Multifunctional Nature of the Arenavirus RING Finger Protein Z

PubMed Central

Fehling, Sarah Katharina; Lennartz, Frank; Strecker, Thomas

2012-01-01

Arenaviruses are a family of enveloped negative-stranded RNA viruses that can cause severe human disease ranging from encephalitis symptoms to fulminant hemorrhagic fever. The bi‑segmented RNA genome encodes four polypeptides: the nucleoprotein NP, the surface glycoprotein GP, the polymerase L, and the RING finger protein Z. Although it is the smallest arenavirus protein with a length of 90 to 99 amino acids and a molecular weight of approx. 11 kDa, the Z protein has multiple functions in the viral life cycle including (i) regulation of viral RNA synthesis, (ii) orchestration of viral assembly and budding, (iii) interaction with host cell proteins, and (iv) interferon antagonism. In this review, we summarize our current understanding of the structural and functional role of the Z protein in the arenavirus replication cycle. PMID:23202512

Arenavirus budding resulting from viral-protein-associated cell membrane curvature

PubMed Central

Schley, David; Whittaker, Robert J.; Neuman, Benjamin W.

2013-01-01

Viral replication occurs within cells, with release (and onward infection) primarily achieved through two alternative mechanisms: lysis, in which virions emerge as the infected cell dies and bursts open; or budding, in which virions emerge gradually from a still living cell by appropriating a small part of the cell membrane. Virus budding is a poorly understood process that challenges current models of vesicle formation. Here, a plausible mechanism for arenavirus budding is presented, building on recent evidence that viral proteins embed in the inner lipid layer of the cell membrane. Experimental results confirm that viral protein is associated with increased membrane curvature, whereas a mathematical model is used to show that localized increases in curvature alone are sufficient to generate viral buds. The magnitude of the protein-induced curvature is calculated from the size of the amphipathic region hypothetically removed from the inner membrane as a result of translation, with a change in membrane stiffness estimated from observed differences in virion deformation as a result of protein depletion. Numerical results are based on experimental data and estimates for three arenaviruses, but the mechanisms described are more broadly applicable. The hypothesized mechanism is shown to be sufficient to generate spontaneous budding that matches well both qualitatively and quantitatively with experimental observations. PMID:23864502

Mining a Kröhnke Pyridine Library for Anti-Arenavirus Activity.

PubMed

Miranda, Pedro O; Cubitt, Beatrice; Jacob, Nicholas T; Janda, Kim D; de la Torre, Juan C

2018-05-11

Several arenaviruses cause hemorrhagic fever (HF) disease in humans and represent important public health problems in their endemic regions. In addition, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus is a neglected human pathogen of clinical significance. There are no licensed arenavirus vaccines, and current antiarenavirus therapy is limited to an off-label use of ribavirin that is only partially effective. Therefore, there is an unmet need for novel therapeutics to combat human pathogenic arenaviruses, a task that will be facilitated by the identification of compounds with antiarenaviral activity that could serve as probes to identify arenavirus-host interactions suitable for targeting, as well as lead compounds to develop future antiarenaviral drugs. Screening of a combinatorial library of Krönhke pyridines identified compound KP-146 [(5-(5-(2,3-dihydrobenzo[ b][1,4] dioxin-6-yl)-4'-methoxy-[1,1'-biphenyl]-3-yl)thiophene-2-carboxamide] as having strong anti-lymphocytic choriomeningitis virus (LCMV) activity in cultured cells. KP-146 did not inhibit LCMV cell entry but rather interfered with the activity of the LCMV ribonucleoprotein (vRNP) responsible for directing virus RNA replication and gene transcription, as well as with the budding process mediated by the LCMV matrix Z protein. LCMV variants with increased resistance to KP-146 did not emerge after serial passages in the presence of KP-146. Our findings support the consideration of Kröhnke pyridine scaffold as a valuable source to identify compounds that could serve as tools to dissect arenavirus-host interactions, as well as lead candidate structures to develop antiarenaviral drugs.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Kun; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou; Lin, Xian-Dan

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 acidmore » (>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.« less

Biological roles and functional mechanisms of arenavirus Z protein in viral replication.

PubMed

Wang, Jialong; Danzy, Shamika; Kumar, Naveen; Ly, Hinh; Liang, Yuying

2012-09-01

Arenaviruses can cause severe hemorrhagic fever diseases in humans, with limited prophylactic or therapeutic measures. A small RING-domain viral protein Z has been shown to mediate the formation of virus-like particles and to inhibit viral RNA synthesis, although its biological roles in an infectious viral life cycle have not been directly addressed. By taking advantage of the available reverse genetics system for a model arenavirus, Pichinde virus (PICV), we provide the direct evidence for the essential biological roles of the Z protein's conserved residues, including the G2 myristylation site, the conserved C and H residues of RING domain, and the poorly characterized C-terminal L79 and P80 residues. Dicodon substitutions within the late (L) domain (PSAPPYEP) of the PICV Z protein, although producing viable mutant viruses, have significantly reduced virus growth, a finding suggestive of an important role for the intact L domain in viral replication. Further structure-function analyses of both PICV and Lassa fever virus Z proteins suggest that arenavirus Z proteins have similar molecular mechanisms in mediating their multiple functions, with some interesting variations, such as the role of the G2 residue in blocking viral RNA synthesis. In summary, our studies have characterized the biological roles of the Z protein in an infectious arenavirus system and have shed important light on the distinct functions of its domains in virus budding and viral RNA regulation, the knowledge of which may lead to the development of novel antiviral drugs.

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

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

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. Inclusion body disease (IBD) is a common infectious disease of captive snakes. IBD is fatal and can cause the loss of entire animal collections. The cause of the disease has remained elusive, and no treatment exists. In addition to being important to pet owners, veterinarians, breeders, zoological parks, and aquariums, the study of animal disease is significant since animals are the source of

Replication of boid inclusion body disease-associated arenaviruses is temperature sensitive in both boid and mammalian cells.

PubMed

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

2015-01-15

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. 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 demonstrated in

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

2012-10-12

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.

Detection of novel divergent arenaviruses in boid snakes with inclusion body disease in The Netherlands.

PubMed

Bodewes, R; Kik, M J L; Raj, V Stalin; Schapendonk, C M E; Haagmans, B L; Smits, S L; Osterhaus, A D M E

2013-06-01

Arenaviruses are bi-segmented negative-stranded RNA viruses, which were until recently only detected in rodents and humans. Now highly divergent arenaviruses have been identified in boid snakes with inclusion body disease (IBD). Here, we describe the identification of a new species and variants of the highly divergent arenaviruses, which were detected in tissues of captive boid snakes with IBD in The Netherlands by next-generation sequencing. Phylogenetic analysis of the complete sequence of the open reading frames of the four predicted proteins of one of the detected viruses revealed that this virus was most closely related to the recently identified Golden Gate virus, while considerable sequence differences were observed between the highly divergent arenaviruses detected in this study. These findings add to the recent identification of the highly divergent arenaviruses in boid snakes with IBD in the United States and indicate that these viruses also circulate among boid snakes in Europe.

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

PubMed

Oppliger, Joel; da Palma, Joel Ramos; Burri, Dominique J; Bergeron, Eric; Khatib, Abdel-Majid; Spiropoulou, Christina F; Pasquato, Antonella; Kunz, Stefan

2016-01-15

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. Arenaviruses are important emerging human pathogens that can cause severe hemorrhagic fevers with high mortality in humans. A crucial step in productive arenavirus infection of human

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

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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A new arenavirus in a cluster of fatal transplant-associated diseases.

PubMed

Palacios, Gustavo; Druce, Julian; Du, Lei; Tran, Thomas; Birch, Chris; Briese, Thomas; Conlan, Sean; Quan, Phenix-Lan; Hui, Jeffrey; Marshall, John; Simons, Jan Fredrik; Egholm, Michael; Paddock, Christopher D; Shieh, Wun-Ju; Goldsmith, Cynthia S; Zaki, Sherif R; Catton, Mike; Lipkin, W Ian

2008-03-06

Three patients who received visceral-organ transplants from a single donor on the same day died of a febrile illness 4 to 6 weeks after transplantation. Culture, polymerase-chain-reaction (PCR) and serologic assays, and oligonucleotide microarray analysis for a wide range of infectious agents were not informative. We evaluated RNA obtained from the liver and kidney transplant recipients. Unbiased high-throughput sequencing was used to identify microbial sequences not found by means of other methods. The specificity of sequences for a new candidate pathogen was confirmed by means of culture and by means of PCR, immunohistochemical, and serologic analyses. High-throughput sequencing yielded 103,632 sequences, of which 14 represented an Old World arenavirus. Additional sequence analysis showed that this new arenavirus was related to lymphocytic choriomeningitis viruses. Specific PCR assays based on a unique sequence confirmed the presence of the virus in the kidneys, liver, blood, and cerebrospinal fluid of the recipients. Immunohistochemical analysis revealed arenavirus antigen in the liver and kidney transplants in the recipients. IgM and IgG antiviral antibodies were detected in the serum of the donor. Seroconversion was evident in serum specimens obtained from one recipient at two time points. Unbiased high-throughput sequencing is a powerful tool for the discovery of pathogens. The use of this method during an outbreak of disease facilitated the identification of a new arenavirus transmitted through solid-organ transplantation. Copyright 2008 Massachusetts Medical Society.

Antibodies to the Glycoprotein GP2 Subunit Cross-React between Old and New World Arenaviruses.

PubMed

Amanat, Fatima; Duehr, James; Oestereich, Lisa; Hastie, Kathryn M; Ollmann Saphire, Erica; Krammer, Florian

2018-01-01

Arenaviruses pose a major public health threat and cause numerous infections in humans each year. Although most viruses belonging to this family do not cause disease in humans, some arenaviruses, such as Lassa virus and Machupo virus, are the etiological agents of lethal hemorrhagic fevers. The absence of a currently licensed vaccine and the highly pathogenic nature of these viruses both make the necessity of developing viable vaccines and therapeutics all the more urgent. Arenaviruses have a single glycoprotein on the surface of virions, the glycoprotein complex (GPC), and this protein can be used as a target for vaccine development. Here, we describe immunization strategies to generate monoclonal antibodies (MAbs) that cross-react between the glycoprotein complexes of both Old World and New World arenaviruses. Several monoclonal antibodies isolated from immunized mice were highly cross-reactive, binding a range of Old World arenavirus glycoproteins, including that of Lassa virus. One such monoclonal antibody, KL-AV-2A1, bound to GPCs of both New World and Old World viruses, including Lassa and Machupo viruses. These cross-reactive antibodies bound to epitopes present on the glycoprotein 2 subunit of the glycoprotein complex, which is relatively conserved among arenaviruses. Monoclonal antibodies binding to these epitopes, however, did not inhibit viral entry as they failed to neutralize a replication-competent vesicular stomatitis virus pseudotyped with the Lassa virus glycoprotein complex in vitro In addition, no protection from virus challenge was observed in in vivo mouse models. Even so, these monoclonal antibodies might still prove to be useful in the development of clinical and diagnostic assays. IMPORTANCE Several viruses in the Arenaviridae family infect humans and cause severe hemorrhagic fevers which lead to high case fatality rates. Due to their pathogenicity and geographic tropisms, these viruses remain very understudied. As a result, an effective

No measurable adverse effects of Lassa, Morogoro and Gairo arenaviruses on their rodent reservoir host in natural conditions.

PubMed

Mariën, Joachim; Borremans, Benny; Gryseels, Sophie; Soropogui, Barré; De Bruyn, Luc; Bongo, Gédéon Ngiala; Becker-Ziaja, Beate; de Bellocq, Joëlle Goüy; Günther, Stephan; Magassouba, N'Faly; Leirs, Herwig; Fichet-Calvet, Elisabeth

2017-04-27

In order to optimize net transmission success, parasites are hypothesized to evolve towards causing minimal damage to their reservoir host while obtaining high shedding rates. For many parasite species however this paradigm has not been tested, and conflicting results have been found regarding the effect of arenaviruses on their rodent host species. The rodent Mastomys natalensis is the natural reservoir host of several arenaviruses, including Lassa virus that is known to cause Lassa haemorrhagic fever in humans. Here, we examined the effect of three arenaviruses (Gairo, Morogoro and Lassa virus) on four parameters of wild-caught Mastomys natalensis: body mass, head-body length, sexual maturity and fertility. After correcting for the effect of age, we compared these parameters between arenavirus-positive (arenavirus RNA or antibody) and negative animals using data from different field studies in Guinea (Lassa virus) and Tanzania (Morogoro and Gairo viruses). Although the sample sizes of our studies (1297, 749 and 259 animals respectively) were large enough to statistically detect small differences in body conditions, we did not observe any adverse effects of these viruses on Mastomys natalensis. We did find that sexual maturity was significantly positively related with Lassa virus antibody presence until a certain age, and with Gairo virus antibody presence in general. Gairo virus antibody-positive animals were also significantly heavier and larger than antibody-free animals. Together, these results suggest that the pathogenicity of arenaviruses is not severe in M. natalensis, which is likely to be an adaptation of these viruses to optimize transmission success. They also suggest that sexual behaviour might increase the probability of M. natalensis to become infected with arenaviruses.

Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Infections

DTIC Science & Technology

1987-10-01

observed with free MTP-PE. In addition to our observations on peritoneal and alveolar macrophages, we also examined the effect of MTP-PE treatment on liver...Ir OIC FILE COPY C2 ILn 00 NM AD _____ N SELECTIVE TARGETING OF ANTIVIRAL AND IMMUNOMODULATING AGENTS IN THE TREATMENT OF ARENAVIRUS INFECTIONS "Kc...Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Injections 12. PERSONAL AUTHOR(S) J. David Gangemi 13a. TYPE OF

Arenaviruses. Genes, proteins, and expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oldstone, M.B.A.

1987-01-01

This book provides a discussion of current knowledge on Arenaviruses. These viruses are the cause of major health problems, such as Lassa fever and Junin virus disease, and have been the Rosetta stone on which many of the major concepts in viral pathogenesis and immunobiology have been built. For example, study of lymphocytic choriomeningitis naturally and experimentally induced infection in the normal mouse host presented the scientific community with the first and definitive work on the following topics: virus induced immune response disease, immunologic tolerance, virus induced immune complex disease, presence and generation of cytotoxic T cells in vitro andmore » in vivo, H-2 restriction and dual recognition phenomena, and viral disease induced by altering physiologic or differential functions of a cell without causing alterations of house keeping or vital functions, i.e. pathology in the absence of cell or tissue lysis.« less

Differential Immune Responses to New World and Old World Mammalian Arenaviruses

PubMed Central

Ly, Hinh

2017-01-01

Some New World (NW) and Old World (OW) mammalian arenaviruses are emerging, zoonotic viruses that can cause lethal hemorrhagic fever (HF) infections in humans. While these are closely related RNA viruses, the infected hosts appear to mount different types of immune responses against them. Lassa virus (LASV) infection, for example, results in suppressed immune function in progressive disease stage, whereas patients infected with Junín virus (JUNV) develop overt pro-inflammatory cytokine production. These viruses have also evolved different molecular strategies to evade host immune recognition and activation. This paper summarizes current progress in understanding the differential immune responses to pathogenic arenaviruses and how the information can be exploited toward the development of vaccines against them. PMID:28498311

Influence of climate change on the incidence and impact of arenavirus diseases: a speculative assessment.

