting broad emission-line variations - II. Tensions between luminosity, characteristic size, and responsivity

    NASA Astrophysics Data System (ADS)

    Goad, M. R.; Korista, K. T.

    2015-11-01

    We investigate the variability behaviour of the broad H β emission-line to driving continuum variations in the best-studied AGN NGC 5548. For a particular choice of broad emission-line region (BLR) geometry, H β surface emissivity based on photoionization models, and using a scaled version of the 13-yr optical continuum light-curve as a proxy for the driving ionizing continuum, we explore several key factors that determine the broad emission-line luminosity L, characteristic size RRW, and variability amplitude (i.e. responsivity) η, as well as the interplay between them. For fixed boundary models which extend as far as the hot dust the predicted delays for H β are on average too long. However, the predicted variability amplitude of H β provides a remarkably good match to observations except during low-continuum states. We suggest that the continuum flux variations which drive the redistribution in H β surface emissivity F(r) do not on their own lead to large enough changes in RRW or ηeff. We thus investigate dust-bounded BLRs for which the location of the effective outer boundary is modulated by the continuum level and the dust-sublimation and dust-condensation time-scales. We find that in order to match the observed variability amplitude of broad H β in NGC 5548 a rather static outer boundary is preferred. Intriguingly, we show that the most effective way of reducing the H β delay, while preserving its responsivity and equivalent width, is to invoke a smaller value in the incident ionizing photon flux ΦH for a given ionizing source-cloud radial distance r, than is normally inferred from the observed UV continuum flux and typical models of the continuum spectral energy distribution.

  18. Broad Bandwidth Laser and Nonlinear Optical Sources for OCT

    NASA Astrophysics Data System (ADS)

    Unterhuber, Angelika; Považay, Boris; Aguirre, Aaron D.; Chen, Yu; Kärtner, Franz X.; Fujimoto, James G.; Drexler, Wolfgang

    OCT achieves very high axial image resolutions independent of focusing conditions because the axial and transverse resolutions are determined independently by different physical mechanisms. This implies that axial OCT resolution can be enhanced using broad bandwidth, low coherence length light sources. The light source not only determines axial OCT resolution via its bandwidth and central emission wavelength but also determines the penetration in the sample (biological tissue), the contrast of the tomogram, and the OCT transverse resolution. A minimum output power with low amplitude noise is also necessary to enable high sensitivity and high-speed - real time - OCT imaging. Hence, it is obvious that the light source is the key technological parameter for an OCT system, and proper choice is imperative. Ultrabroad bandwidth light source technology enables ultrahigh-resolution OCT in the visible and near-infrared wavelength region. Kerr-lens mode-locked solid-state lasers can generate broad bandwidth spectra spanning up to one optical octave. Nonetheless they are restricted to the fluorescence bands of the laser crystal and have a complex architecture making them expensive and preventing widespread industrial use. Spectra far broader than one optical octave can be produced via nonlinear propagation of laser pulses having only moderate energies of a few nJ in microstructured fibers. Complex fibers with one, two, or even no zero-dispersion wavelength can be designed and fabricated to fulfill special requirements as large optical bandwidth and low noise.

  19. Structure and Design of Broadly-Neutralizing Antibodies Against HIV

    PubMed Central

    Ryu, Seong Eon; Hendrickson, Wayne A.

    2012-01-01

    Since the discovery more than 30 years ago of human immunodeficiency virus (HIV) as the causative agent of the deadly disease, acquired immune deficiency disease (AIDS), there have been no efficient vaccines against the virus. For the infection of the virus, the HIV surface glycoprotein gp120 first recognizes the CD4 receptor on the target helper T-cell, which initiates HIV fusion with the target cell and, if unchecked, leads to destruction of the patient’s immune system. Despite the difficulty of developing appropriate immune responses in HIV-infected individuals, patient sera often contain antibodies that have broad neutralization activity, indicating the possibility of immunological treatment and prevention. Recently, through extensive structural studies of neutralizing antibodies of HIV in complex with gp120, the critical mechanisms of broad neutralization against HIV have been elucidated. Based on these discoveries, the structure-aided designs of antibodies and novel scaffolds were performed to create extremely potent neutralizing antibodies against HIV. These new discoveries and advances shed light on the road to development of efficient immunological therapies against AIDS. PMID:22736269

  20. The Occasional Case Against Broad Dissemination and Implementation

    PubMed Central

    Comer, Jonathan S.; Barlow, David H.

    2014-01-01

    Mental illness imposes a staggering public health burden in the United States. Although the past 40 years have witnessed tremendous advances in the identification of evidence-based practices (EBPs) in psychological treatments, gaps persist between treatment in experimental settings and services available in the community. In response, considerable attention and large financial commitments have focused in recent years on broad dissemination and implementation efforts designed to improve the quality of psychological services delivered by a variety of generalist practitioners across practice settings. Increasingly, under the influence of the Patient Protection and Affordable Care Act, it is envisioned that these generalists will practice in integrated primary care settings. These advances hold enormous potential, and yet, given the tremendous diversity of mental health problems and human suffering, broad dissemination and implementation efforts to generalists alone may not be sufficient to adequately address the burden of mental illness. Some EBPs may prove too complex for universal dissemination, and the time and expense required for quality dissemination and implementation preclude large-scale training in the treatment of low base rate disorders. As dissemination and implementation efforts work to ensure a quality generalist mental health care workforce, herein we highlight the vital need for available specialty care in the delivery of psychological treatments. Given traditional barriers that interfere with the accessibility of specialty care, we propose the transformative potential of a specialty behavioral telehealth care workforce, transacting with the generalist practitioner workforce to collectively ensure the highest quality and timely delivery of needed treatments to affected individuals. PMID:23915401

  1. The broad-lined Type Ic supernova 2003jd

    NASA Astrophysics Data System (ADS)

    Valenti, S.; Benetti, S.; Cappellaro, E.; Patat, F.; Mazzali, P.; Turatto, M.; Hurley, K.; Maeda, K.; Gal-Yam, A.; Foley, R. J.; Filippenko, A. V.; Pastorello, A.; Challis, P.; Frontera, F.; Harutyunyan, A.; Iye, M.; Kawabata, K.; Kirshner, R. P.; Li, W.; Lipkin, Y. M.; Matheson, T.; Nomoto, K.; Ofek, E. O.; Ohyama, Y.; Pian, E.; Poznanski, D.; Salvo, M.; Sauer, D. N.; Schmidt, B. P.; Soderberg, A.; Zampieri, L.

    2008-02-01

    The results of a worldwide coordinated observational campaign on the broad-lined Type Ic supernova (SN Ic) 2003jd are presented. In total, 74 photometric data points and 26 spectra were collected using 11 different telescopes. SN 2003jd is one of the most luminous SN Ic ever observed. A comparison with other Type Ic supernovae (SNe Ic) confirms that SN 2003jd represents an intermediate case between broad-line events (2002ap, 2006aj) and highly energetic SNe (1997ef, 1998bw, 2003dh, 2003lw), with an ejected mass of Mej = 3.0 +/- 1Msolar and a kinetic energy of Ek(tot) = 7+3-2 × 1051erg. SN 2003jd is similar to SN 1998bw in terms of overall luminosity, but it is closer to SNe 2006aj and 2002ap in terms of light-curve shape and spectral evolution. The comparison with other SNe Ic suggests that the V-band light curves of SNe Ic can be partially homogenized by introducing a time-stretch factor. Finally, because of the similarity of SN 2003jd to the SN 2006aj/XRF 060218 event, we discuss the possible connection of SN 2003jd with a gamma-ray burst (GRB). E-mail: svalenti@eso.org Based on observations at ESO-Paranal, Prog. 074.D-0161A.

  2. Extreme Variability in a Broad Absorption Line Quasar

    NASA Astrophysics Data System (ADS)

    Stern, Daniel; Graham, Matthew; Arav, Nahum; Djorgovski, Stanislav G.; Chamberlain, Carter; Barth, Aaron J.; Donalek, Ciro; Drake, Andrew J.; Glikman, Eilat; Jun, Hyunsung David; Mahabal, Ashish A.; Steidel, Charles C.

    2016-01-01

    We report on extreme spectral variability seen in a broad absorption line quasar over the past decade, initially identified from the Catalina Real-time Transient Survey (CRTS). Photometrically, the source had a visual magnitude of V = 17.3 between 2002 and 2008. Then, over the following 5 years, the source slowly brightened by approximately one magnitude, to V = 16.2. A combination of archival and newly acquired spectra reveal the source to be an iron low-ionization broad absorption line (Fe-LoBAL) quasar with extreme changes in its absorption spectrum. Some absorption features completely disappear over the 9 years of optical spectra, while other features remain essentially unchanged. Absorption systems separated by several 1000 km/s in velocity show coordinated changes in the depths of their troughs, correlated with the flux changes. Therefore, we interpret the variability in the absorption troughs to be due to changes in photoionization, rather than due to motion of material into our line of sight. This source highlights the sort of rare transition objects that astronomy will now be finding through dedicated time domain surveys.

  3. Effect of gamma irradiation on antinutritional factors in broad bean

    NASA Astrophysics Data System (ADS)

    Al-Kaisey, Mahdi T.; Alwan, Abdul-Kader H.; Mohammad, Manal H.; Saeed, Amjed H.

    2003-06-01

    The effect of gamma irradiation on the level of antinutritional factors (trypsin inhibitor (TI), phytic acid and oligosaccharides) of broad bean was investigated. The seeds were subjected to gamma irradiation at 0, 2.5, 5, 7.5 and 10 kGy, respectively using cobalt-60 gamma radiation with a dose rate 2.37 kGy/h. TI activity was reduced by 4.5%, 6.7%, 8.5% and 9.2% at 2.5, 5, 7.5 and 10 kGy, respectively. Meanwhile, irradiation at 10.2, 12.3, 15.4 and 18.2 kGy reduced the phytic acid content. The flatulence causing oligosaccharides were decreased as the radiation dose increased. The chemical composition (protein, oil, ash and total carbohydrates) of the tested seeds was determined. Gamma radiation seems to be a good procedure to improve the quality of broad bean from the nutritional point of view.

  4. Discrimination of ionic species from broad-beam ion sources

    NASA Technical Reports Server (NTRS)

    Anderson, J. R.

    1993-01-01

    The performance of a broad-beam, three-grid, ion extraction system incorporating radio frequency (RF) mass discrimination was investigated experimentally. This testing demonstrated that the system, based on a modified single-stage Bennett mass spectrometer, can discriminate between ionic species having about a 2-to-1 mass ratio while producing a broad-beam of ions with low kinetic energy (less than 15 eV). Testing was conducted using either argon and krypton ions or atomic and diatomic oxygen ions. A simple one-dimensional model, which ignores magnetic field and space-charge effects, was developed to predict the species separation capabilities as well as the kinetic energies of the extracted ions. The experimental results correlated well with the model predictions. This RF mass discrimination system can be used in applications where both atomic and diatomic ions are produced, but a beam of only one of the species is desired. An example of such an application is a 5 eV atomic oxygen source. This source would produce a beam of atomic oxygen with 5 eV kinetic energy, which would be directed onto a material specimen, to simulate the interaction between the surface of a satellite and the rarefied atmosphere encountered in low-Earth orbit.

  5. Spectral decomposition of broad-line agns and host galaxies

    SciTech Connect

    Vanden Berk, Daniel E.; Shen, Jiajian; Yip, Ching-Wa; Schneider, Donald P.; Connolly, Andrew J.; Burton, Ross E.; Jester, Sebastian; Hall, Patrick B.; Szalay, Alex S.; Brinkmann, John; /Apache Point Observ.

    2005-09-01

    Using an eigenspectrum decomposition technique, we separate the host galaxy from the broad line active galactic nucleus (AGN) in a set of 4666 spectra from the Sloan Digital Sky Survey (SDSS), from redshifts near zero up to about 0.75. The decomposition technique uses separate sets of galaxy and quasar eigenspectra to efficiently and reliably separate the AGN and host spectroscopic components. The technique accurately reproduces the host galaxy spectrum, its contributing fraction, and its classification. We show how the accuracy of the decomposition depends upon S/N, host galaxy fraction, and the galaxy class. Based on the eigencoefficients, the sample of SDSS broad-line AGN host galaxies spans a wide range of spectral types, but the distribution differs significantly from inactive galaxies. In particular, post-starburst activity appears to be much more common among AGN host galaxies. The luminosities of the hosts are much higher than expected for normal early-type galaxies, and their colors become increasingly bluer than early-type galaxies with increasing host luminosity. Most of the AGNs with detected hosts are emitting at between 1% and 10% of their estimated Eddington luminosities, but the sensitivity of the technique usually does not extend to the Eddington limit. There are mild correlations among the AGN and host galaxy eigencoefficients, possibly indicating a link between recent star formation and the onset of AGN activity. The catalog of spectral reconstruction parameters is available as an electronic table.

  6. Broad Specification Fuels Combustion Technology Program, Phase 2

    NASA Technical Reports Server (NTRS)

    Lohmann, R. P.; Jeroszko, R. A.; Kennedy, J. B.

    1990-01-01

    An experimental evaluation of two advanced technology combustor concepts was conducted to evolve and assess their capability for operation on broadened properties fuels. The concepts were based on the results of Phase 1 of the Broad Specification Fuel Combustor Technology Program which indicated that combustors with variable geometry or staged combustion zones had a flexibility of operation that could facilitate operation on these fuels. Emphasis in defining these concepts included the use of single pipe as opposed to duplex or staged fuels systems to avoid the risk of coking associated with the reduction in thermal stability expected in broadened properties fuels. The first concept was a variable geometry combustor in which the airflow into the primary zone could be altered through valves on the front while the second was an outgrowth of the staged Vorbix combustor, evolved under the NASA/P&W ECCP and EEE programs incorporating simplified fuel and air introduction. The results of the investigation, which involved the use of Experimental Referee Broad Specification (ERBS) fuel, indicated that in the form initially conceived, both of these combustor concepts were deficient in performance relative to many of the program goals for performance emissions. However, variations of both combustors were evaluated that incorporated features to simulate conceptual enhancement to demonstrate the long range potential of the combustor. In both cases, significant improvements relative to the program goals were observed.

  7. Sparse detector sensor: profiling experiments for broad-scale classification

    NASA Astrophysics Data System (ADS)

    Russomanno, D. J.; Yeasin, M.; Jacobs, E.; Smith, M.; Sorower, S.

    2008-04-01

    This paper presents a simple prototype sparse detector imaging sensor built using sixteen off-the-shelf, retro-reflective, infrared-sensing elements placed at five-inch intervals in a vertical configuration. Profiling experiments for broad-scale classification of objects, such as humans, humans wearing large backpacks, and humans wearing small backpacks were conducted from data acquired from the sensor. Empirical analysis on models developed using fusion of various classifiers based on a diversity measure shows over ninety percent (90.07%) accuracy (using 10-fold cross validation) in categorizing sensed data into specific classes of interest, such as, humans wearing a large backpack. The results demonstrate that shadow images of sufficient resolution can be captured by the sensor such that broad-scale classification of objects is feasible. The sensor appears to be a low-cost alternative to traditional, high-resolution imaging sensors, and, after industrial packaging, it may be a good candidate for deployment in vast geographic regions in which low-cost, unattended ground sensors with highly accurate classification algorithms are needed.

  8. A COMPREHENSIVE NONPOINT SOURCE FIELD STUDY FOR SEDIMENT, NUTRIENTS, AND PATHOGENS IN THE SOUTH FORK BROAD RIVER WATERSHED IN NORTHEAST GEORGIA

    EPA Science Inventory

    This technical report provides a description of the field project design, quality control, the sampling protocols and analysis methodology used, and standard operating procedures for the South Fork Broad River Watershed (SFBR) Total Maximum Daily Load (TMDL) project. This watersh...

  9. Guide to Building a Broad-Based Coalition: Supporting the Development and Sustainability of a System of Pathways

    ERIC Educational Resources Information Center

    ConnectEd: The California Center for College and Career, 2010

    2010-01-01

    As communities across California commit to developing systems of high school pathways that will engage students in school and prepare them to succeed in postsecondary opportunities and contribute to a vital regional economy, many are realizing the importance of providing "broad-based support" for this work. Students need a choice of pathways…

  10. TOOLS FOR DESIGN, CALIBRATION, CONSTRUCTION AND USE OF LONG-THROATED FLUMES AND BROAD-CRESTED WEIRS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-throated flumes and broad-crested weirs provide a practical, low-cost, flexible means of measuring open-channel flows in new and existing irrigation systems and have distinct advantages over other flume and weir devices. Application of these flumes and weirs has been greatly facilitated by the...

  11. Spatiospectral and picosecond spatiotemporal properties of a broad area operating channeled-substrate-planar laser array

    NASA Technical Reports Server (NTRS)

    Yu, NU; Defreez, Richard K.; Bossert, David J.; Wilson, Geoffrey A.; Elliott, Richard A.

    1991-01-01

    Spatiospectral and spatiotemporal properties of an eight-element channeled-substrate-planar laser array are investigated in both CW and pulsed operating conditions. The closely spaced CSP array with strong optical coupling between array elements is characterized by a broad area laserlike operation determined by its spatial mode spectra. The spatiotemporal evolution of the near and far field exhibits complex dynamic behavior in the picosecond to nanosecond domain. Operating parameters for the laser device have been experimentally determined. These results provide important information for the evaluation of the dynamic behavior of coherent semiconductor laser arrays.

  12. V-shaped resonators for addition of broad-area laser diode arrays

    DOEpatents

    Liu, Bo; Liu, Yun; Braiman, Yehuda Y.

    2012-12-25

    A system and method for addition of broad-area semiconductor laser diode arrays are described. The system can include an array of laser diodes, a V-shaped external cavity, and grating systems to provide feedback for phase-locking of the laser diode array. A V-shaped mirror used to couple the laser diode emissions along two optical paths can be a V-shaped prism mirror, a V-shaped stepped mirror or include multiple V-shaped micro-mirrors. The V-shaped external cavity can be a ring cavity. The system can include an external injection laser to further improve coherence and phase-locking.

  13. An Intrinsic Baldwin Effect in the H Beta Broad Emission Line in the Spectrum of NGC 5548

    NASA Technical Reports Server (NTRS)

    Gilbert, Karoline M.; Peterson, Bradley M.

    2003-01-01

    We investigate the possibility of an intrinsic Baldwin effect (i.e., nonlinear emission-line response to continuum variations) in the broad HP emission line of the active galaxy NGC 5548 using crosscorrelation techniques to remove light-travel time effects from the data. We find a nonlinear relationship between the HP emission line and continuum fluxes that is in good agreement with theoretical predictions. We suggest that similar analysis of multiple lines might provide a useful diagnostic of physical conditions in the broad-line region.

  14. Macrogeographic genetic variation in broad-snouted caiman (Caiman latirostris).

    PubMed

    Villela, Priscilla Marqui Schmidt; Coutinho, Luiz Lehmann; Piña, Carlos Ignacio; Verdade, Luciano M

    2008-12-01

    Broad-snouted caiman's (Caiman latirostris) geographic distribution comprises one of the widest latitudinal ranges among all crocodilians. In this study we analyzed the relationship between geographic distance (along the species latitudinal range) and genetic differentiation using DNA microsatellite loci developed for C. latirostris and Alligator mississippiensis. The results suggest that there is a consistent relationship between geographic distance and genetic differentiation; however, other biogeographical factors seem to be relevant. The Atlantic Chain (Serra do Mar) seems to be an effective geographic barrier, as well as the relatively narrow (< or =1.5 km) sea channel between Cardoso Island and the continent. In addition, coastal populations seem to have been well connected in recent geological time (Pleistocene 16,000 years ago) all along the eastern Brazilian coast. Further studies should focus on the São Francisco River drainage, which is still poorly known for this species. PMID:18661469

  15. Genetically engineered broad-spectrum disease resistance in tomato

    PubMed Central

    Oldroyd, Giles E. D.; Staskawicz, Brian J.

    1998-01-01

    Resistance in tomato to the bacterial pathogen Pseudomonas syringae pathovar tomato requires Pto and Prf. Mutations that eliminate Prf show a loss of both Pto resistance and sensitivity to the organophosphate insecticide fenthion, suggesting that Prf controls both phenotypes. Herein, we report that the overexpression of Prf leads to enhanced resistance to a number of normally virulent bacterial and viral pathogens and leads to increased sensitivity to fenthion. These plants express levels of salicylic acid comparable to plants induced for systemic acquired resistance (SAR) and constitutively express pathogenesis related genes. These results suggest that the overexpression of Prf activates the Pto and Fen pathways in a pathogen-independent manner and leads to the activation of SAR. Transgene-induced SAR has implications for the generation of broad spectrum disease resistance in agricultural crop plants. PMID:9707642

  16. Broad beam and narrow beam attenuation in Lipowitz's metal.

    PubMed

    el-Khatib, E E; Podgorsak, E B; Pla, C

    1987-01-01

    Attenuation properties of Lipowitz's metal have been studied for narrow and broad beams of cobalt-60 gamma rays and 4-10 MV x-rays. The measured transmitted fraction for geometries used in radiotherapy depends on the field size and depth of measurement. Therefore a calculation of dose for partially attenuated beams based on narrow beam attenuation coefficients can cause large errors in dosimetry. Our simple calculation of transmitted fractions based on primary attenuation and scattered radiation agrees quite well with the measured data for therapeutic geometries. Also given is a table for linear, mass attenuation, and mass energy absorption coefficients of Lipowitz's metal in the photon energy range from 10 keV to 10 MeV. PMID:3104738

  17. Novel broad-spectrum inhibitors of bacterial methionine aminopeptidase.

    PubMed

    Rose, Jonathan A; Lahiri, Sushmita D; McKinney, David C; Albert, Rob; Morningstar, Marshall L; Shapiro, Adam B; Fisher, Stewart L; Fleming, Paul R

    2015-08-15

    With increasing emergence of multi-drug resistant infections, there is a dire need for new classes of compounds that act through unique mechanisms. In this work, we describe the discovery and optimization of a novel series of inhibitors of bacterial methionine aminopeptidase (MAP). Through a high-throughput screening campaign, one azepinone amide hit was found that resembled the native peptide substrate and possessed moderate biochemical potency against three bacterial isozymes. X-ray crystallography was used in combination with substrate-based design to direct the rational optimization of analogs with sub-micromolar potency. The novel compounds presented here represent potent broad-spectrum biochemical inhibitors of bacterial MAP and have the potential to lead to the development of new medicines to combat serious multi-drug resistant infections. PMID:26099541

  18. Genetically Engineered Broad-Spectrum Disease Resistance in Tomato

    NASA Astrophysics Data System (ADS)

    Oldroyd, Giles E. D.; Staskawicz, Brian J.

    1998-08-01

    Resistance in tomato to the bacterial pathogen Pseudomonas syringae pathovar tomato requires Pto and Prf. Mutations that eliminate Prf show a loss of both Pto resistance and sensitivity to the organophosphate insecticide fenthion, suggesting that Prf controls both phenotypes. Herein, we report that the overexpression of Prf leads to enhanced resistance to a number of normally virulent bacterial and viral pathogens and leads to increased sensitivity to fenthion. These plants express levels of salicylic acid comparable to plants induced for systemic acquired resistance (SAR) and constitutively express pathogenesis related genes. These results suggest that the overexpression of Prf activates the Pto and Fen pathways in a pathogen-independent manner and leads to the activation of SAR. Transgene-induced SAR has implications for the generation of broad spectrum disease resistance in agricultural crop plants.

  19. The stability of QSO/AGN broad emission line clouds

    NASA Astrophysics Data System (ADS)

    Krinsky, I. S.; Puetter, R. C.

    1992-08-01

    Results of a numerical linear stability analysis of QSO/AGN emission-line clouds (ELCs) embedded within a confining hot intercloud medium (HIM) are reported. A first-order linear perturbation analysis reveals two important ionstabilities. The first instability is thermal in nature and arises in the interface region between the HIM and the ELC where thermal convection dominates gas heating; the growth time of the instability is approximately 1000 s, resulting in an ELC evaporation time of about 10 yr. The second instability is dynamic in nature, with the sound wave amplitude growing in response to radiative forces. The growth time of this instability is about 10 exp 6 s and essentially independent of the wavelength. The results suggest that if QSO/AGN ELCs have properties similar to those of the standard ELC model, then the broad-line region is in a constant state of flux in which ELCs continually form, are destroyed, and then re-formed.

  20. Engineering broadly neutralizing antibodies for HIV prevention and therapy.

    PubMed

    Hua, Casey K; Ackerman, Margaret E

    2016-08-01

    A combination of advances spanning from isolation to delivery of potent HIV-specific antibodies has begun to revolutionize understandings of antibody-mediated antiviral activity. As a result, the set of broadly neutralizing and highly protective antibodies has grown in number, diversity, potency, and breadth of viral recognition and neutralization. These antibodies are now being further enhanced by rational engineering of their anti-HIV activities and coupled to cutting edge gene delivery and strategies to optimize their pharmacokinetics and biodistribution. As a result, the prospects for clinical use of HIV-specific antibodies to treat, clear, and prevent HIV infection are gaining momentum. Here we discuss the diverse methods whereby antibodies are being optimized for neutralization potency and breadth, biodistribution, pharmacokinetics, and effector function with the aim of revolutionizing HIV treatment and prevention options. PMID:26827912

  1. Radio Structures of Compact Quasars with Broad Absorption Lines

    NASA Astrophysics Data System (ADS)

    Kunert-Bajraszewska, Magdalena; Gawroński, Marcin P.

    2010-05-01

    Broad absorption lines (BALs), seen in a small fraction of both the radio-quiet and radio-loud quasar populations, are probably caused by the outflow of gas with high velocities and are part of the accretion process. The presence of BALs is due to a geometrical effect and/or it is connected with the quasar evolution. Using the final release of FIRST survey combined with a catalog of BAL QSOs from SDSS/DR3, we have constructed a new sample of compact radio-loud BAL QSOs, which constitutes the majority of radio-loud BAL QSOs. The main goal of this project is to study the origin of BALs by analysis of the BAL QSOs radio morphology, orientation, and jet evolution using the European VLBI Network (EVN) at 1.6 GHz and the Very Long Baseline Array (VLBA) at 5 and 8.4 GHz.

  2. Broad band invisibility cloak made of normal dielectric multilayer

    NASA Astrophysics Data System (ADS)

    Xu, Xiaofei; Feng, Yijun; Xiong, Shuai; Fan, Jinlong; Zhao, Jun-Ming; Jiang, Tian

    2011-10-01

    We present the design, fabrication, and performance test of a quasi three-dimensional carpet cloak made of normal dielectric in the microwave regime. Taking advantage of a simple linear coordinate transformation, we design a carpet cloak with homogeneous anisotropic medium and then practically realize the device with multilayer of alternating normal dielectric slabs based on the effective medium theory. As a proof-of-concept example, we fabricate the carpet cloak with multilayer of FR4 dielectric slabs with air spacing. The performance of the fabricated design is verified through full-wave numerical simulation and measurement of the far-field scattering electromagnetic waves in a microwave anechoic chamber. Experimental results have demonstrated pronounced cloaking effect in a very broad band from 8 GHz to 18 GHz (whole X and Ku band) due to the low loss, non-dispersive feature of the multilayer dielectric structure.

  3. The Generation Effect: Activating Broad Neural Circuits During Memory Encoding

    PubMed Central

    Rosner, Zachary A.; Elman, Jeremy A.; Shimamura, Arthur P.

    2012-01-01

    The generation effect is a robust memory phenomenon in which actively producing material during encoding acts to improve later memory performance. In an fMRI analysis, we explored the neural basis of this effect. During encoding, participants generated synonyms from word-fragment cues (e.g. GARBAGE-W_ST_) or read other synonym pairs (e.g. GARBAGE-WASTE). Compared to simply reading target words, generating target words significantly improved later recognition memory performance. During encoding, this benefit was associated with a broad neural network that involved both prefrontal (inferior frontal gyrus, middle frontal gyrus) and posterior cortex (inferior temporal gyrus, lateral occipital cortex, parahippocampal gyrus, ventral posterior parietal cortex). These findings define the prefrontal-posterior cortical dynamics associated with the mnemonic benefits underlying the generation effect. PMID:23079490

  4. Conductivity in percolation networks with broad distributions of resistances

    NASA Astrophysics Data System (ADS)

    Machta, J.; Guyer, R. A.; Moore, S. M.

    1986-04-01

    Diluted resistor networks with a broad distribution of resistances are studied near the percolation threshold. A hierarchical model of the backbone of the percolation cluster is employed. Resistor networks are considered where the resistors, R, are chosen from a distribution having a power-law tail such that Prob\\{R>X\\}~X-α as X-->∞, 0<α<1. Such distributions arise naturally in con- tinuum percolation systems. The hierarchical model is studied numerically and using a renormalization-group transformation for the distribution of resistances. The conclusion is that the conductivity exponent t is the greater of to and (d-2)ν+1/α where to is the universal value of the conductivity exponent and ν is the correlation-length exponent. This result is in agreement with Straley's earlier predictions [J. Phys. C 15, 2333 (1982); 15, 2343 (1982)].

  5. A hexokinase with broad sugar specificity from a thermophilic bacterium.

    PubMed

    Bae, Jungdon; Kim, Dooil; Choi, Yongseok; Koh, Sukhoon; Park, Jung Eun; Su Kim, Joong; Moon, Seong Hoon; Park, Bo-Hyun; Park, Miri; Song, Hye-Eun; Hong, Suk-In; Lee, Dae-Sil

    2005-09-01

    A recombinant thermophilic Thermus caldophilus GK24 hexokinase, one of the ROK-type (repressor protein, open reading frames, and sugar kinase) proteins, exists uniquely as a 120 kDa molecule with four subunits (31 kDa), in contrast to eukaryotic and bacterial sugar kinases which are monomers or dimers. The optimal temperature and pH for the enzyme reaction are 70-80 degrees C and 7.5, respectively. This enzyme shows broad specificity toward glucose, mannose, glucosamine, allose, 2-deoxyglucose, and fructose. To understand the sugar specificity at a structural level, the enzyme-ATP/Mg2+-sugar binding complex models have been constructed. It has been shown that the sugar specificity is probably dependent on the interaction energy occurred by the positional proximity of sugars bound in the active site of the enzyme, which exhibits a tolerance to modification at C2 or C3 of glucose. PMID:16053915

  6. Modeling of optical wireless scattering communication channels over broad spectra.

    PubMed

    Liu, Weihao; Zou, Difan; Xu, Zhengyuan

    2015-03-01

    The air molecules and suspended aerosols help to build non-line-of-sight (NLOS) optical scattering communication links using carriers from near infrared to visible light and ultraviolet bands. This paper proposes channel models over such broad spectra. Wavelength dependent Rayleigh and Mie scattering and absorption coefficients of particles are analytically obtained first. They are applied to the ray tracing based Monte Carlo method, which models the photon scattering angle from the scatterer and propagation distance between two consecutive scatterers. Communication link path loss is studied under different operation conditions, including visibility, particle density, wavelength, and communication range. It is observed that optimum communication performances exist across the wavelength under specific atmospheric conditions. Infrared, visible light and ultraviolet bands show their respective features as conditions vary. PMID:26366662

  7. Rufinamide: A Novel Broad-Spectrum Antiepileptic Drug

    PubMed Central

    Wheless, James W; Vazquez, Blanca

    2010-01-01

    The last 20 years have witnessed a tremendous explosion in the number of antiepileptic drugs (AEDs) as well as the introduction of AEDS developed for specific epilepsy syndromes. The study of the efficacy and side effect profile of AEDs for unique epilepsy syndromes has allowed neurologists to utilize evidence-based medicine when treating patients. In late 2008, the Food and Drug Administration approved rufinamide for adjunctive use in the treatment of seizures associated with Lennox–Gastaut syndrome. This unique chemical compound is also the first new AED to reach the market in the United States having a pediatric indication prior to approval for adults. Rufinamide appears to have a broad spectrum of efficacy, is well tolerated, and may be rapidly initiated—properties that will likely extend its use outside of Lennox–Gastaut syndrome. PMID:20126329

  8. Specialty fibers for broad spectra of wavelength and power

    NASA Astrophysics Data System (ADS)

    Artyushenko, Viacheslav; Wojciechowski, Cezar; Ingram, Jim; Kononenko, Vitaly; Lobachev, Vladimir; Sakharova, Tatjana; Ludczak, Jacek; Grzebieniak, Andrzej; Wojciechowski, Zdzislaw

    2005-09-01

    Review of the latest development in production and advanced applications of specialty fibre optics includes specialty silica fibers and IR-fibers drawn from chalcogenide glasses and extruded from crystal solutions of Silver Halides. Transmission range of these 3 types of fibers spans 0.2 to 18μm, while the power of radiation they may deliver varies from microwatts for sensing applications to several kilowatts - when silica fibers are assembled, for example, in high power cables for laser technology applications. Various probes and bundles assembled from specialty fibers are used for remote sensing of IR-emission, temperature, mechanical stress and for process-spectroscopy in very broad range - from 0.2 to 18μm.

  9. Mucin biopolymers as broad-spectrum antiviral agents

    PubMed Central

    Lieleg, Oliver; Lieleg, Corinna; Bloom, Jesse; Buck, Christopher B.; Ribbeck, Katharina

    2012-01-01

    Mucus is a porous biopolymer matrix that coats all wet epithelia in the human body and serves as the first line of defense against many pathogenic bacteria and viruses. However, under certain conditions viruses are able to penetrate this infection barrier, which compromises the protective function of native mucus. Here, we find that isolated porcine gastric mucin polymers, key structural components of native mucus, can protect an underlying cell layer from infection by small viruses such as human papillomavirus (HPV), Merkel cell polyomavirus (MCV), or a strain of influenza A virus. Single particle analysis of virus mobility inside the mucin barrier reveals that this shielding effect is in part based on a retardation of virus diffusion inside the biopolymer matrix. Our findings suggest that purified mucins may be used as a broad-range antiviral supplement to personal hygiene products, baby formula or lubricants to support our immune system. PMID:22475261

  10. SPECTROPOLARIMETRY OF RADIO-SELECTED BROAD ABSORPTION LINE QUASARS

    SciTech Connect

    DiPompeo, M. A.; Brotherton, M. S.; Becker, R. H.; Gregg, M. D.; Tran, H. D.; White, R. L.; Laurent-Muehleisen, S. A.

    2010-07-15

    We report spectropolarimetry of 30 radio-selected broad absorption line (BAL) quasars with the Keck Observatory, 25 from the sample of Becker et al. Both high- and low-ionization BAL quasars are represented, with redshifts ranging from 0.5 to 2.5. The spectropolarimetric properties of radio-selected BAL quasars are very similar to those of radio-quiet BAL quasars: a sizeable fraction (20%) shows large continuum polarization (2%-10%) usually rising toward short wavelengths; emission lines are typically less polarized than the continuum; and absorption line troughs often show large polarization jumps. There are no significant correlations between polarization properties and radio properties, including those indicative of system orientation, suggesting that BAL quasars are not simply normal quasars seen from an edge-on perspective.

  11. Diphosphonium Ionic Liquids as Broad Spectrum Antimicrobial Agents

    PubMed Central

    O’Toole, George A.; Wathier, Michel; Zegans, Michael E.; Shanks, Robert M.Q.; Kowalski, Regis; Grinstaff, Mark W.

    2011-01-01

    Purpose One of the most disturbing trends in recent years is the growth of resistant strains of bacteria with the simultaneous dearth of new antimicrobial agents. Thus, new antimicrobial agents for use on the ocular surface are needed. Methods We synthesized a variety of ionic liquid compounds, which possess two positively charged phosphonium groups separated by ten methylene units in a “bola” type configuration. We tested these compounds for antimicrobial activity versus a variety of ocular pathogens, as well as their cytoxicity in vitro in a corneal cell line and in vivo in mice. Results The ionic liquid Di-Hex C10 demonstrated broad in vitro antimicrobial activity at the low micromolar concentrations versus Gram-negative and Gram-positive organisms, including methicillin-resistant Staphylococcus aureus strains, as well as ocular fungal pathogens. Treatment with Di-Hex C10 resulted in bacterial killing in as little as 15 minutes in vitro. Di-Hex C10 showed little cytotoxicity at 1 μM versus a corneal epithelial cell line or at 10 μM in a mouse corneal wound model. We also show that this bis-phosphonium ionic liquid structure is key, as a comparable mono phosphonium ionic liquid is cytotoxic to both bacteria and corneal epithelial cells. Conclusions Here we report the first use of dicationic bis-phosphonium ionic liquids as antimicrobial agents. Our data suggest that diphosphonium ionic liquids may represent a new class of broad-spectrum antimicrobial agents for use on the ocular surface. PMID:22236790

  12. Correlation between degradation and broadness of the transition in CICC

    NASA Astrophysics Data System (ADS)

    Martovetsky, Nicolai

    2013-10-01

    Cable in conduit conductor (CICC) performance is characterized in terms of relationships involving the electric field (E), voltage (V), temperature (T), current (I), magnetic field (B) and strain. Development of the electrical field in the V-T or V-I transitions in CICCs is exponential. These transitions plotted in the coordinates log E versus T or log E versus I look like straight lines. ITER Nb3Sn CICCs show degradation of properties versus load cycles that could be attributed to plastic deformation of the Nb3Sn strands or fracture of the superconducting filaments. The degradation is expressed in terms of the reduction of the current sharing temperature Tcs or critical current Ic, respectively. It was noticed long ago that degradation is accompanied by a significant broadening of the V-T or V-I transition, that looks like a change in the slope in the semi-log coordinate plot. This paper presents some systematic observations of correlations between the critical parameters and broadness of the transition in many CICCs. In most cases, the broadness of the transition seems to be a more sensitive indicator of the conductor damage even in cases where Tcs degradation is not clearly seen. Tcs degradation typically becomes obvious later in the cycling, especially after warm-up and following cool-down and more cycling. In some cases, a CICC manifests temporary or even a permanent growth of Tcs with load cycles, especially in the latest measurements of the CS conductors with short twist pitches. A possible mechanism of degradation that allows qualitative explanation of this phenomenon is discussed and is supported by the voltage measurements on the cable in the TFUS1 sample with the voltage taps penetrating the jacket to the cable.

  13. Outflow and hot dust emission in broad absorption line quasars

    SciTech Connect

    Zhang, Shaohua; Zhou, Hongyan; Wang, Huiyuan; Wang, Tinggui; Xing, Feijun; Jiang, Peng; Zhang, Kai E-mail: whywang@mail.ustc.edu.cn

    2014-05-01

    We have investigated a sample of 2099 broad absorption line (BAL) quasars with z = 1.7-2.2 built from the Sloan Digital Sky Survey Data Release Seven and the Wide-field Infrared Survey. This sample is collected from two BAL quasar samples in the literature and is refined by our new algorithm. Correlations of outflow velocity and strength with a hot dust indicator (β{sub NIR}) and other quasar physical parameters—such as an Eddington ratio, luminosity, and a UV continuum slope—are explored in order to figure out which parameters drive outflows. Here β{sub NIR} is the near-infrared continuum slope, which is a good indicator of the amount of hot dust emission relative to the accretion disk emission. We confirm previous findings that outflow properties moderately or weakly depend on the Eddington ratio, UV slope, and luminosity. For the first time, we report moderate and significant correlations of outflow strength and velocity with β{sub NIR} in BAL quasars. It is consistent with the behavior of blueshifted broad emission lines in non-BAL quasars. The statistical analysis and composite spectra study both reveal that outflow strength and velocity are more strongly correlated with β{sub NIR} than the Eddington ratio, luminosity, and UV slope. In particular, the composites show that the entire C IV absorption profile shifts blueward and broadens as β{sub NIR} increases, while the Eddington ratio and UV slope only affect the high and low velocity part of outflows, respectively. We discuss several potential processes and suggest that the dusty outflow scenario, i.e., that dust is intrinsic to outflows and may contribute to the outflow acceleration, is most likely.

  14. Virilization of the Broad Line Region in Active Galactic Nuclei—connection between shifts and widths of broad emission lines

    NASA Astrophysics Data System (ADS)

    Jonić, S.; Kovačević-Dojčinović, J.; Ilić, D.; Popović, L. Č.

    2016-03-01

    We investigate the virilization of the emission lines {Hβ } and Mg II in the sample of 287 Type 1 Active Galactic Nuclei taken from the Sloan Digital Sky Survey database. We explore the connections between the intrinsic line shifts and full widths at different levels of maximal intensity. We found that: (i) {Hβ} seems to be a good virial estimator of black hole masses, and an intrinsic redshift of {Hβ} is dominantly caused by the gravitational effect, (ii) there is an anti-correlation between the redshift and width of the wings of the Mg II line, (iii) the broad Mg II line can be used as virial estimator only at 50 % of the maximal intensity, while the widths and intrinsic shifts of the line wings cannot be used for this purpose.

  15. Environmental Education Information Providers Directory.

    ERIC Educational Resources Information Center

    1999

    This report directory provides environmental education training resources and related support to education professionals. Surveys were sent to over 60 organizations asking them to self-identify as Environmental Information Providers or Environmental Education Information Providers. This report includes the list of organizations that responded and…

  16. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

    PubMed Central

    Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing; Gao, Feng; Alam, S. Munir; Boyd, Scott D.; Fire, Andrew Z.; Roskin, Krishna M.; Schramm, Chaim A.; Zhang, Zhenhai; Zhu, Jiang; Shapiro, Lawrence; Mullikin, James C.; Gnanakaran, S.; Hraber, Peter; Wiehe, Kevin; Kelsoe, Garnett; Yang, Guang; Xia, Shi-Mao; Montefiori, David C.; Parks, Robert; Lloyd, Krissey E.; Scearce, Richard M.; Soderberg, Kelly A.; Cohen, Myron; Kaminga, Gift; Louder, Mark K.; Tran, Lillan M.; Chen, Yue; Cai, Fangping; Chen, Sheri; Moquin, Stephanie; Du, Xiulian; Joyce, Gordon M.; Srivatsan, Sanjay; Zhang, Baoshan; Zheng, Anqi; Shaw, George M.; Hahn, Beatrice H.; Kepler, Thomas B.; Korber, Bette T.M.; Kwong, Peter D.; Mascola, John R.; Haynes, Barton F.

    2013-01-01

    Current HIV-1 vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in ~20% of HIV-1-infected individuals, and details of their generation could provide a roadmap for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from time of infection. The mature antibody, CH103, neutralized ~55% of HIV-1 isolates, and its co-crystal structure with gp120 revealed a novel loop-based mechanism of CD4-binding site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the CH103-lineage unmutated common ancestor avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data elucidate the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies and provide insights into strategies to elicit similar antibodies via vaccination. PMID:23552890

  17. Support vector machines for broad-area feature classification in remotely sensed images

    NASA Astrophysics Data System (ADS)

    Perkins, Simon J.; Harvey, Neal R.; Brumby, Steven P.; Lacker, Kevin

    2001-08-01

    Classification of broad area features in satellite imagery is one of the most important applications of remote sensing. It is often difficult and time-consuming to develop classifiers by hand, so many researchers have turned to techniques from the fields of statistics and machine learning to automatically generate classifiers. Common techniques include Maximum Likelihood classifiers, neural networks and genetic algorithms. We present a new system called Afreet, which uses a recently developed machine learning paradigm called Support Vector Machines (SVMs). In contrast to other techniques, SVMs offer a solid mathematical foundation that provides a probabalistic guarantee on how well the classifier will generalize to unseen data. In addition the SVM training algorithm is guaranteed to converge to the globally optimal SVM classifier, can learn highly non-linear discrimination functions, copes extremely well with high-dimensional feature spaces (such as hyperspectral data), and scales well to large problem sizes. Afreet combines an SVM with a sophisticated spatio-spectral feature construction mechanism that allows it to classify spectrally ambiguous pixels. We demonstrate the effectiveness of the system by applying Afreet to several broad area classification problems in remote sensing, and provide a comparison with conventional Maximum Likelihood classification.

  18. SUPPORT VECTOR MACHINES FOR BROAD AREA FEATURE CLASSIFICATION IN REMOTELY SENSED IMAGES

    SciTech Connect

    S. PERKINS; N. HARVEY; ET AL

    2001-03-01

    Classification of broad area features in satellite imagery is one of the most important applications of remote sensing. It is often difficult and time-consuming to develop classifiers by hand, so many researchers have turned to techniques from the fields of statistics and machine learning to automatically generate classifiers. Common techniques include maximum likelihood classifiers, neural networks and genetic algorithms. We present a new system called Afreet, which uses a recently developed machine learning paradigm called Support Vector Machines (SVMs). In contrast to other techniques, SVMs offer a solid mathematical foundation that provides a probabilistic guarantee on how well the classifier will generalize to unseen data. In addition the SVM training algorithm is guaranteed to converge to the globally optimal SVM classifier, can learn highly non-linear discrimination functions, copes extremely well with high-dimensional feature spaces (such as hype spectral data), and scales well to large problem sizes. Afreet combines an SVM with a sophisticated spatio-spectral feature construction mechanism that allows it to classify spectrally ambiguous pixels. We demonstrate the effectiveness of the system by applying Afreet to several broad area classification problems in remote sensing, and provide a comparison with conventional maximum likelihood classification.

  19. Broad-Scale Patterns of Late Jurassic Dinosaur Paleoecology

    PubMed Central

    Noto, Christopher R.; Grossman, Ari

    2010-01-01

    Background There have been numerous studies on dinosaur biogeographic distribution patterns. However, these distribution data have not yet been applied to ecological questions. Ecological studies of dinosaurs have tended to focus on reconstructing individual taxa, usually through comparisons to modern analogs. Fewer studies have sought to determine if the ecological structure of fossil assemblages is preserved and, if so, how dinosaur communities varied. Climate is a major component driving differences between communities. If the ecological structure of a fossil locality is preserved, we expect that dinosaur assemblages from similar environments will share a similar ecological structure. Methodology/Principal Findings This study applies Ecological Structure Analysis (ESA) to a dataset of 100+ dinosaur taxa arranged into twelve composite fossil assemblages from around the world. Each assemblage was assigned a climate zone (biome) based on its location. Dinosaur taxa were placed into ecomorphological categories. The proportion of each category creates an ecological profile for the assemblage, which were compared using cluster and principal components analyses. Assemblages grouped according to biome, with most coming from arid or semi-arid/seasonal climates. Differences between assemblages are tied to the proportion of large high-browsing vs. small ground-foraging herbivores, which separates arid from semi-arid and moister environments, respectively. However, the effects of historical, taphonomic, and other environmental factors are still evident. Conclusions/Significance This study is the first to show that the general ecological structure of Late Jurassic dinosaur assemblages is preserved at large scales and can be assessed quantitatively. Despite a broad similarity of climatic conditions, a degree of ecological variation is observed between assemblages, from arid to moist. Taxonomic differences between Asia and the other regions demonstrate at least one case of

  20. NOVEL ALKYLPHOSPHOCHOLINE ANALOGS FOR BROAD SPECTRUM CANCER IMAGING AND THERAPY

    PubMed Central

    Kuo, John S.; Weichert, Jamey P.; Clark, Paul A.; Kandela, Irawati K.; Vacaro, Abram; Clark, William; Longino, Marc; Pinchuk, Anatoly; Farhoud, Mohammed; Swanson, Kyle I.; Floberg, John; Traynor, Anne; Hall, Lance T.; Pazoles, Christopher

    2014-01-01

    BACKGROUND: We present in vitro and in vivo imaging and therapeutic studies using a novel alkylphosphocholine (APC)-based molecular scaffold (CLR1404) that combines selective targeting of cancer (including cancer stem cells) with broad-spectrum activity against many different cancer types. CLR1404 APC analogs were created to exploit the finding that phospholipid ethers selectively accumulate in many cancers versus normal cells. METHODS: Depending on the iodine isotope used, radioiodinated CLR1404 is either a PET imaging (124I) or molecular radiotherapeutic agent (131I), with fluorescence analogs created by replacing iodide with various fluorophores. Standard tissue culture, xenograft and molecular biology protocols were used for these studies. RESULTS: CLR1404 displayed preferential uptake and retention in cancer and cancer stem cells compared to normal cells in vitro and in vivo. After 24 hours, selective uptake of fluorescent or radioiodinated CLR1404 analogs by multiple human cancer cell lines in vitro compared to patient-matched normal human fibroblasts was observed (2.3-2.8x). CLR1404 showed highly specific labeling of both human patient-matched glioblastoma stem cells and serum-cultured glioblastoma cells (3x over minimal labeling of control normal human astrocytes and neural stem cells). Lipid raft disruption reduced in vitro CLR1404 analog uptake.In vivo, CLR1404 analogs displayed prolonged tumor-selective retention in 55 different rodent and human cancer models (including triple-negative breast, lung, pancreatic, colorectal, prostate, renal, melanoma, GBM). Tumor accumulation was seen by 24 hours with continued normal tissue clearance between 48-120 hours. In vivo cancer stem cell labeling was also demonstrated. CLR1404 analogs do not visualize inflammatory or premalignant lesions (unlike currently used 18F-fluorodeoxy glucose (FDG)-PET tumor imaging).131I-CLR1404 also displayed therapeutic efficacy (tumor growth suppression, survival extension) especially

  1. The intrinsic fraction of broad-absorption line quasars

    NASA Astrophysics Data System (ADS)

    Knigge, Christian; Scaringi, Simone; Goad, Michael R.; Cottis, Christopher E.

    2008-05-01

    We carefully reconsider the problem of classifying broad-absorption line quasars (BALQSOs) and derive a new, unbiased estimate of the intrinsic BALQSO fraction from the Sloan Digital Sky Survey (SDSS) DR3 quasi-stellar object (QSO) catalogue. We first show that the distribution of objects selected by the so-called `absorption index' (AI) is clearly bimodal in logAI, with only one mode corresponding to definite BALQSOs. The surprisingly high BALQSO fractions that have recently been inferred from AI-based samples are therefore likely to be overestimated. We then present two new approaches to the classification problem that are designed to be more robust than the AI, but also more complete than the traditional `balnicity index' (BI). Both approaches yield observed BALQSO fractions around 13.5 per cent, while a conservative third approach suggests an upper limit of 18.3 per cent. Finally, we discuss the selection biases that affect our observed BALQSO fraction. After correcting for these biases, we arrive at our final estimate of the intrinsic BALQSO fraction. This is fBALQSO = 0.17 +/- 0.01(stat) +/- 0.03(sys) with an upper limit of fBALQSO ~= 0.23. We conclude by pointing out that the bimodality of the logAI distribution may be evidence that the BAL-forming region has clearly delineated physical boundaries.

  2. Elimination of HIV-1-infected cells by broadly neutralizing antibodies

    PubMed Central

    Bruel, Timothée; Guivel-Benhassine, Florence; Amraoui, Sonia; Malbec, Marine; Richard, Léa; Bourdic, Katia; Donahue, Daniel Aaron; Lorin, Valérie; Casartelli, Nicoletta; Noël, Nicolas; Lambotte, Olivier; Mouquet, Hugo; Schwartz, Olivier

    2016-01-01

    The Fc region of HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) is required for suppressing viraemia, through mechanisms which remain poorly understood. Here, we identify bNAbs that exert antibody-dependent cellular cytotoxicity (ADCC) in cell culture and kill HIV-1-infected lymphocytes through natural killer (NK) engagement. These antibodies target the CD4-binding site, the glycans/V3 and V1/V2 loops on gp120, or the gp41 moiety. The landscape of Env epitope exposure at the surface and the sensitivity of infected cells to ADCC vary considerably between viral strains. Efficient ADCC requires sustained cell surface binding of bNAbs to Env, and combining bNAbs allows a potent killing activity. Furthermore, reactivated infected cells from HIV-positive individuals expose heterogeneous Env epitope patterns, with levels that are often but not always sufficient to trigger killing by bNAbs. Our study delineates the parameters controlling ADCC activity of bNAbs, and supports the use of the most potent antibodies to clear the viral reservoir. PMID:26936020

  3. The reconfiguration of broad leaves in strong winds and currents

    NASA Astrophysics Data System (ADS)

    Miller, Laura; Hoover, Alex; Marzuola, Jeremy

    2015-11-01

    Flexible plants, fungi, and sessile animals are thought to reconfigure in the wind and water to reduce the drag forces that act upon them. In strong winds, for example, leaves roll up into cone shapes that reduce flutter and drag when compared to paper cut-outs with similar shape and flexibility. Simple mathematical models of a flexible beam immersed in a two-dimensional flow will also exhibit this behavior. What is less understood is how the mechanical properties of a two-dimensional leaf in a three-dimensional flow will passively allow roll up and reduce drag and flutter. In this project, we use computational fluid dynamics and particle image velocimetry to determine how leaves roll up into drag reducing shapes in extreme conditions. Force and flow measurements are taken on real broad leaves and simplified physical models. Corresponding numerical simulations using the immersed boundary method are used to understand which features of the flexible leaves result in proper reconfiguration and drag reduction.

  4. Broad Iron Emission from Gravitationally Lensed Quasars Observed by Chandra

    NASA Astrophysics Data System (ADS)

    Walton, D. J.; Reynolds, M. T.; Miller, J. M.; Reis, R. C.; Stern, D.; Harrison, F. A.

    2015-06-01

    Recent work has demonstrated the potential of gravitationally lensed quasars to extend measurements of black hole spin out to high redshift with the current generation of X-ray observatories. Here we present an analysis of a large sample of 27 lensed quasars in the redshift range 1.0≲ z≲ 4.5 observed with Chandra, utilizing over 1.6 Ms of total observing time, focusing on the rest-frame iron K emission from these sources. Although the X-ray signal-to-noise ratio (S/N) currently available does not permit the detection of iron emission from the inner accretion disk in individual cases in our sample, we find significant structure in the stacked residuals. In addition to the narrow core, seen almost ubiquitously in local active galactic nuclei (AGNs), we find evidence for an additional underlying broad component from the inner accretion disk, with a clear red wing to the emission profile. Based on simulations, we find the detection of this broader component to be significant at greater than the 3σ level. This implies that iron emission from the inner disk is relatively common in the population of lensed quasars, and in turn further demonstrates that, with additional observations, this population represents an opportunity to significantly extend the sample of AGN spin measurements out to high redshift.

  5. Discovery of a fast, broad, transient outflow in NGC 985

    NASA Astrophysics Data System (ADS)

    Ebrero, J.; Kriss, G. A.; Kaastra, J. S.; Ely, J. C.

    2016-02-01

    Aims: We observed the Seyfert 1 galaxy NGC 985 on several occasions to search for variability in its UV and X-ray absorption features to establish their location and physical properties. Methods: We used XMM-Newton to obtain X-ray spectra using the EPIC-pn camera, and the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope (HST) to obtain UV spectra. Our observations were simultaneous and span timescales of days to years. Results: We find that the soft X-ray obscuration that absorbed the low energy continuum of NGC 985 in August 2013 diminished greatly by January 2015. The total X-ray column density decreased from 2.1 × 1022 cm-2 to ~6 × 1021 cm-2. We also detect broad, fast UV absorption lines in COS spectra obtained during the 2013 obscuration event. Lines of C iii*, Lyα, Si iv, and C iv with outflow velocities of -5970 km s-1 and a full-width at half-maximum of 1420 km s-1 are prominent in the 2013 spectrum, but have disappeared in all but Lyα in the 2015 spectra. The ionization state and the column density of the UV absorbing gas is compatible with arising in the same gas as that causing the X-ray obscuration. The high velocity of the UV-absorbing gas suggests that the X-ray obscurer and the associated UV outflow are manifestations of an accretion disk wind.

  6. A study of tachyon dynamics for broad classes of potentials

    NASA Astrophysics Data System (ADS)

    Quiros, Israel; Gonzalez, Tame; Gonzalez, Dania; Napoles, Yunelsy; García-Salcedo, Ricardo; Moreno, Claudia

    2010-11-01

    We investigate in detail the asymptotic properties of tachyon cosmology for a broad class of self-interaction potentials. The present approach relies on an appropriate re-definition of the tachyon field, which, in conjunction with a method formerly applied in the bibliography in a different context allows us to generalize the dynamical systems study of tachyon cosmology to a wider class of self-interaction potentials beyond the (inverse) square-law one. It is revealed that independent of the functional form of the potential, the matter-dominated solution and the ultra-relativistic (also matter-dominated) solution are always associated with equilibrium points in the phase space of the tachyon models. The latter is always the past attractor, while the former is a saddle critical point. For inverse power-law potentials V~phi-2λ the late-time attractor is always the de Sitter solution, while for sinh-like potentials V~sinh -α(λphi), depending on the region of parameter space, the late-time attractor can be either the inflationary tachyon-dominated solution or the matter-scaling (also inflationary) phase. In general, for most part of known quintessential potentials, the late-time dynamics will be associated either with de Sitter inflation, or with matter-scaling, or with scalar field-dominated solutions.

  7. Calculation of effective doses for broad parallel photon beams.

    PubMed

    Kim, C H; Reece, W D; Poston, J W

    1999-02-01

    Values of effective dose (E) were calculated for the entire range of incident directions of broad parallel photon beams for selected photon energies using the Monte Carlo N-Particle (MCNP) transport code with a hermaphroditic phantom. The calculated results are presented in terms of conversion coefficients transforming air kerma to effective dose. This study also compared the numerical values of E and H(E) over the entire range of incident beam directions. E was always less than H(E) considering all beam directions and photon energies, but the differences were not significant except when a photon beam approaches some specific directions (overhead and underfoot). This result suggests that the current H(E) values can be directly interpreted as E or, at least, as a conservative value of E without knowing the details of irradiation geometries. Finally, based on the distributions of H(E) and E over the beam directions, this study proposes ideal angular response factors for personal dosimeters that can be used to improve the angular response properties of personal dosimeters for off-normal incident photons. PMID:9929126

  8. Elimination of HIV-1-infected cells by broadly neutralizing antibodies.

    PubMed

    Bruel, Timothée; Guivel-Benhassine, Florence; Amraoui, Sonia; Malbec, Marine; Richard, Léa; Bourdic, Katia; Donahue, Daniel Aaron; Lorin, Valérie; Casartelli, Nicoletta; Noël, Nicolas; Lambotte, Olivier; Mouquet, Hugo; Schwartz, Olivier

    2016-01-01

    The Fc region of HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) is required for suppressing viraemia, through mechanisms which remain poorly understood. Here, we identify bNAbs that exert antibody-dependent cellular cytotoxicity (ADCC) in cell culture and kill HIV-1-infected lymphocytes through natural killer (NK) engagement. These antibodies target the CD4-binding site, the glycans/V3 and V1/V2 loops on gp120, or the gp41 moiety. The landscape of Env epitope exposure at the surface and the sensitivity of infected cells to ADCC vary considerably between viral strains. Efficient ADCC requires sustained cell surface binding of bNAbs to Env, and combining bNAbs allows a potent killing activity. Furthermore, reactivated infected cells from HIV-positive individuals expose heterogeneous Env epitope patterns, with levels that are often but not always sufficient to trigger killing by bNAbs. Our study delineates the parameters controlling ADCC activity of bNAbs, and supports the use of the most potent antibodies to clear the viral reservoir. PMID:26936020

  9. Preliminary design studies on the Broad Application Test Reactor

    SciTech Connect

    Terry, W.J.; Terry, W.K.; Ryskamp, J.M.; Jahshan, S.N.; Fletcher, C.D.; Moore, R.L.; Leyse, C.F.; Ottewitte, E.H.; Motloch, C.G.; Lacy, J.M.

    1992-08-01

    This report describes progress made at the Idaho National Engineering Laboratory during the first three quarters of Fiscal Year (FY) 1992 on the Laboratory-Directed Research and Development (LDRD) project to perform preliminary design studies on the Broad Application Test Reactor (BATR). This work builds on the FY-92 BATR studies, which identified anticipated mission and safety requirements for BATR and assessed a variety of reactor concepts for their potential capability to meet those requirements. The main accomplishment of the FY-92 BATR program is the development of baseline reactor configurations for the two conventional conceptual test reactors recommended in the FY-91 report. Much of the present report consists of descriptions and neutronics and thermohydraulics analyses of these baseline configurations. In addition, we considered reactor safety issues, compared the consequences of steam explosions for alternative conventional fuel types, explored a Molten Chloride Fast Reactor concept as an alternate BATR design, and examined strategies for the reduction of operating costs. Work planned for the last quarter of FY-92 is discussed, and recommendations for future work are also presented.

  10. Quasar Broad Absorption Line Variability on Multiyear Timescales

    NASA Astrophysics Data System (ADS)

    Gibson, Robert R.; Brandt, W. N.; Schneider, Donald P.; Gallagher, S. C.

    2008-03-01

    We use quantitative metrics to characterize the variation of C IV λ1549 broad absorption lines (BALs) over 3-6 (rest-frame) years in a sample of 13 quasars at 1.7 <= z<= 2.8 and compare the results to previous studies of BAL variability on shorter timescales. The strong BALs in our study change in complex ways over 3-6 yr. Variation occurs in discrete regions only a few thousand kilometers per second wide, and the distribution of the change in absorption equivalent width broadens over time. We constrain the typical C IV BAL lifetime to be at least a few decades. While we do not find evidence to support a scenario in which the variation is primarily driven by photoionization on multiyear timescales, there is some indication that the variation is produced by changes in outflow geometry. We do not observe significant changes in the BAL onset velocity, indicating that the absorber is either far from the source or is being continually replenished and is azimuthally symmetric. It is not possible in a human lifetime to expand the timescales in our study by more than a factor of a few using optical spectroscopy. However, the strong variation we have observed in some BALs indicates that future studies of large numbers of BAL QSOs will be valuable to constrain BAL lifetimes and the physics of variation.