PubMed

Clegg, J C

2009-06-01

The current worldwide incidence of viral haemorrhagic fevers caused by arenaviruses is briefly reviewed. The recently published Assessment Report of the Intergovernmental Panel on Climate Change has described the changes in global climate that are expected to occur over the course of the present century and beyond. Climate modelling and forecasting have not yet reached the stage where confident predictions of regional changes at the level of a virus endemic area can be made. However, in the regions where pathogenic arenaviruses now circulate, significant effects are likely to include increases in surface temperature, changes in the extent and distribution of rainfall, the occurrence of extreme weather events, glacier retreat, and coastal flooding as a result of sea level rise. The possible impact of these changes on the geographical location and the incidence of arenavirus diseases and its human impact are discussed.

A Cell-Cell Fusion Assay to Assess Arenavirus Envelope Glycoprotein Membrane-Fusion Activity.

PubMed

York, Joanne; Nunberg, Jack H

2018-01-01

For many viruses that enter their target cells through pH-dependent fusion of the viral and endosomal membranes, cell-cell fusion assays can provide an experimental platform for investigating the structure-function relationships that promote envelope glycoprotein membrane-fusion activity. Typically, these assays employ effector cells expressing the recombinant envelope glycoprotein on the cell surface and target cells engineered to quantitatively report fusion with the effector cell. In the protocol described here, Vero cells are transfected with a plasmid encoding the arenavirus envelope glycoprotein complex GPC and infected with the vTF7-3 vaccinia virus expressing the bacteriophage T7 RNA polymerase. These effector cells are mixed with target cells infected with the vCB21R-lacZ vaccinia virus encoding a β-galactosidase reporter under the control of the T7 promoter. Cell-cell fusion is induced upon exposure to low-pH medium (pH 5.0), and the resultant expression of the β-galactosidase reporter is quantitated using a chemiluminescent substrate. We have utilized this robust microplate cell-cell fusion assay extensively to study arenavirus entry and its inhibition by small-molecule fusion inhibitors.

Evolutionary analysis of Old World arenaviruses reveals a major adaptive contribution of the viral polymerase.

PubMed

Pontremoli, Chiara; Forni, Diego; Cagliani, Rachele; Pozzoli, Uberto; Riva, Stefania; Bravo, Ignacio G; Clerici, Mario; Sironi, Manuela

2017-10-01

The Old World (OW) arenavirus complex includes several species of rodent-borne viruses, some of which (i.e., Lassa virus, LASV and Lymphocytic choriomeningitis virus, LCMV) cause human diseases. Most LCMV and LASV infections are caused by rodent-to-human transmissions. Thus, viral evolution is largely determined by events that occur in the wildlife reservoirs. We used a set of human- and rodent-derived viral sequences to investigate the evolutionary history underlying OW arenavirus speciation, as well as the more recent selective events that accompanied LASV spread in West Africa. We show that the viral RNA polymerase (L protein) was a major positive selection target in OW arenaviruses and during LASV out-of-Nigeria migration. No evidence of selection was observed for the glycoprotein, whereas positive selection acted on the nucleoprotein (NP) during LCMV speciation. Positively selected sites in L and NP are surrounded by highly conserved residues, and the bulk of the viral genome evolves under purifying selection. Several positively selected sites are likely to modulate viral replication/transcription. In both L and NP, structural features (solvent exposed surface area) are important determinants of site-wise evolutionary rate variation. By incorporating several rodent-derived sequences, we also performed an analysis of OW arenavirus codon adaptation to the human host. Results do not support a previously hypothesized role of codon adaptation in disease severity for non-Nigerian strains. In conclusion, L and NP represent the major selection targets and possible determinants of disease presentation; these results suggest that field surveys and experimental studies should primarily focus on these proteins. © 2017 John Wiley & Sons Ltd.

Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses.

PubMed

Clark, Lars E; Mahmutovic, Selma; Raymond, Donald D; Dilanyan, Taleen; Koma, Takaaki; Manning, John T; Shankar, Sundaresh; Levis, Silvana C; Briggiler, Ana M; Enria, Delia A; Wucherpfennig, Kai W; Paessler, Slobodan; Abraham, Jonathan

2018-05-14

While five arenaviruses cause human hemorrhagic fevers in the Western Hemisphere, only Junin virus (JUNV) has a vaccine. The GP1 subunit of their envelope glycoprotein binds transferrin receptor 1 (TfR1) using a surface that substantially varies in sequence among the viruses. As such, receptor-mimicking antibodies described to date are type-specific and lack the usual breadth associated with this mode of neutralization. Here we isolate, from the blood of a recipient of the live attenuated JUNV vaccine, two antibodies that cross-neutralize Machupo virus with varying efficiency. Structures of GP1-Fab complexes explain the basis for efficient cross-neutralization, which involves avoiding receptor mimicry and targeting a conserved epitope within the receptor-binding site (RBS). The viral RBS, despite its extensive sequence diversity, is therefore a target for cross-reactive antibodies with activity against New World arenaviruses of public health concern.

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

Unpaired 5' ppp-nucleotides, as found in arenavirus double-stranded RNA panhandles, are not recognized by RIG-I.

PubMed

Marq, Jean-Baptiste; Kolakofsky, Daniel; Garcin, Dominique

2010-06-11

Arenavirus and bunyavirus RNA genomes are unusual in that they are found in circular nucleocapsids, presumably due to the annealing of their complementary terminal sequences. Moreover, arenavirus genome synthesis initiates with GTP at position +2 of the template rather than at the precise 3' end (position +1). After formation of a dinucleotide, 5' pppGpC(OH) is then realigned on the template before this primer is extended. The net result of this "prime and realign" mechanism of genome initiation is that 5' pppG is found as an unpaired 5' nucleotide when the complementary genome ends anneal to form a double-stranded (dsRNA) panhandle. Using 5' pppRNA made in vitro and purified so that all dsRNA side products are absent, we have determined that both this 5' nucleotide overhang, as well as mismatches within the dsRNA (as found in some arenavirus genomes), clearly reduce the ability of these model dsRNAs to induce interferon upon transfection into cells. The presence of this unpaired 5' ppp-nucleotide is thus another way that some viruses appear to use to avoid detection by cytoplasmic pattern recognition receptors.

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

Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression

PubMed Central

Kalkavan, Halime; Sharma, Piyush; Kasper, Stefan; Helfrich, Iris; Pandyra, Aleksandra A.; Gassa, Asmae; Virchow, Isabel; Flatz, Lukas; Brandenburg, Tim; Namineni, Sukumar; Heikenwalder, Mathias; Höchst, Bastian; Knolle, Percy A.; Wollmann, Guido; von Laer, Dorothee; Drexler, Ingo; Rathbun, Jessica; Cannon, Paula M.; Scheu, Stefanie; Bauer, Jens; Chauhan, Jagat; Häussinger, Dieter; Willimsky, Gerald; Löhning, Max; Schadendorf, Dirk; Brandau, Sven; Schuler, Martin; Lang, Philipp A.; Lang, Karl S.

2017-01-01

Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV) and the clinically used Junin virus vaccine (Candid#1) preferentially replicate in tumour cells in a variety of murine and human cancer models. Viral replication leads to prolonged local immune activation, rapid regression of localized and metastatic cancers, and long-term disease control. Mechanistically, LCMV induces antitumour immunity, which depends on the recruitment of interferon-producing Ly6C+ monocytes and additionally enhances tumour-specific CD8+ T cells. In comparison with other clinically evaluated oncolytic viruses and to PD-1 blockade, LCMV treatment shows promising antitumoural benefits. In conclusion, therapeutically administered arenavirus replicates in cancer cells and induces tumour regression by enhancing local immune responses. PMID:28248314

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

York, Joanne; Agnihothram, Sudhakar S.; Romanowski, Victor

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,more » 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.« less

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

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

PubMed

McLay, Lisa; Liang, Yuying; Ly, Hinh

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.

Myristoylation of the Arenavirus Envelope Glycoprotein Stable Signal Peptide Is Critical for Membrane Fusion but Dispensable for Virion Morphogenesis.

PubMed

York, Joanne; Nunberg, Jack H

2016-09-15

Arenaviruses are responsible for severe and often fatal hemorrhagic disease. In the absence of effective antiviral therapies and vaccines, these viruses pose serious threats to public health and biodefense. Arenaviruses enter the host cell by fusion of the viral and endosomal membranes, a process mediated by the virus envelope glycoprotein GPC. Unlike other class I viral fusion proteins, GPC retains its stable signal peptide (SSP) as an essential third subunit in the mature complex. SSP spans the membrane twice and is myristoylated at its cytoplasmic N terminus. Mutations that abolish SSP myristoylation have been shown to reduce pH-induced cell-cell fusion activity of ectopically expressed GPC to ∼20% of wild-type levels. In order to examine the role of SSP myristoylation in the context of the intact virus, we used reverse genetics to generate Junín viruses (Candid #1 isolate) in which the critical glycine-2 residue in SSP was either replaced by alanine (G2A) or deleted (ΔG2). These mutant viruses produced smaller foci of infection in Vero cells and showed an ∼5-fold reduction in specific infectivity, commensurate with the defect in cell-cell fusion. However, virus assembly and GPC incorporation into budded virions were unaffected. Our findings suggest that the myristate moiety is cryptically disposed in the prefusion GPC complex and may function late in the fusion process to promote merging of the viral and cellular membranes. Hemorrhagic fever arenaviruses pose significant threats to public health and biodefense. Arenavirus entry into the host cell is promoted by the virus envelope glycoprotein GPC. Unlike other viral envelope glycoproteins, GPC contains a myristoylated stable signal peptide (SSP) as an essential third subunit. Myristoylation has been shown to be important for the membrane fusion activity of recombinantly expressed GPC. Here, we use reverse genetics to study the role of SSP myristoylation in the context of the intact virion. We find that

Status of arenavirus vaccines and their application

PubMed Central

Johnson, Karl M.

1975-01-01

A limited but definite need exists for vaccines against Lassa, Junin, and Machupo viruses. Medical and laboratory personnel, as well as defined high-risk population groups, require protection from these highly virulent agents. To date little work has been done on inactivated vaccines for these viruses. A live attenuated Junin vaccine has been tested successfully in more than 600 persons, and a high-passage Machupo virus strain has protected rhesus monkeys against lethal infection produced by a homologous field strain. Work has been initiated on possible heterologous protection induced by infection or antigenic stimulation with arenaviruses not pathogenic for man. Crucial for the eventual development of effective vaccines are the construction of more maximum security laboratories and the further elucidation of the experimental and natural biology of the agents in lower animals and man. PMID:182407

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

Arenavirus Budding: A Common Pathway with Mechanistic Differences

PubMed Central

Wolff, Svenja; Ebihara, Hideki; Groseth, Allison

2013-01-01

The Arenaviridae is a diverse and growing family of viruses that includes several agents responsible for important human diseases. Despite the importance of this family for public health, particularly in Africa and South America, much of its biology remains poorly understood. However, in recent years significant progress has been made in this regard, particularly relating to the formation and release of new enveloped virions, which is an essential step in the viral lifecycle. While this process is mediated chiefly by the viral matrix protein Z, recent evidence suggests that for some viruses the nucleoprotein (NP) is also required to enhance the budding process. Here we highlight and compare the distinct budding mechanisms of different arenaviruses, concentrating on the role of the matrix protein Z, its known late domain sequences, and the involvement of cellular endosomal sorting complex required for transport (ESCRT) pathway components. Finally we address the recently described roles for the nucleoprotein NP in budding and ribonucleoprotein complex (RNP) incorporation, as well as discussing possible mechanisms related to its involvement. PMID:23435234

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burri, Dominique J.; Pasquato, Antonella; Ramos da Palma, Joel

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 trimersmore » 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.« less

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.

The flexible C-terminal arm of the Lassa arenavirus Z-protein mediates interactions with multiple binding partners.

PubMed

May, Eric R; Armen, Roger S; Mannan, Aristotle M; Brooks, Charles L

2010-08-01

The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation, and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics (MD) was used to refine the structures, which were then subsequently clustered. Population-weighted ensembles of low-energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was identified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during MD trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein-binding recognition motifs for Tsg101 and eIF4E and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. (c) 2010 Wiley-Liss, Inc.

The Flexible C-terminal Arm of the Lassa Arenavirus Z-Protein Mediates Interactions with Multiple Binding Partners

PubMed Central

May, Eric R.; Armen, Roger S.; Mannan, Aristotle M.; Brooks, Charles L.

2010-01-01

The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics were employed to refine the structures, which were then subsequently clustered. Population weighted ensembles of low energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was indentified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during molecular dynamics trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein binding recognition motifs for Tsg101 and eIF4E, and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. PMID:20544962

Visualization of Arenavirus RNA Species in Individual Cells by Single-Molecule Fluorescence In Situ Hybridization Suggests a Model of Cyclical Infection and Clearance during Persistence.

PubMed

King, Benjamin R; Samacoits, Aubin; Eisenhauer, Philip L; Ziegler, Christopher M; Bruce, Emily A; Zenklusen, Daniel; Zimmer, Christophe; Mueller, Florian; Botten, Jason

2018-06-15

Lymphocytic choriomeningitis mammarenavirus (LCMV) is an enveloped, negative-strand RNA virus that causes serious disease in humans but establishes an asymptomatic, lifelong infection in reservoir rodents. Different models have been proposed to describe how arenaviruses regulate the replication and transcription of their bisegmented, single-stranded RNA genomes, particularly during persistent infection. However, these models were based largely on viral RNA profiling data derived from entire populations of cells. To better understand LCMV replication and transcription at the single-cell level, we established a high-throughput, single-molecule fluorescence in situ hybridization (smFISH) image acquisition and analysis pipeline and examined viral RNA species at discrete time points from virus entry through the late stages of persistent infection in vitro We observed the transcription of viral nucleoprotein and polymerase mRNAs from the incoming S and L segment genomic RNAs, respectively, within 1 h of infection, whereas the transcription of glycoprotein mRNA from the S segment antigenome required ∼4 to 6 h. This confirms the temporal separation of viral gene expression expected due to the ambisense coding strategy of arenaviruses and also suggests that antigenomic RNA contained in virions is not transcriptionally active upon entry. Viral replication and transcription peaked at 36 h postinfection, followed by a progressive loss of viral RNAs over the next several days. During persistence, the majority of cells showed repeating cyclical waves of viral transcription and replication followed by the clearance of viral RNA. Thus, our data support a model of LCMV persistence whereby infected cells can spontaneously clear infection and become reinfected by viral reservoir cells that remain in the population. IMPORTANCE Arenaviruses are human pathogens that can establish asymptomatic, lifelong infections in their rodent reservoirs. Several models have been proposed to explain

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

PubMed

Hayward, Alexander; Grabherr, Manfred; Jern, Patric

2013-12-10

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.