  11. Multijunction organic photovoltaics with a broad spectral response.

    PubMed

    Macko, Jill A; Lunt, Richard R; Osedach, Timothy P; Brown, Patrick R; Barr, Miles C; Gleason, Karen K; Bulovic, Vladimir

    2012-11-14

    We demonstrate series-integrated multijunction organic photovoltaics fabricated monolithically by vapor-deposition in a transposed subcell order with the near-infrared-absorbing subcell in front of the green-absorbing subcell. This transposed subcell order is enabled by the highly complementary absorption spectra of a near-infrared-absorbing visibly-transparent subcell and a visible-absorbing subcell and motivated by the non-spatially-uniform optical intensity in nanoscale photovoltaics. The subcell order and thicknesses are optimized via transfer-matrix formalism and short-circuit current simulations. An efficient charge recombination zone consisting of layers of BCP/Ag/MoOx leads to negligible voltage and series-resistance losses. Under 1-sun illumination the multijunction solar cells exhibit a power conversion efficiency of 5.5 ± 0.2% with an FF of 0.685 ± 0.002 and a V(OC) of 1.65 ± 0.02 V, corresponding to the sum of the V(OC) of the component subcells. These devices exhibit a broad spectral response (in the wavelength range of 350 nm to 850 nm) but are limited by subcell external quantum efficiencies between 20% and 30% over the photoactive spectrum. PMID:23014483

  12. Quasar Outflow Constraints using Broad Absorption Line Variability Studies

    NASA Astrophysics Data System (ADS)

    McGraw, Sean; Shields, Joseph C.; Hamann, Fred; Capellupo, Daniel M.; Gallagher, Sarah; Brandt, W. Niel; Herbst, Hanna

    2016-01-01

    Quasar outflows are plausible candidates for AGN feedback processes influencing the host galaxy and may explain the established correlations between the supermassive black hole (SMBH) and the surrounding bulge. In order to better understand feedback and the physical conditions of the outflowing gas, observational constraints on absorber kinematics and energetics are needed. We are utilizing multiple epoch, rest frame UV quasar spectra to establish limits on outflow locations and total column densities for the purpose of estimating wind kinetic energies and momenta. We are also investigating the variability patterns of broad absorption lines (BALs) and mini-BALs across a range of ionization states to probe underlying connections between the various classes of absorbers. This work employs observations from the Sloan Digital Sky Survey, Hobby Eberly Telescope, and MDM observatory. We detect BAL variability in 3 out of 12 FeLoBAL quasars over multiple year timescales and conclude that the variable absorbers lie within tens of parsecs of the SMBH based on interpretations of the Fe II and Mg II BALS. We also measure significant BAL changes across daily to yearly timescales in a sample of 71 quasars with plausible detections of the P V 1117,1128 BAL. Detecting phosphorus in absorption is notable because it traces high column density outflows and is therefore relevant for studying AGN feedback. Constraints on outflow energetics and other selected results will be presented.

  13. Broad-Spectrum Allosteric Inhibition of Herpesvirus Proteases

    PubMed Central

    2015-01-01

    Herpesviruses rely on a homodimeric protease for viral capsid maturation. A small molecule, DD2, previously shown to disrupt dimerization of Kaposi’s sarcoma-associated herpesvirus protease (KSHV Pr) by trapping an inactive monomeric conformation and two analogues generated through carboxylate bioisosteric replacement (compounds 2 and 3) were shown to inhibit the associated proteases of all three human herpesvirus (HHV) subfamilies (α, β, and γ). Inhibition data reveal that compound 2 has potency comparable to or better than that of DD2 against the tested proteases. Nuclear magnetic resonance spectroscopy and a new application of the kinetic analysis developed by Zhang and Poorman [Zhang, Z. Y., Poorman, R. A., et al. (1991) J. Biol. Chem. 266, 15591–15594] show DD2, compound 2, and compound 3 inhibit HHV proteases by dimer disruption. All three compounds bind the dimer interface of other HHV proteases in a manner analogous to binding of DD2 to KSHV protease. The determination and analysis of cocrystal structures of both analogues with the KSHV Pr monomer verify and elaborate on the mode of binding for this chemical scaffold, explaining a newly observed critical structure–activity relationship. These results reveal a prototypical chemical scaffold for broad-spectrum allosteric inhibition of human herpesvirus proteases and an approach for the identification of small molecules that allosterically regulate protein activity by targeting protein–protein interactions. PMID:24977643

  14. Convergence of broad-scale migration strategies in terrestrial birds.

    PubMed

    La Sorte, Frank A; Fink, Daniel; Hochachka, Wesley M; Kelling, Steve

    2016-01-27

    Migration is a common strategy used by birds that breed in seasonal environments. Selection for greater migration efficiency is likely to be stronger for terrestrial species whose migration strategies require non-stop transoceanic crossings. If multiple species use the same transoceanic flyway, then we expect the migration strategies of these species to converge geographically towards the most optimal solution. We test this by examining population-level migration trajectories within the Western Hemisphere for 118 migratory species using occurrence information from eBird. Geographical convergence of migration strategies was evident within specific terrestrial regions where geomorphological features such as mountains or isthmuses constrained overland migration. Convergence was also evident for transoceanic migrants that crossed the Gulf of Mexico or Atlantic Ocean. Here, annual population-level movements were characterized by clockwise looped trajectories, which resulted in faster but more circuitous journeys in the spring and more direct journeys in the autumn. These findings suggest that the unique constraints and requirements associated with transoceanic migration have promoted the spatial convergence of migration strategies. The combination of seasonal atmospheric and environmental conditions that has facilitated the use of similar broad-scale migration strategies may be especially prone to disruption under climate and land-use change. PMID:26791618

  15. Application of Broad-Spectrum Resequencing Microarray for Genotyping Rhabdoviruses▿

    PubMed Central

    Dacheux, Laurent; Berthet, Nicolas; Dissard, Gabriel; Holmes, Edward C.; Delmas, Olivier; Larrous, Florence; Guigon, Ghislaine; Dickinson, Philip; Faye, Ousmane; Sall, Amadou A.; Old, Iain G.; Kong, Katherine; Kennedy, Giulia C.; Manuguerra, Jean-Claude; Cole, Stewart T.; Caro, Valérie; Gessain, Antoine; Bourhy, Hervé

    2010-01-01

    The rapid and accurate identification of pathogens is critical in the control of infectious disease. To this end, we analyzed the capacity for viral detection and identification of a newly described high-density resequencing microarray (RMA), termed PathogenID, which was designed for multiple pathogen detection using database similarity searching. We focused on one of the largest and most diverse viral families described to date, the family Rhabdoviridae. We demonstrate that this approach has the potential to identify both known and related viruses for which precise sequence information is unavailable. In particular, we demonstrate that a strategy based on consensus sequence determination for analysis of RMA output data enabled successful detection of viruses exhibiting up to 26% nucleotide divergence with the closest sequence tiled on the array. Using clinical specimens obtained from rabid patients and animals, this method also shows a high species level concordance with standard reference assays, indicating that it is amenable for the development of diagnostic assays. Finally, 12 animal rhabdoviruses which were currently unclassified, unassigned, or assigned as tentative species within the family Rhabdoviridae were successfully detected. These new data allowed an unprecedented phylogenetic analysis of 106 rhabdoviruses and further suggest that the principles and methodology developed here may be used for the broad-spectrum surveillance and the broader-scale investigation of biodiversity in the viral world. PMID:20610710

  16. VERY LARGE TELESCOPE SPECTROPOLARIMETRY OF BROAD ABSORPTION LINE QSOs

    SciTech Connect

    DiPompeo, M. A.; Brotherton, M. S.; De Breuck, C.

    2011-03-15

    We present spectropolarimetry of 19 confirmed and four possible bright, southern broad absorption line (BAL) quasars from the European Southern Observatory Very Large Telescope. A wide range of redshifts is covered in the sample (from 0.9 to 3.4), and both low- and high-ionization quasars are represented, as well as radio-loud and radio-quiet BALQSOs. We continue to confirm previously established spectropolarimetric properties of BALQSOs, including the generally rising continuum polarization with shorter wavelengths and comparatively large fraction with high broadband polarization (6 of 19 with polarizations >2%). Emission lines are polarized less than or similar to the continuum, except in a few unusual cases, and absorption troughs tend to have higher polarizations. A search for correlations between polarization properties has been done, identifying two significant or marginally significant correlations. These are an increase in continuum polarization with decreasing optical luminosity (increasing absolute B magnitude) and decreasing C IV emission-line polarization with increased continuum polarization.

  17. Series-fed circularly polarized microstrip antennas with broad bandwidth

    NASA Astrophysics Data System (ADS)

    Mao, Shau-Gang; Chen, Shiou-Li; Yeh, Jen-Chun; Lin, Tien-Min

    2007-08-01

    A new series-fed circularly polarized antenna (SFCPA) in microstrip configuration, which consists of a traveling-wave-type crank-line antenna (CLA) and a resonant-type square-ring slot antenna (SRSA), is developed. Unlike the conventional crank-line (CL) antenna array with an open end or a resistive load, the proposed SFCPA uses the SRSA at the termination of the CLA and thus exhibits not only a broad circularly polarized (CP) bandwidth but also a large antenna gain. The characteristics of the SFCPA, including the leaky-wave radiation and the circular polarization, are examined in terms of the dispersion diagram and the current distribution. The SFCPA with the two-cell CLA and the terminated SRSA is fabricated and measured to demonstrate the 10-dB return loss and 3-dB axial ratio (AR) bandwidths of 34.3% and 30.5%, respectively. The frequency-scanning radiation patterns with a 5-7 dBi antenna gain are also presented in the operating band.

  18. Approaches to a broad range of high performance PDT sensitizers

    NASA Astrophysics Data System (ADS)

    d'A. Rocha Gonsalves, António M.; Serra, Arménio C.; Pineiro, Marta; Botelho, M. Filomena

    2009-02-01

    Starting from expertise in the area of chemical synthesis, particularly in tetrapyrrolic macrocycles and an interest in modelling structures for particular objectives, we came to the point of aiming at modelling photochemical sensitizers designed for photodynamic therapy (PDT) purposes. Our endeavours were gratifying when it was proved that our synthetic methodologies allowed for the easy availability of properly halogenated porphyrins with high quantum yield singlet oxygen efficiency. Joining the presence of this heavy atom and other functionalities as substituents in selected positions of macrocyclic structures we were able to generate novel porphyrin structures whose photophysical and photochemical properties, singlet oxygen formation quantum yields, photobleaching and logP were measured. Cellular uptake measurements and cytotoxicity assays on WiDr adenocarcinoma and A375 tumor cell lines were carried out and some of our porphyrins demonstrated very high performance as PDT sensitizers comparatively to known compounds approved for clinical use and in the market. Further developments of our studies allowed for the generation of different and more efficient structures, easily made available by our own synthetic methodologies. Our studies in this area allowed us to reach a stage which we believe to correspond to a significant knowledge and capacity to synthesise a broad range of simple structures, whose selectivity and efficiency as PDT sensitizers can be modulated for different cellular and tissue specificities. Our most recent developments in this area will be presented in this communication.

  19. Two photon absorption in high power broad area laser diodes

    NASA Astrophysics Data System (ADS)

    Dogan, Mehmet; Michael, Christopher P.; Zheng, Yan; Zhu, Lin; Jacob, Jonah H.

    2014-03-01

    Recent advances in thermal management and improvements in fabrication and facet passivation enabled extracting unprecedented optical powers from laser diodes (LDs). However, even in the absence of thermal roll-over or catastrophic optical damage (COD), the maximum achievable power is limited by optical non-linear effects. Due to its non-linear nature, two-photon absorption (TPA) becomes one of the dominant factors that limit efficient extraction of laser power from LDs. In this paper, theoretical and experimental analysis of TPA in high-power broad area laser diodes (BALD) is presented. A phenomenological optical extraction model that incorporates TPA explains the reduction in optical extraction efficiency at high intensities in BALD bars with 100μm-wide emitters. The model includes two contributions associated with TPA: the straightforward absorption of laser photons and the subsequent single photon absorption by the holes and electrons generated by the TPA process. TPA is a fundamental limitation since it is inherent to the LD semiconductor material. Therefore scaling the LDs to high power requires designs that reduce the optical intensity by increasing the mode size.

  20. Numerical Models of Broad-Bandwidth Nanosecond Optical Parametric Oscillators

    SciTech Connect

    Bowers, M.S.; Gehr. R.J.; Smith, A.V.

    1998-10-22

    We present three new methods for modeling broad-bandwidth, nanosecond optitcal parametric oscillators in the plane-wave approximation. Each accounts for the group-velocity differences that determine the operating linewidth of unseeded optical parametric oscillators, and each allows the signal and idler waves to develop from quantum noise. The first two methods are based on split-step integration methods in which nonlinear mixing and propagation are calculated separately on alternate steps. One method relies on Fourier transforming handle propagation, wiih mixing integrated over a the fields between t and u to Az step: the other transforms between z and k= in the propagation step, with mixing integrated over At. The third method is based on expansion of the three optical fields in terms of their respective longitudinal empty cavity modes, taking into account the cavity boundary condi- tions. Equations describing the time development of the mode amplitudes are solved to yield the time dependence of the three output fields. These plane-wave models exclude diffractive effects, but can be readily extended to include them.

  1. Extension of the Bgl Broad Group Cross Section Library

    NASA Astrophysics Data System (ADS)

    Kirilova, Desislava; Belousov, Sergey; Ilieva, Krassimira

    2009-08-01

    The broad group cross-section libraries BUGLE and BGL are applied for reactor shielding calculation using the DOORS package based on discrete ordinates method and multigroup approximation of the neutron cross-sections. BUGLE and BGL libraries are problem oriented for PWR or VVER type of reactors respectively. They had been generated by collapsing the problem independent fine group library VITAMIN-B6 applying PWR and VVER one-dimensional radial model of the reactor middle plane using the SCALE software package. The surveillance assemblies (SA) of VVER-1000/320 are located on the baffle above the reactor core upper edge in a region where geometry and materials differ from those of the middle plane and the neutron field gradient is very high which would result in a different neutron spectrum. That is why the application of the fore-mentioned libraries for the neutron fluence calculation in the region of SA could lead to an additional inaccuracy. This was the main reason to study the necessity for an extension of the BGL library with cross-sections appropriate for the SA region. Comparative analysis of the neutron spectra of the SA region calculated by the VITAMIN-B6 and BGL libraries using the two-dimensional code DORT have been done with purpose to evaluate the BGL applicability for SA calculation.

  2. In vitro irradiation station for broad beam radiobiological experiments

    NASA Astrophysics Data System (ADS)

    Wéra, A.-C.; Riquier, H.; Heuskin, A.-C.; Michiels, C.; Lucas, S.

    2011-12-01

    The study of the interaction of charged particles with living matter is of prime importance to the fields of radiotherapy, radioprotection and space radiobiology. Particle accelerators and their associated equipment are proven to be helpful tools in performing basic science in all these fields. Indeed, they can accelerate virtually any ions to a given energy and flux and let them interact with living matter either in vivo or in vitro. In this context, the University of Namur has developed a broad beam in vitro irradiation station for use in radiobiological experiments. Cells are handled in GLP conditions and can be irradiated at various fluxes with ions ranging from hydrogen to carbon. The station is mounted on a 2 MV tandem accelerator, and the energy range can be set up in the linear energy transfer (LET) ranges that are useful for radiobiological experiments. This paper describes the current status of the hardware that has been developed, and presents results related to its performance in term of dose-rate, energy range and beam uniformity for protons, alpha particles and carbon ions. The results of clonogenic assays of A549 lung adenocarcinoma cells irradiated with protons and alpha particles are also presented and compared with literature.

  3. Kibdelomycin Is a Bactericidal Broad-Spectrum Aerobic Antibacterial Agent

    PubMed Central

    Dayananth, Priya; Balibar, Carl J.; Garlisi, Charles G.; Lu, Jun; Kishii, Ryuta; Takei, Masaya; Fukuda, Yasumichi; Ha, Sookhee; Young, Katherine

    2015-01-01

    Bacterial resistance to antibiotics continues to grow and pose serious challenges, while the discovery rate for new antibiotics declines. Kibdelomycin is a recently discovered natural-product antibiotic that inhibits bacterial growth by inhibiting the bacterial DNA replication enzymes DNA gyrase and topoisomerase IV. It was reported to be a broad-spectrum aerobic Gram-positive agent with selective inhibition of the anaerobic bacterium Clostridium difficile. We have extended the profiling of kibdelomycin by using over 196 strains of Gram-positive and Gram-negative aerobic pathogens recovered from worldwide patient populations. We report the MIC50s, MIC90s, and bactericidal activities of kibdelomycin. We confirm the Gram-positive spectrum and report for the first time that kibdelomycin shows strong activity (MIC90, 0.125 μg/ml) against clinical strains of the Gram-negative nonfermenter Acinetobacter baumannii but only weak activity against Pseudomonas aeruginosa. We confirm that well-characterized resistant strains of Staphylococcus aureus and Streptococcus pneumoniae show no cross-resistance to kibdelomycin and quinolones and coumarin antibiotics. We also show that kibdelomycin is not subject to efflux in Pseudomonas, though it is in Escherichia coli, and it is generally affected by the outer membrane permeability entry barrier in the nonfermenters P. aeruginosa and A. baumannii, which may be addressable by structure-based chemical modification. PMID:25845866

  4. The Physical Nature of Polar Broad Absorption Line Quasars

    NASA Technical Reports Server (NTRS)

    Ghost, Kajal; Punsly, Brian

    2007-01-01

    It has been shown based on radio variability arguments that some BALQSOs (broad absorption line quasars) are viewed along the polar axis (o rthogonal to accretion disk) in the recent article of Zhou et a. Thes e arguments are based on the brightness temperature, T(sub b) exceedi ng 10(exp 12) K which leads to the well-known inverse Compton catastr ophe unless the radio jet is relativistic and is viewed along its axi s. In this letter, we expand the Zhou et al sample of polar BALQSOs u sing their techniques applied to SDSS DR5. In the process, we clarify a mistake in their calculation of brightness temperature. The expanded sample of high T(sub b) BALQSOS, has an inordinately large fraction of LoBALQSOs (low ionization BALQSOs). We consider this an important clue to understanding the nature of the polar BALQSOs. This is expec ted in the polar BALQSO analytical/numerical models of Punsly that pr edicted that LoBALQSOs occur when the line of sight is very close to the polar axis, where the outflow density is the highest.

  5. Work-related suicide in Victoria, Australia: a broad perspective.

    PubMed

    Routley, Virginia Hazel; Ozanne-Smith, Joan E

    2012-01-01

    While unintentional work-related injury is increasingly recognised as important and preventable, population studies of the full range of work related suicides have received less attention. The objective of this study is to investigate the epidemiology of work-related suicide in Victoria, July 2000-December 2007. The study draws on a database of all work-related deaths reported to the Victorian Coroner, inclusive of broadly defined work-relatedness. Inclusion criteria for work-related suicide were at least one of: suicide means was work related, work stressors were identified in police reports to the Coroners or the Coroner's finding, the suicide method involved another person's work (e.g. rail suicide, heavy vehicle) or the suicide location was a workplace. Cases still open for investigation were excluded. Of 642 work-related suicides, 55% had an association with work stressors; 32% jumped or lay in front of a train or heavy vehicle; 7% involved a work location and 6% involved work agents. Work stressor cases identified included business difficulties, recent or previous work injury, unemployment/redundancy or conflict with supervisors/colleagues (including workplace bullying). Work-related suicide is a substantial problem, for which few detailed population wide studies are available. Further research is required to understand the contribution of work stressors and effective interventions. PMID:22132703

  6. Recognition determinants of broadly neutralizing human antibodies against dengue viruses.

    PubMed

    Rouvinski, Alexander; Guardado-Calvo, Pablo; Barba-Spaeth, Giovanna; Duquerroy, Stéphane; Vaney, Marie-Christine; Kikuti, Carlos M; Navarro Sanchez, M Erika; Dejnirattisai, Wanwisa; Wongwiwat, Wiyada; Haouz, Ahmed; Girard-Blanc, Christine; Petres, Stéphane; Shepard, William E; Desprès, Philippe; Arenzana-Seisdedos, Fernando; Dussart, Philippe; Mongkolsapaya, Juthathip; Screaton, Gavin R; Rey, Félix A

    2015-04-01

    Dengue disease is caused by four different flavivirus serotypes, which infect 390 million people yearly with 25% symptomatic cases and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3, 4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes. Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop and the two conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell, explaining its conservation across serotypes and highlighting an Achilles' heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus. PMID:25581790

  7. X-Ray Continua of Broad Absorption Line Quasars

    NASA Technical Reports Server (NTRS)

    Mathur, S.

    1999-01-01

    The targets for this program, PG1416-129 and LBQS 2212-1759 were known to be Broad Absorption Line Quasars (BALQSOs). BALQSOs are highly absorbed in soft X-rays. Good high energy response of Rossi-XTE made them ideal targets for observation. We observed LBQS 2212-1759 with PCA. We have now analyzed the data and found that the source was not detected. Since our target was expected to be faint, reliable estimate of background was very important. With the release of new FTOOLS (version 4.1) we were able to do so. We also analyzed a well known bright object and verified our results with the published data. This gave us confidence in the non-detection of our target LBQS 2212-1759. We are currently investigating the implications of this non-detection. Due to some scheduling problems, our second target PG1416-129 was not observed in A01. It was observed on 06/26/98. This target was detected with RXTE. We are now working on the spectral analysis with XSPEC.

  8. Broad-band Lg attenuation modelling in the Middle East

    NASA Astrophysics Data System (ADS)

    Pasyanos, Michael E.; Matzel, Eric M.; Walter, William R.; Rodgers, Arthur J.

    2009-06-01

    We present a broad-band tomographic model of Lg attenuation in the Middle East derived from source- and site-corrected amplitudes. Absolute amplitude measurements are made on hand-selected and carefully windowed seismograms for tens of stations and thousands of crustal earthquakes resulting in excellent coverage of the region. A conjugate gradient method is used to tomographically invert the amplitude data set of over 8000 paths over a 45° × 40° region of the Middle East. We solve for Q variation, as well as site and source terms, for a wide range of frequencies ranging from 0.5 to 10 Hz. We have modified the standard attenuation tomography technique to more explicitly define the earthquake source expression in terms of the seismic moment. This facilitates the use of the model to predict the expected amplitudes of new events, an important consideration for earthquake hazard or explosion monitoring applications. The attenuation results have a strong correlation to tectonics. Shields have low attenuation, whereas tectonic regions have high attenuation, with the highest attenuation at 1 Hz found in eastern Turkey. The results also compare favourably to other studies in the region made using Lg propagation efficiency, Lg/Pg amplitude ratios and two-station methods. We tomographically invert the amplitude measurements for each frequency independently. In doing so, it appears the frequency dependence of attenuation in all regions is not compatible with the power-law representation of Q(f), an assumption that is often made.

  9. Analysis of mammalian gene function through broad based phenotypic screens across a consortium of mouse clinics

    PubMed Central

    Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Mike; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; El Fertak, Lahcen; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl MJ; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Ed; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie

    2015-01-01

    The function of the majority of genes in the mouse and human genomes remains unknown. The mouse ES cell knockout resource provides a basis for characterisation of relationships between gene and phenotype. The EUMODIC consortium developed and validated robust methodologies for broad-based phenotyping of knockouts through a pipeline comprising 20 disease-orientated platforms. We developed novel statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no prior functional annotation. We captured data from over 27,000 mice finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. Novel phenotypes were uncovered for many genes with unknown function providing a powerful basis for hypothesis generation and further investigation in diverse systems. PMID:26214591

  10. Radiation pressure confinement - III. The origin of the broad ionization distribution in AGN outflows

    NASA Astrophysics Data System (ADS)

    Stern, Jonathan; Behar, Ehud; Laor, Ari; Baskin, Alexei; Holczer, Tomer

    2014-12-01

    The winds of ionized gas driven by active galactic nuclei (AGN) can be studied through absorption lines in their X-ray spectra. A recurring feature of these outflows is their broad ionization distribution, including essentially all ionization levels (e.g., Fe0+ to Fe25+). This characteristic feature can be quantified with the absorption measure distribution (AMD), defined as the distribution of column density with ionization parameter |dN/d log ξ|. Observed AMDs extend over 0.1 ≲ ξ ≲ 104 (cgs), and are remarkably similar in different objects. Power-law fits (|dN/d log ξ| ≈ N1ξa) yield N1 = 3 × 1021 cm- 2 ± 0.4 dex and a = 0-0.4. What is the source of this broad ionization distribution, and what sets the small range of observed N1 and a? A common interpretation is a multiphase outflow, with a wide range of gas densities in a uniform gas pressure medium. However, the incident radiation pressure leads to a gas pressure gradient in the photoionized gas, and therefore to a broad range of ionization states within a single slab. We show that this compression of the gas by the radiation pressure leads to an AMD with |dN/d log ξ| = 8 × 1021 ξ0.03 cm-2, remarkably similar to that observed. The calculated values of N1 and a depend weakly on the gas metallicity, the ionizing spectral slope, the distance from the nucleus, the ambient density, and the total absorber column. Thus, radiation pressure compression (RPC) of the photoionized gas provides a natural explanation for the observed AMD. RPC predicts that the gas pressure increases with decreasing ionization, which can be used to test the validity of RPC in ionized AGN outflows.

  11. Active infrared hyperspectral imaging system using a broadly tunable optical parametric oscillator

    NASA Astrophysics Data System (ADS)

    Malcolm, G. P. A.; Maker, G. T.; Robertson, G.; Dunn, M. H.; Stothard, D. J. M.

    2009-09-01

    The in situ identification and spatial location of gases, discrete liquid droplets and residues on surfaces is a technically challenging problem. Active Infrared (IR) hyperspectral imaging is a powerful technique that combines real-time imaging and optical spectroscopy for "standoff" detection of suspected chemical substances, including chemical warfare agents, toxic industrial chemicals, explosives and narcotics. An active IR hyperspectral imaging system requires a coherent, broadly tunable IR light source of high spectral purity, in order to detect a broad range of target substances. In this paper we outline a compact and power-efficient IR illumination source with high stability, efficiency, tuning range and spectral purity based upon an optical parametric oscillator (OPO). The fusion of established OPO technology with novel diode-pumped laser technology and electro-mechanical scanning has enabled a broadly applicable imaging system. This system is capable of hyperspectral imaging at both Near-IR (1.3 - 1.9 μm) and Mid-IR (2.3 - 4.6 μm) wavelengths simultaneously with a line width of < 3 cm-1. System size and complexity are minimised by using a dual InGaAs/InSb single element detector, and images are acquired by raster scanning the coaxial signal and idler beams simultaneously, at ranges up to 20 m. Reflection, absorption and scatter of incident radiation by chemical targets and their surroundings provide a method for spatial location, and characteristic spectra obtained from each sample can be used to identify targets uniquely. To date, we have recognized liquids in sample sizes as small 20 μl-and gases with sensitivity as high as 10ppm.m-at detection standoff distances > 10 m.

  12. Locally Optimally Emitting Clouds and the Variable Broad Emission Line Spectrum of NGC 5548

    NASA Astrophysics Data System (ADS)

    Korista, Kirk T.; Goad, Michael R.

    2000-06-01

    In recent work Baldwin et al. proposed that in the geometrically extended broad-line regions (BLRs) of quasars and active galactic nuclei, a range in line-emitting gas properties (e.g., density, column density) might exist at each radius and showed that under these conditions the broad emission line spectra of these objects may be dominated by selection effects introduced by the atomic physics and general radiative transfer within the large pool of line-emitting entities. In this picture, the light we see originates in a vast amalgam of emitters but is dominated by those emitters best able to reprocess the incident continuum into a particular emission line. We test this ``locally optimally emitting clouds'' (LOC) model against the extensive spectroscopic database of the Seyfert 1 galaxy NGC 5548. The time-averaged, integrated-light UV broad emission line spectrum from the 1993 Hubble Space Telescope (HST) monitoring campaign is reproduced via the optimization of three global geometric parameters: the outer radius, the index controlling the radial cloud covering fraction of the continuum source, and the integrated cloud covering fraction. We make an ad hoc selection from the range of successful models, and for a simple spherical BLR geometry we simulate the emission-line light curves for the 1989 IUE and 1993 HST campaigns, using the respective observed UV continuum light curves as drivers. We find good agreement between the predicted and observed light curves and lags-a demonstration of the LOC picture's viability as a means to understanding the BLR environment. Finally, we discuss the next step in developing the LOC picture, which involves the marriage of echo-mapping techniques with spectral simulation grids such as those presented here, using the constraints provided by a high-quality, temporally well-sampled spectroscopic data set.

  13. Broad Street elevation of James H. Windrim and George Summers’s ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Broad Street elevation of James H. Windrim and George Summers’s neoclassical competition design for the New Masonic Temple, Philadelphia, 1867 - Masonic Temple, 1 North Broad Street, Philadelphia, Philadelphia County, PA

  14. Impact of broad-specification fuels on future jet aircraft. [engine components and performance

    NASA Technical Reports Server (NTRS)

    Grobman, J. S.

    1978-01-01

    The effects that broad specification fuels have on airframe and engine components were discussed along with the improvements in component technology required to use broad specification fuels without sacrificing performance, reliability, maintainability, or safety.

  15. Choosing a primary care provider

    MedlinePlus

    Family doctor - how to choose one; Primary care provider - how to choose one; Doctor - how to choose a family doctor ... A PCP is your main health care provider in non-emergency ... and teach healthy lifestyle choices Identify and treat common ...

  16. Family Day Care Provider Handbook

    ERIC Educational Resources Information Center

    New York State Office of Children and Family Services, 2006

    2006-01-01

    Family day care providers are responsible for creating a high-quality program where children have opportunities to grow, learn and thrive. Part of providing high-quality child care includes complying with the family day care regulations from the New York State Office of Children and Family Services (OCFS). This Handbook will help day care…

  17. Ability to develop broadly neutralizing HIV-1 antibodies is not restricted by the germline Ig gene repertoire.

    PubMed

    Scheepers, Cathrine; Shrestha, Ram K; Lambson, Bronwen E; Jackson, Katherine J L; Wright, Imogen A; Naicker, Dshanta; Goosen, Mark; Berrie, Leigh; Ismail, Arshad; Garrett, Nigel; Abdool Karim, Quarraisha; Abdool Karim, Salim S; Moore, Penny L; Travers, Simon A; Morris, Lynn

    2015-05-01

    The human Ig repertoire is vast, producing billions of unique Abs from a limited number of germline Ig genes. The IgH V region (IGHV) is central to Ag binding and consists of 48 functional genes. In this study, we analyzed whether HIV-1-infected individuals who develop broadly neutralizing Abs show a distinctive germline IGHV profile. Using both 454 and Illumina technologies, we sequenced the IGHV repertoire of 28 HIV-infected South African women from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 002 and 004 cohorts, 13 of whom developed broadly neutralizing Abs. Of the 259 IGHV alleles identified in this study, approximately half were not found in the International Immunogenetics Database (IMGT). This included 85 entirely novel alleles and 38 alleles that matched rearranged sequences in non-IMGT databases. Analysis of the rearranged H chain V region genes of mAbs isolated from seven of these women, as well as previously isolated broadly neutralizing Abs from other donors, provided evidence that at least eight novel or non-IMGT alleles contributed to functional Abs. Importantly, we found that, despite a wide range in the number of IGHV alleles in each individual, including alleles used by known broadly neutralizing Abs, there were no significant differences in germline IGHV repertoires between individuals who do and do not develop broadly neutralizing Abs. This study reports novel IGHV repertoires and highlights the importance of a fully comprehensive Ig database for germline gene usage prediction. Furthermore, these data suggest a lack of genetic bias in broadly neutralizing Ab development in HIV-1 infection, with positive implications for HIV vaccine design. PMID:25825450

  18. Ability to develop broadly neutralizing HIV-1 antibodies is not restricted by the germline immunoglobulin gene repertoire1

    PubMed Central

    Scheepers, Cathrine; Shrestha, Ram K.; Lambson, Bronwen E.; Jackson, Katherine J. L.; Wright, Imogen A.; Naicker, Dshanta; Goosen, Mark; Berrie, Leigh; Ismail, Arshad; Garrett, Nigel; Karim, Quarraisha Abdool; Karim, Salim S. Abdool; Moore, Penny L.; Travers, Simon A.; Morris, Lynn

    2015-01-01

    The human immunoglobulin repertoire is vast, producing billions of unique antibodies from a limited number of germline immunoglobulin genes. The immunoglobulin heavy chain variable region (IGHV) is central to antigen binding and is comprised of 48 functional genes. Here we analyzed whether HIV-1 infected individuals who develop broadly neutralizing antibodies show a distinctive germline IGHV profile. Using both 454 and Illumina technologies we sequenced the IGHV repertoire of 28 HIV-infected South African women from the Center for the AIDS Programme of Research in South African (CAPRISA) 002 and 004 cohorts, 13 of whom developed broadly neutralizing antibodies. Of the 259 IGHV alleles identified in this study, approximately half were not found in the International Immunogenetics Database (IMGT). This included 85 entirely novel alleles and 38 alleles that matched rearranged sequences in non-IMGT databases. Analysis of the rearranged H chain V region genes of monoclonal antibodies isolated from 7 of the CAPRISA women and previously isolated broadly neutralizing antibodies from other donors provided evidence that at least 8 novel or non-IMGT alleles contributed to functional antibodies. Importantly, we found that despite a wide range in the number of IGHV alleles in each individual, including alleles used by known broadly neutralizing antibodies, there were no significant differences in germline IGHV repertoires between individuals who do and do not develop broadly neutralizing antibodies. This study reports novel IGHV repertoires and highlights the importance of a fully comprehensive immunoglobulin database for germline gene usage prediction. Furthermore, these data suggest a lack of genetic bias in broadly neutralizing antibody development in HIV-1 infection, with implications for HIV vaccine design. PMID:25825450

  19. Tackling Disrespectful, Unprofessional Provider Behaviors.

    PubMed

    2016-06-01

    To address problematic provider behaviors that can affect patient safety, physician leaders at Vanderbilt University Medical Center (VUMC) developed the Coworker Observation Reporting System (CORS), a systematized approach for retrieving and addressing concerns about providers reported by staff. To encourage staff members to report concerns, they have to trust that the organization is going to respond, and they also have to feel that they have a certain element of psychological safety. Selected peer messengers share staff complaints with providers, enabling them to offer their perspectives on the issues or events in question. Three years into the implementation of CORS, investigators found that the majority of providers self-correct their behaviors when reports about staff concerns are shared. Additional level 1, level 2, and level 3 interventions are built into the CORS system for providers who fail to self-correct after one or two reports. PMID:27295820

  20. Broad targeting of angiogenesis for cancer prevention and therapy.

    PubMed

    Wang, Zongwei; Dabrosin, Charlotta; Yin, Xin; Fuster, Mark M; Arreola, Alexandra; Rathmell, W Kimryn; Generali, Daniele; Nagaraju, Ganji P; El-Rayes, Bassel; Ribatti, Domenico; Chen, Yi Charlie; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Nowsheen, Somaira; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S Salman; Helferich, Bill; Yang, Xujuan; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Halicka, Dorota; Mohammed, Sulma I; Azmi, Asfar S; Bilsland, Alan; Keith, W Nicol; Jensen, Lasse D

    2015-12-01

    Deregulation of angiogenesis--the growth of new blood vessels from an existing vasculature--is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development. Unfortunately the clinically approved anti-angiogenic drugs in use today are only effective in a subset of the patients, and many who initially respond develop resistance over time. Also, some of the anti-angiogenic drugs are toxic and it would be of great importance to identify alternative compounds, which could overcome these drawbacks and limitations of the currently available therapy. Finding "the most important target" may, however, prove a very challenging approach as the tumor environment is highly diverse, consisting of many different cell types, all of which may contribute to tumor angiogenesis. Furthermore, the tumor cells themselves are genetically unstable, leading to a progressive increase in the number of different angiogenic factors produced as the cancer progresses to advanced stages. As an alternative approach to targeted therapy, options to broadly interfere with angiogenic signals by a mixture of non-toxic natural compound with pleiotropic actions were viewed by this team as an opportunity to develop a complementary anti-angiogenesis treatment option. As a part of the "Halifax Project" within the "Getting to know cancer" framework, we have here, based on a thorough review of the literature, identified 10 important aspects of tumor angiogenesis and the

  1. Broad targeting of angiogenesis for cancer prevention and therapy

    PubMed Central

    Wang, Zongwei; Dabrosin, Charlotta; Yin, Xin; Fuster, Mark M.; Arreola, Alexandra; Rathmell, W. Kimryn; Generali, Daniele; Nagaraju, Ganji P.; El-Rayes, Bassel; Ribatti, Domenico; Chen, Yi Charlie; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Nowsheen, Somaira; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Helferich, Bill; Yang, Xujuan; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Halicka, Dorota; Mohammed, Sulma I.; Azmi, Asfar S.; Bilsland, Alan; Keith, W. Nicol; Jensen, Lasse D.

    2015-01-01

    Deregulation of angiogenesis – the growth of new blood vessels from an existing vasculature – is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development. Unfortunately the clinically approved anti-angiogenic drugs in use today are only effective in a subset of the patients, and many who initially respond develop resistance over time. Also, some of the anti-angiogenic drugs are toxic and it would be of great importance to identify alternative compounds, which could overcome these drawbacks and limitations of the currently available therapy. Finding “the most important target” may, however, prove a very challenging approach as the tumor environment is highly diverse, consisting of many different cell types, all of which may contribute to tumor angiogenesis. Furthermore, the tumor cells themselves are genetically unstable, leading to a progressive increase in the number of different angiogenic factors produced as the cancer progresses to advanced stages. As an alternative approach to targeted therapy, options to broadly interfere with angiogenic signals by a mixture of non-toxic natural compound with pleiotropic actions were viewed by this team as an opportunity to develop a complementary anti-angiogenesis treatment option. As a part of the “Halifax Project” within the “Getting to know cancer” framework, we have here, based on a thorough review of the literature, identified 10 important aspects of tumor

  2. Galactose as Broad Ligand for Multiple Tumor Imaging and Therapy

    PubMed Central

    Ma, Yuxiang; Chen, Haiyan; Su, Shanyuhan; Wang, Tong; Zhang, Congying; Fida, Guissi; Cui, Sisi; Zhao, Juan; Gu, Yueqing

    2015-01-01

    Galactose residues could be specifically recognized by the asialoglycoprotein receptor (ASGPR) which is highly exhibited on liver tissues. However, ASGPR has not been widely investigated on different tumor cell lines except for hepatoma carcinoma cells, which motivates us to investigate the possibility of galactose serving as a board tumor ligand. In this study, a galactose (Gal)-based probe conjugated with fluorescence dye MPA (Gal-MPA) was constructed for the evaluation of tumor affinities/targeted ability on different tumor cell lines. In the vitro cell study, it was indicated that the fluorescence probe Gal-MPA displayed higher cell affinity to tumor cells (HepG2, MCF-7 and A549) than that of the normal liver cells l02. In the vivo dynamic study of Gal-MPA in tumor-bearing mice (HepG2, MCF-7, A549, HCT116, U87, MDA-MB-231 and S180), it was shown that its high tumor targeted ability with the maximal tumor/normal tissue ratio reached up to 6.8. Meanwhile, the fast tumor-targeted ability within 2 hours and long retention on tumor site up to 120 hours were observed. Our results demonstrated that galactose should be a promising broad ligand for multiple tumor imaging and targeted therapy. Subsequently, Gal was covalently conjugated to doxorubicin (DOX) to form prodrug Gal-DOX for tumor targeted therapy. The therapeutic results of Gal-DOX than DOX being better suggested that galactosylated prodrugs might have the prospective potential in tumor targeted therapy. PMID:26078797

  3. WINNERSS - Reaching a broad audience from an academic institution

    NASA Astrophysics Data System (ADS)

    Limaye, S. S.; Pertzborn, R. A.

    2001-12-01

    "Wisconsin Idea National Network - Education and Research in Space Sciences: Our Home in the Universe" is a Thematic Outreach Program from the University of Wisconsin-Madison. WINNERSS addresses the main current and future research topics in space sciences - origins of the universe, beginning(s) of life in the universe, the abitability of our home planet. These themes have origins in what we have learned in the age of space exploration and bring together the diverse disciplines of physics, astronomy, astrophysics, geology and geophysics, chemistry, atmospheric science, oceanography, astrobiology - or collectively, the space sciences. This has come about through evolution of our knowledge and our understanding of the role of different processes that have shaped our environment. These include the asteroid impacts on the earth and in our solar system, the discovery of possible microbial of life in Martian rocks that came to earth as meteorites, the discovery of planetary systems around other stars. At the same time, there has been a significant evolution in our knowledge and understanding of the universe and the fragility of the environment on our home planet. The sustainability and global environment are highlighted by global change processes such as weather extremes, "ozone hole", and concerns about the global warming illustrated by events such as the break-up of Antarctic icebergs the size of Rhode sland. Following the long tradition of the Wisconsin Idea, WINNERSS will strive to highlight research in these and related topics through Informal Science Education, K-12 programs and teacher development in space sciences. Broad geographic reach is enabled through the alumni clubs and the UW-Madison Speakers Bureau. WINNERSS is funded by the Wisconin Idea Program of the University of Wisconsin and is being implemented in collaboration with the Wisconsin Alumni Association, and the following components of the University of Wisconsin-Madison: the Graduate School, College

  4. Predicting broad-scale occurrences of vertebrates in patchy landscapes

    USGS Publications Warehouse

    Boone, R.B.; Krohn, W.B.

    2000-01-01

    Spatially explicit landscape-scale models that predict species distributions, where patches of habitat are shown as having potential to be occupied or unoccupied, are increasingly common. To successfully use such data, one should understand how these predicted distributions are created and how their relative accuracies are assessed. Geographic ranges, defined upon observations (e.g., atlases), literature review, and expert review, are a primary data layer. A map of land cover is created, often from interpretation of satellite imagery or other remotely-sensed data. Species/habitat associations are defined based upon a literature review and expert review, describing associations for habitats derived from the cover map. Included as ancillary associations are how species relate to physical features, where appropriate, such as elevation and hydrography. The three layers of information (range, land cover, and associations) are merged, often using raster-based algebraic statements that exclude unused habitats or patches outside the range of a species. The accuracy of predictions for a suite of species is typically assessed with surveys by comparing the species predicted to occur in an area to the species observed. Omission (i.e., present in species lists but not predicted) and commission (i.e., predicted but not present in lists) errors are reported. Errors may be due to many sources. For example, ranges of species change, cover types may be misidentified, species/habitat associations may be incorrect or change, or species may be rare and unlikely to be seen in surveys and judged in-error even though the species may be present. An example is given of an appropriate use of broad-scale species predicted distributions, in which patterns and threats to Maine terrestrial vertebrate diversity are summarized.

  5. Directed abstraction: Encouraging broad, personal generalizations following a success experience.

    PubMed

    Zunick, Peter V; Fazio, Russell H; Vasey, Michael W

    2015-07-01

    People with negative self-views may fail to generalize appropriately from success experiences (e.g., Wood, Heimpel, Newby-Clark, & Ross, 2005). We drew on theories regarding self-views (Swann, Griffin, Predmore, & Gaines, 1987) and abstraction (Semin & Fiedler, 1991), as well as past linguistic framing work (e.g., Marigold, Holmes, & Ross, 2007, 2010; Salancik, 1974), to create a new technique to encourage people with negative self-views to generalize broadly from a success experience to the self-concept. We call this technique directed abstraction. In Experiment 1, participants with negative self-views who completed a directed abstraction writing task following success feedback regarding a novel laboratory task generalized more from that success, reporting higher ability levels and greater expectations of future success in the relevant domain. In Experiment 2, directed abstraction produced similar results (including more positive self-related affect, e.g., pride) after participants recalled a past public speaking success. In Experiment 3, participants high in fear of public speaking gave two speeches in a context designed to be challenging yet also to elicit successful performances. Directed abstraction helped these participants generalize from their success to beliefs about their abilities, expectations about the future, and confidence as a speaker. In Experiment 4, directed abstraction following success on a verbal task increased persistence in the face of failure on a subsequent verbal task. We discuss implications for understanding how and when people generalize from a success, compare directed abstraction to existing interventions, and suggest practical applications for this influence technique. PMID:25984786

  6. Broad absorption line variability in radio-loud quasars

    NASA Astrophysics Data System (ADS)

    Welling, C. A.; Miller, B. P.; Brandt, W. N.; Capellupo, D. M.; Gibson, R. R.

    2014-05-01

    We investigate C IV broad absorption line (BAL) variability within a sample of 46 radio-loud quasars (RLQs), selected from Sloan Digital Sky Survey (SDSS)/Faint Images of the Radio Sky at Twenty-Centimeters (FIRST) data to include both core-dominated (39) and lobe-dominated (7) objects. The sample consists primarily of high-ionization BAL quasars, and a substantial fraction have large BAL velocities or equivalent widths; their radio luminosities and radio-loudness values span ˜2.5 orders of magnitude. We have obtained 34 new Hobby-Eberly Telescope spectra of 28 BAL RLQs to compare to earlier SDSS data, and we also incorporate archival coverage (primarily dual-epoch SDSS) for a total set of 78 pairs of equivalent width measurements for 46 BAL RLQs, probing rest-frame time-scales of ˜80-6000 d (median 500 d). In general, only modest changes in the depths of segments of absorption troughs are observed, akin to those seen in prior studies of BAL radio-quiet quasars (RQQs). Also similar to previous findings for RQQs, the RLQs studied here are more likely to display BAL variability on longer rest-frame time-scales. However, typical values of |{Δ}EW| and |{Δ}EW|/ are ˜40 ± 20 per cent lower for BAL RLQs when compared with those of a time-scale-matched sample of BAL RQQs. Optical continuum variability is of similar amplitude in BAL RLQs and BAL RQQs; for both RLQs and RQQs, continuum variability tends to be stronger on longer time-scales. BAL variability in RLQs does not obviously depend upon their radio luminosities or radio-loudness values, but we do find tentative evidence for greater fractional BAL variability within lobe-dominated RLQs. Enhanced BAL variability within more edge-on (lobe-dominated) RLQs supports some geometrical dependence to the outflow structure.

  7. 32 CFR 724.203 - Broad objectives of naval discharge review.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Broad objectives of naval discharge review. 724... PERSONNEL NAVAL DISCHARGE REVIEW BOARD Authority/Policy for Departmental Discharge Review § 724.203 Broad objectives of naval discharge review. Naval discharge review shall have as its broad objectives: (a)...

  8. 32 CFR 724.203 - Broad objectives of naval discharge review.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Broad objectives of naval discharge review. 724... PERSONNEL NAVAL DISCHARGE REVIEW BOARD Authority/Policy for Departmental Discharge Review § 724.203 Broad objectives of naval discharge review. Naval discharge review shall have as its broad objectives: (a)...

  9. DO QUASAR BROAD-LINE VELOCITY WIDTHS ADD ANY INFORMATION TO VIRIAL BLACK HOLE MASS ESTIMATES?

    SciTech Connect

    Croom, Scott M.

    2011-08-01

    We examine how much information measured broad-line widths add to virial black hole (BH) mass estimates for flux-limited samples of quasars. We do this by comparing the BH mass estimates to those derived by randomly reassigning the quasar broad-line widths to different objects and re-calculating the BH mass. For 9000 BH masses derived from the H{beta} line we find that the distributions of original and randomized BH masses in the M{sub BH}-redshift plane and the M{sub BH}-luminosity plane are formally identical. A two-dimensional Kolmogorov-Smirnov test does not find a difference at >90% confidence. For the Mg II line (32,000 quasars) we do find very significant differences between the randomized and original BH masses, but the amplitude of the difference is still small. The difference for the C IV line (14,000 quasars) is 2{sigma}-3{sigma} and again the amplitude of the difference is small. Subdividing the data into redshift and luminosity bins we find that the median absolute difference in BH mass between the original and randomized data is 0.025, 0.01, and 0.04 dex for H{beta}, Mg II, and C IV, respectively. The maximum absolute difference is always {<=}0.1 dex. We investigate whether our results are sensitive to corrections to Mg II virial masses, such as those suggested by Onken and Kollmeier. These corrections do not influence our results, other than to reduce the significance of the difference between original and randomized BH masses to only 1{sigma}-2{sigma} for Mg II. Moreover, we demonstrate that the correlation between mass residuals and Eddington ratio discussed by Onken and Kollmeier is more directly attributable to the slope of the relation between H{beta} and Mg II line width. The implication is that the measured quasar broad-line velocity widths provide little extra information, after allowing for the mean velocity width. In this case virial estimates are equivalent to M{sub BH}{proportional_to}L{sup {alpha}}, with L/L{sub Edd

  10. Broad-stripe single longitudinal mode laser based on metal slots

    NASA Astrophysics Data System (ADS)

    Jia, Peng; Qin, Li; Chen, Yongyi; Zhang, Jianwei; Zhang, Jian; Zhang, Xing; Zeng, Yugang; Shan, Xiaonan; Ning, Yongqiang; Wang, Lijun

    2016-04-01

    Single-longitudinal-mode end-emitting laser with 10 periods of metal slots at around 956 nm has been fabricated. 100 μm wide broad-stripe and ten periods of 9.5 μm periodicity metal slots are defined by i-line lithography and dry etching. Experimentally, continuous-wave power of 213 mW has achieved, at a slope efficiency of 520 mW/A, having a 3 dB spectrum width of less than 0.04 nm at 900 mA, and operating in a stable single longitudinal mode with the side-mode suppression ratio (SMSR) of 42 dB. We prove that metal slots introduce sufficient loss into the cavity to filter out the wanted mode, and is more efficient on our chip structure than traditional slot laser. This paper provides a new method for the realizing high power broad-stripe (~100 μm) laser and array with single longitudinal mode operation.

  11. Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress.

    PubMed

    Fox, Julie M; Long, Feng; Edeling, Melissa A; Lin, Hueylie; van Duijl-Richter, Mareike K S; Fong, Rachel H; Kahle, Kristen M; Smit, Jolanda M; Jin, Jing; Simmons, Graham; Doranz, Benjamin J; Crowe, James E; Fremont, Daved H; Rossmann, Michael G; Diamond, Michael S

    2015-11-19

    We screened a panel of mouse and human monoclonal antibodies (MAbs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. Passive transfer of broadly neutralizing MAbs protected mice against infection by chikungunya, Mayaro, and O'nyong'nyong alphaviruses. Using alanine-scanning mutagenesis, loss-of-function recombinant proteins and viruses, and multiple functional assays, we determined that broadly neutralizing MAbs block multiple steps in the viral lifecycle, including entry and egress, and bind to a conserved epitope on the B domain of the E2 glycoprotein. A 16 Å resolution cryo-electron microscopy structure of a Fab fragment bound to CHIKV E2 B domain provided an explanation for its neutralizing activity. Binding to the B domain was associated with repositioning of the A domain of E2 that enabled cross-linking of neighboring spikes. Our results suggest that B domain antigenic determinants could be targeted for vaccine or antibody therapeutic development against multiple alphaviruses of global concern. PMID:26553503

  12. Linking genetically-defined neurons to behavior through a broadly applicable silencing allele

    PubMed Central

    Kim, Jun Chul.; Cook, Melloni N.; Carey, Megan R.; Shen, Chung; Regehr, Wade G.; Dymecki, Susan M.

    2009-01-01

    Summary Tools for suppressing synaptic transmission gain power when able to target highly selective neuron subtypes, thereby sharpening attainable links between neuron type, behavior, and disease; and when able to silence most any neuron subtype, thereby offering broad applicability. Here we present such a tool, RC::PFtox, that harnesses breadth in scope along with high cell-type selection via combinatorial gene expression to deliver tetanus toxin light chain (tox), an inhibitor of vesicular neurotransmission. When applied in mice, we observed cell-type specific disruption of vesicle exocytosis accompanied by loss of excitatory postsynaptic currents and commensurately perturbed behaviors. Among various test populations, we applied RC::PFtox to silence serotonergic neurons, en masse or a subset defined combinatorially. Of the behavioral phenotypes observed upon en masse serotonergic silencing, only one mapped to the combinatorially defined subset. These findings provide evidence for separability by genetic lineage of serotonin-modulated behaviors; collectively, these findings demonstrate broad utility of RC::PFtox for dissecting neuron functions. PMID:19679071

  13. A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens

    PubMed Central

    Abdi, Abdirahman; Perez, Mathilde Foglierini; Geiger, Roger; Tully, Claire Maria; Jarrossay, David; Maina Ndungu, Francis; Wambua, Juliana; Bejon, Philip; Fregni, Chiara Silacci; Fernandez-Rodriguez, Blanca; Barbieri, Sonia; Bianchi, Siro; Marsh, Kevin; Thathy, Vandana; Corti, Davide; Sallusto, Federica

    2016-01-01

    Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies1–4. Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine. PMID:26700814

  14. A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens.

    PubMed

    Tan, Joshua; Pieper, Kathrin; Piccoli, Luca; Abdi, Abdirahman; Foglierini, Mathilde; Geiger, Roger; Tully, Claire Maria; Jarrossay, David; Ndungu, Francis Maina; Wambua, Juliana; Bejon, Philip; Fregni, Chiara Silacci; Fernandez-Rodriguez, Blanca; Barbieri, Sonia; Bianchi, Siro; Marsh, Kevin; Thathy, Vandana; Corti, Davide; Sallusto, Federica; Bull, Peter; Lanzavecchia, Antonio

    2016-01-01

    Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies. Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 98 amino acid collagen-binding domain of LAIR1, an immunoglobulin superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B-cell clone and carry distinct somatic mutations in the LAIR1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine. PMID:26700814

  15. Roles of glycans in interactions between gp120 and HIV broadly neutralizing antibodies.

    PubMed

    Qi, Yifei; Jo, Sunhwan; Im, Wonpil

    2016-03-01

    Many novel broadly neutralizing antibodies against human immunodeficiency virus (HIV) have been identified during the past decade, providing promising templates for the development of an effective HIV-1 vaccine. Structural studies reveal that the epitopes of some of these antibodies involve one or more crucial glycans, without which the binding is completely abolished. In this study, we have investigated the critical roles of glycans in interactions between HIV-1 gp120 and two broadly neutralizing antibodies PG9 (targeting V1/V2) and PGT128 (targeting V3) that are able to neutralize more than 70% of HIV-1 isolates. We have performed molecular dynamics simulations of a number of systems including antibody-gp120 complex with and without glycans, antibody, gp120 with and without glycans, and glycan-only systems. The simulation results show that the complex structures are stabilized by the glycans, and the multivalent interactions between the antibody and gp120 promote cooperativities to further enhance the binding. In the free gp120, the glycans increase the flexibility of the V1/V2 and V3 loops, which likely increases the entropy cost of the antibody recognition. However, the antibodies are able to bind the flexible interface by recognizing the preexisting glycan conformation, and penetrating the glycan shield with flexible complementarity determining region loops that sample the bound conformations occasionally. PMID:26537503

  16. Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein.

    PubMed

    Chen, Edwin; Salinas, Nichole D; Huang, Yining; Ntumngia, Francis; Plasencia, Manolo D; Gross, Michael L; Adams, John H; Tolia, Niraj Harish

    2016-05-31

    Plasmodium vivax Duffy Binding Protein (PvDBP) is the most promising vaccine candidate for P. vivax malaria. The polymorphic nature of PvDBP induces strain-specific immune responses, however, and the epitopes of broadly neutralizing antibodies are unknown. These features hamper the rational design of potent DBP-based vaccines and necessitate the identification of globally conserved epitopes. Using X-ray crystallography, small-angle X-ray scattering, hydrogen-deuterium exchange mass spectrometry, and mutational mapping, we have defined epitopes for three inhibitory mAbs (mAbs 2D10, 2H2, and 2C6) and one noninhibitory mAb (3D10) that engage DBP. These studies expand the currently known inhibitory epitope repertoire by establishing protective motifs in subdomain three outside the receptor-binding and dimerization residues of DBP, and introduce globally conserved protective targets. All of the epitopes are highly conserved among DBP alleles. The identification of broadly conserved epitopes of inhibitory antibodies provides critical motifs that should be retained in the next generation of potent vaccines for P. vivax malaria. PMID:27194724

  17. Design of wide bandwidth pyramidal microwave absorbers using ferrite composites with broad magnetic loss spectra

    NASA Astrophysics Data System (ADS)

    Park, Myung-Jun; Kim, Sung-Soo

    2016-07-01

    Wide bandwidth microwave absorbers with a pyramidal shape and a significantly reduced thickness can be designed using high lossy ferrite materials with broad magnetic loss spectra. The microwave absorbing properties of pyramidal cone absorbers are analyzed using the transmission line approximation, which provides the reflection loss as a function of the material parameters and absorber geometry. Three types of ferrite materials (NiZn spinel ferrite, Co2Z hexaferrite, and RuCoM hexaferrite) are used as the absorbent fillers in a rubber matrix. Among these, Co2Z ferrite is the most suitable material for wide bandwidth pyramidal absorbers, due to its broad magnetic loss spectrum in the GHz frequency range. The optimal geometry of the pyramidal absorber is also determined using the transmission line theory. With the reduced total height of the pyramidal absorber (approximately 60 mm), a wide bandwidth (1.5-18 GHz with respect to the -20 dB reflection loss) can be realized. The proposed absorbers have a thickness advantage over the classical pyramidal ohmic absorbers; thus, they are suitable for small and semi-anechoic chambers.

  18. Broad-band soft x-ray diagnostic instruments at the LLNL Novette laser facility

    SciTech Connect

    Tirsell, K.G.; Lee, P.H.Y.; Nilson, D.G.; Medecki, H.

    1983-09-15

    Complementary broad-band instruments have been developed to measure time dependent, absolute soft x-ray spectra at the Lawrence Livermore National Laboratory (LLNL) Nd glass laser irradiation facilities. Absolute flux measurements of x rays emitted from laser-produced plasmas are important for understanding laser absorption and energy transport. We will describe two new 10-channel XRD systems that have been installed at the LLNL Novette facility for use in the 0.15- to 1.5-keV range. Since XRD channel time response is limited by available oscilloscope performance to 120 ps, a soft x-ray streak camera has been developed for better time resolution (20 ps) and greater dynamic range (approx.10/sup 3/) in the same x-ray energy region. Using suitable filters, grazing incidence mirrors, and a gold or cesium-iodide transmission cathode, this streak camera instrument has been installed at Novette to provide one broad and four relatively narrow channels. It can also be used in a single channel, spatially discriminating mode by means of pinhole imaging. The complementary nature of these instruments has been enhanced by locating them in close proximity and matching their channel energy responses. As an example of the use of these instruments, we present results from Novette 2..omega..(0.53 ..mu..m) gold disk irradiations at 1 ns and 10/sup 14/ to 10/sup 15/ W/cm/sup 2/.

  19. Radiation safety for anesthesia providers.

    PubMed

    Phillips, Gillian; Monaghan, W Patrick

    2011-06-01

    Many modern diagnostic and surgical procedures rely heavily on the use of ionizing radiation. These procedures include computed tomography, nuclear medicine procedures, interventional radiology, and cardiac catheterization and electrophysiology procedures. Recent trends toward increased patient visits and patients with multiple challenging comorbidities have meant that anesthesia providers are increasingly required to provide services in the ancillary areas using ionizing radiation. As a result, anesthesia providers are at a greater-than-ever risk for excessive radiation doses. An overview of some of the basic principles of radiation biology, radiation physics, and radiation protection and specific guidelines related to radiation exposure and pregnancy are described. The effects of radiation exposure are cumulative and permanent, and an understanding of these principles and practices will help anesthesia providers keep their occupational exposure to a minimum. PMID:21751695

  20. Types of health care providers

    MedlinePlus

    ... GYN as their primary care provider. Nurse practitioners (NPs) are nurses with graduate training. They can serve ... common concerns and routine screenings) and family planning. NPs can prescribe medications. A physician assistant (PA) can ...

  1. Predeployment Medical Training for Providers.

    PubMed

    Holloway, Michael D

    2016-01-01

    Following the attacks of September 11, 2001, the United States became simultaneously engaged in military conflicts in 2 theaters of operation. At that time there was no organized program to train medical providers assigned to deployable Role 1 or Role 2 aid stations. To fill this gap, the Tactical Combat Medical Care (TCMC) course was developed and instituted at Fort Sam Houston, Texas, in 2004 to provide the training platform for providers in preparation for assignment to and deployment with combat units. The TCMC course has become the standard for prehospital wartime care training. All military healthcare providers (physicians, physician assistants, nurses, combat medics) requiring training to supplement their basic medical education and facility-based experiences are eligible to attend this course. PMID:27215892

  2. Choosing Your Prenatal Care Provider

    MedlinePlus

    ... also called OB) is a doctor who has special education and training to take care of pregnant women ... midwife is a health care provider who has special education and training to take care of women of ...

  3. Choosing a primary care provider

    MedlinePlus

    Family doctor - how to choose one; Primary care provider - how to choose one; Doctor - how to choose a family doctor ... can give you a trusting, ongoing relationship with one medical professional over time. You can choose from ...

  4. A Single Amino Acid Deletion in the Matrix Protein of Porcine Reproductive and Respiratory Syndrome Virus Confers Resistance to a Polyclonal Swine Antibody with Broadly Neutralizing Activity

    PubMed Central

    Popescu, Luca N.; Monday, Nicholas; Calvert, Jay G.; Rowland, Raymond R. R.