T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections.

PubMed

Furuta, Yousuke; Takahashi, Kazumi; Shiraki, Kimiyasu; Sakamoto, Kenichi; Smee, Donald F; Barnard, Dale L; Gowen, Brian B; Julander, Justin G; Morrey, John D

2009-06-01

A series of pyrazinecarboxamide derivatives T-705 (favipiravir), T-1105 and T-1106 were discovered to be candidate antiviral drugs. These compounds have demonstrated good activity in treating viral infections in laboratory animals caused by various RNA viruses, including influenza virus, arenaviruses, bunyaviruses, West Nile virus (WNV), yellow fever virus (YFV), and foot-and-mouth disease virus (FMDV). Treatment has in some cases been effective when initiated up to 5-7 days after virus infection, when the animals already showed signs of illness. Studies on the mechanism of action of T-705 have shown that this compound is converted to the ribofuranosyltriphosphate derivative by host enzymes, and this metabolite selectively inhibits the influenza viral RNA-dependent RNA polymerase without cytotoxicity to mammalian cells. Interestingly, these compounds do not inhibit host DNA and RNA synthesis and inosine 5'-monophosphate dehydrogenase (IMPDH) activity. From in vivo studies using several animal models, the pyrazinecarboxamide derivatives were found to be effective in protecting animals from death, reducing viral burden, and limiting disease manifestations, even when treatment was initiated after virus inoculation. Importantly, T-705 imparts its beneficial antiviral effects without significant toxicity to the host. Prompt development of these compounds is expected to provide effective countermeasures against pandemic influenza virus and several bioweapon threats, all of which are of great global public health concern given the current paucity of highly effective broad-spectrum drugs.

Protective Effect of Anti-Phosphatidylserine Antibody in a Guinea Pig Model of Advanced Hemorrhagic Arenavirus Infection.

PubMed

Thomas, John M; Thorpe, Philip E

2017-01-01

Host derived markers on virally infected cells or virions may provide targets for the generation of antiviral agents. Recently, we identified phosphatidylserine (PS) as a host marker of virions and virally-infected cells. Under normal physiological conditions, PS is maintained on the inner leaflet of the plasma membrane facing the cytosol. Following viral infection, activation or pre-apoptotic changes cause PS to become externalized. We have previously shown that bavituximab, a chimeric human-mouse antibody that binds PS complexed with β2-glycoprotein I (β2GP1), protected rodents against lethal Pichinde virus and cytomegalovirus infections. Here, we determined the antiviral activity of a fully human monoclonal antibody, PGN632, that directly binds to PS. Treatment with PGN632 protected 20% of guinea pigs with advanced infections of the hemorrhagic arenavirus, Pichinde, from death. Combining PGN632 with ribavirin improved the antiviral activity of both agents, such that the combination rescued 50% of animals from death. The major mechanisms of action of PGN632 appear to be opsonization of virus and antibody-dependent cellular cytotoxicity of virally-infected cells. PS-targeting agents may have utility in the treatment of viral diseases.

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

Serological evidence of arenavirus circulation among fruit bats in Trinidad.

PubMed

Malmlov, Ashley; Seetahal, Janine; Carrington, Christine; Ramkisson, Vernie; Foster, Jerome; Miazgowicz, Kerri L; Quackenbush, Sandra; Rovnak, Joel; Negrete, Oscar; Munster, Vincent; Schountz, Tony

2017-01-01

Tacaribe virus (TCRV) was isolated in the 1950s from artibeus bats captured on the island of Trinidad. The initial characterization of TCRV suggested that artibeus bats were natural reservoir hosts. However, nearly 60 years later experimental infections of Jamaican fruit bats (Artibeus jamaicensis) resulted in fatal disease or clearance, suggesting artibeus bats may not be a reservoir host. To further evaluate the TCRV reservoir host status of artibeus bats, we captured bats of six species in Trinidad for evidence of infection. Bats of all four fruigivorous species captured had antibodies to TCRV nucleocapsid, whereas none of the insectivore or nectarivore species did. Many flat-faced fruit-eating bats (A. planirostris) and great fruit-eating bats (A. literatus) were seropositive by ELISA and western blot to TCRV nucleocapsid antigen, as were two of four Seba's fruit bats (Carollia perspicillata) and two of three yellow-shouldered fruit bats (Sturnira lilium). Serum neutralization tests failed to detect neutralizing antibodies to TCRV from these bats. TCRV RNA was not detected in lung tissues or lung homogenates inoculated onto Vero cells. These data indicate that TCRV or a similar arenavirus continues to circulate among fruit bats of Trinidad but there was no evidence of persistent infection, suggesting artibeus bats are not reservoir hosts.

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

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

Activation of the RLR/MAVS Signaling Pathway by the L Protein of Mopeia Virus

PubMed Central

Zhang, Lei-Ke; Xin, Qi-Lin; Zhu, Sheng-Lin; Wan, Wei-Wei; Wang, Wei

2016-01-01

ABSTRACT The family Arenaviridae includes several important human pathogens that can cause severe hemorrhagic fever and greatly threaten public health. As a major component of the innate immune system, the RLR/MAVS signaling pathway is involved in recognizing viral components and initiating antiviral activity. It has been reported that arenavirus infection can suppress the innate immune response, and NP and Z proteins of pathogenic arenaviruses can disrupt RLR/MAVS signaling, thus inhibiting production of type I interferon (IFN-I). However, recent studies have shown elevated IFN-I levels in certain arenavirus-infected cells. The mechanism by which arenavirus infection induces IFN-I responses remains unclear. In this study, we determined that the L polymerase (Lp) of Mopeia virus (MOPV), an Old World (OW) arenavirus, can activate the RLR/MAVS pathway and thus induce the production of IFN-I. This activation is associated with the RNA-dependent RNA polymerase activity of Lp. This study provides a foundation for further studies of interactions between arenaviruses and the innate immune system and for the elucidation of arenavirus pathogenesis. IMPORTANCE Distinct innate immune responses are observed when hosts are infected with different arenaviruses. It has been widely accepted that NP and certain Z proteins of arenaviruses inhibit the RLR/MAVS signaling pathway. The viral components responsible for the activation of the RLR/MAVS signaling pathway remain to be determined. In the current study, we demonstrate for the first time that the Lp of MOPV, an OW arenavirus, can activate the RLR/MAVS signaling pathway and thus induce the production of IFN-I. Based on our results, we proposed that dynamic interactions exist among Lp-produced RNA, NP, and the RLR/MAVS signaling pathway, and the outcome of these interactions may determine the final IFN-I response pattern: elevated or reduced. Our study provides a possible explanation for how IFN-I can become activated during

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…

Genomic and Biological Characterization of Aggressive and Docile Strains of LCMV Rescued from a Plasmid-Based Reverse Genetics System

PubMed Central

Chen, Minjie; Lan, Shuiyun; Ou, Rong; Price, Graeme E.; Jiang, Hong; de la Torre, Juan Carlos; Moskophidis, Demetrius

2008-01-01

Arenaviruses include several causative agents of hemorrhagic fever disease in humans. In addition, the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a superb model for the study of virus-host interactions, including the basis of viral persistence and associated diseases. The molecular mechanisms concerning the regulation and specific role of viral proteins in modulating arenavirus-host cell interactions associated either with an acute or persistent infection and associated disease remain little understood. Here we report the genomic and biological characterization of LCMV strains Docile (persistent) and Aggressive (not persistent) recovered from cloned cDNA via reverse genetics. Our results confirmed that the cloned viruses accurately recreated the in vivo phenotypes associated with the corresponding natural Docile and Aggressive viral isolates. In addition, we provide evidence that the ability of the Docile strain to persist is determined by the nature of both S and L RNA segments. Thus, our findings provide the foundation for studies aimed at gaining a detailed understanding of viral determinants of LCMV persistence in its natural host that may aid in the development of vaccines to prevent or treat the diseases caused by arenaviruses in humans. PMID:18474558

Molecular determinants of Pichinde virus infection of guinea pigs--a small animal model system for arenaviral hemorrhagic fevers.

PubMed

Liang, Yuying; Lan, Shuiyun; Ly, Hinh

2009-09-01

Arenaviruses are enveloped single-strand RNA viruses that mostly have natural hosts in rodents. Upon infection of humans, several arenaviruses can cause severe hemorrhagic fever diseases, including Lassa fever that is endemic in West Africa. The virulence mechanism of these deadly arenaviruses can be studied in a safe and economical small animal model-guinea pigs infected by a nonpathogenic arenavirus Pichinde virus (PICV), a virulent strain of which can cause similar disease syndromes in guinea pigs as arenaviral hemorrhagic fevers in humans. We have recently developed molecular clones for both the virulent and avirulent strains of PICV. Using the available reverse genetics tools, we are characterizing the molecular determinants of virulent arenavirus infections in vivo.

Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.

PubMed

Westover, Jonna B; Sefing, Eric J; Bailey, Kevin W; Van Wettere, Arnaud J; Jung, Kie-Hoon; Dagley, Ashley; Wandersee, Luci; Downs, Brittney; Smee, Donald F; Furuta, Yousuke; Bray, Mike; Gowen, Brian B

2016-02-01

Favipiravir is approved in Japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of RNA viruses, including Ebola. Ribavirin is the only other licensed drug with activity against multiple RNA viruses. Recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. Convalescent immune globulin is the only approved treatment for Argentine hemorrhagic fever caused by the rodent-borne Junin arenavirus. We previously reported that favipiravir is highly effective in a number of small animal models of Argentine hemorrhagic fever. We now report that addition of low dose of ribavirin synergistically potentiates the activity of favipiravir against Junin virus infection of guinea pigs and another arenavirus, Pichinde virus infection of hamsters. This suggests that the efficacy of favipiravir against hemorrhagic fever viruses can be further enhanced through the addition of low-dose ribavirin. Copyright © 2015 Elsevier B.V. All rights reserved.

[First evidence of lymphocytic choriomeningitis virus (Arenavirus) infection in Mus musculus rodents captured in the urban area of the municipality of Sincelejo, Sucre, Colombia].

PubMed

Castellar, Anais; Guevara, Marco; Rodas, Juan D; Londoño, Andrés F; Arroyave, Esteban; Díaz, Francisco J; Levis, Silvana; Blanco, Pedro J

2017-04-01

The lymphocytic choriomeningitis virus is an Old World arenavirus that infects Mus musculus, and can cause congenital hydrocephalus, chorioretinitis and multisystemic failure in transplant human recipients. Although the disease has not been clinically diagnosed in Colombia yet, there have been reports of infection with the Pichindé virus in rodents from Cauca and Valle del Cauca departments, and with the Guanarito virus in rodents from Córdoba department. To identify the lymphocytic choriomeningitis virus from Mus musculus captured in the municipality of Sincelejo. We evaluated 80 samples of plasma by ELISA using antigen from lymphocytic choriomeningitis virus. Additionally, a nested RT-PCR was performed to seropositive and seronegative samples for the S-segment. We found a 10% seroprevalence (8/80) and the viral genome was detected in 16 brain samples; the alignment (BLAST) and the phylogenetic analysis (MrBayes, version 3.2.2) confirmed the presence of the lymphocytic choriomeningitis virus. The results indicated that human infection with the lymphocytic choriomeningitis virus in humans could occur in the urban area of Sincelejo, although no cases have been reported so far.

Short double-stranded RNAs with an overhanging 5' ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys.

PubMed

Marq, Jean-Baptiste; Hausmann, Stéphane; Veillard, Nicolas; Kolakofsky, Daniel; Garcin, Dominique

2011-02-25

Arenavirus RNA genomes are initiated by a "prime and realign" mechanism, such that the initiating GTP is found as a single unpaired (overhanging) nucleotide when the complementary genome ends anneal to form double-stranded (ds) RNA panhandle structures. dsRNAs modeled on these structures do not induce interferon (IFN), as opposed to blunt-ended (5' ppp)dsRNA. This study examines whether these viral structures can also act as decoys, by trapping RIG-I in inactive dsRNA complexes. We examined the ability of various dsRNAs to activate the RIG-I ATPase (presumably a measure of helicase translocation on dsRNA) relative to their ability to induce IFN. We found that there is no simple relationship between these two properties, as if RIG-I can translocate on short dsRNAs without inducing IFN. Moreover, we found that (5' ppp)dsRNAs with a single unpaired 5' ppp-nucleotide can in fact competitively inhibit the ability of blunt-ended (5' ppp)dsRNAs to induce IFN when co-transfected into cells and that this inhibition is strongly dependent on the presence of the 5' ppp. In contrast, (5' ppp)dsRNAs with a single unpaired 5' ppp-nucleotide does not inhibit poly(I-C)-induced IFN activation, which is independent of the presence of a 5' ppp group.

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.

The C-terminal region of lymphocytic choriomeningitis virus nucleoprotein contains distinct and segregable functional domains involved in NP-Z interaction and counteraction of the type I interferon response.

PubMed

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

2011-12-01

Several arenaviruses cause hemorrhagic fever (HF) disease in humans that is associated with high morbidity and significant mortality. Arenavirus nucleoprotein (NP), the most abundant viral protein in infected cells and virions, encapsidates the viral genome RNA, and this NP-RNA complex, together with the viral L polymerase, forms the viral ribonucleoprotein (vRNP) that directs viral RNA replication and gene transcription. Formation of infectious arenavirus progeny requires packaging of vRNPs into budding particles, a process in which arenavirus matrix-like protein (Z) plays a central role. In the present study, we have characterized the NP-Z interaction for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). The LCMV NP domain that interacted with Z overlapped with a previously documented C-terminal domain that counteracts the host type I interferon (IFN) response. However, we found that single amino acid mutations that affect the anti-IFN function of LCMV NP did not disrupt the NP-Z interaction, suggesting that within the C-terminal region of NP different amino acid residues critically contribute to these two distinct and segregable NP functions. A similar NP-Z interaction was confirmed for the HF arenavirus Lassa virus (LASV). Notably, LCMV NP interacted similarly with both LCMV Z and LASV Z, while LASV NP interacted only with LASV Z. Our results also suggest the presence of a conserved protein domain within NP but with specific amino acid residues playing key roles in determining the specificity of NP-Z interaction that may influence the viability of reassortant arenaviruses. In addition, this NP-Z interaction represents a potential target for the development of antiviral drugs to combat human-pathogenic arenaviruses.

Broad-Enrich: functional interpretation of large sets of broad genomic regions.