    2015-01-01

    Assessment of virus neutralization (VN) activity in 176 pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) identified one pig with broadly neutralizing activity. A Tyr-10 deletion in the matrix protein provided escape from broad neutralization without affecting homologous neutralizing activity. The role of the Tyr-10 deletion was confirmed through an infectious clone with a Tyr-10 deletion. The results demonstrate differences in the properties and specificities of VN responses elicited during PRRSV infection. PMID:25855739

  5. Ecosystem services provided by waterbirds.

    PubMed

    Green, Andy J; Elmberg, Johan

    2014-02-01

    Ecosystem services are ecosystem processes that directly or indirectly benefit human well-being. There has been much recent literature identifying different services and the communities and species that provide them. This is a vital first step towards management and maintenance of these services. In this review, we specifically address the waterbirds, which play key functional roles in many aquatic ecosystems, including as predators, herbivores and vectors of seeds, invertebrates and nutrients, although these roles have often been overlooked. Waterbirds can maintain the diversity of other organisms, control pests, be effective bioindicators of ecological conditions, and act as sentinels of potential disease outbreaks. They also provide important provisioning (meat, feathers, eggs, etc.) and cultural services to both indigenous and westernized societies. We identify key gaps in the understanding of ecosystem services provided by waterbirds and areas for future research required to clarify their functional role in ecosystems and the services they provide. We consider how the economic value of these services could be calculated, giving some examples. Such valuation will provide powerful arguments for waterbird conservation. PMID:23786594

  6. Ancillary Services Provided from DER

    SciTech Connect

    Campbell, J.B.

    2005-12-21

    Distributed energy resources (DER) are quickly making their way to industry primarily as backup generation. They are effective at starting and then producing full-load power within a few seconds. The distribution system is aging and transmission system development has not kept up with the growth in load and generation. The nation's transmission system is stressed with heavy power flows over long distances, and many areas are experiencing problems in providing the power quality needed to satisfy customers. Thus, a new market for DER is beginning to emerge. DER can alleviate the burden on the distribution system by providing ancillary services while providing a cost adjustment for the DER owner. This report describes 10 types of ancillary services that distributed generation (DG) can provide to the distribution system. Of these 10 services the feasibility, control strategy, effectiveness, and cost benefits are all analyzed as in the context of a future utility-power market. In this market, services will be provided at a local level that will benefit the customer, the distribution utility, and the transmission company.

  7. Sensor Network Provides Environmental Data

    NASA Technical Reports Server (NTRS)

    2007-01-01

    The National Biocomputation Center, a joint partnership between the Stanford University School of Medicine's Department of Surgery and NASA's Ames Research Center, is the test bed for much of NASA's research in telemedicine, the remote delivery of medical care. In early 2005, researchers at the National Biocomputation Center formed a spinoff company, Intelesense Technologies, to use the telemedicine sensors to provide integrated global monitoring systems. Intelesense uses the systems to better understand how environments and people are linked, monitor and protect natural resources, predict and adapt to environmental changes, provide for sustainable development, reduce the costs and impacts of natural disasters, and provide an effective and intelligent response to such disasters. Current projects range from protecting the environment to tracking emerging infectious diseases like avian influenza (bird flu) and helping people from around the world connect and interact with each other to better understand their environment and themselves.

  8. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes.

    PubMed

    Chen, Kaifu; Chen, Zhong; Wu, Dayong; Zhang, Lili; Lin, Xueqiu; Su, Jianzhong; Rodriguez, Benjamin; Xi, Yuanxin; Xia, Zheng; Chen, Xi; Shi, Xiaobing; Wang, Qianben; Li, Wei

    2015-10-01

    Tumor suppressors are mostly defined by inactivating mutations in tumors, yet little is known about their epigenetic features in normal cells. Through integrative analysis of 1,134 genome-wide epigenetic profiles, mutations from >8,200 tumor-normal pairs and our experimental data from clinical samples, we discovered broad peaks for trimethylation of histone H3 at lysine 4 (H3K4me3; wider than 4 kb) as the first epigenetic signature for tumor suppressors in normal cells. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity, which together lead to exceptionally high gene expression, and is distinct from other broad epigenetic features, such as super-enhancers. Genes with broad H3K4me3 peaks conserved across normal cells may represent pan-cancer tumor suppressors, such as TP53 and PTEN, whereas genes with cell type-specific broad H3K4me3 peaks may represent cell identity genes and cell type-specific tumor suppressors. Furthermore, widespread shortening of broad H3K4me3 peaks in cancers is associated with repression of tumor suppressors. Thus, the broad H3K4me3 epigenetic signature provides mutation-independent information for the discovery and characterization of new tumor suppressors. PMID:26301496

  9. The broad view of nuclear technology for aerospace

    NASA Astrophysics Data System (ADS)

    Buden, David; Angelo, Joseph A., Jr.

    1991-01-01

    Nuclear technologies can directly support advanced space initiatives. For near-Earth missions, nuclear technology can be used to power air traffic control, communications and manufacturing platforms, provide emergency power for manned platforms, provide power for maneuvering units, move asteroids for mining, measure the natural radiation environment, provide radiation protection instruments, and design radiation hardened robotic systems. For the Lunar and Mars surfaces, nuclear technology can be used for base stationary, mobile, and emergency power, energy storage, process heat, nuclear thermal and electric rocket propulsion, excavation and underground engineering, water and sewage treatment and sterilization, food processing and preservation, mineral exploration, self-luminous systems, radiation protection instrumentation, radiation environmental warning systems, and habitat shielding design. Outer planet missions can make use of nuclear technology for power and propulsion. Programs need to be initiated to ensure the full beneficial use of nuclear technologies in advanced space missions.

  10. Mentor Program Provides STEM Options

    ERIC Educational Resources Information Center

    Abdul-alim, Jamaal

    2011-01-01

    The ACE Mentor Program provides early career exposure, mentoring, and scholarships to high school students in an attempt to encourage them to enter one of the three fields that make up the ACE acronym: (1) architecture; (2) construction; and (3) engineering. Founded in 1993 by longtime engineering consultant Charles Thornton, the program is…

  11. Providing Data to Your Board.

    ERIC Educational Resources Information Center

    Dawson, Linda J.

    2002-01-01

    Describes four principles to guide superintendents' presentation of data to their schools boards: Insist the board establish districtwide goals for student achievement; assist the board in receiving customized training on analyzing data related to student-outcome goals; insist the board adopt a code-of-conduct policy on data use; and provide data…

  12. Twitter for travel medicine providers.

    PubMed

    Mills, Deborah J; Kohl, Sarah E

    2016-03-01

    Travel medicine practitioners, perhaps more so than medical practitioners working in other areas of medicine, require a constant flow of information to stay up-to-date, and provide best practice information and care to their patients. Many travel medicine providers are unaware of the popularity and potential of the Twitter platform. Twitter use among our travellers, as well as by physicians and health providers, is growing exponentially. There is a rapidly expanding body of published literature on this information tool. This review provides a brief overview of the ways Twitter is being used by health practitioners, the advantages that are peculiar to Twitter as a platform of social media, and how the interested practitioner can get started. Some key points about the dark side of Twitter are highlighted, as well as the potential benefits of using Twitter as a way to disseminate accurate medical information to the public. This article will help readers develop an increased understanding of Twitter as a tool for extracting useful facts and insights from the ever increasing volume of health information. PMID:26988200

  13. A broadly tunable autocorrelator for ultra-short, ultra-high power infrared optical pulses

    SciTech Connect

    Szarmes, E.B.; Madey, J.M.J.

    1995-12-31

    We describe the design of a crossed-beam, optical autocorrelator that uses an uncoated, birefringent beamsplitter to split a linearly polarized incident pulse into two orthogonally polarized pulses, and a Type II, SHG crystal to generate the intensity autocorrelation function. The uncoated beamsplitter accommodates extremely broad tunability while precluding any temporal distortion of ultrashort optical pulses at the dielectric interface, and the specific design provides efficient operation between 1 {mu}m and 4 {mu}m. Furthermore, the use of Type II SHG completely eliminates any single-beam doubling, so the autocorrelator can be operated at very shallow crossed-beam angles without generating a background pedestal. The autocorrelator has been constructed and installed in the Mark III laboratory at Duke University as a broadband diagnostic for ongoing compression experiments on the chirped-pulse FEL.

  14. How to adapt broad-band gravitational-wave searches for r-modes

    SciTech Connect

    Owen, Benjamin J.

    2010-11-15

    Up to now there has been no search for gravitational waves from the r-modes of neutron stars in spite of the theoretical interest in the subject. Several oddities of r-modes must be addressed to obtain an observational result: The gravitational radiation field is dominated by the mass current (gravitomagnetic) quadrupole rather than the usual mass quadrupole, and the consequent difference in polarization affects detection statistics and parameter estimation. To astrophysically interpret a detection or upper limit it is necessary to convert the gravitational-wave amplitude to an r-mode amplitude. Also, it is helpful to know indirect limits on gravitational-wave emission to gauge the interest of various searches. Here I address these issues, thereby providing the ingredients to adapt broad-band searches for continuous gravitational waves to obtain r-mode results. I also show that searches of existing data can already have interesting sensitivities to r-modes.

  15. Note: A simple broad bandwidth undersampling frequency-domain digital diffuse optical spectroscopy system.

    PubMed

    Jung, Justin; Istfan, Raeef; Roblyer, Darren

    2014-07-01

    Near-Infrared frequency-domain technologies, such as Diffuse Optical Spectroscopy (DOS), have demonstrated growing potential in a number of clinical applications. The broader dissemination of this technology is limited by the complexity and cost of instrumentation. We present here a simple system constructed with off-the-shelf components that utilizes undersampling for digital frequency-domain dDOS measurements. Broadband RF sweeps (50-300 MHz) were digitally sampled at 25 MSPS; amplitude, phase, and optical property extractions were within 5% of network analyzer derived values. The use of undersampling for broad bandwidth dDOS provides a significant reduction in complexity, power consumption, and cost compared with high-speed ADCs and analog techniques. PMID:25085193

  16. Note: A simple broad bandwidth undersampling frequency-domain digital diffuse optical spectroscopy system

    NASA Astrophysics Data System (ADS)

    Jung, Justin; Istfan, Raeef; Roblyer, Darren

    2014-07-01

    Near-Infrared frequency-domain technologies, such as Diffuse Optical Spectroscopy (DOS), have demonstrated growing potential in a number of clinical applications. The broader dissemination of this technology is limited by the complexity and cost of instrumentation. We present here a simple system constructed with off-the-shelf components that utilizes undersampling for digital frequency-domain dDOS measurements. Broadband RF sweeps (50-300 MHz) were digitally sampled at 25 MSPS; amplitude, phase, and optical property extractions were within 5% of network analyzer derived values. The use of undersampling for broad bandwidth dDOS provides a significant reduction in complexity, power consumption, and cost compared with high-speed ADCs and analog techniques.

  17. Note: A simple broad bandwidth undersampling frequency-domain digital diffuse optical spectroscopy system

    PubMed Central

    Jung, Justin; Istfan, Raeef; Roblyer, Darren

    2014-01-01

    Near-Infrared frequency-domain technologies, such as Diffuse Optical Spectroscopy (DOS), have demonstrated growing potential in a number of clinical applications. The broader dissemination of this technology is limited by the complexity and cost of instrumentation. We present here a simple system constructed with off-the-shelf components that utilizes undersampling for digital frequency-domain dDOS measurements. Broadband RF sweeps (50–300 MHz) were digitally sampled at 25 MSPS; amplitude, phase, and optical property extractions were within 5% of network analyzer derived values. The use of undersampling for broad bandwidth dDOS provides a significant reduction in complexity, power consumption, and cost compared with high-speed ADCs and analog techniques. PMID:25085193

  18. Declassified American Government Documents Show a Broad and In-Depth Interest in Soviet Space Activities

    NASA Astrophysics Data System (ADS)

    Pesavento, P.

    Back in 1993, when this author was able to acquire one of the first US National Intelligence Estimate (NIE) documents declassified on the Soviet Space Program [1], there was a dearth of materials concerning the USSR's space activities from a US intelligence perspective. Now, a decade on, the situation has dramatically changed. As a plethora of US government agencies labor to disgorge their materials from the era of the Cold War, space historians and observers now have access to many new documents, which shed both exciting and new light on Soviet space activities, and how the US viewed as well as interpreted them. Coupled with the fact that many of these are now available to be read via the Internet, and with most of the documents available only recently, a new era in space history research is now in hand. This article is intended to provide a broad overview of what is now available, and mention some highlights.

  19. Immune Pathways in Atopic Dermatitis, and Definition of Biomarkers through Broad and Targeted Therapeutics

    PubMed Central

    Mansouri, Yasaman; Guttman-Yassky, Emma

    2015-01-01

    Atopic dermatitis (AD) is the most common inflammatory skin disease. Recent research findings have provided an insight into the complex pathogenic mechanisms involved in this disease. Despite a rising prevalence, effective and safe therapeutics for patients with moderate-to-severe AD are still lacking. Biomarkers of lesional, nonlesional skin, and blood have been developed for baseline as well as after treatment with broad and specific treatments (i.e., cyclosporine A and dupilumab). These biomarkers will help with the development of novel targeted therapeutics and assessment of disease reversal, with the promise of a more personalized treatment approach. Since AD involves more than one subtype (i.e., intrinsic/extrinsic, pediatric/adult, etc.), these molecular fingerprints needs to be validated in all subpopulations with AD. PMID:26239452

  20. Peracetic Acid Treatment Generates Potent Inactivated Oral Vaccines from a Broad Range of Culturable Bacterial Species

    PubMed Central

    Moor, Kathrin; Wotzka, Sandra Y.; Toska, Albulena; Diard, Médéric; Hapfelmeier, Siegfried; Slack, Emma

    2016-01-01

    Our mucosal surfaces are the main sites of non-vector-borne pathogen entry, as well as the main interface with our commensal microbiota. We are still only beginning to understand how mucosal adaptive immunity interacts with commensal and pathogenic microbes to influence factors such as infectivity, phenotypic diversity, and within-host evolution. This is in part due to difficulties in generating specific mucosal adaptive immune responses without disrupting the mucosal microbial ecosystem itself. Here, we present a very simple tool to generate inactivated mucosal vaccines from a broad range of culturable bacteria. Oral gavage of 1010 peracetic acid-inactivated bacteria induces high-titer-specific intestinal IgA in the absence of any measurable inflammation or species invasion. As a proof of principle, we demonstrate that this technique is sufficient to provide fully protective immunity in the murine model of invasive non-typhoidal Salmonellosis, even in the face of severe innate immune deficiency. PMID:26904024

  1. Pacific Broad Tapeworm Adenocephalus pacificus as a Causative Agent of Globally Reemerging Diphyllobothriosis

    PubMed Central

    Serrano-Martínez, Marcus Enrique; Scholz, Tomas

    2015-01-01

    The Pacific broad tapeworm Adenocephalus pacificus (syn. Diphyllobothrium pacificum) is the causative agent of the third most common fish-borne cestodosis among humans. Although most of the nearly 1,000 cases among humans have been reported in South America (Peru, Chile, and Ecuador), cases recently imported to Europe demonstrate the potential for spread of this tapeworm throughout the world as a result of global trade of fresh or chilled marine fish and travel or migration of humans. We provide a comprehensive survey of human cases of infection with this zoonotic parasite, summarize the history of this re-emerging disease, and identify marine fish species that may serve as a source of human infection when eaten raw or undercooked. PMID:26402440

  2. Induction of broadly neutralizing H1N1 influenza antibodies by vaccination.

    PubMed

    Wei, Chih-Jen; Boyington, Jeffrey C; McTamney, Patrick M; Kong, Wing-Pui; Pearce, Melissa B; Xu, Ling; Andersen, Hanne; Rao, Srinivas; Tumpey, Terrence M; Yang, Zhi-Yong; Nabel, Gary J

    2010-08-27

    The rapid dissemination of the 2009 pandemic influenza virus underscores the need for universal influenza vaccines that elicit protective immunity to diverse viral strains. Here, we show that vaccination with plasmid DNA encoding H1N1 influenza hemagglutinin (HA) and boosting with seasonal vaccine or replication-defective adenovirus 5 vector encoding HA stimulated the production of broadly neutralizing influenza antibodies. This prime/boost combination increased the neutralization of diverse H1N1 strains dating from 1934 to 2007 as compared to either component alone and conferred protection against divergent H1N1 viruses in mice and ferrets. These antibodies were directed to the conserved stem region of HA and were also elicited in nonhuman primates. Cross-neutralization of H1N1 subtypes elicited by this approach provides a basis for the development of a universal influenza vaccine for humans. PMID:20647428

  3. Peracetic Acid Treatment Generates Potent Inactivated Oral Vaccines from a Broad Range of Culturable Bacterial Species.

    PubMed

    Moor, Kathrin; Wotzka, Sandra Y; Toska, Albulena; Diard, Médéric; Hapfelmeier, Siegfried; Slack, Emma

    2016-01-01

    Our mucosal surfaces are the main sites of non-vector-borne pathogen entry, as well as the main interface with our commensal microbiota. We are still only beginning to understand how mucosal adaptive immunity interacts with commensal and pathogenic microbes to influence factors such as infectivity, phenotypic diversity, and within-host evolution. This is in part due to difficulties in generating specific mucosal adaptive immune responses without disrupting the mucosal microbial ecosystem itself. Here, we present a very simple tool to generate inactivated mucosal vaccines from a broad range of culturable bacteria. Oral gavage of 10(10) peracetic acid-inactivated bacteria induces high-titer-specific intestinal IgA in the absence of any measurable inflammation or species invasion. As a proof of principle, we demonstrate that this technique is sufficient to provide fully protective immunity in the murine model of invasive non-typhoidal Salmonellosis, even in the face of severe innate immune deficiency. PMID:26904024

  4. Broad-band analysis of the spectral evolution of GX 339-4

    NASA Astrophysics Data System (ADS)

    Clavel, M.; Rodriguez, J.; Corbel, S.

    2015-07-01

    Black Hole X-ray binaries display large outbursts during which their spectral properties are strongly variable. Their high-energy emission includes the contribution of thermal and non-thermal components that are respectively attributed to the emission of an accretion disk and the one of a jet. How these structures form and evolve over time is still under investigation. The aim of our group is to provide the most up to date generic properties of these objects, as observed along the course of their outbursts, in order to constrain the theoretical models. Therefore, I will present the systematic broad-band analysis of the spectral properties of black hole binaries that we are currently developing, using the 2010 outburst of GX 339-4 as an example. I will give an overview of the results we obtained using observations at all wavelengths from proprietary radio data to hard X-rays.

  5. Data-intensive science applied to broad-scale citizen science.

    PubMed

    Hochachka, Wesley M; Fink, Daniel; Hutchinson, Rebecca A; Sheldon, Daniel; Wong, Weng-Keen; Kelling, Steve

    2012-02-01

    Identifying ecological patterns across broad spatial and temporal extents requires novel approaches and methods for acquiring, integrating and modeling massive quantities of diverse data. For example, a growing number of research projects engage continent-wide networks of volunteers ('citizen-scientists') to collect species occurrence data. Although these data are information rich, they present numerous challenges in project design, implementation and analysis, which include: developing data collection tools that maximize data quantity while maintaining high standards of data quality, and applying new analytical and visualization techniques that can accurately reveal patterns in these data. Here, we describe how advances in data-intensive science provide accurate estimates in species distributions at continental scales by identifying complex environmental associations. PMID:22192976

  6. Pacific Broad Tapeworm Adenocephalus pacificus as a Causative Agent of Globally Reemerging Diphyllobothriosis.

    PubMed

    Kuchta, Roman; Serrano-Martínez, Marcus Enrique; Scholz, Tomas

    2015-10-01

    The Pacific broad tapeworm Adenocephalus pacificus (syn. Diphyllobothrium pacificum) is the causative agent of the third most common fish-borne cestodosis among humans. Although most of the nearly 1,000 cases among humans have been reported in South America (Peru, Chile, and Ecuador), cases recently imported to Europe demonstrate the potential for spread of this tapeworm throughout the world as a result of global trade of fresh or chilled marine fish and travel or migration of humans. We provide a comprehensive survey of human cases of infection with this zoonotic parasite, summarize the history of this re-emerging disease, and identify marine fish species that may serve as a source of human infection when eaten raw or undercooked. PMID:26402440

  7. Ecosystem services provided by bats.

    PubMed

    Kunz, Thomas H; Braun de Torrez, Elizabeth; Bauer, Dana; Lobova, Tatyana; Fleming, Theodore H

    2011-03-01

    Ecosystem services are the benefits obtained from the environment that increase human well-being. Economic valuation is conducted by measuring the human welfare gains or losses that result from changes in the provision of ecosystem services. Bats have long been postulated to play important roles in arthropod suppression, seed dispersal, and pollination; however, only recently have these ecosystem services begun to be thoroughly evaluated. Here, we review the available literature on the ecological and economic impact of ecosystem services provided by bats. We describe dietary preferences, foraging behaviors, adaptations, and phylogenetic histories of insectivorous, frugivorous, and nectarivorous bats worldwide in the context of their respective ecosystem services. For each trophic ensemble, we discuss the consequences of these ecological interactions on both natural and agricultural systems. Throughout this review, we highlight the research needed to fully determine the ecosystem services in question. Finally, we provide a comprehensive overview of economic valuation of ecosystem services. Unfortunately, few studies estimating the economic value of ecosystem services provided by bats have been conducted to date; however, we outline a framework that could be used in future studies to more fully address this question. Consumptive goods provided by bats, such as food and guano, are often exchanged in markets where the market price indicates an economic value. Nonmarket valuation methods can be used to estimate the economic value of nonconsumptive services, including inputs to agricultural production and recreational activities. Information on the ecological and economic value of ecosystem services provided by bats can be used to inform decisions regarding where and when to protect or restore bat populations and associated habitats, as well as to improve public perception of bats. PMID:21449963

  8. Physical properties of emitting plasma near massive black holes: the Broad Line Region

    NASA Astrophysics Data System (ADS)

    Ilić, D.; Mura, G. La; Popović, L. Č.; Shapovalova, A. I.; Ciroi, S.; Chavushyan, V. H.; Rafanelli, P.; Burenkov, A. N.; Marcado, A.

    2007-04-01

    The dominant emission in Active Galactic Nuclei (AGN) spectra comes from the Broad Emission Lines (BEL) which originate in the Broad Line Region (BLR). The BLR can potentially provide a useful probe of the central part of an AGN, and consequently of the characteristics of the massive Black Hole (BH) that is assumed to be in the center of these objects. The understanding of the physics and kinematics of the BLR is crucial because of the following three reasons: (i) kinematics of the BLR is probably determined by the massive BH, with the competing effects of gravity and radiation pressure, (ii) the BLR reprocesses the UV energy emitted by the continuum source, consequently BEL can provide indirect information about the continuum source, (iii) there is indication that the physical and kinematical parameters of the BEL can be connected with the general characteristics of an AGN (e.g. mass of the BH). In order to connect the physical and kinematical parameters of the BLR, in this work we consider the intensities and widths of Balmer lines of a sample of 90 AGN from Sloan Digital Sky Survey (SDSS). Additionally, we consider the variation of the intensities and widths of Balmer lines from the BLR of NGC 5548 observed from 1996 till 2004. We apply the Boltzmann-Plot method (Popovic 2003, Popovic et al. 2006) to the Balmer line intensities and estimated the electron temperature of a typical BLR. Moreover, we discuss the possibility that the BLR is in general composed from two emitting regions: one that is closer to the BH and contributes to the BEL's wings, and another that is further from the central BH and contributes to the BEL's core.

  9. Essential Tension: Specialization with Broad and General Training in Psychology

    ERIC Educational Resources Information Center

    Roberts, Michael C.

    2006-01-01

    The practice fields of psychology develop through specialization in training and education. The recognized specialties play a major role in developing new opportunities for professional psychology and providing quality services for the public. The essential tension comes from the balance of innovation and tradition and, in professional psychology,…

  10. Intergroup Dialogue: Education for a Broad Conception of Civic Engagement

    ERIC Educational Resources Information Center

    Gurin, Patricia; Nagda, Biren A.; Sorensen, Nicholas

    2011-01-01

    Intergroup dialogue provides what students need in order to relate and collaborate across differences, something they have to do in community projects that usually involve interactions across racial, social class, religious, and geographical divides. In this article, the authors demonstrate the efficacy of intergroup dialogue, drawing from a…

  11. Some comments on providing broadband light to users

    SciTech Connect

    Benson, S.

    1997-12-01

    Though the free-electron laser gain medium is inherently broadband and several labs have demonstrated wavelength tuning over a range of several octaves, it is quite challenging to deliver such a broad bandwidth to users. The challenge arises from providing high quality, high power light, transporting the light to the users, and providing diagnostics to the user over a very large wavelength range. This paper summarizes some of the issues which must be considered and discusses some of the solutions which user facilities around the world have used to address the problems.

  12. The great risk shift: a strategic road map for providers.

    PubMed

    Ringwood, William; Bosko, Tawnya

    2016-04-01

    Healthcare providers that are assessing their readiness to assume financial risk for care delivery should understand the full range of risk options available to them. Available options fall into two broad categories: episode-based risk (e.g., the Medicare BPCI initiative and CJR model, commercial insurance models, and direct-to-employer models) and population-based risk (e.g., shared savings models and professional or institutional capitation models). Providers also require a deep understanding of both internal and market-based factors that are essential for success under any risk option being contemplated. PMID:27244977

  13. [Broad injury panorama in children who swallowed a battery].

    PubMed

    Tuma, Louise; Ehrén, Henrik

    Most ingested batteries in children pass through the gastrointestinal canal without problems. The risk for complications is at its highest if the battery gets stuck in the esophagus or if the child is less than 6 years of age or the size of the battery exceeds 15 mm. Thorough database searches only identified a limited number of articles, all were considered to provide low-grade evidence. PMID:25514670

  14. Amplifier similariton laser with extra-broad bandwidth output pulse

    NASA Astrophysics Data System (ADS)

    Korobko, D. A.; Okhotnikov, O. G.; Zolotovskii, I. O.

    2016-03-01

    We propose an advanced scheme of amplifier similariton laser providing an output pulse spectrum much wider than the gain bandwidth. The upgrade is an additional dispersive element introduced into the cavity to locally increase the peak pulse power. The proposed scheme demonstrates a drastic increase in the output pulse spectrum width, reduction of the pulse duration, and an increase in the output peak pulse power after compression.

  15. A systematic literature review of individuals' perspectives on broad consent and data sharing in the United States

    PubMed Central

    Garrison, Nanibaa' A.; Sathe, Nila A.; Antommaria, Armand H. Matheny; Holm, Ingrid A.; Sanderson, Saskia C.; Smith, Maureen E.; McPheeters, Melissa L.; Clayton, Ellen W.

    2016-01-01

    Purpose: In 2011, an Advanced Notice of Proposed Rulemaking proposed that de-identified human data and specimens be included in biobanks only if patients provide consent. The National Institutes of Health Genomic Data Sharing policy went into effect in 2015, requiring broad consent from almost all research participants. Genet Med 18 7, 663–671. Methods: We conducted a systematic literature review of attitudes toward biobanking, broad consent, and data sharing. Bibliographic databases included MEDLINE, Web of Science, EthxWeb, and GenETHX. Study screening was conducted using DistillerSR. Genet Med 18 7, 663–671. Results: The final 48 studies included surveys (n = 23), focus groups (n = 8), mixed methods (n = 14), interviews (n = 1), and consent form analyses (n = 2). Study quality was characterized as good (n = 19), fair (n = 27), and poor (n = 2). Although many participants objected, broad consent was often preferred over tiered or study-specific consent, particularly when broad consent was the only option, samples were de-identified, logistics of biobanks were communicated, and privacy was addressed. Willingness for data to be shared was high, but it was lower among individuals from under-represented minorities, individuals with privacy and confidentiality concerns, and when pharmaceutical companies had access to data. Genet Med 18 7, 663–671. Conclusions: Additional research is needed to understand factors affecting willingness to give broad consent for biobank research and data sharing in order to address concerns to enhance acceptability. Genet Med 18 7, 663–671. PMID:26583683

  16. Strengthening patient-provider relationships.

    PubMed

    Wilkinson, Connie Rasmussen; Williams, Marjory

    2002-01-01

    In support of the Veterans Health Administration commitment to the promotion of shared decision-making between providers and patients, this study investigated the relationship between the provision of a patient appointment guidebook, designed to promote and support patient participation in the health care visit, and patient perceptions of primary care visit effectiveness. This study compared perceptions among 277 randomly selected patients randomly assigned to one of two groups. Patients assigned to an intervention group received a patient appointment guidebook along with the standard appointment reminder letter prior to the scheduled routine visit. Patients assigned to a control group received only the standard appointment reminder letter. Patient perceptions were assessed with a follow-up questionnaire designed to measure patient agreement with six statements pertaining to primary care visit effectiveness. No significant differences were noted in the proportion of patients in the two groups that agreed with any of the six statements pertaining to primary care visit effectiveness. Significant differences were noted, however, in the proportion of patients in the groups who received preventive health care interventions of influenza vaccination, pneumococcal vaccination, and gender-specific cancer screening. Approximately 37% of the patients in the intervention group provided positive comments about the patient appointment guidebook, while only 7% provided negative comments. Although statistically inconclusive, the narrative comments indicate that a patient appointment guidebook may assist veterans in preparing for primary care appointments. The lack of significant difference between the two groups on the measures of primary care visit effectiveness may be due, in part, to positive perceptions among the sample in general, as reflected by high levels of agreement and predominantly positive comments for both control and intervention groups. PMID:12048339

  17. Broad-spectrum identification and discrimination between biothreat agents and near-neighbor species

    NASA Astrophysics Data System (ADS)

    Malanoski, Anthony P.; Leski, Tomasz A.; Cheng, Luke; Wang, Zheng; Stenger, David A.; Lin, Baochuan

    2009-05-01

    A comprehensive resequencing microarray "Tropical and Emerging Infections (TessArray RPM-TEI 1.0 array)" has been developed to identify and distinguish between biothreat organisms of interest and genetically close related species. This array has undergone validation using an innovative approach where synthetic DNA fragments are used for organisms that it is not safe to work with outside a biosafety 3 facilities. The approach was confirmed from testing a subset of target organisms, such as Ebola viruses and Lassa viruses, at USAMRIID. Most potential biothreat organisms are actually endemic in some part of the world. Proper surveillance of biothreat agents will require some form of monitoring the evolution of the indigenous organisms under their natural environment, so when changes in the organisms occur, the diagnostic assays for these organisms can be reviewed to assure they still provide detection. Using the resequencing microarray (RPM) for detection in locations such as the Africa can support indigenous monitoring as it provides sequence information. An ongoing collaboration with Njala University aims to establish a broad-spectrum pathogen surveillance capability in the Republic of Sierra Leone, West Africa using RPM technology combined with a Geographic Information System. This has the potential to improve the public health efforts in an infected area as well as provide monitoring of the changes occurring to a biothreat organism, i.e. Lassa viruses, in its natural location.

  18. Broad-spectrum moisturizer effectively prevents molecular reactions to UVA radiation.

    PubMed

    Seité, Sophie; Reinhold, Katja; Jaenicke, Thomas; Brenden, Heidi; Krutmann, Jean; Grether-Beck, Susanne

    2012-12-01

    The damaging effects of UVA radiation have been well-documented. UVA radiation is known to induce molecular, cellular, and clinical damage. Such harm may lead to photoaging, immune system depression, altered gene expression, or oncogene and tumor suppressor gene modulation, all of which are partly responsible for the development of skin cancer. In parallel to an increased understanding of the added damage caused by UVA radiation, progress has been made in sunscreen formulation. A variety of UVA filters are now available for formulators to combine with UVB filters to reach high-level photostable protection using a minimum concentration of active ingredients. The efficacy of products that contain these UV filter combinations usually is determined by noninvasive assessments, which cause either UVA-induced erythema or skin pigmentation. However, the biologic relevance of these end points for UVA radiation-induced skin damage is unknown. In our study, we confirm that the assessment of UVA radiation-induced gene expression in skin specimens obtained from UVA-irradiated human skin by quantitative real-time polymerase chain reaction is a sensitive, reliable, and robust method to prove the efficacy of 2 daily moisturizers containing broad-spectrum sunscreen. Specifically, we demonstrate in vivo that topical application of a daily moisturizer with broad-spectrum sunscreen prevents UVA radiation-induced transcriptional expression of genes that are directly linked to skin aging (ie, matrix metalloproteinase 1 [MMP-1]) and also reflect the skin's antioxidative stress defense response (ie, catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx]). Furthermore, we demonstrate that the protection against UV-induced skin damage provided by products with different sun protection factor (SPF) but the same UVA protection factor (UVA-PF) is similar, which emphasizes the importance of high UVA protection to maintain unaltered essential biologic functions. These data

  19. Viruses other than arenaviruses from West African wild mammals

    PubMed Central

    Kemp, Graham E.

    1975-01-01

    At least thirty-seven different viruses have been isolated from wild mammals in West Africa since 1962. Some of these, including Lassa virus, are already known to cause serious human morbidity and mortality. Crimean haemorrhagic fever-Congo virus, Dugbe virus, Mokola virus, and a smallpox-like agent from a gerbil in Dahomey are briefly discussed. An account of social and ecologic factors affecting man, domestic animals, and their interaction with wild mammals is given. PMID:1085217

  20. Arenavirus Diversity and Phylogeography of Mastomys natalensis Rodents, Nigeria

    PubMed Central

    Obadare, Adeoba; Oyeyiola, Akinlabi; Igbokwe, Joseph; Fasogbon, Ayobami; Igbahenah, Felix; Ortsega, Daniel; Asogun, Danny; Umeh, Prince; Vakkai, Innocent; Abejegah, Chukwuyem; Pahlman, Meike; Becker-Ziaja, Beate; Günther, Stephan; Fichet-Calvet, Elisabeth

    2016-01-01

    Mastomys natalensis rodents are natural hosts for Lassa virus (LASV). Detection of LASV in 2 mitochondrial phylogroups of the rodent near the Niger and Benue Rivers in Nigeria underlines the potential for LASV emergence in fresh phylogroups of this rodent. A Mobala-like sequence was also detected in eastern Nigeria. PMID:26982388

  1. Broad Phylogenomic Sampling and the Sister Lineage of Land Plants

    PubMed Central

    Timme, Ruth E.; Bachvaroff, Tsvetan R.; Delwiche, Charles F.

    2012-01-01

    The tremendous diversity of land plants all descended from a single charophyte green alga that colonized the land somewhere between 430 and 470 million years ago. Six orders of charophyte green algae, in addition to embryophytes, comprise the Streptophyta s.l. Previous studies have focused on reconstructing the phylogeny of organisms tied to this key colonization event, but wildly conflicting results have sparked a contentious debate over which lineage gave rise to land plants. The dominant view has been that ‘stoneworts,’ or Charales, are the sister lineage, but an alternative hypothesis supports the Zygnematales (often referred to as “pond scum”) as the sister lineage. In this paper, we provide a well-supported, 160-nuclear-gene phylogenomic analysis supporting the Zygnematales as the closest living relative to land plants. Our study makes two key contributions to the field: 1) the use of an unbiased method to collect a large set of orthologs from deeply diverging species and 2) the use of these data in determining the sister lineage to land plants. We anticipate this updated phylogeny not only will hugely impact lesson plans in introductory biology courses, but also will provide a solid phylogenetic tree for future green-lineage research, whether it be related to plants or green algae. PMID:22253761

  2. Broad phylogenomic sampling and the sister lineage of land plants.

    PubMed

    Timme, Ruth E; Bachvaroff, Tsvetan R; Delwiche, Charles F

    2012-01-01

    The tremendous diversity of land plants all descended from a single charophyte green alga that colonized the land somewhere between 430 and 470 million years ago. Six orders of charophyte green algae, in addition to embryophytes, comprise the Streptophyta s.l. Previous studies have focused on reconstructing the phylogeny of organisms tied to this key colonization event, but wildly conflicting results have sparked a contentious debate over which lineage gave rise to land plants. The dominant view has been that 'stoneworts,' or Charales, are the sister lineage, but an alternative hypothesis supports the Zygnematales (often referred to as "pond scum") as the sister lineage. In this paper, we provide a well-supported, 160-nuclear-gene phylogenomic analysis supporting the Zygnematales as the closest living relative to land plants. Our study makes two key contributions to the field: 1) the use of an unbiased method to collect a large set of orthologs from deeply diverging species and 2) the use of these data in determining the sister lineage to land plants. We anticipate this updated phylogeny not only will hugely impact lesson plans in introductory biology courses, but also will provide a solid phylogenetic tree for future green-lineage research, whether it be related to plants or green algae. PMID:22253761

  3. X-Ray Absorbed, Broad-Lined, Red AGN and the Cosmic X-Ray Background

    NASA Technical Reports Server (NTRS)

    Mushotzky, Richard (Technical Monitor); Wilkes, Belinda

    2005-01-01

    We have obtained XMM spectra for five red, 2MASS AGN, selected from a sample observed by Chandra to be X-ray bright and to cover a range of hardness ratios. Our results confirm the presence of substantial absorbing material in three sources which have optical classifications ranging from Type 1 to Type 2, with an intrinsically flat (hard) power law continuum indicated in the other two. The presence of both X-ray absorption and broad optical emission lines with the usual strength suggests either a small (nuclear) absorber or a favored viewing angle so as to cover the X-ray source but not the broad emission line region (BELR). A soft excess is detected in all three Type 1 sources. We speculate that this soft X-ray emission may arise in an extended region of ionized gas, perhaps linked with the polarized (scattered) light which is a feature of these sources. The spectral complexity revealed by XMM emphasizes the limitations of the low S/N Chandra data. Overall, the new XMM results strengthen our conclusions (Wilkes et al. 2002) that the observed X-ray continua of red AGN are unusually hard at energies greater than 2 keV. Whether due to substantial line-of-sight absorption or to an intrinsically hard or reflection-dominated spectrum, these 'red' AGN have an observed spectral form consistent with contributing significantly to the missing had absorbed population of the Cosmic X-ray Background (CXRB). When absorption and or reflection is taken into account, all these AGN have power law slopes typical of broad-line (Type 1) AGN (Gamma approximately 1.9). This appears to resolve the spectral paradox which for so long has existed between the CXRB and the AGN thought to be the dominant contributors. It also suggests two scenarios whereby Type 1 AGN/QSOs may be responsible for a significant fraction of the CXRB at energies above 2 keV: 1) X-ray absorbed AGN/QSOs with visible broad emission lines; 2) AGN/QSOs with complex spectra whose hardness greater than 2 keV is not

  4. Knudsen Gas Provides Nanobubble Stability

    NASA Astrophysics Data System (ADS)

    Seddon, James R. T.; Zandvliet, Harold J. W.; Lohse, Detlef

    2011-09-01

    We provide a model for the remarkable stability of surface nanobubbles to bulk dissolution. The key to the solution is that the gas in a nanobubble is of Knudsen type. This leads to the generation of a bulk liquid flow which effectively forces the diffusive gas to remain local. Our model predicts the presence of a vertical water jet immediately above a nanobubble, with an estimated speed of ˜3.3m/s, in good agreement with our experimental atomic force microscopy measurement of ˜2.7m/s. In addition, our model also predicts an upper bound for the size of nanobubbles, which is consistent with the available experimental data.

  5. Broadly protective Shigella vaccine based on type III secretion apparatus proteins.

    PubMed

    Martinez-Becerra, Francisco J; Kissmann, Julian M; Diaz-McNair, Jovita; Choudhari, Shyamal P; Quick, Amy M; Mellado-Sanchez, Gabriela; Clements, John D; Pasetti, Marcela F; Picking, Wendy L

    2012-03-01

    Shigella spp. are food- and waterborne pathogens that cause severe diarrheal and dysenteric disease associated with high morbidity and mortality. Individuals most often affected are children under 5 years of age in the developing world. The existence of multiple Shigella serotypes and the heterogenic distribution of pathogenic strains, as well as emerging antibiotic resistance, require the development of a broadly protective vaccine. All Shigella spp. utilize a type III secretion system (TTSS) to initiate infection. The type III secretion apparatus (TTSA) is the molecular needle and syringe that form the energized conduit between the bacterial cytoplasm and the host cell to transport effector proteins that manipulate cellular processes to benefit the pathogen. IpaB and IpaD form a tip complex atop the TTSA needle and are required for pathogenesis. Because they are common to all virulent Shigella spp., they are ideal candidate antigens for a subunit-based, broad-spectrum vaccine. We examined the immunogenicity and protective efficacy of IpaB and IpaD, alone or combined, coadministered with a double mutant heat-labile toxin (dmLT) from Escherichia coli, used as a mucosal adjuvant, in a mouse model of intranasal immunization and pulmonary challenge. Robust systemic and mucosal antibody- and T cell-mediated immunities were induced against both proteins, particularly IpaB. Mice immunized in the presence of dmLT with IpaB alone or IpaB combined with IpaD were fully protected against lethal pulmonary infection with Shigella flexneri and Shigella sonnei. We provide the first demonstration that the Shigella TTSAs IpaB and IpaD are promising antigens for the development of a cross-protective Shigella vaccine. PMID:22202122

  6. Reducing Insecticide Use in Broad-Acre Grains Production: An Australian Study

    PubMed Central

    Macfadyen, Sarina; Hardie, Darryl C.; Fagan, Laura; Stefanova, Katia; Perry, Kym D.; DeGraaf, Helen E.; Holloway, Joanne; Spafford, Helen; Umina, Paul A.

    2014-01-01

    Prophylactic use of broad-spectrum insecticides is a common feature of broad-acre grains production systems around the world. Efforts to reduce pesticide use in these systems have the potential to deliver environmental benefits to large areas of agricultural land. However, research and extension initiatives aimed at decoupling pest management decisions from the simple act of applying a cheap insecticide have languished. This places farmers in a vulnerable position of high reliance on a few products that may lose their efficacy due to pests developing resistance, or be lost from use due to regulatory changes. The first step towards developing Integrated Pest Management (IPM) strategies involves an increased efficiency of pesticide inputs. Especially challenging is an understanding of when and where an insecticide application can be withheld without risking yield loss. Here, we quantify the effect of different pest management strategies on the abundance of pest and beneficial arthropods, crop damage and yield, across five sites that span the diversity of contexts in which grains crops are grown in southern Australia. Our results show that while greater insecticide use did reduce the abundance of many pests, this was not coupled with higher yields. Feeding damage by arthropod pests was seen in plots with lower insecticide use but this did not translate into yield losses. For canola, we found that plots that used insecticide seed treatments were most likely to deliver a yield benefit; however other insecticides appear to be unnecessary and economically costly. When considering wheat, none of the insecticide inputs provided an economically justifiable yield gain. These results indicate that there are opportunities for Australian grain growers to reduce insecticide inputs without risking yield loss in some seasons. We see this as the critical first step towards developing IPM practices that will be widely adopted across intensive production systems. PMID:24586535

  7. Characterization of FGFR1 Locus in sqNSCLC Reveals a Broad and Heterogeneous Amplicon

    PubMed Central

    Rooney, Claire; Geh, Catherine; Williams, Victoria; Heuckmann, Johannes M.; Menon, Roopika; Schneider, Petra; Al-Kadhimi, Katherine; Dymond, Michael; Smith, Neil R.; Baker, Dawn; French, Tim; Smith, Paul D.; Harrington, Elizabeth A.; Barrett, J. Carl; Kilgour, Elaine

    2016-01-01

    FGFR1 amplification occurs in ~20% of sqNSCLC and trials with FGFR inhibitors have selected FGFR1 amplified patients by FISH. Lung cancer cell lines were profiled for sensitivity to AZD4547, a potent, selective inhibitor of FGFRs 1–3. Sensitivity to FGFR inhibition was associated with but not wholly predicted by increased FGFR1 gene copy number. Additional biomarker assays evaluating expression of FGFRs and correlation between amplification and expression in clinical tissues are therefore warranted. We validated nanoString for mRNA expression analysis of 194 genes, including FGFRs, from clinical tumour tissue. In a panel of sqNSCLC tumours 14.4% (13/90) were FGFR1 amplified by FISH. Although mean FGFR1 expression was significantly higher in amplified samples, there was significant overlap in the range of expression levels between the amplified and non-amplified cohorts with several non-amplified samples expressing FGFR1 to levels equivalent to amplified samples. Statistical analysis revealed increased expression of FGFR1 neighboring genes on the 8p12 amplicon (BAG4, LSM1 and WHSC1L1) in FGFR1 amplified tumours, suggesting a broad rather than focal amplicon and raises the potential for codependencies. High resolution aCGH analysis of pre-clinical and clinical samples supported the presence of a broad and heterogeneous amplicon around the FGFR1 locus. In conclusion, the range of FGFR1 expression levels in both FGFR1 amplified and non-amplified NSCLC tissues, together with the breadth and intra-patient heterogeneity of the 8p amplicon highlights the need for gene expression analysis of clinical samples to inform the understanding of determinants of response to FGFR inhibitors. In this respect the nanoString platform provides an attractive option for RNA analysis of FFPE clinical samples. PMID:26905262

  8. Access and success with less: improving productivity in broad-access postsecondary institutions.

    PubMed

    Jenkins, Davis; Rodríguez, Olga

    2013-01-01

    Achieving national goals for increased college completion in a time of scarce resources will require the postsecondary institutions that enroll the majority of undergraduates--community colleges and less-selective public universities--to graduate more students at a lower cost. Davis Jenkins and Olga Rodriguez examine research on how these "broad-access" institutions can do so without sacrificing access or quality. Research indicates that the strategies broad-access institutions have relied on in the past to cut costs--using part-time instructors and increasing student-faculty ratios--may in fact reduce productivity and efficiency. The limited evidence available suggests that some of the most popular strategies for improving student success are not cost-effective. New strategies to cut costs and improve college success are therefore imperative. Some believe that redesigning courses to make use of instructional technologies will lead to better outcomes at lower cost, although the evidence is mixed. Recently, a growing number of institutions are going beyond redesigning courses and instead changing the way they organize programs and supports along the student's "pathway" through college. These efforts are promising, but their effects on cost per completion are not yet certain. Meager funding has so far hampered efforts by policy makers to fund colleges based on outcomes rather than how many students they enroll, but some states are beginning to increase the share of appropriations tied to outcomes. Jenkins and Rodriquez argue that as policy makers push colleges to lower the cost per graduate, they must avoid providing incentives to lower academic standards. They encourage policy makers to capitalize on recent research on the economic value of postsecondary education to measure quality, and urge colleges and universities to redouble efforts to define learning outcomes and measure student mastery. PMID:25522651

  9. Reducing insecticide use in broad-acre grains production: an Australian study.

    PubMed

    Macfadyen, Sarina; Hardie, Darryl C; Fagan, Laura; Stefanova, Katia; Perry, Kym D; DeGraaf, Helen E; Holloway, Joanne; Spafford, Helen; Umina, Paul A

    2014-01-01

    Prophylactic use of broad-spectrum insecticides is a common feature of broad-acre grains production systems around the world. Efforts to reduce pesticide use in these systems have the potential to deliver environmental benefits to large areas of agricultural land. However, research and extension initiatives aimed at decoupling pest management decisions from the simple act of applying a cheap insecticide have languished. This places farmers in a vulnerable position of high reliance on a few products that may lose their efficacy due to pests developing resistance, or be lost from use due to regulatory changes. The first step towards developing Integrated Pest Management (IPM) strategies involves an increased efficiency of pesticide inputs. Especially challenging is an understanding of when and where an insecticide application can be withheld without risking yield loss. Here, we quantify the effect of different pest management strategies on the abundance of pest and beneficial arthropods, crop damage and yield, across five sites that span the diversity of contexts in which grains crops are grown in southern Australia. Our results show that while greater insecticide use did reduce the abundance of many pests, this was not coupled with higher yields. Feeding damage by arthropod pests was seen in plots with lower insecticide use but this did not translate into yield losses. For canola, we found that plots that used insecticide seed treatments were most likely to deliver a yield benefit; however other insecticides appear to be unnecessary and economically costly. When considering wheat, none of the insecticide inputs provided an economically justifiable yield gain. These results indicate that there are opportunities for Australian grain growers to reduce insecticide inputs without risking yield loss in some seasons. We see this as the critical first step towards developing IPM practices that will be widely adopted across intensive production systems. PMID:24586535

  10. Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains.

    PubMed

    Fera, Daniela; Schmidt, Aaron G; Haynes, Barton F; Gao, Feng; Liao, Hua-Xin; Kepler, Thomas B; Harrison, Stephen C

    2014-07-15

    Rapidly evolving pathogens, such as human immunodeficiency and influenza viruses, escape immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies require a deeper understanding of antibody affinity maturation and evolution of the immune response to vaccination or infection. In HIV-infected individuals, viruses and B cells evolve together, creating a virus-antibody "arms race." Analysis of samples from an individual designated CH505 has illustrated the interplay between an antibody lineage, CH103, and autologous viruses at various time points. The CH103 antibodies, relatively broad in their neutralization spectrum, interact with the CD4 binding site of gp120, with a contact dominated by CDRH3. We show by analyzing structures of progenitor and intermediate antibodies and by correlating them with measurements of binding to various gp120s that there was a shift in the relative orientation of the light- and heavy-chain variable domains during evolution of the CH103 lineage. We further show that mutations leading to this conformational shift probably occurred in response to insertions in variable loop 5 (V5) of the HIV envelope. The shift displaced the tips of the light chain away from contact with V5, making room for the inserted residues, which had allowed escape from neutralization by the progenitor antibody. These results, which document the selective mechanism underlying this example of a virus-antibody arms race, illustrate the functional significance of affinity maturation by mutation outside the complementarity determining region surface of the antibody molecule. PMID:24982157

  11. Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains

    PubMed Central

    Fera, Daniela; Schmidt, Aaron G.; Haynes, Barton F.; Gao, Feng; Liao, Hua-Xin; Kepler, Thomas B.; Harrison, Stephen C.

    2014-01-01

    Rapidly evolving pathogens, such as human immunodeficiency and influenza viruses, escape immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies require a deeper understanding of antibody affinity maturation and evolution of the immune response to vaccination or infection. In HIV-infected individuals, viruses and B cells evolve together, creating a virus−antibody “arms race.” Analysis of samples from an individual designated CH505 has illustrated the interplay between an antibody lineage, CH103, and autologous viruses at various time points. The CH103 antibodies, relatively broad in their neutralization spectrum, interact with the CD4 binding site of gp120, with a contact dominated by CDRH3. We show by analyzing structures of progenitor and intermediate antibodies and by correlating them with measurements of binding to various gp120s that there was a shift in the relative orientation of the light- and heavy-chain variable domains during evolution of the CH103 lineage. We further show that mutations leading to this conformational shift probably occurred in response to insertions in variable loop 5 (V5) of the HIV envelope. The shift displaced the tips of the light chain away from contact with V5, making room for the inserted residues, which had allowed escape from neutralization by the progenitor antibody. These results, which document the selective mechanism underlying this example of a virus−antibody arms race, illustrate the functional significance of affinity maturation by mutation outside the complementarity determining region surface of the antibody molecule. PMID:24982157

  12. A computationally optimized broadly reactive H5 hemagglutinin vaccine provides protection against homologous and heterologous H5N1 highly pathogenic avian influenza virus infection in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since its emergence in 1996 in China, H5N1 highly pathogenic avian influenza (HPAI) virus has continuously evolved into different genetic clades that have created challenges to maintaining antigenically relevant H5N1 vaccine seeds. Therefore, a universal (multi-hemagglutinin [HA] subtype) or more c...

  13. Genome Sequence of the Versatile Fish Pathogen Edwardsiella tarda Provides Insights into its Adaptation to Broad Host Ranges and Intracellular Niches

    PubMed Central

    Xiao, Jingfan; Wu, Haizhen; Wang, Xin; Lv, Yuanzhi; Xu, Lili; Zheng, Huajun; Wang, Shengyue; Zhao, Guoping; Liu, Qin; Zhang, Yuanxing

    2009-01-01

    Background Edwardsiella tarda is the etiologic agent of edwardsiellosis, a devastating fish disease prevailing in worldwide aquaculture industries. Here we describe the complete genome of E. tarda, EIB202, a highly virulent and multi-drug resistant isolate in China. Methodology/Principal Findings E. tarda EIB202 possesses a single chromosome of 3,760,463 base pairs containing 3,486 predicted protein coding sequences, 8 ribosomal rRNA operons, and 95 tRNA genes, and a 43,703 bp conjugative plasmid harboring multi-drug resistant determinants and encoding type IV A secretion system components. We identified a full spectrum of genetic properties related to its genome plasticity such as repeated sequences, insertion sequences, phage-like proteins, integrases, recombinases and genomic islands. In addition, analysis also indicated that a substantial proportion of the E. tarda genome might be devoted to the growth and survival under diverse conditions including intracellular niches, with a large number of aerobic or anaerobic respiration-associated proteins, signal transduction proteins as well as proteins involved in various stress adaptations. A pool of genes for secretion systems, pili formation, nonfimbrial adhesions, invasions and hemagglutinins, chondroitinases, hemolysins, iron scavenging systems as well as the incomplete flagellar biogenesis might feature its surface structures and pathogenesis in a fish body. Conclusion/Significance Genomic analysis of the bacterium offered insights into the phylogeny, metabolism, drug-resistance, stress adaptation, and virulence characteristics of this versatile pathogen, which constitutes an important first step in understanding the pathogenesis of E. tarda to facilitate construction of a practical effective vaccine used for combating fish edwardsiellosis. PMID:19865481

  14. LDRD final report on high power broadly tunable Mid-IR quantum cascade lasers for improved chemical species detection.

    SciTech Connect

    Wanke, Michael Clement; Hudgens, James J.; Fuller, Charles T.; Samora, Sally; Klem, John Frederick; Young, Erik W.

    2006-01-01

    The goal of our project was to examine a novel quantum cascade laser design that should inherently increase the output power of the laser while simultaneously providing a broad tuning range. Such a laser source enables multiple chemical species identification with a single laser and/or very broad frequency coverage with a small number of different lasers, thus reducing the size and cost of laser based chemical detection systems. In our design concept, the discrete states in quantum cascade lasers are replaced by minibands made of multiple closely spaced electron levels. To facilitate the arduous task of designing miniband-to-miniband quantum cascade lasers, we developed a program that works in conjunction with our existing modeling software to completely automate the design process. Laser designs were grown, characterized, and iterated. The details of the automated design program and the measurement results are summarized in this report.

  15. Medicinal plants, human health and biodiversity: a broad review.

    PubMed

    Sen, Tuhinadri; Samanta, Samir Kumar

    2015-01-01

    Biodiversity contributes significantly towards human livelihood and development and thus plays a predominant role in the well being of the global population. According to WHO reports, around 80 % of the global population still relies on botanical drugs; today several medicines owe their origin to medicinal plants. Natural substances have long served as sources of therapeutic drugs, where drugs including digitalis (from foxglove), ergotamine (from contaminated rye), quinine (from cinchona), and salicylates (willow bark) can be cited as some classical examples.Drug discovery from natural sources involve a multifaceted approach combining botanical, phytochemical, biological, and molecular techniques. Accordingly, medicinal-plant-based drug discovery still remains an important area, hitherto unexplored, where a systematic search may definitely provide important leads against various pharmacological targets.Ironically, the potential benefits of plant-based medicines have led to unscientific exploitation of the natural resources, a phenomenon that is being observed globally. This decline in biodiversity is largely the result of the rise in the global population, rapid and sometimes unplanned industrialization, indiscriminate deforestation, overexploitation of natural resources, pollution, and finally global climate change.Therefore, it is of utmost importance that plant biodiversity be preserved, to provide future structural diversity and lead compounds for the sustainable development of human civilization at large. This becomes even more important for developing nations, where well-planned bioprospecting coupled with nondestructive commercialization could help in the conservation of biodiversity, ultimately benefiting mankind in the long run.Based on these findings, the present review is an attempt to update our knowledge about the diverse therapeutic application of different plant products against various pharmacological targets including cancer, human brain

  16. Providing global WLCG transfer monitoring

    NASA Astrophysics Data System (ADS)

    Andreeva, J.; Dieguez Arias, D.; Campana, S.; Flix, J.; Keeble, O.; Magini, N.; Molnar, Z.; Oleynik, D.; Petrosyan, A.; Ro, G.; Saiz, P.; Salichos, M.; Tuckett, D.; Uzhinsky, A.; Wildish, T.

    2012-12-01

    The WLCG[1] Transfers Dashboard is a monitoring system which aims to provide a global view of WLCG data transfers and to reduce redundancy in monitoring tasks performed by the LHC experiments. The system is designed to work transparently across LHC experiments and across the various technologies used for data transfer. Currently each LHC experiment monitors data transfers via experiment-specific systems but the overall cross-experiment picture is missing. Even for data transfers handled by FTS, which is used by 3 LHC experiments, monitoring tasks such as aggregation of FTS transfer statistics or estimation of transfer latencies are performed by every experiment separately. These tasks could be performed once, centrally, and then served to all experiments via a well-defined set of APIs. In the design and development of the new system, experience accumulated by the LHC experiments in the data management monitoring area is taken into account and a considerable part of the code of the ATLAS DDM Dashboard is being re-used. The paper describes the architecture of the Global Transfer monitoring system, the implementation of its components and the first prototype.

  17. Environmental standards provide competitive advantage

    SciTech Connect

    Chynoweth, E.; Kirshner, E.

    1993-04-28

    Quality organizations are breaking new ground with the development of international standards for environmental management. These promise to provide the platform for chemical companies wanting to establish their environmental credibility with a global audience. [open quotes]It will be similar to auditing our customers to ISO 9000[close quote], says the environmental manager for a European chemical firm. [open quote]We will only want to deal with people who have got their environmental act together. And we'll be in a better competitive positions[close quote]. The International Organization for Standardization (ISO;Geneva) has set up a taskforce to develop an environmental management standard, which is expected to be completed by the mid-1990s. Observers think the ISO standard will draw heavily on the British Standard Institute's (BSI;London) environmental management standard, BS7750, which will likely be the first system adopted in the world. Published last year, BS7750 has been extensively piloted in the UK (CW, Sept. 30, 1992, p. 62) and is now set to be revised before being offically adopted by BSI. The UK's Chemical Industries Association (CIA;London) is anxious to prevent a proliferation of standards, and its report on BS7750 pilot projects calls for an approach integrating quality, environment, and health and safety. But standard setters, including ISO, appear to be moving in the opposite direction. In the US, the American national Standards Institute (ANSI;Washington) has started work on an environmental management standard.

  18. Computerized provider order entry systems.

    PubMed

    2001-01-01

    Computerized provider order entry (CPOE) systems are designed to replace a hospital's paper-based ordering system. They allow users to electronically write the full range of orders, maintain an online medication administration record, and review changes made to an order by successive personnel. They also offer safety alerts that are triggered when an unsafe order (such as for a duplicate drug therapy) is entered, as well as clinical decision support to guide caregivers to less expensive alternatives or to choices that better fit established hospital protocols. CPOE systems can, when correctly configured, markedly increase efficiency and improve patient safety and patient care. However, facilities need to recognize that currently available CPOE systems require a tremendous amount of time and effort to be spent in customization before their safety and clinical support features can be effectively implemented. What's more, even after they've been customized, the systems may still allow certain unsafe orders to be entered. Thus, CPOE systems are not currently a quick or easy remedy for medical errors. ECRI's Evaluation of CPOE systems--conducted in collaboration with the Institute for Safe Medication Practices (ISMP)--discusses these and other related issues. It also examines and compares CPOE systems from three suppliers: Eclipsys Corp., IDX Systems Corp., and Siemens Medical Solutions Health Services Corp. Our testing focuses primarily on the systems' interfacing capabilities, patient safeguards, and ease of use. PMID:11696968

  19. Pinellia ternata agglutinin expression in chloroplasts confers broad spectrum resistance against aphid, whitefly, Lepidopteran insects, bacterial and viral pathogens

    PubMed Central

    Jin, Shuangxia; Zhang, Xianlong; Daniell, Henry

    2012-01-01

    Summary Broad spectrum protection against different insects and pathogens requires multigene engineering. However, such broad spectrum protection against biotic stress is provided by a single protein in some medicinal plants. Therefore, tobacco chloroplasts were transformed with the agglutinin gene from Pinellia ternata (pta), a widely cultivated Chinese medicinal herb. Pinellia ternata agglutinin (PTA) was expressed up to 9.2% of total soluble protein in mature leaves. Purified PTA showed similar hemagglutination activity as snowdrop lectin. Artificial diet with purified PTA from transplastomic plants showed marked and broad insecticidal activity. In planta bioassays conducted with T0 or T1 generation PTA lines showed that the growth of aphid Myzus persicae (Sulzer) was reduced by 89%–92% when compared with untransformed (UT) plants. Similarly, the larval survival and total population of whitefly (Bemisia tabaci) on transplastomic lines were reduced by 91%–93% when compared with UT plants. This is indeed the first report of lectin controlling whitefly infestation. When transplastomic PTA leaves were fed to corn earworm (Helicoverpa zea), tobacco budworm (Heliothis virescens) or the beet armyworm (spodoptera exigua), 100% mortality was observed against all these three insects. In planta bioassays revealed Erwinia population to be 10 000-fold higher in control than in PTA lines. Similar results were observed with tobacco mosaic virus (TMV) challenge. Therefore, broad spectrum resistance to homopteran (sap-sucking), Lepidopteran insects as well as anti-bacterial or anti-viral activity observed in PTA lines provides a new option to engineer protection against biotic stress by hyper-expression of an unique protein that is naturally present in a medicinal plant. PMID:22077160

  20. Broad scan linkage analysis in a large Tourette family pedigree

    SciTech Connect

    Peiffer, A.; Leppert, M.; Wetering, B.J.M. van der

    1994-09-01

    Attempts to find a gene causing Tourette syndrome (TS) using linkage analysis have been unsuccessful even though as much as 65% of the autosomal genetic map has been excluded by the pooled results from several laboratories collaborating worldwide. One reason for this failure may be the misclassification of affection status of marry-in spouses. Specifically, we have found that six unrelated spouses in our Utah TS pedigree suffer from TS, obsessive-compulsive disorder or chronic motor tics. In light of these findings we decided to conduct a complete genomic scan from this Utah kindred with polymorphic markers in three related sibships in which there was no assortative mating. A linkage study assuming autosomal dominant inheritance was done using tetranucleotide repeat markers developed at the University of Utah. We selected markers that were less than 300 bp in size and that gave a heterozygosity of over 70% upon analysis in 4 CEPH families. Results to date with 95 markers run at an interval of 30 cM (covering 61% of the genome) show no evidence of linkage. We intend to extend the coverage to 100% of the genome. Pending completion of this scan, failure to provide evidence of linkage in our TS pedigree might then be attributed to phenotypic misclassification or erroneous assumptions regarding the genetic model of transmission.