PubMed

Cavalcante, Raymond G; Lee, Chee; Welch, Ryan P; Patil, Snehal; Weymouth, Terry; Scott, Laura J; Sartor, Maureen A

2014-09-01

Functional enrichment testing facilitates the interpretation of Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) data in terms of pathways and other biological contexts. Previous methods developed and used to test for key gene sets affected in ChIP-seq experiments treat peaks as points, and are based on the number of peaks associated with a gene or a binary score for each gene. These approaches work well for transcription factors, but histone modifications often occur over broad domains, and across multiple genes. To incorporate the unique properties of broad domains into functional enrichment testing, we developed Broad-Enrich, a method that uses the proportion of each gene's locus covered by a peak. We show that our method has a well-calibrated false-positive rate, performing well with ChIP-seq data having broad domains compared with alternative approaches. We illustrate Broad-Enrich with 55 ENCODE ChIP-seq datasets using different methods to define gene loci. Broad-Enrich can also be applied to other datasets consisting of broad genomic domains such as copy number variations. http://broad-enrich.med.umich.edu for Web version and R package. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever

PubMed Central

Golden, Joseph W.; Maes, Piet; Kwilas, Steven A.; Ballantyne, John

2016-01-01

ABSTRACT Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaviruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaviruses. In the present study, we produced arenavirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junín virus (JUNV), Machupo virus (MACV), and Guanarito virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT50), exceeded 5,000 against homologous viruses. Antisera against each targeted virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (∼30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenavirus immunotherapeutic. IMPORTANCE Arenaviruses are an important family of emerging viruses. In infected humans, convalescent-phase plasma containing neutralizing antibodies can

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

Crystal Structure of the Oligomeric Form of Lassa Virus Matrix Protein Z.

PubMed

Hastie, Kathryn M; Zandonatti, Michelle; Liu, Tong; Li, Sheng; Woods, Virgil L; Saphire, Erica Ollmann

2016-05-01

The arenavirus matrix protein Z is highly multifunctional and occurs in both monomeric and oligomeric forms. The crystal structure of a dodecamer of Z from Lassa virus, presented here, illustrates a ring-like structure with a highly basic center. Mutagenesis demonstrates that the dimeric interface within the dodecamer and a Lys-Trp-Lys triad at the center of the ring are important for oligomerization. This structure provides an additional template to explore the many functions of Z. The arenavirus Lassa virus causes hundreds of thousands of infections each year, many of which develop into fatal hemorrhagic fever. The arenavirus matrix protein Z is multifunctional, with at least four distinct roles. Z exists in both monomeric and oligomeric forms, each of which likely serves a specific function in the viral life cycle. Here we present the dodecameric form of Lassa virus Z and demonstrate that Z forms a "wreath" with a highly basic center. This structure and that of monomeric Z now provide a pair of critical templates by which the multiple roles of Z in the viral life cycle may be interpreted. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1.

PubMed

Mizenina, Olga; Hsu, Mayla; Jean-Pierre, Ninochka; Aravantinou, Meropi; Levendosky, Keith; Paglini, Gabriela; Zydowsky, Thomas M; Robbiani, Melissa; Fernández-Romero, José A

2017-12-01

We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs. Like other NNRTIs, MIV-150 has EC 50 values in the subnanomolar to nanomolar range against wild type and NNRTI or RT-resistant HIVs. While less potent than NNRTIs, ZA was shown to be active in primary cells against laboratory-adapted and primary HIV-1 isolates and HIV-1 isolates/clones with NNRTI and RT resistance mutations, with EC 50 values between 20 and 110 μM. The MIV-150/ZA combination had a potent and broad antiviral activity in primary cells. In vitro resistance selection studies revealed that previously described NNRTI-resistant mutations were selected by MIV-150. ZA-resistant virus retained susceptibility to MIV-150 (and other RTIs) and MIV-150-selected virus remained sensitive to ZA. Notably, resistant virus was not selected when cultured in the presence of both ZA and MIV-150. This underscores the potency and breadth of the MIV-150/ZA combination, supporting preclinical macaque studies and the advancement of MZC microbicides into clinical testing.

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-

Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever.

PubMed

Golden, Joseph W; Maes, Piet; Kwilas, Steven A; Ballantyne, John; Hooper, Jay W

2016-01-20

Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaviruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaviruses. In the present study, we produced arenavirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junín virus (JUNV), Machupo virus (MACV), and Guanarito virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT(50)), exceeded 5,000 against homologous viruses. Antisera against each targeted virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (∼30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenavirus immunotherapeutic. Arenaviruses are an important family of emerging viruses. In infected humans, convalescent-phase plasma containing neutralizing antibodies can mitigate the

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaing, C; Gardner, S

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 genomemore » 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.« less

Efficient budding of the tacaribe virus matrix protein z requires the nucleoprotein.

PubMed

Groseth, Allison; Wolff, Svenja; Strecker, Thomas; Hoenen, Thomas; Becker, Stephan

2010-04-01

The Z protein has been shown for several arenaviruses to serve as the viral matrix protein. As such, Z provides the principal force for the budding of virus particles and is capable of forming virus-like particles (VLPs) when expressed alone. For most arenaviruses, this activity has been shown to be linked to the presence of proline-rich late-domain motifs in the C terminus; however, for the New World arenavirus Tacaribe virus (TCRV), no such motif exists within Z. It was recently demonstrated that while TCRV Z is still capable of functioning as a matrix protein to induce the formation of VLPs, neither its ASAP motif, which replaces a canonical PT/SAP motif in related viruses, nor its YxxL motif is involved in budding, leading to the suggestion that TCRV uses a novel budding mechanism. Here we show that in comparison to its closest relative, Junin virus (JUNV), TCRV Z buds only weakly when expressed in isolation. While this budding activity is independent of the ASAP or YxxL motif, it is significantly enhanced by coexpression with the nucleoprotein (NP), an effect not seen with JUNV Z. Interestingly, both the ASAP and YxxL motifs of Z appear to be critical for the recruitment of NP into VLPs, as well as for the enhancement of TCRV Z-mediated budding. While it is known that TCRV budding remains dependent on the endosomal sorting complex required for transport, our findings provide further evidence that TCRV uses a budding mechanism distinct from that of other known arenaviruses and suggest an essential role for NP in this process.

Activation of the innate immune system provides broad-spectrum protection against influenza A viruses with pandemic potential in mice

PubMed Central

Lau, Yuk-Fai; Tang, Lay-Hoon; Ooi, Eng-Eong; Subbarao, Kanta

2010-01-01

The efficacy of a stabilized chemical analog of double-stranded ribonucleic acid (RNA), PIKA, as prophylaxis against infection with 5 different influenza A virus subtypes, including the 2009 swine-origin pandemic H1N1 virus, was evaluated in mice. Intranasal treatment with PIKA resulted in significant reduction of viral replication in the respiratory tract. The inhibitory effect was mediated by rapid infiltration of immune cells into the lungs, and production of inflammatory cytokines. While TLR3 is important for the optimal production of these inflammatory cytokines, inhibition of viral replication was still observed in TLR3−/− mice. In addition, a significant synergistic effect in inhibiting H5N1 virus replication was observed when PIKA was co-administered with oseltamivir. The broad-spectrum protection provided by PIKA makes it an attractive option for prophylaxis from infection with influenza A viruses. PMID:20667572

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

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…

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

Visual attention spreads broadly but selects information locally.

PubMed

Shioiri, Satoshi; Honjyo, Hajime; Kashiwase, Yoshiyuki; Matsumiya, Kazumichi; Kuriki, Ichiro

2016-10-19

Visual attention spreads over a range around the focus as the spotlight metaphor describes. Spatial spread of attentional enhancement and local selection/inhibition are crucial factors determining the profile of the spatial attention. Enhancement and ignorance/suppression are opposite effects of attention, and appeared to be mutually exclusive. Yet, no unified view of the factors has been provided despite their necessity for understanding the functions of spatial attention. This report provides electroencephalographic and behavioral evidence for the attentional spread at an early stage and selection/inhibition at a later stage of visual processing. Steady state visual evoked potential showed broad spatial tuning whereas the P3 component of the event related potential showed local selection or inhibition of the adjacent areas. Based on these results, we propose a two-stage model of spatial attention with broad spread at an early stage and local selection at a later stage.

Mosaic H5 Hemagglutinin Provides Broad Humoral and Cellular Immune Responses against Influenza Viruses

PubMed Central

Kamlangdee, Attapon; Kingstad-Bakke, Brock

2016-01-01

ABSTRACT The most effective way to prevent influenza virus infection is via vaccination. However, the constant mutation of influenza viruses due to antigenic drift and shift compromises vaccine efficacy. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. Using the modified vaccinia Ankara (MVA) virus, we had previously generated a recombinant vaccine against highly pathogenic avian influenza virus (H5N1) based on an in silico mosaic approach. This MVA-H5M construct protected mice against multiple clades of H5N1 and H1N1 viruses. We have now further characterized the immune responses using immunodepletion of T cells and passive serum transfer, and these studies indicate that antibodies are the main contributors in homosubtypic protection (H5N1 clades). Compared to a MVA construct expressing hemagglutinin (HA) from influenza virus A/VN/1203/04 (MVA-HA), the MVA-H5M vaccine markedly increased and broadened B cell and T cell responses against H5N1 virus. The MVA-H5M also provided effective protection with no morbidity against H5N1 challenge, whereas MVA-HA-vaccinated mice showed clinical signs and experienced significant weight loss. In addition, MVA-H5M induced CD8+ T cell responses that play a major role in heterosubtypic protection (H1N1). Finally, expression of the H5M gene as either a DNA vaccine or a subunit protein protected mice against H5N1 challenge, indicating the effectiveness of the mosaic sequence without viral vectors for the development of a universal influenza vaccine. IMPORTANCE Influenza viruses infect up to one billion people around the globe each year and are responsible for 300,000 to 500,000 deaths annually. Vaccines are still the main intervention to prevent infection, but they fail to provide effective protection against heterologous strains of viruses. We developed broadly reactive H5N1 vaccine based on an in silico mosaic approach and previously

78 FR 20119 - Broad Stakeholder Survey

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-03

... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2012-0042] Broad Stakeholder Survey AGENCY... concerning the Broad Stakeholder Survey. DHS previously published this ICR in the Federal Register on August... across the Nation. The Broad Stakeholder Survey is designed to gather stakeholder feedback on the...

Broad-spectrum antibiotics in Norwegian hospitals.

PubMed

Holen, Øyunn; Alberg, Torunn; Blix, Hege Salvesen; Smith, Ingrid; Neteland, Marion Iren; Eriksen, Hanne Merete

2017-03-01

BACKGROUND One of the objectives in the action plan to reduce antimicrobial resistance in the health services in Norway is to reduce the use of broad-spectrum antibiotics in Norwegian hospitals. This study describes the use of certain broad-spectrum antibiotics mentioned in the action plan in Norwegian hospitals, and assesses prescribing practices in relation to the Norwegian guidelines for antibiotic use in hospitals.MATERIAL AND METHOD Data were analysed from a nationwide non-identifiable point prevalence survey in May 2016 where all systemic use of antibiotics was recorded.RESULTS Broad-spectrum antibiotics accounted for 33 % of all antibiotics prescribed. Altogether 84 % of all broad-spectrum antibiotics were prescribed as treatment, 8 % were for prophylactic use, and 8 % were classified as other/unknown. Lower respiratory tract infections were the most frequent indication for treatment with broad-spectrum antibiotics, involving 30 % of all broad-spectrum treatment.INTERPRETATION This point prevalence survey in Norwegian hospitals in spring 2016 indicates a possibility for reducing the use of broad-spectrum antibiotics in the treatment of lower respiratory tract infections and for prophylactic use. Reduction of healthcare-associated infections may also contribute.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guerras, E.; Mediavilla, E.; Jimenez-Vicente, J.

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}more » = 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.« less

Broad-Band Analysis of Polar Motion Excitations

NASA Astrophysics Data System (ADS)

Chen, J.

2016-12-01

Earth rotational changes, i.e. polar motion and length-of-day (LOD), are driven by two types of geophysical excitations: 1) mass redistribution within the Earth system, and 2) angular momentum exchange between the solid Earth (more precisely the crust) and other components of the Earth system. Accurate quantification of Earth rotational excitations has been difficult, due to the lack of global-scale observations of mass redistribution and angular momentum exchange. The over 14-years time-variable gravity measurements from the Gravity Recovery and Climate Experiment (GRACE) have provided a unique means for quantifying Earth rotational excitations from mass redistribution in different components of the climate system. Comparisons between observed Earth rotational changes and geophysical excitations estimated from GRACE, satellite laser ranging (SLR) and climate models show that GRACE-derived excitations agree remarkably well with polar motion observations over a broad-band of frequencies. GRACE estimates also suggest that accelerated polar region ice melting in recent years and corresponding sea level rise have played an important role in driving long-term polar motion as well. With several estimates of polar motion excitations, it is possible to estimate broad-band noise variance and noise power spectra in each, given reasonable assumptions about noise independence. Results based on GRACE CSR RL05 solutions clearly outperform other estimates with the lowest noise levels over a broad band of frequencies.

Photoionization Modelling of the Giant Broad-Line Region in NGC 3998.

NASA Astrophysics Data System (ADS)

Devereux, Nicholas

2018-01-01

Prior high angular resolution spectroscopic observations of the low-ionization nuclear emission-line region in NGC 3998 obtained with the Space Telescope Imaging Spectrograph aboard the Hubble Space Telescope revealed a rich UV-visible spectrum consisting of broad permitted and broad forbidden emission lines. The photoionization code XSTAR is employed together with reddening-insensitive emission line diagnostics to constrain a dynamical model for the broad-line region (BLR) in NGC 3998. The BLR is modelled as a large H+ region ~ 7 pc in radius consisting of dust-free, low density ~ 104 cm-3, low metallicity ~ 0.01 Z/Z⊙ gas. Modelling the shape of the broad Hα emission line significantly discriminates between two independent measures of the black hole mass, favouring the estimate of de Francesco (2006). Interpreting the broad Hα emission line in terms of a steady-state spherically symmetric inflow leads to a mass inflow rate of 1.4 x 10-2 M⊙/yr, well within the present uncertainty of calculations that attempt to explain the observed X-ray emission in terms of an advection-dominated accretion flow (ADAF). Collectively, the model provides an explanation for the shape of the Hα emission line, the relative intensities and luminosities for the H Balmer, [OIII], and potentially several of the broad UV emission lines, as well as refining the initial conditions needed for future modelling of the ADAF.

Alveolar macrophages are critical for broadly-reactive antibody-mediated protection against influenza A virus in mice.

PubMed

He, Wenqian; Chen, Chi-Jene; Mullarkey, Caitlin E; Hamilton, Jennifer R; Wong, Christine K; Leon, Paul E; Uccellini, Melissa B; Chromikova, Veronika; Henry, Carole; Hoffman, Kevin W; Lim, Jean K; Wilson, Patrick C; Miller, Matthew S; Krammer, Florian; Palese, Peter; Tan, Gene S

2017-10-10

The aim of candidate universal influenza vaccines is to provide broad protection against influenza A and B viruses. Studies have demonstrated that broadly reactive antibodies require Fc-Fc gamma receptor interactions for optimal protection; however, the innate effector cells responsible for mediating this protection remain largely unknown. Here, we examine the roles of alveolar macrophages, natural killer cells, and neutrophils in antibody-mediated protection. We demonstrate that alveolar macrophages play a dominant role in conferring protection provided by both broadly neutralizing and non-neutralizing antibodies in mice. Our data also reveal the potential mechanisms by which alveolar macrophages mediate protection in vivo, namely antibody-induced inflammation and antibody-dependent cellular phagocytosis. This study highlights the importance of innate effector cells in establishing a broad-spectrum antiviral state, as well as providing a better understanding of how multiple arms of the immune system cooperate to achieve an optimal antiviral response following influenza virus infection or immunization.Broadly reactive antibodies that recognize influenza A virus HA can be protective, but the mechanism is not completely understood. Here, He et al. show that the inflammatory response and phagocytosis mediated by the interaction between protective antibodies and macrophages are essential for protection.

48 CFR 235.016 - Broad agency announcement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Broad agency announcement..., DEPARTMENT OF DEFENSE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 235.016 Broad... contained in broad agency announcements for exclusive competition among historically black colleges and...

48 CFR 235.016 - Broad agency announcement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Broad agency announcement..., DEPARTMENT OF DEFENSE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 235.016 Broad... contained in broad agency announcements for exclusive competition among historically black colleges and...

48 CFR 235.016 - Broad agency announcement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Broad agency announcement..., DEPARTMENT OF DEFENSE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 235.016 Broad... contained in broad agency announcements for exclusive competition among historically black colleges and...

48 CFR 235.016 - Broad agency announcement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Broad agency announcement..., DEPARTMENT OF DEFENSE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 235.016 Broad... contained in broad agency announcements for exclusive competition among historically black colleges and...

48 CFR 235.016 - Broad agency announcement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Broad agency announcement..., DEPARTMENT OF DEFENSE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 235.016 Broad... contained in broad agency announcements for exclusive competition among historically black colleges and...

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…

Establishing Normative Reference Values for Standing Broad Jump Among Hungarian Youth.

PubMed

Saint-Maurice, Pedro F; Laurson, Kelly R; Kaj, Mónika; Csányi, Tamás

2015-06-26

The purpose of this study was to examine age and sex trends in anaerobic power assessed by a standing broad jump and to determine norm-referenced values for youth in Hungary. A sample of 2,427 Hungarian youth (1,360 boys and 1,067 girls) completed the standing broad jump twice, and the highest distance score was recorded. Quantile regression was used to fit standing broad jump trends across linear and quadratic functions of age. Statistical significance was determined with bootstrap confidence intervals and the Wald test with p < .05. Age-by-sex specific centiles were generated and the 50th percentile was used to describe the overall patterns. Standing broad jump scores increased steadily in boys from age 11 through 18 years with a discrete plateau at the end of adolescence. Girls' standing broad jump scores of those who performed above the median increased with age and plateaued later in the adolescence. Both linear and quadratic age terms were statistically significant predictors of standing broad jump trends across age (p < .05), but the relations varied depending on the percentile. The 50th percentile values resulted in 147.0 cm, 162.0 cm, 175.0 cm, 186.0 cm, 195.0 cm, 202.0 cm, 207.0 cm, and 210.0 cm for boys aged 11 to 18 years old, respectively, and 140.0 cm, 143.9 cm, 147.3 cm, 150.0 cm, 152.1 cm, 153.7 cm, 154.6 cm, and 155.0 cm for girls aged 11 to 18 years old, respectively. This study provides normative reference charts that take into account age and sex differences in standing broad jump performance. The proposed reference values can be used to interpret standing broad jump scores in Hungarian youth.

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

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

PubMed

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

2016-03-01

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.

48 CFR 35.016 - Broad agency announcement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Broad agency announcement... CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 35.016 Broad agency announcement. (a) General. This paragraph prescribes procedures for the use of the broad agency announcement (BAA) with Peer or...

48 CFR 35.016 - Broad agency announcement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Broad agency announcement... CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 35.016 Broad agency announcement. (a) General. This paragraph prescribes procedures for the use of the broad agency announcement (BAA) with Peer or...

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... CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 35.016 Broad agency announcement. (a) General. This paragraph prescribes procedures for the use of the broad agency announcement (BAA) with Peer or...

48 CFR 35.016 - Broad agency announcement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Broad agency announcement... CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 35.016 Broad agency announcement. (a) General. This paragraph prescribes procedures for the use of the broad agency announcement (BAA) with Peer or...

Photoionization modelling of the giant broad-line region in NGC 3998

NASA Astrophysics Data System (ADS)

Devereux, Nick

2018-01-01

Prior high angular resolution spectroscopic observations of the Low-ionization nuclear emission-line region (Liner) in NGC 3998 obtained with the Space Telescope Imaging Spectrograph (STIS) aboard the Hubble Space Telescope (HST) revealed a rich UV-visible spectrum consisting of broad permitted and broad forbidden emission lines. The photoionization code XSTAR is employed together with reddening-insensitive emission line diagnostics to constrain a dynamical model for the broad-line region (BLR) in NGC 3998. The BLR is modelled as a large H+ region ∼ 7 pc in radius consisting of dust-free, low-density ∼ 104 cm-3, low-metallicity ∼ 0.01 Z/Z⊙ gas. Modelling the shape of the broad H α emission line significantly discriminates between two independent measures of the black hole (BH) mass, favouring the estimate of de Francesco, Capetti & Marconi (2006). Interpreting the broad H α emission line in terms of a steady-state spherically symmetric inflow leads to a mass inflow rate of 1.4 × 10-2 M⊙ yr-1, well within the present uncertainty of calculations that attempt to explain the observed X-ray emission in terms of an advection-dominated accretion flow (ADAF). Collectively, the model provides an explanation for the shape of the H α emission line, the relative intensities and luminosities for the H Balmer, [O III], and potentially several of the broad UV emission lines, as well as refining the initial conditions needed for future modelling of the ADAF.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hidalgo, Paola Rodriguez; Eracleous, Michael; Charlton, Jane

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 broadmore » 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.« less

Flat field concave holographic grating with broad spectral region and moderately high resolution.

PubMed

Wu, Jian Fen; Chen, Yong Yan; Wang, Tai Sheng

2012-02-01

In order to deal with the conflicts between broad spectral region and high resolution in compact spectrometers based on a flat field concave holographic grating and line array CCD, we present a simple and practical method to design a flat field concave holographic grating that is capable of imaging a broad spectral region at a moderately high resolution. First, we discuss the principle of realizing a broad spectral region and moderately high resolution. Second, we provide the practical method to realize our ideas, in which Namioka grating theory, a genetic algorithm, and ZEMAX are used to reach this purpose. Finally, a near-normal-incidence example modeled in ZEMAX is shown to verify our ideas. The results show that our work probably has a general applicability in compact spectrometers with a broad spectral region and moderately high resolution.

Using Mixed Methods to Assess Initiatives with Broad-Based Goals

ERIC Educational Resources Information Center

Inkelas, Karen Kurotsuchi

2017-01-01

This chapter describes a process for assessing programmatic initiatives with broad-ranging goals with the use of a mixed-methods design. Using an example of a day-long teaching development conference, this chapter provides practitioners step-by-step guidance on how to implement this assessment process.

Structural basis for antibody-mediated neutralization of Lassa virus.

PubMed

Hastie, Kathryn M; Zandonatti, Michelle A; Kleinfelter, Lara M; Heinrich, Megan L; Rowland, Megan M; Chandran, Kartik; Branco, Luis M; Robinson, James E; Garry, Robert F; Saphire, Erica Ollmann

2017-06-02

The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health. Copyright © 2017, American Association for the Advancement of Science.

77 FR 50144 - Broad Stakeholder Survey

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-20

... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2012-0042] Broad Stakeholder Survey AGENCY... Survey. DATES: Comments are encouraged and will be accepted until October 19, 2012. This process is.... The Broad Stakeholder Survey is designed to gather stakeholder feedback on the effectiveness of OEC...

Diversity among Tacaribe serocomplex viruses (family Arenaviridae) naturally associated with the Mexican woodrat (Neotoma mexicana)

PubMed Central

Cajimat, Maria N. B.; Milazzo, Mary Louise; Borchert, Jeff N.; Abbott, Ken D.; Bradley, Robert D.; Fulhorst, Charles F.

2008-01-01

The results of analyses of glycoprotein precursor and nucleocapsid protein gene sequences indicated that an arenavirus isolated from a Mexican woodrat (Neotoma mexicana) captured in Arizona is a strain of a novel species (proposed name Skinner Tank virus) and that arenaviruses isolated from Mexican woodrats captured in Colorado, New Mexico, and Utah are strains of Whitewater Arroyo virus or species phylogenetically closely related to Whitewater Arroyo virus. Pairwise comparisons of glycoprotein precursor sequences and nucleocapsid protein sequences revealed a high level of divergence among the viruses isolated from the Mexican woodrats captured in Colorado, New Mexico, and Utah and the Whitewater Arroyo virus prototype strain AV 9310135, which originally was isolated from a white-throated woodrat (Neotoma albigula) captured in New Mexico. Conceptually, the viruses from Colorado, New Mexico, and Utah and strain AV 9310135 could be grouped together in a species complex in the family Arenaviridae, genus Arenavirus. PMID:18304671

Acid-fast Smear and Histopathology Results Provide Guidance for the Appropriate Use of Broad-Range Polymerase Chain Reaction and Sequencing for Mycobacteria.

PubMed

Miller, Kennon; Harrington, Susan M; Procop, Gary W

2015-08-01

New molecular diagnostic tests are attractive because of the potential they hold for improving diagnostics in microbiology. The value of these tests, which is often assumed, should be investigated to determine the best use of these potentially powerful tools. To investigate the usefulness of broad-range polymerase chain reaction (PCR), followed by sequencing, in mycobacterial infections. We reviewed the test performance of acid-fast bacilli (AFB) PCR and traditional diagnostic methods (histopathology, AFB smear, and culture). We assessed the diagnostic effect and cost of the unrestricted ordering of broad-range PCR for the detection and identification of mycobacteria in clinical specimens. The AFB PCR was less sensitive than culture and histopathology and was less specific than culture, AFB smear, and histopathology. During 18 months, $93 063 was spent on 183 patient specimens for broad-range PCR and DNA sequencing for mycobacteria to confirm one culture-proven Mycobacterium tuberculosis infection that was also known to be positive by AFB smear and histopathology. In this cohort, there was a false-negative AFB PCR for M tuberculosis and a false-positive AFB PCR for Mycobacterium lentiflavum . Testing of AFB smear-negative specimens from patients without an inflammatory response supportive of a mycobacterial infection is costly and has not been proven to improve patient care. Traditional diagnostics (histopathology, AFB smear, and culture) should remain the primary methods for the detection of mycobacteria in clinical specimens.

Broad Consent for Research on Biospecimens: The Views of Actual Donors at Four U.S. Medical Centers.

PubMed

Warner, Teddy D; Weil, Carol J; Andry, Christopher; Degenholtz, Howard B; Parker, Lisa; Carithers, Latarsha J; Feige, Michelle; Wendler, David; Pentz, Rebecca D

2018-04-01

Commentators are concerned that broad consent may not provide biospecimen donors with sufficient information regarding possible future research uses of their tissue. We surveyed with interviews 302 cancer patients who had recently provided broad consent at four diverse academic medical centers. The majority of donors believed that the consent form provided them with sufficient information regarding future possible uses of their biospecimens. Donors expressed very positive views regarding tissue donation in general and endorsed the use of their biospecimens in future research across a wide range of contexts. Concerns regarding future uses were limited to for-profit research and research by investigators in other countries. These results support the use of broad consent to store and use biological samples in future research.

33 CFR 117.233 - Broad Creek.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Broad Creek. 117.233 Section 117.233 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Delaware § 117.233 Broad Creek. (a) The draw of the Conrail...

33 CFR 117.233 - Broad Creek.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Broad Creek. 117.233 Section 117.233 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Delaware § 117.233 Broad Creek. (a) The draw of the Conrail...

33 CFR 117.233 - Broad Creek.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Broad Creek. 117.233 Section 117.233 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Delaware § 117.233 Broad Creek. (a) The draw of the Conrail...

33 CFR 117.233 - Broad Creek.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Broad Creek. 117.233 Section 117.233 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Delaware § 117.233 Broad Creek. (a) The draw of the Conrail...

33 CFR 117.233 - Broad Creek.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Broad Creek. 117.233 Section 117.233 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Delaware § 117.233 Broad Creek. (a) The draw of the Conrail...

Phenolics and compartmentalization in the sapwood of broad-leaved trees

Treesearch

Kevin T. Smith

1997-01-01

Tree survival depends on the chemistry of phenolic compounds, a broad class of chemicals characterized by a hydroxylated benzene ring. In trees, phenolics occur frequently as polymers, acids, or glycosylated esters and perform diverse functions. For example, lignin, a phenylpropane heteropolymer, provides structural strength to wood. The induced production of phenols...

Self-Association of Lymphocytic Choriomeningitis Virus Nucleoprotein Is Mediated by Its N-Terminal Region and Is Not Required for Its Anti-Interferon Function

PubMed Central

Ortiz-Riaño, Emilio; Cheng, Benson Yee Hin

2012-01-01

Arenaviruses have a bisegmented, negative-strand RNA genome. Both the large (L) and small (S) genome segments use an ambisense coding strategy to direct the synthesis of two viral proteins. The L segment encodes the virus polymerase (L protein) and the matrix Z protein, whereas the S segment encodes the nucleoprotein (NP) and the glycoprotein precursor (GPC). NPs are the most abundant viral protein in infected cells and virions and encapsidate genomic RNA species to form an NP-RNA complex that, together with the virus L polymerase, forms the virus ribonucleoprotein (RNP) core capable of directing both replication and transcription of the viral genome. RNP formation predicts a self-association property of NPs. Here we document self-association (homotypic interaction) of the NP of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), as well as those of the hemorrhagic fever (HF) arenaviruses Lassa virus (LASV) and Machupo virus (MACV). We also show heterotypic interaction between NPs from both closely (LCMV and LASV) and distantly (LCMV and MACV) genetically related arenaviruses. LCMV NP self-association was dependent on the presence of single-stranded RNA and mediated by an N-terminal region of the NP that did not overlap with the previously described C-terminal NP domain involved in either counteracting the host type I interferon response or interacting with LCMV Z. PMID:22258244

33 CFR 117.921 - Broad River.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Broad River. 117.921 Section 117.921 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements South Carolina § 117.921 Broad River. (a) The draw of the S170...

33 CFR 117.921 - Broad River.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Broad River. 117.921 Section 117.921 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements South Carolina § 117.921 Broad River. (a) The draw of the S170...

33 CFR 117.921 - Broad River.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Broad River. 117.921 Section 117.921 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements South Carolina § 117.921 Broad River. (a) The draw of the S170...

33 CFR 117.921 - Broad River.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Broad River. 117.921 Section 117.921 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements South Carolina § 117.921 Broad River. (a) The draw of the S170...

33 CFR 117.921 - Broad River.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Broad River. 117.921 Section 117.921 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements South Carolina § 117.921 Broad River. (a) The draw of the S170...

Broad Academy's Growing Reach Draws Scrutiny

ERIC Educational Resources Information Center

Samuels, Christina A.