  1. Periaxin mutations cause a broad spectrum of demyelinating neuropathies.

    PubMed

    Takashima, Hiroshi; Boerkoel, Cornelius F; De Jonghe, Peter; Ceuterick, Chantal; Martin, Jean-Jacques; Voit, Thomas; Schröder, J-Michael; Williams, Anna; Brophy, Peter J; Timmerman, Vincent; Lupski, James R

    2002-06-01

    Previous studies have demonstrated that apparent loss-of-function mutations in the periaxin gene cause autosomal recessive Dejerine-Sottas neuropathy or severe demyelinating Charcot-Marie-Tooth disease. In this report, we extend the associated phenotypes with the identification of two additional families with novel periaxin gene mutations (C715X and R82fsX96) and provide detailed neuropathology. Each patient had marked sensory involvement; two siblings with a homozygous C715X mutation had much worse sensory impairment than motor impairment. Despite early disease onset, these siblings with the C715X mutation had relatively slow disease progression and adult motor impairment typical of classic demyelinating Charcot-Marie-Tooth neuropathy. In contrast, a patient with the homozygous R82fsX96 mutation had a disease course consistent with Dejerine-Sottas neuropathy. The neuropathology of patients in both families was remarkable for demyelination, onion bulb and occasional tomacula formation with focal myelin thickening, abnormalities of the paranodal myelin loops, and focal absence of paranodal septate-like junctions between the terminal loops and axon. Our study indicates a prominent sensory neuropathy resulting from periaxin gene mutations and suggests a role for the carboxyl terminal domain of the periaxin protein. PMID:12112076

  2. Identification of Ebsulfur Analogues with Broad-Spectrum Antifungal Activity.

    PubMed

    Ngo, Huy X; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2016-07-19

    Invasive fungal infections are on the rise due to an increased population of critically ill patients as a result of HIV infections, chemotherapies, and organ transplantations. Current antifungal drugs are helpful, but are insufficient in addressing the problem of drug-resistant fungal infections. Thus, there is a growing need for novel antimycotics that are safe and effective. The ebselen scaffold has been evaluated in clinical trials and has been shown to be safe in humans. This makes ebselen an attractive scaffold for facile translation from bench to bedside. We recently reported a library of ebselen-inspired ebsulfur analogues with antibacterial properties, but their antifungal activity has not been characterized. In this study, we repurposed ebselen, ebsulfur, and 32 additional ebsulfur analogues as antifungal agents by evaluating their antifungal activity against a panel of 13 clinically relevant fungal strains. The effect of induction of reactive oxygen species (ROS) by three of these compounds was evaluated. Their hemolytic and cytotoxicity activities were also determined using mouse erythrocytes and mammalian cells. The MIC values of these compounds were found to be in the range of 0.02-12.5 μg mL(-1) against the fungal strains tested. Notably, yeast cells treated with our compounds showed an accumulation of ROS, which may further contribute to the growth-inhibitory effect against fungi. This study provides new lead compounds for the development of antimycotic agents. PMID:27334363

  3. Broad electrical tuning of plasmonic nanoantennas at visible frequencies

    NASA Astrophysics Data System (ADS)

    Hoang, Thang B.; Mikkelsen, Maiken H.

    2016-05-01

    We report an experimental demonstration of electrical tuning of plasmon resonances of optical nanopatch antennas over a wide wavelength range. The antennas consist of silver nanocubes separated from a gold film by a thin 8 nm polyelectrolyte spacer layer. By using ionic liquid and indium tin oxide coated glass as a top electrode, we demonstrate dynamic and reversible tuning of the plasmon resonance over 100 nm in the visible wavelength range using low applied voltages between -3.0 V and 2.8 V. The electrical potential is applied across the nanoscale gap causing changes in the gap thickness and dielectric environment which, in turn, modifies the plasmon resonance. The observed tuning range is greater than the full-width-at-half-maximum of the plasmon resonance, resulting in a tuning figure of merit of 1.05 and a tuning contrast greater than 50%. Our results provide an avenue to create active and reconfigurable integrated nanophotonic components for applications in optoelectronics and sensing.

  4. Broad-Bandwidth FPGA-Based Digital Polyphase Spectrometer

    NASA Technical Reports Server (NTRS)

    Jamot, Robert F.; Monroe, Ryan M.

    2012-01-01

    With present concern for ecological sustainability ever increasing, it is desirable to model the composition of Earth s upper atmosphere accurately with regards to certain helpful and harmful chemicals, such as greenhouse gases and ozone. The microwave limb sounder (MLS) is an instrument designed to map the global day-to-day concentrations of key atmospheric constituents continuously. One important component in MLS is the spectrometer, which processes the raw data provided by the receivers into frequency-domain information that cannot only be transmitted more efficiently, but also processed directly once received. The present-generation spectrometer is fully analog. The goal is to include a fully digital spectrometer in the next-generation sensor. In a digital spectrometer, incoming analog data must be converted into a digital format, processed through a Fourier transform, and finally accumulated to reduce the impact of input noise. While the final design will be placed on an application specific integrated circuit (ASIC), the building of these chips is prohibitively expensive. To that end, this design was constructed on a field-programmable gate array (FPGA). A family of state-of-the-art digital Fourier transform spectrometers has been developed, with a combination of high bandwidth and fine resolution. Analog signals consisting of radiation emitted by constituents in planetary atmospheres or galactic sources are downconverted and subsequently digitized by a pair of interleaved analog-to-digital converters (ADCs). This 6-Gsps (gigasample per second) digital representation of the analog signal is then processed through an FPGA-based streaming fast Fourier transform (FFT). Digital spectrometers have many advantages over previously used analog spectrometers, especially in terms of accuracy and resolution, both of which are particularly important for the type of scientific questions to be addressed with next-generation radiometers.

  5. A 1.2--Millimeter Broad--Band Polarimeter

    NASA Astrophysics Data System (ADS)

    Glenn, Jason; Walker, Christopher K.; Young, Erick T.

    1996-05-01

    We describe a 1.2--millimeter polarimeter to be used on the Steward Observatory and Max--Planck--Institut fur Radioastronomie 10--meter Submillimeter Telescope Observatory. The construction, performance parameters, and scientific purpose of the instrument are presented. The detector is a Ge bolometer with a Si absorber operated in a cavity cooled to 0.36 K by a liquid He(3) refrigerator. The bandpass has a central wavelength of 1.2 mm and a width of 0.3 mm. The system noise equivalent power is 1.5*E(-14) W Hz(-{1/2}) at 20 Hz. Polarimetric modulation is accomplished with a room temperature, rotating Rexolite half-wave plate. Unidirectional grooves provide the lambda /2 phase shift between the orthogonal senses of polarization. The polarization analyzer is a stationary, room temperature, unidirectional wire grid that transmits only one sense of polarization with 99% efficiency. The system polarimetric efficiency is 87% and the laboratory instrumental polarization is a well defined 3.7%. Detection of a 1% linear polarization is possible at the several sigma level. The primary scientific goal of this instrument is to probe the magnetic field orientations in the protostellar dust cores of molecular clouds. Non--spherical dust grains are aligned in the presence of a magnetic field resulting in linear polarization of the far--infrared thermal dust emission perpendicular to the magnetic field vector. Observed field orientations will be compared to protostellar molecular outflow orientations and magnetic fields on larger scales. With these comparisons we will assess the role of magnetic fields in cloud collapse and star formation.

  6. Multifarious Roles of Intrinsic Disorder in Proteins Illustrate Its Broad Impact on Plant Biology

    PubMed Central

    Sun, Xiaolin; Rikkerink, Erik H.A.; Jones, William T.; Uversky, Vladimir N.

    2013-01-01

    Intrinsically disordered proteins (IDPs) are highly abundant in eukaryotic proteomes. Plant IDPs play critical roles in plant biology and often act as integrators of signals from multiple plant regulatory and environmental inputs. Binding promiscuity and plasticity allow IDPs to interact with multiple partners in protein interaction networks and provide important functional advantages in molecular recognition through transient protein–protein interactions. Short interaction-prone segments within IDPs, termed molecular recognition features, represent potential binding sites that can undergo disorder-to-order transition upon binding to their partners. In this review, we summarize the evidence for the importance of IDPs in plant biology and evaluate the functions associated with intrinsic disorder in five different types of plant protein families experimentally confirmed as IDPs. Functional studies of these proteins illustrate the broad impact of disorder on many areas of plant biology, including abiotic stress, transcriptional regulation, light perception, and development. Based on the roles of disorder in the protein–protein interactions, we propose various modes of action for plant IDPs that may provide insight for future experimental approaches aimed at understanding the molecular basis of protein function within important plant pathways. PMID:23362206

  7. Assessing the status and trend of bat populations across broad geographic regions with dynamic distribution models

    USGS Publications Warehouse

    Rodhouse, Thomas J.; Ormsbee, Patricia C.; Irvine, Kathryn M.; Vierling, Lee A.; Szewczak, Joseph M.; Vierling, Kerri T.

    2012-01-01

    Despite its common status, M. lucifugus was only detected during ∼50% of the surveys in occupied sample units. The overall naïve estimate for the proportion of the study region occupied by the species was 0.69, but after accounting for imperfect detection, this increased to ∼0.90. Our models provide evidence of an association between NPP and forest cover and M. lucifugus distribution, with implications for the projected effects of accelerated climate change in the region, which include net aridification as snowpack and stream flows decline. Annual turnover, the probability that an occupied sample unit was a newly occupied one, was estimated to be low (∼0.04–0.14), resulting in flat trend estimated with relatively high precision (SD = 0.04). We mapped the variation in predicted occurrence probabilities and corresponding prediction uncertainty along the productivity gradient. Our results provide a much needed baseline against which future anticipated declines in M. lucifugus occurrence can be measured. The dynamic distribution modeling approach has broad applicability to regional bat monitoring efforts now underway in several countries and we suggest ways to improve and expand our grid-based monitoring program to gain robust insights into bat population status and trend across large portions of North America.

  8. Personal glucose meters for detection and quantification of a broad range of analytes

    SciTech Connect

    Lu, Yi; Xiang, Yu

    2015-02-03

    A general methodology for the development of highly sensitive and selective sensors that can achieve portable, low-cost and quantitative detection of a broad range of targets using only a personal glucose meter (PGM) is disclosed. The method uses recognition molecules that are specific for a target agent, enzymes that can convert an enzyme substrate into glucose, and PGM. Also provided are sensors, which can include a solid support to which is attached a recognition molecule that permits detection of a target agent, wherein the recognition molecule specifically binds to the target agent in the presence of the target agent but not significantly to other agents as well as an enzyme that can catalyze the conversion of a substance into glucose, wherein the enzyme is attached directly or indirectly to the recognition molecule, and wherein in the presence of the target agent the enzyme can convert the substance into glucose. The disclosed sensors can be part of a lateral flow device. Methods of using such sensors for detecting target agents are also provided.

  9. Coaxially electrospun fiber-based microbicides facilitate broadly tunable release of maraviroc.

    PubMed

    Ball, Cameron; Chou, Shih-Feng; Jiang, Yonghou; Woodrow, Kim A

    2016-06-01

    Electrospun fibers show potential as a topical delivery system for vaginal microbicides. Previous reports have demonstrated delivery of anti-HIV and anti-STI (sexually transmitted infection) agents from fibers formulated using hydrophilic, hydrophobic, or pH-responsive polymers that result in rapid, prolonged, or stimuli-responsive release, respectively. However, coaxial electrospun fibers have yet to be evaluated as a highly tunable microbicide delivery vehicle. In this research, we explored the opportunities and limitations of a model coaxial electrospun fiber system to provide broad and tunable release rates for the HIV entry inhibitor maraviroc. Specifically, we prepared ethyl cellulose (EC)-shell and polyvinylpyrrolidone (PVP)-core fibers that were capable of releasing actives over a range of hours to several days. We further demonstrated simple and effective methods for combining core-shell fibers with rapid-release formulations to provide combined instantaneous and sustained maraviroc release. In addition, we investigated the effect of varying release media on maraviroc release from core-shell fibers, and found that release was strongly influenced by media surface tension and drug ionization. Finally, in vitro cell culture studies show that our fiber formulations were not cytotoxic and that electrospun maraviroc maintained similar antiviral activity compared to neat maraviroc. PMID:27040202

  10. A broad-band microseismometer for planetary operations

    NASA Technical Reports Server (NTRS)

    Banerdt, W. B.; Vanzandt, T.; Kaiser, W. J.; Kenny, T. W.

    1993-01-01

    There has recently been renewed interest in the development of instrumentation for making measurements on the surface of Mars. This is due to the Mars Environmental Survey (MESUR) Mission, for which approximately 16 small, long-lived (2-10 years), relatively inexpensive surface stations will be deployed in a planet-wide network. This will allow the investigation of processes (such as seismology and meteorology) which require the simultaneous measurement of phenomena at many widely spaced locations on the surface over a considerable length of time. Due to the large number of vehicles involved, the mass, power, and cost of the payload will be severely constrained. A seismometer has been identified as one of the highest priority instruments in the MESUR straw-man payload. The requirements for an effective seismic experiment on Mars place a number of constraints on any viable sensor design. First, a large number of sensors must be deployed in a long-lived global network in order to be able to locate many events reliably, provide good spatial sampling of the interior, and increase the probability of seismic detection in the event of localized seismicity and/or high attenuation. From a practical standpoint, this means that individual surface stations will necessarily be constrained in terms of cost, mass, and power. Landing and thermal control systems will probably be simple, in order to minimize cost, resulting in large impact accelerations and wide daily and seasonal thermal swings. The level of seismic noise will determine the maximum usable sensitivity for seismometer. Unfortunately, the ambient seismic noise level for Mars is not well known. However lunar seismic noise levels are several orders of magnitude below that of the Earth. Sensitivities on the order of 10(exp -11)g over a bandwidth of .04 to 20 Hz are thought to be necessary to fulfill the science objectives for a seimometer placed on the Martian surface. Silicon micromachined sensor technology offers

  11. 26 CFR 1.509(a)-3 - Broadly, publicly supported organizations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Broadly, publicly supported organizations. 1.509(a)-3 Section 1.509(a)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(a)-3 Broadly, publicly supported organizations. (a) In...

  12. 26 CFR 1.509(a)-3 - Broadly, publicly supported organizations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Broadly, publicly supported organizations. 1.509(a)-3 Section 1.509(a)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(a)-3 Broadly, publicly supported organizations. (a) In...

  13. Potential Sources of Resistance to Broad Mites (Polyphagotarsonemus latus) in Watermelon Germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two hundred and nineteen United States plant introductions (PI) belonging to the watermelon core collection were evaluated for broad mite, Polyphagotarsonemus latus (Banks) infestation and injury that occurred naturally in a field planting. Of the 219 PI, nine (4%) had no visible broad mite injury ...

  14. Public Entrepreneurs and the Adoption of Broad-Based Merit Aid beyond the Southeastern United States

    ERIC Educational Resources Information Center

    Ingle, William Kyle; Petroff, Ruth Ann

    2013-01-01

    The concentration of broad-based merit aid adoption in the southeastern United States has been well noted in the literature. However, there are states that have adopted broad-based merit aid programs outside of the Southeast. Guided by multiple theoretical frameworks, including innovation diffusion theory (e.g., Gray, 1973, 1994; Rogers, 2003),…

  15. 33 CFR 110.27 - Lynn Harbor in Broad Sound, Mass.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Lynn Harbor in Broad Sound, Mass. 110.27 Section 110.27 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.27 Lynn Harbor in Broad Sound, Mass. North...

  16. 33 CFR 110.27 - Lynn Harbor in Broad Sound, Mass.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Lynn Harbor in Broad Sound, Mass. 110.27 Section 110.27 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.27 Lynn Harbor in Broad Sound, Mass. North...

  17. 33 CFR 110.27 - Lynn Harbor in Broad Sound, Mass.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Lynn Harbor in Broad Sound, Mass. 110.27 Section 110.27 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.27 Lynn Harbor in Broad Sound, Mass. North...

  18. 33 CFR 110.27 - Lynn Harbor in Broad Sound, Mass.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Lynn Harbor in Broad Sound, Mass. 110.27 Section 110.27 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.27 Lynn Harbor in Broad Sound, Mass. North...

  19. 78 FR 38311 - Broad River Electric Cooperative and Cherokee Falls Associates; Aquenergy Systems, Inc.; Notice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-26

    ... Energy Regulatory Commission Broad River Electric Cooperative and Cherokee Falls Associates; Aquenergy... Intervene On June 18, 2013, Broad River Electric Cooperative and Cherokee Falls Associates (transferors) and Aquenergy Systems, Inc. (transferee) filed an application for transfer of license for the Cherokee...

  20. 26 CFR 1.509(a)-3 - Broadly, publicly supported organizations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 7 2012-04-01 2012-04-01 false Broadly, publicly supported organizations. 1.509(a)-3 Section 1.509(a)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(a)-3 Broadly, publicly supported organizations. (a) In...

  1. 26 CFR 1.509(a)-3 - Broadly, publicly supported organizations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 7 2013-04-01 2013-04-01 false Broadly, publicly supported organizations. 1.509(a)-3 Section 1.509(a)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(a)-3 Broadly, publicly supported organizations. (a) In...

  2. 26 CFR 1.509(a)-3 - Broadly, publicly supported organizations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Broadly, publicly supported organizations. 1.509(a)-3 Section 1.509(a)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(a)-3 Broadly, publicly supported organizations. (a) In...

  3. The Broad Challenge to Democratic Leadership: The Other Crisis in Education

    ERIC Educational Resources Information Center

    Miller, Vachel W.

    2012-01-01

    This article interrogates the workings of the Broad Superintendents Academy, as a specific illustration of the influence of venture philanthropy in American public education. It introduces the Broad Foundation's agenda for educational leadership training, foregrounding how it frames the problem of leadership and the implications of such training…

  4. 10 CFR 33.17 - Conditions of specific licenses of broad scope.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... required; or (4) Add or cause the addition of byproduct material to any food, beverage, cosmetic, drug, or... approved by the licensee's radiation safety committee. (c) Each Type B specific license of broad scope... radiological safety officer. (d) Each Type C specific license of broad scope issued under this part shall...

  5. 33 CFR 110.27 - Lynn Harbor in Broad Sound, Mass.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Lynn Harbor in Broad Sound, Mass. 110.27 Section 110.27 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.27 Lynn Harbor in Broad Sound, Mass. North...

  6. Approaches to predicting broad-scale regime shifts using changing pattern-process relationships across scales

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding and predicting the occurrence of alternative ecosystem states (i.e., regime shifts) at broad scales is a pressing challenge for ecologists given the scope and nature of global change. In many cases, regime shifts at broad-scales are affected by pattern-process relationships across a ra...

  7. 77 FR 8865 - Recent Postings of Broadly Applicable Alternative Test Methods

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... 72 FR 4257 (January 30, 2007) and found on the EPA's Web site at www.epa.gov/ttn/emc/approalt.html... outlined at 72 FR 4257 (January 30, 2007). We will continue to announce approvals for broadly applicable... AGENCY Recent Postings of Broadly Applicable Alternative Test Methods AGENCY: Environmental...

  8. Sex Differences and Within-Family Associations in the Broad Autism Phenotype

    ERIC Educational Resources Information Center

    Klusek, Jessica; Losh, Molly; Martin, Gary E.

    2014-01-01

    While there is a strong sex bias in the presentation of autism, it is unknown whether this bias is also present in subclinical manifestations of autism among relatives, or the broad autism phenotype. This study examined this question and investigated patterns of co-occurrence of broad autism phenotype traits within families of individuals with…

  9. Expression of the Broad Autism Phenotype in Simplex Autism Families from the Simons Simplex Collection

    ERIC Educational Resources Information Center

    Davidson, Julie; Goin-Kochel, Robin P.; Green-Snyder, Lee Anne; Hundley, Rachel J.; Warren, Zachary; Peters, Sarika U.

    2014-01-01

    The broad autism phenotype (BAP) refers to the phenotypic expression of an underlying genetic liability to autism, manifest in non-autistic relatives. This study examined the relationship among the "Broad Autism Phenotype Questionnaire" (BAPQ), "Social Responsiveness Scale: Adult Research Version" (SRS:ARV), and "Family…

  10. Broad Mite (Polyphagotarsonemus latus) infestation and injury in watermelon and potential sources of resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During the summer of 2006, we observed severe broad mite (Polyphagotarsonemus latus) injury and infestations on watermelon plant introductions (PI) and commercial cultivars grown in the field in Charleston, SC. Broad mites have previously not been reported on watermelons in the U.S.A. However, the...

  11. Broad base biological assay using liquid based detection assays

    SciTech Connect

    Milanovich, F; Albala, J; Colston, B; Langlois, R; Venkateswaren, K

    2000-10-31

    The release of a biological agent by terrorists represents a serious threat to the safety of US citizens. At present there are over 50 pathogens and toxins on various agency threat lists. Most of these pathogens are rarely seen by public health personnel so the ability to rapidly identify their infection is limited. Since many pathogenic infections have symptomatic delays as long as several days, effective treatment is often compromised. This translates into two major deficiencies in our ability to counter biological terrorism (1) the lack of any credible technology to rapidly detect and identify all the pathogens or toxins on current threat lists and (2) the lack of a credible means to rapidly diagnose thousands of potential victims. In this SI we are developing a rapid, flexible, inexpensive, high throughput, and deeply multiplex-capable biological assay technology. The technology, which we call the Liquid Array (LA), utilizes optical encoding of small diameter beads which serve as the templates for biological capture assays. Once exposed to a fluid sample these beads can be identified and probed for target pathogens at rates of several thousand beads per second. Since each bead can be separately identified, one can perform parallel assays by assigning a different assay to each bead in the encoded set. The goal for this development is a detection technology capable of simultaneously identifying 100s of different bioagents and/or of rapidly diagnosing several thousand individuals. We are pursuing this research in three thrusts. In the first we are exploring the fundamental interactions of the beads with proteins and nucleic acids in complex mixtures. This will provide us with a complete understanding of the limits of the technology with respect to throughput and complex environment. A major spin-off of this activity is in the rapidly emerging field of proteomics where we may be able to rapidly assess the interactions responsible for cell metabolism, structural

  12. Broad-band X-ray emission and the reality of the broad iron line from the neutron star-white dwarf X-ray binary 4U 1820-30

    NASA Astrophysics Data System (ADS)

    Mondal, Aditya S.; Dewangan, G. C.; Pahari, M.; Misra, R.; Kembhavi, A. K.; Raychaudhuri, B.

    2016-09-01

    Broad relativistic iron lines from neutron star X-ray binaries are important probes of the inner accretion disc. The X-ray reflection features can be weakened due to strong magnetic fields or very low iron abundances such as is possible in X-ray binaries with low mass, first generation stars as companions. Here, we investigate the reality of the broad iron line detected earlier from the neutron-star low-mass X-ray binary 4U 1820-30 with a degenerate helium dwarf companion. We perform a comprehensive, systematic broad-band spectral study of the atoll source using Suzaku and simultaneous NuSTAR and Swift observations. We have used different continuum models involving accretion disc emission, thermal blackbody and thermal Comptonization of either disc or blackbody photons. The Suzaku data show positive and negative residuals in the region of Fe K band. These features are well described by two absorption edges at 7.67 ± 0.14 keV and 6.93 ± 0.07 keV or partial covering photoionized absorption or by blurred reflection. Though, the simultaneous Swift and NuSTAR data do not clearly reveal the emission or absorption features, the data are consistent with the presence of either absorption or emission features. Thus, the absorption based models provide an alternative to the broad iron line or reflection model. The absorption features may arise in winds from the inner accretion disc. The broad-band spectra appear to disfavour continuum models in which the blackbody emission from the neutron-star surface provides the seed photons for thermal Comptonization. Our results suggest emission from a thin accretion disc (kTdisc ˜ 1 keV), Comptonization of disc photons in a boundary layer most likely covering a large fraction of the neutron-star surface and innermost parts of the accretion disc, and blackbody emission (kTbb ˜ 2 keV) from the polar regions.

  13. Broad T-Cell Receptor Repertoire in T-Lymphocytes Derived from Human Induced Pluripotent Stem Cells

    PubMed Central

    Chang, Chia-Wei; Lai, Yi-Shin; Lamb, Lawrence S.; Townes, Tim M.

    2014-01-01

    Human induced pluripotent stem cells (hiPSCs) have enormous potential for the treatment of inherited and acquired disorders. Recently, antigen-specific T lymphocytes derived from hiPSCs have been reported. However, T lymphocyte populations with broad T cell receptor (TCR) diversity have not been generated. We report that hiPSCs derived from skin biopsy are capable of producing T lymphocyte populations with a broad TCR repertoire. In vitro T cell differentiation follows a similar developmental program as observed in vivo, indicated by sequential expression of CD7, intracellular CD3 and surface CD3. The γδ TCR locus is rearranged first and is followed by rearrangement of the αβ locus. Both γδ and αβ T cells display a diverse TCR repertoire. Upon activation, the cells express CD25, CD69, cytokines (TNF-α, IFN-γ, IL-2) and cytolytic proteins (Perforin and Granzyme-B). These results suggest that most, if not all, mechanisms required to generate functional T cells with a broad TCR repertoire are intact in our in vitro differentiation protocol. These data provide a foundation for production of patient-specific T cells for the treatment of acquired or inherited immune disorders and for cancer immunotherapy. PMID:24828440

  14. Dependence of the broad Fe Kα line on the physical parameters of AGN

    NASA Astrophysics Data System (ADS)

    Liu, Zhu; Yuan, Weimin; Lu, Youjun; Carrera, Francisco J.; Falocco, Serena; Dong, Xiao-Bo

    2016-08-01

    In this paper, the dependence of the broad Fe Kα line on the physical parameters of AGN, such as the black hole mass MBH, accretion rate (equivalently represented by Eddington ratio λEdd), and optical classification, is investigated by applying the X-ray spectra stacking method to a large sample of AGN which have well measured optical parameters. A broad line feature is detected (>3σ) in the stacked spectra of the high λEdd sub-sample (log λEdd > -0.9). The profile of the broad line can be well fitted with relativistic broad line model, with the line energy consistent with highly ionized Fe Kα line (i.e. Fe XXVI). A model consisting of multiple narrow lines cannot be ruled out, however. We found hints that the Fe K line becomes broader as the λEdd increases. No broad line feature is shown in the sub-sample of broad-line Seyfert 1 (BLS1) galaxies and in the full sample, while a broad line might be present, though at low significance, in the sub-sample of narrow-line Seyfert 1 (NLS1) galaxies. We find no strong dependence of the broad line on black hole masses. Our results indicate that the detection/properties of the broad Fe Kα line may strongly depend on λEdd, which can be explained if the ionization state and/or truncation radius of the accretion disc changes with λEdd. The non-detection of the broad line in the BLS1 sub-sample can be explained if the the average EW of the relativistic Fe Kα line is weak or/and the fraction of sources with relativistic Fe Kα line is small in BLS1 galaxies.

  15. Providing Data Access for Interdisciplinary Research

    NASA Astrophysics Data System (ADS)

    Hooper, R. P.; Couch, A.

    2012-12-01

    Developing an interdisciplinary understanding of human and environmental interactions with water requires access to a variety of data kinds collected by various organizations. The CUAHSI Hydrologic Information System (HIS) is a standards-based, services-oriented architecture designed for time-series data. Such data represents an important type of data in water studies. Through the efforts of HIS, a standard transmission language, WaterML2, has been adopted by the Open Geospatial Consortium and is under consideration by the World Meteorologic Organization as an international standards. Web services have also been developed to retrieve data and metadata. HIS is completed with a metadata catalog, hosted by San Diego Supercomputing Center, which indexes more than 20 million time series provided from over 90 different services. This catalog is supported through a hierarchically organized controlled vocabulary that is open for community input and mediation. Data publishers include federal agencies, universities, state agencies, and non-profit organizations such as watershed associations. Accessing data from such a broad spectrum of sources through a uniform service standard promises to truly transform the way in which hydrologic research is done. CUAHSI HIS is a large-scale prototype at this time, but a proposal is under consideration by the National Science Foundation to operationalize HIS through a data facility, tentatively called the CUAHSI Water Data Center. Establishing HIS is an important step to enable research into human-environment interactions with water, but it is only one step. Other data structures will need to be made accessible and interoperable to support this research. Some data—such as two-dimensional GIS coverages—already have widely used standards for transmission and sharing. The US Federal government has long operated a clearinghouse for federal geographic data that is now being augmented with other services such as ArcGIS OnLine. Other data

  16. Detection of Extremely Broad Water Emission from the Molecular Cloud Interacting Supernova Remnant G349.7+0.2

    NASA Astrophysics Data System (ADS)

    Rho, J.; Hewitt, J. W.; Boogert, A.; Kaufman, M.; Gusdorf, A.

    2015-10-01

    We performed Herschel HIFI, PACS, and SPIRE observations toward the molecular cloud interacting supernova remnant G349.7+0.2. An extremely broad emission line was detected at 557 GHz from the ground state transition 110-101 of ortho-water. This water line can be separated into three velocity components with widths of 144, 27, and 4 km s-1. The 144 km s-1 component is the broadest water line detected to date in the literature. This extremely broad line width shows the importance of probing shock dynamics. PACS observations revealed three additional ortho-water lines, as well as numerous high-J carbon monoxide (CO) lines. No para-water lines were detected. The extremely broad water line is indicative of a high velocity shock, which is supported by the observed CO rotational diagram that was reproduced with a J-shock model with a density of 104 cm-3 and a shock velocity of 80 km s-1. Two far-infrared fine-structure lines, [O i] at 145 μm and [C ii] line at 157 μm, are also consistent with the high velocity J-shock model. The extremely broad water line could be simply from short-lived molecules that have not been destroyed in high velocity J-shocks; however, it may be from more complicated geometry such as high-velocity water bullets or a shell expanding in high velocity. We estimate the CO and H2O densities, column densities, and temperatures by comparison with RADEX and detailed shock models. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.