2011-01-01

Billionaire businessman Eli Broad, one of the country's most active philanthropists, founded the Broad Superintendents Academy in 2002 with an extraordinarily optimistic goal: Find leaders from both inside and outside education, train them, and have them occupying the superintendencies in a third of the 75 largest school districts--in just two…

Broad Academy's Growing Reach Draws Scrutiny

ERIC Educational Resources Information Center

Samuels, Christina A.

2011-01-01

Billionaire businessman Eli Broad, one of the country's most active philanthropists, founded the "Broad Superintendents Academy" in 2002 with an extraordinarily optimistic goal: Find leaders from both inside and outside education, train them, and have them occupying the superintendencies in a third of the 75 largest school districts--all in just…

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…

Lesions of the Broad Ligament: A Review.

PubMed

Heller, Debra S

2015-01-01

The differential diagnosis of lesions arising in the broad ligament is quite large. Many of these lesions can be clinically interpreted before surgery as adnexal or uterine neoplasms. Although some lesions are similar to those arising in other müllerian sites, there are unique lesions as well. The lesions are uncommon and may prove challenging to clinicians. The purpose was to review the scope of lesions affecting the broad ligament. A literature review was conducted. A Medline search was performed using the terms broad ligament, mesosalpinx, and mesovarium. A review of the scope of broad ligament lesions is presented to assist in developing a differential diagnosis if a patient with such a lesion is encountered. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

The broad utility of Trizac diamond tile

NASA Astrophysics Data System (ADS)

Gagliardi, John I.; Romero, Vincent D.; Sventek, Bruce; Zu, Lijun

2017-10-01

Sample finishing data from a broad range of materials — glasses, sapphire, silicon carbide, silicon, zirconium oxide, lithium tantalate, and flooring materials — are shown effectively processed with Trizact™ Diamond Tile (TDT). This data should provide the reader with an understanding of what to expect when using TDT on hard to grind or brittle materials. Keys to maintaining effective TDT pad wear rates, and therefore cost effect and stable processes, are described as managing 1) the proper lubricant flow rate for glasses and silicon-type materials and 2) the conditioning particle concentration for harder-to-grind materials

Social cognition, social skill, and the broad autism phenotype.

PubMed

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

2013-11-01

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 examined whether the social-cognitive deficits associated with the broad autism phenotype extend to the general population and relate to reduced social skill. A total of 74 undergraduates completed the Broad Autism Phenotype Questionnaire, three standardized social-cognitive tasks, and a live social interaction with an unfamiliar research assistant. Social broad autism phenotype traits were significantly associated with deficits in social cognition and reduced social skill. In addition, the relationship between social broad autism phenotype traits and social skill was partially mediated by social cognition, suggesting that the reduced interpersonal ability associated with the broad autism phenotype occurs in part because of poorer social-cognitive ability. Together, these findings indicate that the impairments in social cognition and social skill that characterize autism spectrum disorder extend in milder forms to the broad autism phenotype in the general population and suggest a framework for understanding how social broad autism phenotype traits may manifest in diminished social ability.

Loss of function of a rice TPR-domain RNA-binding protein confers broad-spectrum disease resistance.

PubMed

Zhou, Xiaogang; Liao, Haicheng; Chern, Mawsheng; Yin, Junjie; Chen, Yufei; Wang, Jianping; Zhu, Xiaobo; Chen, Zhixiong; Yuan, Can; Zhao, Wen; Wang, Jing; Li, Weitao; He, Min; Ma, Bingtian; Wang, Jichun; Qin, Peng; Chen, Weilan; Wang, Yuping; Liu, Jiali; Qian, Yangwen; Wang, Wenming; Wu, Xianjun; Li, Ping; Zhu, Lihuang; Li, Shigui; Ronald, Pamela C; Chen, Xuewei

2018-03-20

Crops carrying broad-spectrum resistance loci provide an effective strategy for controlling infectious disease because these loci typically confer resistance to diverse races of a pathogen or even multiple species of pathogens. Despite their importance, only a few crop broad-spectrum resistance loci have been reported. Here, we report the identification and characterization of the rice bsr-k1 (broad-spectrum resistance Kitaake-1) mutant, which confers broad-spectrum resistance against Magnaporthe oryzae and Xanthomonas oryzae pv oryzae with no major penalty on key agronomic traits. Map-based cloning reveals that Bsr-k1 encodes a tetratricopeptide repeats (TPRs)-containing protein, which binds to mRNAs of multiple OsPAL ( OsPAL1-7 ) genes and promotes their turnover. Loss of function of the Bsr-k1 gene leads to accumulation of OsPAL1-7 mRNAs in the bsr-k1 mutant. Furthermore, overexpression of OsPAL1 in wild-type rice TP309 confers resistance to M. oryzae , supporting the role of OsPAL1 Our discovery of the bsr-k1 allele constitutes a significant conceptual advancement and provides a valuable tool for breeding broad-spectrum resistant rice. Copyright © 2018 the Author(s). Published by PNAS.

48 CFR 1335.016 - Broad agency announcement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Broad agency announcement. 1335.016 Section 1335.016 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 1335.016 Broad agency announcement. ...

48 CFR 1335.016 - Broad agency announcement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Broad agency announcement. 1335.016 Section 1335.016 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 1335.016 Broad agency announcement. ...

48 CFR 1335.016 - Broad agency announcement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Broad agency announcement. 1335.016 Section 1335.016 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 1335.016 Broad agency announcement. ...

48 CFR 1335.016 - Broad agency announcement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Broad agency announcement. 1335.016 Section 1335.016 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 1335.016 Broad agency announcement. ...

48 CFR 1335.016 - Broad agency announcement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Broad agency announcement. 1335.016 Section 1335.016 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 1335.016 Broad agency announcement. ...

The microtubule motor protein KIF13A is involved in intracellular trafficking of the Lassa virus matrix protein Z.

PubMed

Fehling, Sarah Katharina; Noda, Takeshi; Maisner, Andrea; Lamp, Boris; Conzelmann, Karl-Klaus; Kawaoka, Yoshihiro; Klenk, Hans-Dieter; Garten, Wolfgang; Strecker, Thomas

2013-02-01

The small matrix protein Z of arenaviruses has been identified as the main driving force to promote viral particle production at the plasma membrane. Although multiple functions of Z in the arenaviral life cycle have been uncovered, the mechanism of intracellular transport of Z to the site of virus budding is poorly understood and cellular motor proteins that mediate Z trafficking remain to be identified. In the present study, we report that the Z protein of the Old World arenavirus Lassa virus (LASV) interacts with the kinesin family member 13A (KIF13A), a plus-end-directed microtubule-dependent motor protein. Plasmid-driven overexpression of KIF13A results in relocalization of Z to the cell periphery, while functional blockage of endogenous KIF13A by overexpression of a dominant-negative mutant or KIF13A-specific siRNA causes a perinuclearaccumulation and decreased production of both Z-induced virus-like particles and infectious LASV. The interaction of KIF13A with Z proteins from both Old and New World arenaviruses suggests a conserved intracellular transport mechanism. In contrast, the intracellular distribution of the matrix proteins of prototypic members of the paramyxo- and rhabdovirus family is independent of KIF13A. In summary, our studies identify for the first time a molecular motor protein as a critical mediator for intracellular microtubule-dependent transport of arenavirus matrix proteins. © 2012 Blackwell Publishing Ltd.

Thin Line, Broad Shadows

NASA Image and Video Library

2011-02-21

Saturn rings appear as only a thin line seen edge-on in the middle of this view from NASA Cassini spacecraft, but the rings cast broad shadows on the southern hemisphere of the planet in the lower left of the image.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki; Oshita, Masatoshi

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 neutralizingmore » 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.« less

Broad-Spectrum Molecular Detection of Fungal Nucleic Acids by PCR-Based Amplification Techniques.

PubMed

Czurda, Stefan; Lion, Thomas

2017-01-01

Over the past decade, the incidence of life-threatening invasive fungal infections has dramatically increased. Infections caused by hitherto rare and emerging fungal pathogens are associated with significant morbidity and mortality among immunocompromised patients. These observations render the coverage of a broad range of clinically relevant fungal pathogens highly important. The so-called panfungal or, perhaps more correctly, broad-range nucleic acid amplification techniques do not only facilitate sensitive detection of all clinically relevant fungal species but are also rapid and can be applied to analyses of any patient specimens. They have therefore become valuable diagnostic tools for sensitive screening of patients at risk of invasive fungal infections. This chapter summarizes the currently available molecular technologies employed in testing of a wide range of fungal pathogens, and provides a detailed workflow for patient screening by broad-spectrum nucleic acid amplification techniques.

Second Interim Report of the Broadly-Based Community Study of Exceptional Education.

ERIC Educational Resources Information Center

Milwaukee Public Schools, WI. Div. of Curriculum and Instruction.

Presented are recommendations of a Milwaukee public school study for the purpose of providing a meaningful, effective, and comprehensive educational program for exceptional students. Fourteen recommendations covering the broad policy of exceptional education include policies on integration into normal school programs, transportation, and early…

High resolution energy analyzer for broad ion beam characterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanarov, V.; Hayes, A.; Yevtukhov, R.

2008-09-15

Characterization of the ion energy distribution function (IEDF) of low energy high current density ion beams by conventional retarding field and deflection type energy analyzers is limited due to finite ion beam emittance and beam space charge spreading inside the analyzer. These deficiencies are, to a large extent, overcome with the recent development of the variable-focusing retarding field energy analyzer (RFEA), which has a cylindrical focusing electrode preceding the planar retarding grid. The principal concept of this analyzer is conversion of a divergent charged particle beam into a quasiparallel beam before analyzing it by the planar retarding field. This allowsmore » analysis of the beam particle total kinetic energy distribution with greatly improved energy resolution. Whereas this concept was first applied to analyze 5-10 keV pulsed electron beams, the present authors have adapted it to analyze the energy distribution of a low energy ({<=}1 KeV) broad ion beam. In this paper we describe the RFEA design, which was modified from the original, mainly as required by the specifics of broad ion beam energy analysis, and the device experimental characterization and modeling results. Among the modifications, an orifice electrode placed in front of the RFEA provides better spatial resolution of the broad ion beam ion optics emission region and reduces the beam plasma density in the vicinity of analyzer entry. An electron repeller grid placed in front of the RFEA collector was found critical for suppressing secondary electrons, both those incoming to the collector and those released from its surface, and improved energy spectrum measurement repeatability and accuracy. The use of finer mesh single- and double-grid retarding structures reduces the retarding grid lens effect and improves the analyzer energy resolution and accuracy of the measured spectrum mean energy. However, additional analyzer component and configuration improvements did not further change the

Biological activity of sedaxane---a novel broad-spectrum fungicide for seed treatment.

PubMed

Zeun, Ronald; Scalliet, Gabriel; Oostendorp, Michael

2013-04-01

Sedaxane is a new broad-spectrum seed treatment fungicide developed by Syngenta Crop Protection for control of seed- and soil-borne diseases in a broad range of crops. Its physicochemical properties and activity spectrum have been optimised for use as a seed treatment providing both local and systemic protection of the seed and roots of target crops. Sedaxane inhibits respiration by binding to the succinate dehydrogenase complex in the fungal mitochondrium. Its activity spectrum covers seed-borne fungi such as Ustilago nuda, Tilletia caries, Monographella nivalis and Pyrenophora graminea, as well as the soil-borne fungi Rhizoctonia solani, R. cerealis and Typhula incarnata. Under greenhouse conditions, sedaxane showed high levels and consistent protection against U. nuda, P. graminea and Rhizoctonia spp. Under field conditions, efficacy against Rhizoctonia spp. resulted in increased yield compared with the untreated check. Efficacy against snow mould has been shown under very high disease pressure conditions. The combination of sedaxane plus fludioxonil against snow mould can provide resistance management for sustainable use. The broad spectrum and high level of activity in combination with excellent crop tolerance allow the use of sedaxane as a seed treatment in a wide variety of crops. It is a potential tool for precautionary resistance management when combined with other fungicides, especially against pathogens showing a potential for resistance development, such as M. nivalis. © 2012 Society of Chemical Industry.

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

7. BROAD STREET STATION (demolished 1953). Photocopy of ca. 1894 ...

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

7. BROAD STREET STATION (demolished 1953). Photocopy of ca. 1894 photograph by William H. Rau. Original photograph at Pennsylvania Railroad - Pennsylvania Railroad Station, Broad Street Station, Broad & Market Streets, Philadelphia, Philadelphia County, PA

Elevation of dwelling at 80 North Broad Place, SW, originally ...

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

Elevation of dwelling at 80 North Broad Place, SW, originally built to house workers from the nearby Merrimack Mill - 80 North Broad Place, Southwest (House), 80 North Broad Place, Southwest, Huntsville, Madison County, AL

3. PERSPECTIVE VIEW OF CORNER OF BROAD AND WATER STREETS ...

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

3. PERSPECTIVE VIEW OF CORNER OF BROAD AND WATER STREETS (FRAUNCES TAVERN IS ON FAR LEFT, LOOKING DOWN BROAD STREET) - Fraunces Tavern Block, Bounded by Pearl, Water & Broad Streets & Coeties Slip, New York County, NY

Relativistic redshifts in quasar broad lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tremaine, Scott; Shen, Yue; Liu, Xin

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 randomlymore » 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.« less

Cooperation between Strain-Specific and Broadly Neutralizing Responses Limited Viral Escape and Prolonged the Exposure of the Broadly Neutralizing Epitope

PubMed Central

Anthony, Colin; York, Talita; Bekker, Valerie; Matten, David; Selhorst, Philippe; Ferreria, Roux-Cil; Garrett, Nigel J.; Karim, Salim S. Abdool; Morris, Lynn; Wood, Natasha T.; Moore, Penny L.