  17. Epitopes for Broad and Potent Neutralizing Antibody Responses during Chronic Infection with Human Immunodeficiency Virus Type 1

    PubMed Central

    Nandi, Avishek; Lavine, Christine L.; Wang, Pengcheng; Lipchina, Inna; Goepfert, Paul A.; Shaw, George M.; Tomaras, Georgia D.; Montefiori, David C.; Haynes, Barton F.; Easterbrook, Philippa; Robinson, James E.; Sodroski, Joseph G.; Yang, Xinzhen

    2009-01-01

    Neutralizing antibody (nAb) response is sporadic and has limited potency and breadth during infection with human immunodeficiency virus type 1 (HIV-1). In rare cases, broad and potent nAbs are actually induced in vivo. Identifying specific epitopes targeted by such broad and potent nAb response is valuable in guiding the design of a prophylactic vaccine aimed to induce nAb. In this study, we have defined neutralizing epitope usage in 7 out of 17 subjects with broad and potent nAbs by using targeted mutagenesis in known neutralizing epitopes of HIV-1 glycoproteins and by using in vitro depletion of serum neutralizing activity by various recombinant HIV-1 glycoproteins. Consistent with recent reports, the CD4 binding site (CD4BS) is targeted by nAbs in vivo (4 of the 7 subjects with defined neutralizing epitopes). The new finding from this study is that epitopes in the gp120 outer domain are also targeted by nAbs in vivo (5 of the 7 subjects). The outer domain epitopes include glycan-dependent epitopes (2 subjects), conserved non-linear epitope in the V3 region (2 subjects), and a CD4BS epitope composed mainly of the elements in the outer domain (1 subject). Importantly, we found indication for epitope poly-specificity, a dual usage of the V3 and CD4BS epitopes, in only one subject. This study provides a more complete profile of epitope usage for broad and potent nAb responses during HIV-1 infection. PMID:19922969

  18. CLIMATE CONDITIONS AFFECTING THE WITHIN-PLANT SPREAD OF BROAD MITES ON AZALEA.

    PubMed

    Mechant, E; Pauwels, E; Gobin, B

    2014-01-01

    The broad mite Polyphagotarsonemus latus (Banks) is considered a major pest in potted azalea, Flanders' flagship ornamental crop of Rhododendron simsii hybrids. In addition to severe economic damage, the broad mite is dreaded for its increasing resistance to acaricides. Due to restrictions in the use of broad spectrum acaricides, Belgian azalea growers are left with only three compounds, belonging to two mode of action groups and restricted in their number of applications, for broad mite control: abamectin, milbemectin and pyrethrin. Although P. latus can be controlled with predatory mites, the high cost of this system makes it (not yet) feasible for integration into standard azalea pest management systems. Hence, a maximum efficacy of treatments with available compounds is essential. Because abamectin, milbemectin and pyrethrin are contact acaricides with limited trans laminar flow, only broad mites located on shoot tips of azalea plants will be controlled after spraying. Consequently, the efficacy of chemical treatments is influenced by the location and spread of P. latus on the plant. Unfortunately, little is known on broad mites' within-plant spread or how it is affected by climatic conditions like temperature and relative humidity. Therefore, experiments were set up to verify whether climate conditions have an effect on the location and migration of broad mites on azalea. Broad mite infected azalea plants were placed in standard growth chambers under different temperature (T:2.5-25°C) and relative humidity (RH:55-80%) treatments. Within-plant spread was determined by counting mites on the shoot tips and inner leaves of azalea plants. Results indicate that temperature and relative humidity have no significant effect on the within-plant spread of P. latus. To formulate recommendations for optimal spray conditions to maximize the efficacy of broad mite control with acaricides, further experiments on the effect of light intensity and rain are scheduled. PMID

  19. High-power, low-lateral divergence broad area quantum cascade lasers with a tilted front facet

    SciTech Connect

    Ahn, Sangil Schwarzer, Clemens; Zederbauer, Tobias; MacFarland, Donald C.; Detz, Hermann; Andrews, Aaron M.; Schrenk, Werner; Strasser, Gottfried

    2014-02-03

    We introduce a simple technique to improve the beam quality of broad area quantum cascade lasers. Moderately tilted front facets of the laser provide suppression of higher order lateral waveguide modes. A device with a width of 60 μm and a front facet angle of 17° shows a nearly diffraction limited beam profile. In addition, the peak output power and the slope efficiency of the device are increased since most of the light inside the cavity is emitted through the tilted front facet by an asymmetric light intensity distribution along the cavity.

  20. Infrared hyperspectral imaging using a broadly tunable external cavity quantum cascade laser and microbolometer focal plane array

    SciTech Connect

    Phillips, Mark C.; Ho, Nicolas

    2008-02-04

    A versatile mid-infrared hyperspectral imaging system is demonstrated by combining a broadly tunable external cavity quantum cascade laser and a microbolometer focal plane array. The tunable mid-infrared laser provided high brightness illumination over a tuning range from 985 cm-1 to 1075 cm-1 (9.30-10.15 μm). Hypercubes containing images at 300 wavelengths separated by 0.3 cm 1 were obtained in 12 s. High spectral resolution chemical imaging of methanol vapor was demonstrated for both static and dynamic systems. The system was also used to image and characterize multiple component liquid and solid samples.

  1. Comparison of UV-B measurements performed with a Brewer spectrophotometer and a new UVB-1 broad band detector

    NASA Technical Reports Server (NTRS)

    Bais, Alkiviadis F.; Zerefos, Christos S.; Meleti, Charicleia; Ziomas, Ioannis C.

    1994-01-01

    Measurements of the UV-B erythemal dose, based on solar spectra acquired with a Brewer spectrophotometer at Thessaloniki, Greece, are compared to measurements performed with the recently introduced, by the Yankee Environmental Systems, (Robertson type) broad band solar UV-B detector. The spectral response function of this detector, when applied to the Brewer spectral UV-B measurements, results in remarkably comparable estimates of the erythemal UV-B dose. The two instruments provide similar information on the UV-B dose when they are cross-examined under a variety of meteorological and atmospheric conditions and over the a large range of solar zenith angles and total ozone.

  2. Generation of broad ion beams in sources based on Penning system with nonequipotential cathode

    NASA Astrophysics Data System (ADS)

    Nikulin, S. P.; Chichigin, D. F.; Tretnikov, P. V.

    2004-05-01

    A method of generation of uniform plasma in low-pressure glow discharges with oscillating electrons has been developed. The method is based on the separation of the cathode into several elements, with potentials of the parts being different. Experimental results show that the use of the nonequipotential cathode in the Penning system enables effective control of spatial plasma distribution. This makes it possible to obtain nearly uniform ion emission current distributions and to form broad beams. Two variants of ion sources are under investigation. The first source generates low energy (˜1 keV) ions, which are often used for cleaning of surfaces. A treated target plays a role in one of the cathodes and acceleration of ions is realized directly in the cathode sheath. The required level of ion energy is provided by applying a corresponding voltage between the target and the anode of the system. The second source generates an ion beam with higher (several tens of keV) energy. Accelerating-decelerating ion optics is used in this variant. The efficiency of ion extraction, defined as the ratio of beam and discharge currents, is equal to 30%.

  3. Gravitational microlensing of a reverberating quasar broad-line region - I. Method and qualitative results

    NASA Astrophysics Data System (ADS)

    Garsden, H.; Bate, N. F.; Lewis, G. F.

    2011-12-01

    The kinematics and morphology of the broad emission-line region (BELR) of quasars are the subject of significant debate. The two leading methods for constraining BELR properties are microlensing and reverberation mapping. Here we combine these two methods with a study of the microlensing behaviour of the BELR in Q2237+0305, as a change in continuum emission (a 'flare') passes through it. Beginning with some generic models of the BELR - sphere, bicones, disc - we slice in velocity and time to produce brightness profiles of the BELR over the duration of the flare. These are numerically microlensed to determine whether microlensing of reverberation mapping provides new information about the properties of BELRs. We describe our method and show images of the models as they are flaring, and the unlensed and lensed spectra that are produced. Qualitative results and a discussion of the spectra are given in this paper, highlighting some effects that could be observed. Our conclusion is that the influence of microlensing, while not strong, can produce significant observable effects that will help in differentiating the properties of BELRs. Research undertaken as part of the Commonwealth Cosmology Initiative (CCI: ), an international collaboration supported by the Australian Research Council.

  4. Identification of a novel family of carbohydrate-binding modules with broad ligand specificity

    PubMed Central

    Duan, Cheng-Jie; Feng, Yu-Liang; Cao, Qi-Long; Huang, Ming-Yue; Feng, Jia-Xun

    2016-01-01

    Most enzymes that act on carbohydrates include non-catalytic carbohydrate-binding modules (CBMs) that recognize and target carbohydrates. CBMs bring their appended catalytic modules into close proximity with the target substrate and increase the hydrolytic rate of enzymes acting on insoluble substrates. We previously identified a novel CBM (CBMC5614-1) at the C-terminus of endoglucanase C5614-1 from an uncultured microorganism present in buffalo rumen. In the present study, that the functional region of CBMC5614-1 involved in ligand binding was localized to 134 amino acids. Two representative homologs of CBMC5614-1, sharing the same ligand binding profile, targeted a range of β-linked polysaccharides that adopt very different conformations. Targeted substrates included soluble and insoluble cellulose, β-1,3/1,4-mixed linked glucans, xylan, and mannan. Mutagenesis revealed that three conserved aromatic residues (Trp-380, Tyr-411, and Trp-423) play an important role in ligand recognition and targeting. These results suggest that CBMC5614-1 and its homologs form a novel CBM family (CBM72) with a broad ligand-binding specificity. CBM72 members can provide new insight into CBM-ligand interactions and may have potential in protein engineering and biocatalysis. PMID:26765840

  5. Multihapten approach leading to a sensitive ELISA with broad cross-reactivity to microcystins and nodularin.

    PubMed

    Samdal, Ingunn A; Ballot, Andreas; Løvberg, Kjersti E; Miles, Christopher O

    2014-07-15

    Microcystins (MCs) are a group of biotoxins (>150) produced by cyanobacteria, with a worldwide distribution. MCs are hepatotoxic, and acute exposure causes severe liver damage in humans and animals. Rapid and cheap methods of analysis are therefore required to protect people and livestock, especially in developing countries. To include as many MCs as possible in a single analysis, we developed a new competitive ELISA. Ovine polyclonal antibodies were raised using an immunogen made by conjugating a mixture of microcystins to cationised bovine serum albumin, and the plate-coating antigen was prepared by conjugating [Asp3]MC-RY to ovalbumin. This strategy was used also to minimize specificity for particular microcystin congeners. Cross-reactivity studies indicate that the ELISA has broad specificity to microcystins and also detects nodularin, providing a sensitive and rapid analytical method for screening large numbers of samples. The limit of quantitation for microcystins in drinking water is 0.04 μg/L, well below the WHO's maximum recommendation of 1 μg/L. The ELISA can be used for quantifying total microcystins in various matrices, including drinking water, cyanobacterial cultures, extracts, and algal blooms, and may be useful in detecting metabolites and conjugates of MCs. PMID:24941031

  6. Analytical evaluation of the impact of broad specification fuels on high bypass turbofan engine combustors

    NASA Technical Reports Server (NTRS)

    Taylor, J. R.

    1979-01-01

    Six conceptual combustor designs for the CF6-50 high bypass turbofan engine and six conceptual combustor designs for the NASA/GE E3 high bypass turbofan engine were analyzed to provide an assessment of the major problems anticipated in using broad specification fuels in these aircraft engine combustion systems. Each of the conceptual combustor designs, which are representative of both state-of-the-art and advanced state-of-the-art combustion systems, was analyzed to estimate combustor performance, durability, and pollutant emissions when using commercial Jet A aviation fuel and when using experimental referee board specification fuel. Results indicate that lean burning, low emissions double annular combustor concepts can accommodate a wide range of fuel properties without a serious deterioration of performance or durability. However, rich burning, single annular concepts would be less tolerant to a relaxation of fuel properties. As the fuel specifications are relaxed, autoignition delay time becomes much smaller which presents a serious design and development problem for premixing-prevaporizing combustion system concepts.

  7. A Lactobacillus plantarum Esterase Active on a Broad Range of Phenolic Esters

    PubMed Central

    Esteban-Torres, María; Landete, José María; Reverón, Inés; Santamaría, Laura; de las Rivas, Blanca

    2015-01-01

    Lactobacillus plantarum is the lactic acid bacterial species most frequently found in the fermentation of food products of plant origin on which phenolic compounds are abundant. L. plantarum strains showed great flexibility in their ability to adapt to different environments and growth substrates. Of 28 L. plantarum strains analyzed, only cultures from 7 strains were able to hydrolyze hydroxycinnamic esters, such as methyl ferulate or methyl caffeate. As revealed by PCR, only these seven strains possessed the est_1092 gene. When the est_1092 gene was introduced into L. plantarum WCFS1 or L. lactis MG1363, their cultures acquired the ability to degrade hydroxycinnamic esters. These results support the suggestion that Est_1092 is the enzyme responsible for the degradation of hydroxycinnamic esters on the L. plantarum strains analyzed. The Est_1092 protein was recombinantly produced and biochemically characterized. Surprisingly, Est_1092 was able to hydrolyze not only hydroxycinnamic esters, since all the phenolic esters assayed were hydrolyzed. Quantitative PCR experiments revealed that the expression of est_1092 was induced in the presence of methyl ferulate, an hydroxycinnamic ester, but was inhibited on methyl gallate, an hydroxybenzoic ester. As Est_1092 is an enzyme active on a broad range of phenolic esters, simultaneously possessing feruloyl esterase and tannase activities, its presence on some L. plantarum strains provides them with additional advantages to survive and grow on plant environments. PMID:25746986

  8. Electrostatic force microscopy as a broadly applicable method for characterizing pyroelectric materials.

    PubMed

    Martin-Olmos, Cristina; Stieg, Adam Z; Gimzewski, James K

    2012-06-15

    A general method based on the combination of electrostatic force microscopy with thermal cycling of the substrate holder is presented for direct, nanoscale characterization of the pyroelectric effect in a range of materials and sample configurations using commercial atomic force microscope systems. To provide an example of its broad applicability, the technique was applied to the examination of natural tourmaline gemstones. The method was validated using thermal cycles similar to those experienced in ambient conditions, where the induced pyroelectric response produced localized electrostatic surface charges whose magnitude demonstrated a correlation with the iron content and heat dissipation of each gemstone variety. In addition, the surface charge was shown to persist even at thermal equilibrium. This behavior is attributed to constant, stochastic cooling of the gemstone surface through turbulent contact with the surrounding air and indicates a potential utility for energy harvesting in applications including environmental sensors and personal electronics. In contrast to previously reported methods, ours has a capacity to carry out such precise nanoscale measurements with little or no restriction on the sample of interest, and represents a powerful new tool for the characterization of pyroelectric materials and devices. PMID:22595697

  9. MoS2-InGaZnO Heterojunction Phototransistors with Broad Spectral Responsivity.

    PubMed

    Yang, Jaehyun; Kwak, Hyena; Lee, Youngbin; Kang, Yu-Seon; Cho, Mann-Ho; Cho, Jeong Ho; Kim, Yong-Hoon; Jeong, Seong-Jun; Park, Seongjun; Lee, Hoo-Jeong; Kim, Hyoungsub

    2016-04-01

    We introduce an amorphous indium-gallium-zinc-oxide (a-IGZO) heterostructure phototransistor consisting of solution-based synthetic molybdenum disulfide (few-layered MoS2, with a band gap of ∼1.7 eV) and sputter-deposited a-IGZO (with a band gap of ∼3.0 eV) films as a novel sensing element with a broad spectral responsivity. The MoS2 and a-IGZO films serve as a visible light-absorbing layer and a high mobility channel layer, respectively. Spectroscopic measurements reveal that appropriate band alignment at the heterojunction provides effective transfer of the visible light-induced electrons generated in the few-layered MoS2 film to the underlying a-IGZO channel layer with a high carrier mobility. The photoresponse characteristics of the a-IGZO transistor are extended to cover most of the visible range by forming a heterojunction phototransistor that harnesses a visible light responding MoS2 film with a small band gap prepared through a large-area synthetic route. The MoS2-IGZO heterojunction phototransistors exhibit a photoresponsivity of approximately 1.7 A/W at a wavelength of 520 nm (an optical power of 1 μW) with excellent time-dependent photoresponse dynamics. PMID:26989951

  10. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design.

    PubMed

    Burton, Dennis R; Hangartner, Lars

    2016-05-20

    HIV employs multiple means to evade the humoral immune response, particularly the elicitation of and recognition by broadly neutralizing antibodies (bnAbs). Such antibodies can act antivirally against a wide spectrum of viruses by targeting relatively conserved regions on the surface HIV envelope trimer spike. Elicitation of and recognition by bnAbs are hindered by the arrangement of spikes on virions and the relatively difficult access to bnAb epitopes on spikes, including the proximity of variable regions and a high density of glycans. Yet, in a small proportion of HIV-infected individuals, potent bnAb responses do develop, and isolation of the corresponding monoclonal antibodies has been facilitated by identification of favorable donors with potent bnAb sera and by development of improved methods for human antibody generation. Molecular studies of recombinant Env trimers, alone and in interaction with bnAbs, are providing new insights that are fueling the development and testing of promising immunogens aimed at the elicitation of bnAbs. PMID:27168247

  11. Co-Gradient Variation in Growth Rate and Development Time of a Broadly Distributed Butterfly

    PubMed Central

    Barton, Madeleine; Sunnucks, Paul; Norgate, Melanie; Murray, Neil; Kearney, Michael

    2014-01-01

    Widespread species often show geographic variation in thermally-sensitive traits, providing insight into how species respond to shifts in temperature through time. Such patterns may arise from phenotypic plasticity, genetic adaptation, or their interaction. In some cases, the effects of genotype and temperature may act together to reduce, or to exacerbate, phenotypic variation in fitness-related traits across varying thermal environments. We find evidence for such interactions in life-history traits of Heteronympha merope, a butterfly distributed across a broad latitudinal gradient in south-eastern Australia. We show that body size in this butterfly is negatively related to developmental temperature in the laboratory, in accordance with the temperature-size rule, but not in the field, despite very strong temperature gradients. A common garden experiment on larval thermal responses, spanning the environmental extremes of H. merope's distribution, revealed that butterflies from low latitude (warmer climate) populations have relatively fast intrinsic growth and development rates compared to those from cooler climates. These synergistic effects of genotype and temperature across the landscape (co-gradient variation) are likely to accentuate phenotypic variation in these traits, and this interaction must be accounted for when predicting how H. merope will respond to temperature change through time. These results highlight the importance of understanding how variation in life-history traits may arise in response to environmental change. Without this knowledge, we may fail to detect whether organisms are tracking environmental change, and if they are, whether it is by plasticity, adaptation or both. PMID:24743771

  12. Toward broad-band x-ray detected ferromagnetic resonance in longitudinal geometry

    SciTech Connect

    Ollefs, K.; Meckenstock, R.; Spoddig, D.; Römer, F. M.; Hassel, Ch.; Schöppner, Ch.; Farle, M.; Ney, V.; Ney, A.

    2015-06-14

    An ultrahigh-vacuum-compatible setup for broad-band X-ray detected ferromagnetic resonance (XFMR) in longitudinal geometry is introduced which relies on a low-power, continuous-wave excitation of the ferromagnetic sample. A simultaneous detection of the conventional ferromagnetic resonance via measuring the reflected microwave power and the XFMR signal of the X-ray absorption is possible. First experiments on the Fe and Co L{sub 3}-edges of a permalloy film covered with Co nanostripes as well as the Fe and Ni K-edges of a permalloy film are presented and discussed. Two different XFMR signals are found, one of which is independent of the photon energy and therefore does not provide element-selective information. The other much weaker signal is element-selective, and the dynamic magnetic properties could be detected for Fe and Co separately. The dependence of the latter XFMR signal on the photon helicity of the synchrotron light is found to be distinct from the usual x-ray magnetic circular dichroism effect.

  13. AAV ANCESTRAL RECONSTRUCTION LIBRARY ENABLES SELECTION OF BROADLY INFECTIOUS VIRAL VARIANTS

    PubMed Central

    Santiago-Ortiz, Jorge; Ojala, David S.; Westesson, Oscar; Weinstein, John R.; Wong, Sophie Y.; Steinsapir, Andrew; Kumar, Sanjay; Holmes, Ian; Schaffer, David V.

    2015-01-01

    Adeno-associated virus (AAV) vectors have achieved clinical efficacy in treating several diseases. Enhanced vectors are required to extend these landmark successes to other indications, however, and protein engineering approaches may provide the necessary vector improvements to address such unmet medical needs. To generate new capsid variants with potentially enhanced infectious properties, and to gain insights into AAV’s evolutionary history, we computationally designed and experimentally constructed a putative ancestral AAV library. Combinatorial variations at 32 amino acid sites were introduced to account for uncertainty in their identities. We then analyzed the evolutionary flexibility of these residues, the majority of which have not been previously studied, by subjecting the library to iterative selection on a representative cell line panel. The resulting variants exhibited transduction efficiencies comparable to the most efficient extant serotypes, and in general ancestral libraries were broadly infectious across the cell line panel, indicating that they favored promiscuity over specificity. Interestingly, putative ancestral AAVs were more thermostable than modern serotypes and did not utilize sialic acids, galactose, or heparan sulfate proteoglycans for cellular entry. Finally, variants mediated 19–31 fold higher gene expression in muscle compared to AAV1, a clinically utilized serotype for muscle delivery, highlighting their promise for gene therapy. PMID:26186661

  14. Screening of recombinant glycosyltransferases reveals the broad acceptor specificity of stevia UGT-76G1.

    PubMed

    Dewitte, Griet; Walmagh, Maarten; Diricks, Margo; Lepak, Alexander; Gutmann, Alexander; Nidetzky, Bernd; Desmet, Tom

    2016-09-10

    UDP-glycosyltransferases (UGTs) are a promising class of biocatalysts that offer a sustainable alternative for chemical glycosylation of natural products. In this study, we aimed to characterize plant-derived UGTs from the GT-1 family with an emphasis on their acceptor promiscuity and their potential application in glycosylation processes. Recombinant expression in E. coli provided sufficient amounts of enzyme for the in-depth characterization of the salicylic acid UGT from Capsella rubella (UGT-SACr) and the stevia UGT from Stevia rebaudiana (UGT-76G1Sr). The latter was found to have a remarkably broad specificity with activities on a wide diversity of structures, from aliphatic and branched alcohols, over small phenolics to larger flavonoids, terpenoids and even higher glycoside compounds. As an example for its industrial potential, the glycosylation of curcumin was thoroughly evaluated. Under optimized conditions, 96% of curcumin was converted within 24h into the corresponding curcumin β-glycosides. In addition, the reaction was performed in a coupled system with sucrose synthase from Glycine max, to enable the cost-efficient (re)generation of UDP-Glc from sucrose as abundant and renewable resource. PMID:27378621

  15. Inhibition of infection-mediated preterm birth by administration of broad spectrum chemokine inhibitor in mice.

    PubMed

    Shynlova, Oksana; Dorogin, Anna; Li, Yunqing; Lye, Stephen

    2014-09-01

    Preterm birth (PTB) is the single most important cause of perinatal and infant mortality worldwide. Maternal infection can result in PTB. We investigated the ability of a Broad Spectrum Chemokine Inhibitor (BSCI) to prevent infection-induced PTB in mice. PTB was initiated in pregnant mice by intraperitoneal injection of lipopolysaccharide (LPS; 50 μg). Half the mice received BSCI (10 mg/kg) 24 hrs prior to and immediately before LPS administration. The impact of LPS alone or LPS plus BSCI was assessed on (i) injection-to-delivery interval, foetal survival rate, placental and neonates' weight; (ii) amniotic fluid and maternal plasma cytokine levels (by Luminex assay); foetal and maternal tissue cytokine gene expression levels (by Real-Time RT-PCR); (iii) immune cells infiltration into the uterine tissue (by stereological immunohistochemistry). Pre-treatment with BSCI (i) decreased LPS-induced PTB (64% versus 100%, P < 0.05); (ii) significantly attenuated cytokine/chemokine expression in maternal tissues (plasma, liver, myometrium, decidua); (iii) significantly decreased neutrophil infiltration in the mouse myometrium. BSCI-treated mice in which PTB was delayed till term had live foetuses with normal placental and foetal weight. BSCI represents a promising new class of therapeutics for PTB. In a mouse model of preterm labour, BCSI suppresses systemic inflammation in maternal tissues which resulted in the reduced incidence of LPS-mediated PTB. These data provide support for efforts to target inflammatory responses as a means of preventing PTB. PMID:24894878

  16. AAV ancestral reconstruction library enables selection of broadly infectious viral variants.

    PubMed

    Santiago-Ortiz, J; Ojala, D S; Westesson, O; Weinstein, J R; Wong, S Y; Steinsapir, A; Kumar, S; Holmes, I; Schaffer, D V

    2015-12-01

    Adeno-associated virus (AAV) vectors have achieved clinical efficacy in treating several diseases. However, enhanced vectors are required to extend these landmark successes to other indications and protein engineering approaches may provide the necessary vector improvements to address such unmet medical needs. To generate new capsid variants with potentially enhanced infectious properties and to gain insights into AAV's evolutionary history, we computationally designed and experimentally constructed a putative ancestral AAV library. Combinatorial variations at 32 amino acid sites were introduced to account for uncertainty in their identities. We then analyzed the evolutionary flexibility of these residues, the majority of which have not been previously studied, by subjecting the library to iterative selection on a representative cell line panel. The resulting variants exhibited transduction efficiencies comparable to the most efficient extant serotypes and, in general, ancestral libraries were broadly infectious across the cell line panel, indicating that they favored promiscuity over specificity. Interestingly, putative ancestral AAVs were more thermostable than modern serotypes and did not use sialic acids, galactose or heparan sulfate proteoglycans for cellular entry. Finally, variants mediated 19- to 31-fold higher gene expression in the muscle compared with AAV1, a clinically used serotype for muscle delivery, highlighting their promise for gene therapy. PMID:26186661

  17. New gammaproteobacteria associated with blood-feeding leeches and a broad phylogenetic analysis of leech endosymbionts.

    PubMed

    Perkins, Susan L; Budinoff, Rebecca B; Siddall, Mark E

    2005-09-01

    Many monophagous animals have coevolutionary relationships with bacteria that provide unavailable nutrients to the host. Frequently, these microbial partners are vertically inherited and reside in specialized structures or tissues. Here we report three new lineages of bacterial symbionts of blood-feeding leeches, one from the giant Amazonian leech, Haementeria ghilianii, and two others from Placobdelloides species. These hosts each possess a different mycetome or esophageal organ morphology where the bacterial cells are located. DNA sequencing of the bacterial 16S rRNA genes and fluorescent in situ hybridization placed these symbionts in two separate clades in the class Gammaproteobacteria. We also conducted a broad phylogenetic analysis of the herein-reported DNA sequences as well as others from bacterial symbionts reported elsewhere in the literature, including alphaproteobacterial symbionts from the leech genus Placobdella as well as Aeromonas veronii from the medicinal leech, Hirudo medicinalis, and a Rickettsia sp. detected in Hemiclepsis marginata. Combined, these results indicate that blood-feeding leeches have forged bacterial partnerships at least five times during their evolutionary history. PMID:16151107

  18. Streptolysin S of Streptococcus anginosus exhibits broad-range hemolytic activity.

    PubMed

    Asam, Daniela; Mauerer, Stefanie; Spellerberg, Barbara

    2015-04-01

    Streptococcus anginosus is a commensal of mucous membranes and an emerging human pathogen. Some strains, including the type strain, display a prominent β-hemolytic phenotype. A gene cluster (sag), encoding a variant of streptolysin S (SLS) has recently been identified as the genetic background for β-hemolysin production in S. anginosus. In this study, we further characterized the hemolytic and cytolytic activity of the S. anginosus hemolysin in comparison with other streptococcal hemolysins. The results indicate that SLS of S. anginosus is a broad-range hemolysin able to lyse erythrocytes of different species, including horse, bovine, rabbit and even chicken. The hemolytic activity is temperature dependent, and a down-regulation of the hemolysin expression is induced in the presence of high glucose levels. Survival assays indicate that in contrast to other streptococcal species, S. anginosus does not require SLS for survival in the presence of human granulocytes. Cross-complementation studies using the sagB and sagD genes of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis demonstrated functional similarities to the S. anginosus SLS. Nevertheless, distinct differences to other streptolysin S variants were noted and provide further insights into the molecular mechanisms of SLS pathogen host interactions. PMID:25381594

  19. Efficacy of broadly neutralizing monoclonal antibody PG16 in HIV-infected humanized mice.

    PubMed

    Stoddart, Cheryl A; Galkina, Sofiya A; Joshi, Pheroze; Kosikova, Galina; Long, Brian R; Maidji, Ekaterina; Moreno, Mary E; Rivera, Jose M; Sanford, Ukina R; Sloan, Barbara; Cieplak, Witold; Wrin, Terri; Chan-Hui, Po-Ying

    2014-08-01

    Highly potent broadly neutralizing human monoclonal antibodies hold promise for HIV prophylaxis and treatment. We used the SCID-hu Thy/Liv and BLT humanized mouse models to study the efficacy of these antibodies, primarily PG16, against HIV-1 clades A, B, and C. PG16 targets a conserved epitope in the V1/V2 region of gp120 common to 70-80% of HIV-1 isolates from multiple clades and has extremely potent in vitro activity against HIVJR-CSF. PG16 was highly efficacious in SCID-hu mice as a single intraperitoneal administration the day before inoculation of R5-tropic HIV directly into their Thy/Liv implants and demonstrated even greater efficacy if PG16 administration was continued after Thy/Liv implant HIV inoculation. However, PG16 as monotherapy had no activity in humanized mice with established R5-tropic HIV infection. These results provide evidence of tissue penetration of the antibodies, which could aid in their ability to prevent infection if virus crosses the mucosal barrier. PMID:24971704

  20. Efficacy of Broadly Neutralizing Monoclonal Antibody PG16 in HIV-infected Humanized Mice

    PubMed Central

    Stoddart, Cheryl A.; Galkina, Sofiya A.; Joshi, Pheroze; Kosikova, Galina; Long, Brian R.; Maidji, Ekaterina; Moreno, Mary E.; Rivera, Jose M.; Sanford, Ukina R.; Sloan, Barbara; Cieplak, Witold; Wrin, Terri; Chan-Hui, Po-Ying

    2014-01-01

    Highly potent broadly neutralizing human monoclonal antibodies hold promise for HIV prophylaxis and treatment. We used the SCID-hu Thy/Liv and BLT humanized mouse models to study the efficacy of these antibodies, primarily PG16, against HIV-1 clade A, B, and C. PG16 targets a conserved epitope in the V1/V2 region of gp120 common to 70–80% of HIV-1 isolates from multiple clades and has extremely potent in vitro activity against HIVJR-CSF. PG16 was highly efficacious in SCID-hu mice as a single intraperitoneal administration the day before inoculation of R5-tropic HIV-1 directly into their Thy/Liv implants and demonstrated even greater efficacy if PG16 administration was continued after Thy/Liv implant HIV-1 infection. However, PG16 as monotherapy had no activity in humanized mice with established R5-tropic HIV-1 infection. These results provide evidence of tissue penetration of the antibodies, which could aid in their ability to prevent infection if virus crosses the mucosal barrier. PMID:24971704