2017-01-01

ABSTRACT V3-glycan-targeting broadly neutralizing antibodies (bNAbs) are a focus of HIV-1 vaccine development. Understanding the viral dynamics that stimulate the development of these antibodies can provide insights for immunogen design. We used a deep-sequencing approach, together with neutralization phenotyping, to investigate the rate and complexity of escape from V3-glycan-directed bNAbs compared to overlapping early strain-specific neutralizing antibody (ssNAb) responses to the V3/C3 region in donor CAP177. Escape from the ssNAb response occurred rapidly via an N334-to-N332 glycan switch, which took just 7.5 weeks to reach >50% frequency. In contrast, escape from the bNAbs was mediated via multiple pathways and took longer, with escape first occurring through an increase in V1 loop length, which took 46 weeks to reach 50% frequency, followed by an N332-to-N334 reversion, which took 66 weeks. Importantly, bNAb escape was incomplete, with contemporaneous neutralization observed up to 3 years postinfection. Both the ssNAb response and the bNAb response were modulated by the presence/absence of the N332 glycan, indicating an overlap between the two epitopes. Thus, selective pressure by ssNAbs to maintain the N332 glycan may have constrained the bNAb escape pathway. This slower and incomplete viral escape resulted in prolonged exposure of the bNAb epitope, which may in turn have aided the maturation of the bNAb lineage. IMPORTANCE The development of an HIV-1 vaccine is of paramount importance, and broadly neutralizing antibodies are likely to be a key component of a protective vaccine. The V3-glycan-targeting bNAb responses are among the most promising vaccine targets, as they are commonly elicited during infection. Understanding the interplay between viral evolution and the development of these antibodies provides insights that may guide immunogen design. Our work contrasted the dynamics of the early strain-specific antibodies and the later broadly neutralizing

9. The southeast face of the Broad Street bridge with ...

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

9. The southeast face of the Broad Street bridge with City Hall in the background as seen from Amphitheater Park. - Broad Street Bridge, Spanning Scioto River at U.S. Route 40 (Broad Street), Columbus, Franklin County, OH

2. SOUTH FRONT, MAIN SECTION, LOOKING NORTH; 92 BROAD STREET ...

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

2. SOUTH FRONT, MAIN SECTION, LOOKING NORTH; 92 BROAD STREET VISIBLE AT LEFT EDGE OF PHOTOGRAPH, INFILL SECTION OF 90 BROAD STREET VISIBLE AT RIGHT EDGE OF PHOTOGRAPH - 90 Broad Street (Commercial Building), Charleston, Charleston County, SC

4. A river level view of the Broad Street bridge ...

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

4. A river level view of the Broad Street bridge and Columbus skyline from the railroad truss north of the bridge. - Broad Street Bridge, Spanning Scioto River at U.S. Route 40 (Broad Street), Columbus, Franklin County, OH

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

Main elevation of 3516 South Broad Place, SW. This house ...

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

Main elevation of 3516 South Broad Place, SW. This house was used by the agent for Merrimack Mills, and now is the headquarters of Impact Ministries - 3516 South Broad Place, Southwest (House), 3516 South Broad Place, Southwest, Huntsville, Madison County, AL

7. The north face of the Broad Street bridge as ...

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

7. The north face of the Broad Street bridge as seen from Veterans Memorial Auditorium, located on the west bank of the river. - Broad Street Bridge, Spanning Scioto River at U.S. Route 40 (Broad Street), Columbus, Franklin County, OH

3. View looking S down West Broad Street sidewalk showing ...

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

3. View looking S down West Broad Street sidewalk showing S half of Gate in foreground, Wickersham fence running parallel to West Broad St. and Passenger Station in background. - Central of Georgia Railway, Cotton Yard Gates, West Broad Street, Savannah, Chatham County, GA

Broad beam transmission properties of some common shielding materials for use in diagnostic radiology.

PubMed

Rossi, R P; Ritenour, R; Christodoulou, E

1991-11-01

Broad beam geometry was used to measure the x-ray transmission properties of gypsum wallboard, steel, plate glass, and concrete for x-ray tube potentials of 50-125 kVp using an x-ray generator having a three-phase, twelve-pulse waveform and total initial beam filtration sufficient to provide half-value layers representative of those found in common practice and required by regulatory agencies. Measurement results are presented graphically and as numerical fits to a mathematical model of broad beam transmission to permit their use in the design of protective barriers for medical diagnostic x-ray facilities.

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

Structure built for Merrimack Mill at 11 North Broad Place, ...

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

Structure built for Merrimack Mill at 11 North Broad Place, SW, originally for use at the first mill village school. It has been modified into a three-unit dwelling - 11 North Broad Place, Southwest (House), 11 North Broad Place, Southwest, Huntsville, Madison County, AL

3. Panoramic view of Broad Street bridge in foreground and ...

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

3. Panoramic view of Broad Street bridge in foreground and a major portion of the historic bridge. As seem from the top of the American Electric Power building looking south. - Broad Street Bridge, Spanning Scioto River at U.S. Route 40 (Broad Street), Columbus, Franklin County, OH

10 CFR 33.17 - Conditions of specific licenses of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Conditions of specific licenses of broad scope. 33.17 Section 33.17 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.17 Conditions of specific licenses of broad scope. (a...

10 CFR 33.12 - Applications for specific licenses of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Applications for specific licenses of broad scope. 33.12 Section 33.12 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.12 Applications for specific licenses of broad scope. A...

10 CFR 33.12 - Applications for specific licenses of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Applications for specific licenses of broad scope. 33.12 Section 33.12 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.12 Applications for specific licenses of broad scope. A...

10 CFR 33.17 - Conditions of specific licenses of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Conditions of specific licenses of broad scope. 33.17 Section 33.17 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.17 Conditions of specific licenses of broad scope. (a...

10 CFR 33.17 - Conditions of specific licenses of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Conditions of specific licenses of broad scope. 33.17 Section 33.17 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.17 Conditions of specific licenses of broad scope. (a...

10 CFR 33.12 - Applications for specific licenses of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Applications for specific licenses of broad scope. 33.12 Section 33.12 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.12 Applications for specific licenses of broad scope. A...

10 CFR 33.12 - Applications for specific licenses of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Applications for specific licenses of broad scope. 33.12 Section 33.12 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.12 Applications for specific licenses of broad scope. A...

10 CFR 33.12 - Applications for specific licenses of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Applications for specific licenses of broad scope. 33.12 Section 33.12 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.12 Applications for specific licenses of broad scope. A...

10 CFR 33.17 - Conditions of specific licenses of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Conditions of specific licenses of broad scope. 33.17 Section 33.17 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.17 Conditions of specific licenses of broad scope. (a...

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. SOUTH FRONT AND EAST SIDE, LOOKING NORTHWEST; 90 BROAD ...

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

9. SOUTH FRONT AND EAST SIDE, LOOKING NORTHWEST; 90 BROAD STREET (HABS NO. SC-656) AND 92 BROAD STREET VISIBLE AT LEFT SIDE OF PHOTOGRAPH; 10, 12, AND 14 COURT HOUSE SQUARE VISIBLE AT RIGHT EDGE OF PHOTOGRAPH - Old Jewish Orphanage, 88 Broad Street, Charleston, Charleston County, SC

32 CFR 724.203 - Broad objectives of naval discharge review.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 5 2013-07-01 2013-07-01 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) The...

32 CFR 724.203 - Broad objectives of naval discharge review.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 5 2012-07-01 2012-07-01 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) The...

32 CFR 724.203 - Broad objectives of naval discharge review.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 5 2014-07-01 2014-07-01 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) The...

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) The...

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) The...

Effect of Shufeng Jiedu capsules as a broad-spectrum antibacterial.

PubMed

Bao, Yanyan; Gao, Yingjie; Cui, Xiaolan

2016-02-01

This study sought to investigate the broad-spectrum antibacterial action of an alternative medicine, Shufeng Jiedu capsules (SFJDC). Antibacterial testing was performed to determine whether SFJDC had broad-spectrum antibacterial action in vitro, and testing was performed to verify whether SFJDC prevented death due to a Streptococcus or Staphylococcus aureus infection in mice. Results of antibacterial testing suggested that SFJDC are a broad-spectrum antibacterial and that SFJDC are superior to Lianhua Qingwen capsules as a broad-spectrum antibacterial. Results of testing revealed that SFJDC lowered the mortality rate, it reduced mortality, it increased average survival time, and it increased the lifespan of mice dying due to a Staphylococcus aureus or Streptococcus infection. Thus, SFJDC could become a complement to broad-spectrum antimicrobials in clinical settings.

10 CFR 33.11 - Types of specific licenses of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Types of specific licenses of broad scope. 33.11 Section 33.11 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.11 Types of specific licenses of broad scope. (a) A “Type A...

10 CFR 33.11 - Types of specific licenses of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Types of specific licenses of broad scope. 33.11 Section 33.11 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.11 Types of specific licenses of broad scope. (a) A “Type A...

10 CFR 33.11 - Types of specific licenses of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Types of specific licenses of broad scope. 33.11 Section 33.11 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.11 Types of specific licenses of broad scope. (a) A “Type A...

10 CFR 33.11 - Types of specific licenses of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Types of specific licenses of broad scope. 33.11 Section 33.11 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.11 Types of specific licenses of broad scope. (a) A “Type A...

10 CFR 33.11 - Types of specific licenses of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Types of specific licenses of broad scope. 33.11 Section 33.11 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.11 Types of specific licenses of broad scope. (a) A “Type A...

A "Trojan horse" bispecific-antibody strategy for broad protection against ebolaviruses.

PubMed

Wec, Anna Z; Nyakatura, Elisabeth K; Herbert, Andrew S; Howell, Katie A; Holtsberg, Frederick W; Bakken, Russell R; Mittler, Eva; Christin, John R; Shulenin, Sergey; Jangra, Rohit K; Bharrhan, Sushma; Kuehne, Ana I; Bornholdt, Zachary A; Flyak, Andrew I; Saphire, Erica Ollmann; Crowe, James E; Aman, M Javad; Dye, John M; Lai, Jonathan R; Chandran, Kartik

2016-10-21

There is an urgent need for monoclonal antibody (mAb) therapies that broadly protect against Ebola virus and other filoviruses. The conserved, essential interaction between the filovirus glycoprotein, GP, and its entry receptor Niemann-Pick C1 (NPC1) provides an attractive target for such mAbs but is shielded by multiple mechanisms, including physical sequestration in late endosomes. Here, we describe a bispecific-antibody strategy to target this interaction, in which mAbs specific for NPC1 or the GP receptor-binding site are coupled to a mAb against a conserved, surface-exposed GP epitope. Bispecific antibodies, but not parent mAbs, neutralized all known ebolaviruses by coopting viral particles themselves for endosomal delivery and conferred postexposure protection against multiple ebolaviruses in mice. Such "Trojan horse" bispecific antibodies have potential as broad antifilovirus immunotherapeutics. Copyright © 2016, American Association for the Advancement of Science.

Broad-range PCR: past, present, or future of bacteriology?

PubMed

Renvoisé, A; Brossier, F; Sougakoff, W; Jarlier, V; Aubry, A

2013-08-01

PCR targeting the gene encoding 16S ribosomal RNA (commonly named broad-range PCR or 16S PCR) has been used for 20 years as a polyvalent tool to study prokaryotes. Broad-range PCR was first used as a taxonomic tool, then in clinical microbiology. We will describe the use of broad-range PCR in clinical microbiology. The first application was identification of bacterial strains obtained by culture but whose phenotypic or proteomic identification remained difficult or impossible. This changed bacterial taxonomy and allowed discovering many new species. The second application of broad-range PCR in clinical microbiology is the detection of bacterial DNA from clinical samples; we will review the clinical settings in which the technique proved useful (such as endocarditis) and those in which it did not (such as characterization of bacteria in ascites, in cirrhotic patients). This technique allowed identifying the etiological agents for several diseases, such as Whipple disease. This review is a synthesis of data concerning the applications, assets, and drawbacks of broad-range PCR in clinical microbiology. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein.

PubMed

Khamina, Kseniya; Lercher, Alexander; Caldera, Michael; Schliehe, Christopher; Vilagos, Bojan; Sahin, Mehmet; Kosack, Lindsay; Bhattacharya, Anannya; Májek, Peter; Stukalov, Alexey; Sacco, Roberto; James, Leo C; Pinschewer, Daniel D; Bennett, Keiryn L; Menche, Jörg; Bergthaler, Andreas

2017-12-01

RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics. A subsequent mass-spectrometric analysis of L protein pulldowns from infected human cells revealed a comprehensive network of interacting host proteins. The obtained LCMV L protein interactome was bioinformatically integrated with known host protein interactors of RdRps from other RNA viruses, emphasizing interconnected modules of human proteins. Functional characterization of selected interactors highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors. To corroborate these findings, we infected Trim21-/- mice with LCMV and found impaired virus control in chronic infection. These results provide insights into the complex interactions of the arenavirus LCMV and other viral RdRps with the host proteome and contribute to a better molecular understanding of how chronic viruses interact with their host.

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.

Sex differences and within-family associations in the broad autism phenotype.

PubMed

Klusek, Jessica; Losh, Molly; Martin, Gary E

2014-02-01

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 autism. Pragmatic language and personality features of the broad autism phenotype were studied in 42 fathers and 50 mothers of individuals with autism using direct assessment tools used in prior family studies of the broad autism phenotype. Higher rates of aloof personality style were detected among fathers, while no sex differences were detected for other broad autism phenotype traits. Within individuals, pragmatic language features were associated with the social personality styles of the broad autism phenotype in mothers but not in fathers. A number of broad autism phenotype features were correlated within spousal pairs. Finally, the associations were detected between paternal broad autism phenotype characteristics and the severity of children's autism symptoms in all three domains (social, communication, and repetitive behaviors). Mother-child correlations were detected for aspects of communication only. Together, the findings suggest that most features of the broad autism phenotype express comparably in males and females and raise some specific questions about how such features might inform studies of the genetic basis of autism.

Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond.

PubMed

Boldescu, Veaceslav; Behnam, Mira A M; Vasilakis, Nikos; Klein, Christian D

2017-08-01

Infections with flaviviruses, such as dengue, West Nile virus and the recently re-emerging Zika virus, are an increasing and probably lasting global risk. This Review summarizes and comments on the opportunities for broad-spectrum agents that are active against multiple flaviviruses. Broad-spectrum activity is particularly desirable to prepare for the next flaviviral epidemic, which could emerge from as-yet unknown or neglected viruses. Potential molecular targets for broad-spectrum antiflaviviral compounds include viral proteins, such as the viral protease or polymerase, and host targets that are exploited by these viruses during entry and replication, including α-glucosidase and proteins involved in nucleoside biosynthesis. Numerous compounds with broad-spectrum antiviral activity have already been identified by target-specific or phenotypic assays. For other compounds, broad-spectrum activity can be anticipated because of their mode of action and molecular targets.

The Broad Superintendents Academy, 2007

ERIC Educational Resources Information Center

Broad Foundation, 2007

2007-01-01

The Broad Superintendents Academy is an executive training program that identifies and prepares prominent leaders--executives with experience successfully leading large organizations and a passion for public service--then places them in urban school districts to dramatically improve the quality of education for America's students. This brochure…

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

The Broad Autism Phenotype Questionnaire

ERIC Educational Resources Information Center

Hurley, Robert S. E.; Losh, Molly; Parlier, Morgan; Reznick, J. Steven; Piven, Joseph

2007-01-01

The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the…

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…

BROAD Hβ EMISSION-LINE VARIABILITY IN A SAMPLE OF 102 LOCAL ACTIVE GALAXIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Runco, Jordan N.; Cosens, Maren; Bennert, Vardha N.

2016-04-10

A sample of 102 local (0.02 ≤ z ≤ 0.1) Seyfert galaxies with black hole masses M{sub BH} > 10{sup 7}M{sub ⊙} was selected from the Sloan Digital Sky Survey (SDSS) and observed using the Keck 10 m telescope to study the scaling relations between M{sub BH} 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 M{sub BH}, but also because its strengthmore » 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.« less

Broad-spectrum inhibition of Phytophthora infestans by fungal endophytes

PubMed Central

von Dahlen, Janina K; Schnake, Anika; Ginschel, Sarah; Schulz, Barbara; Rose, Laura E

2018-01-01

ABSTRACT Phytophthora infestans is a devastating pathogen of tomato and potato. It readily overcomes resistance genes and applied agrochemicals and hence even today causes large yield losses. Fungal endophytes provide a largely unexplored avenue of control of Phy. infestans. Not only do endophytes produce a wide array of bioactive metabolites, they may also directly compete with and defeat pathogens in planta. Here, we tested 12 fungal endophytes isolated from different plant species in vitro for their production of metabolites with anti- Phytophthora activity. Four well-performing isolates were evaluated for their ability to suppress nine isolates of Phy. infestans on agar medium and in planta. Two endophytes reliably inhibited all Phy. infestans isolates on agar medium, of which Phoma eupatorii isolate 8082 was the most promising. It nearly abolished infection by Phy. infestans in planta. Our data indicate a role for the production of anti-Phytophthora compounds by the fungus and/or an enhanced plant defense response, as evident by an enhanced anthocyanin production. Here, we present a potential biocontrol agent, which can inhibit a broad-spectrum of Phy. infestans isolates. Such broadly acting inhibition is ideal, because it allows for effective control of genetically diverse isolates and may slow the adaptation of Phy. infestans. PMID:29528408

Broad Absorption Line Quasars with Polar Outflows

NASA Astrophysics Data System (ADS)

Wang, Junxian

2005-10-01

It is widely accepted that the broad absorption line (BAL) outflow exists in most (if not all) quasars with a small covering factor. Various evidences show that equatorial outflows are responsible for the BALs in most BAL QSOs. By searching for radio variable quasars in SDSS, we built the first sample of 6 BAL QSOs with polar BAL outflows. It is very likely that polar outflows are associated with relativistic jets, and their origins should be different from the equatorial outflows in the majority of BAL QSOs. We propose an XMM snapshot survey to a) check whether strong X-ray absorption, one of the most prominent characteristics of most BAL QSOs, also exist in the polar outflows b) check whether face-on BAL QSOs are otherwise X-ray normal c) provide a baseline for future extensive X-ray studies.

A Broad 22 Micron Emission Feature in the Carina Nebula H ii Region.

PubMed

Chan; Onaka

2000-04-10

We report the detection of a broad 22 µm emission feature in the Carina Nebula H ii region by the Infrared Space Observatory (ISO) short-wavelength spectrometer. The feature shape is similar to that of the 22 µm emission feature of newly synthesized dust observed in the Cassiopeia A supernova remnant. This finding suggests that both of the features are arising from the same carrier and that supernovae are probably the dominant production sources of this new interstellar grain. A similar broad emission dust feature is also found in the spectra of two starburst galaxies from the ISO archival data. This new dust grain could be an abundant component of interstellar grains and can be used to trace the supernova rate or star formation rate in external galaxies. The existence of the broad 22 µm emission feature complicates the dust model for starburst galaxies and must be taken into account correctly in the derivation of dust color temperature. Mg protosilicate has been suggested as the carrier of the 22 µm emission dust feature observed in Cassiopeia A. The present results provide useful information in studies on the chemical composition and emission mechanism of the carrier.

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.

Angiomyofibroblastoma of the Broad Ligament: A Case Report.

PubMed

Huang, Hsiao-Chin; Chen, Ying-Ren; Tsai, Horng-Der; Cheng, Ya-Min; Hsiao, Yi-Hsuan

2017-09-01

Angiomyofibroblastoma (AMF) is a distinctive, rare, benign mesenchymal tumor that often occurs in the lower genital region of women. The most commonly reported location of an AMF is in the vulvovaginal area. We describe a rare case of an AMF located in the broad ligament in a 47-yr-old woman. The patient experienced menorrhagia, dysmenorrhea, and subsequent menstrual spotting. She sought help at the National Cheng Kung University Hospital. Ultrasonography showed an echo-complex mass in the left adnexal area. The patient underwent laparoscopic surgery to remove the soft tissue mass located in the left broad ligament. The final pathology of the mass was reported as an AMF. We reviewed all of the AMF cases reported in the English-language literature found in Pubmed. This case is the first of AMF located in the broad ligament.

Novel Broad Spectrum Inhibitors Targeting the Flavivirus Methyltransferase

PubMed Central

Liu, Binbin; Banavali, Nilesh K.; Jones, Susan A.; Zhang, Jing; Li, Zhong; Kramer, Laura D.; Li, Hongmin

2015-01-01

The flavivirus methyltransferase (MTase) is an essential enzyme that sequentially methylates the N7 and 2’-O positions of the viral RNA cap, using S-adenosyl-L-methionine (SAM) as a methyl donor. We report here that small molecule compounds, which putatively bind to the SAM-binding site of flavivirus MTase and inhibit its function, were identified by using virtual screening. In vitro methylation experiments demonstrated significant MTase inhibition by 13 of these compounds, with the most potent compound displaying sub-micromolar inhibitory activity. The most active compounds showed broad spectrum activity against the MTase proteins of multiple flaviviruses. Two of these compounds also exhibited low cytotoxicity and effectively inhibited viral replication in cell-based assays, providing further structural insight into flavivirus MTase inhibition. PMID:26098995

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

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

Broad-scale consequences of land management: Columbia basin example.

Treesearch

Richard W. Haynes; Thomas M. Quigley

2001-01-01

Integrating management actions to consistently achieve broad ecological and socioeconomic goals is a challenge largely unmet. The presumed or real conflict between these goals establishes a forum for debate. Broad measures are needed to describe tradeoffs, trends in conditions under varying management scenarios, and a transparent science underpinning. The Interior...

Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies.

PubMed

Zhang, Zhiqing; Li, Shaowei; Gu, Ying; Xia, Ningshao

2016-11-18

Human immunodeficiency virus type 1 (HIV-1) infection causes acquired immune deficiency syndrome (AIDS), a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART) but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env protein and the reciprocal broadly neutralizing antibodies, and discuss the ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy as well as antibody combinations, bispecific antibodies, and methods that improve therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs) with latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate these broadly neutralizing and inhibitory antibodies offer the advantage of decreasing virus load and clearing infected cells, which is a promising prospect in HIV-1 prevention and treatment.

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…

Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization.

PubMed

Zeltina, Antra; Krumm, Stefanie A; Sahin, Mehmet; Struwe, Weston B; Harlos, Karl; Nunberg, Jack H; Crispin, Max; Pinschewer, Daniel D; Doores, Katie J; Bowden, Thomas A

2017-07-03

Transmission of hemorrhagic fever New World arenaviruses from their rodent reservoirs to human populations poses substantial public health and economic dangers. These zoonotic events are enabled by the specific interaction between the New World arenaviral attachment glycoprotein, GP1, and cell surface human transferrin receptor (hTfR1). Here, we present the structural basis for how a mouse-derived neutralizing antibody (nAb), OD01, disrupts this interaction by targeting the receptor-binding surface of the GP1 glycoprotein from Junín virus (JUNV), a hemorrhagic fever arenavirus endemic in central Argentina. Comparison of our structure with that of a previously reported nAb complex (JUNV GP1-GD01) reveals largely overlapping epitopes but highly distinct antibody-binding modes. Despite differences in GP1 recognition, we find that both antibodies present a key tyrosine residue, albeit on different chains, that inserts into a central pocket on JUNV GP1 and effectively mimics the contacts made by the host TfR1. These data provide a molecular-level description of how antibodies derived from different germline origins arrive at equivalent immunological solutions to virus neutralization.

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.

Broad Surveys of DNA Viral Diversity Obtained through Viral Metagenomics of Mosquitoes

PubMed Central

Ng, Terry Fei Fan; Willner, Dana L.; Lim, Yan Wei; Schmieder, Robert; Chau, Betty; Nilsson, Christina; Anthony, Simon; Ruan, Yijun; Rohwer, Forest; Breitbart, Mya

2011-01-01

Viruses are the most abundant and diverse genetic entities on Earth; however, broad surveys of viral diversity are hindered by the lack of a universal assay for viruses and the inability to sample a sufficient number of individual hosts. This study utilized vector-enabled metagenomics (VEM) to provide a snapshot of the diversity of DNA viruses present in three mosquito samples from San Diego, California. The majority of the sequences were novel, suggesting that the viral community in mosquitoes, as well as the animal and plant hosts they feed on, is highly diverse and largely uncharacterized. Each mosquito sample contained a distinct viral community. The mosquito viromes contained sequences related to a broad range of animal, plant, insect and bacterial viruses. Animal viruses identified included anelloviruses, circoviruses, herpesviruses, poxviruses, and papillomaviruses, which mosquitoes may have obtained from vertebrate hosts during blood feeding. Notably, sequences related to human papillomaviruses were identified in one of the mosquito samples. Sequences similar to plant viruses were identified in all mosquito viromes, which were potentially acquired through feeding on plant nectar. Numerous bacteriophages and insect viruses were also detected, including a novel densovirus likely infecting Culex erythrothorax. Through sampling insect vectors, VEM enables broad survey of viral diversity and has significantly increased our knowledge of the DNA viruses present in mosquitoes. PMID:21674005

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

PubMed

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

2016-01-01

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. 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. 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. Redemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section.

12. Photocopy of oil painting, LOOKING UP BROAD STREET FROM ...

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

12. Photocopy of oil painting, LOOKING UP BROAD STREET FROM THE STONE BRIDGE, 1795 and after (from Historical Collection of the State of New Jersey) - South Broad Street Bridge, Spanning Elizabeth River, Elizabeth, Union County, NJ

11. Photocopy of oil painting, LOOKING UP BROAD STREET FROM ...

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

11. Photocopy of oil painting, LOOKING UP BROAD STREET FROM THE STONE BRIDGE, 1795 and after (from Historical Collection of the State of New Jersey) - South Broad Street Bridge, Spanning Elizabeth River, Elizabeth, Union County, NJ

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…

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.

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…

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.

Essential tension: specialization with broad and general training in psychology.

PubMed

Roberts, Michael C

2006-11-01

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, from the balance of fragmentation and unification. As an example, specialization in clinical child psychology is integrated within the broad and general traditions. The greater degree of focused science and practice in a specialty is the logical consequence of advances of the discipline and profession of psychology. ((c) 2006 APA, all rights reserved).

42 CFR 435.223 - Individuals who would be eligible for AFDC if coverage under the State's AFDC plan were as broad...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 4 2012-10-01 2012-10-01 false Individuals who would be eligible for AFDC if coverage under the State's AFDC plan were as broad as allowed under title IV-A. 435.223 Section 435.223... plan were as broad as allowed under title IV-A. (a) The agency may provide Medicaid to any group or...

42 CFR 435.223 - Individuals who would be eligible for AFDC if coverage under the State's AFDC plan were as broad...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Individuals who would be eligible for AFDC if coverage under the State's AFDC plan were as broad as allowed under title IV-A. 435.223 Section 435.223... plan were as broad as allowed under title IV-A. (a) The agency may provide Medicaid to any group or...

42 CFR 435.223 - Individuals who would be eligible for AFDC if coverage under the State's AFDC plan were as broad...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Individuals who would be eligible for AFDC if coverage under the State's AFDC plan were as broad as allowed under title IV-A. 435.223 Section 435.223... plan were as broad as allowed under title IV-A. (a) The agency may provide Medicaid to any group or...

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.

Parallel evaluation of broad virus detection methods.

PubMed

Modrof, Jens; Berting, Andreas; Kreil, Thomas R

2014-01-01

The testing for adventitious viruses is of critical importance during development and production of biological products. The recent emergence and ongoing development of broad virus detection methods calls for an evaluation of whether these methods can appropriately be implemented into current adventitious agent testing procedures. To assess the suitability of several broad virus detection methods, a comparative experimental study was conducted: four virus preparations, which were spiked at two different concentrations each into two different cell culture media, were sent to four investigators in a blinded fashion for analysis with broad virus detection methods such as polymerase chain reaction-electrospray ionization mass spectrometry (PCR-ESI/MS), microarray, and two approaches utilizing massively parallel sequencing. The results that were reported by the investigators revealed that all methods were able to identify the majority of samples correctly (mean 83%), with a surprisingly narrow range among the methods, that is, between 72% (PCR-ESI/MS) and 95% (microarray). In addition to the correct results, a variety of unexpected assignments were reported for a minority of samples, again with little variation regarding the methods used (range 20-45%), while false negatives were reported for 0-25% of the samples. Regarding assay sensitivity, the viruses were detected by all methods included in this study at concentrations of about 4-5 log10 quantitative PCR copies/mL, and probably with higher sensitivity in some cases. In summary, the broad virus detection methods investigated were shown to be suitable even for detection of relatively low virus concentrations. However, there is also some potential for the production of false-positive as well as false-negative assignments, which indicates the requirement for further improvements before these methods can be considered for routine use. © PDA, Inc. 2014.

Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus.

PubMed

Giang, Erick; Dorner, Marcus; Prentoe, Jannick C; Dreux, Marlène; Evans, Matthew J; Bukh, Jens; Rice, Charles M; Ploss, Alexander; Burton, Dennis R; Law, Mansun

2012-04-17

Hepatitis C virus (HCV) infects ∼2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human mAbs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies to HCV.

48 CFR 1835.016-70 - Foreign participation under broad agency announcements (BAAs).

Code of Federal Regulations, 2010 CFR

2010-10-01

... broad agency announcements (BAAs). 1835.016-70 Section 1835.016-70 Federal Acquisition Regulations... DEVELOPMENT CONTRACTING 1835.016-70 Foreign participation under broad agency announcements (BAAs). (a) Policy. (1) NASA seeks the broadest participation in response to broad agency announcements, including...

48 CFR 1835.016-70 - Foreign participation under broad agency announcements (BAAs).

Code of Federal Regulations, 2012 CFR

2012-10-01

... under broad agency announcements (BAAs). 1835.016-70 Section 1835.016-70 Federal Acquisition Regulations... DEVELOPMENT CONTRACTING 1835.016-70 Foreign participation under broad agency announcements (BAAs). (a) Policy. (1) NASA seeks the broadest participation in response to broad agency announcements, including...

48 CFR 1835.016-70 - Foreign participation under broad agency announcements (BAAs).

Code of Federal Regulations, 2014 CFR

2014-10-01

... under broad agency announcements (BAAs). 1835.016-70 Section 1835.016-70 Federal Acquisition Regulations... DEVELOPMENT CONTRACTING 1835.016-70 Foreign participation under broad agency announcements (BAAs). (a) Policy. (1) NASA seeks the broadest participation in response to broad agency announcements, including...

48 CFR 1835.016-70 - Foreign participation under broad agency announcements (BAAs).

Code of Federal Regulations, 2013 CFR

2013-10-01

... under broad agency announcements (BAAs). 1835.016-70 Section 1835.016-70 Federal Acquisition Regulations... DEVELOPMENT CONTRACTING 1835.016-70 Foreign participation under broad agency announcements (BAAs). (a) Policy. (1) NASA seeks the broadest participation in response to broad agency announcements, including...

48 CFR 1835.016-70 - Foreign participation under broad agency announcements (BAAs).

Code of Federal Regulations, 2011 CFR

2011-10-01

... under broad agency announcements (BAAs). 1835.016-70 Section 1835.016-70 Federal Acquisition Regulations... DEVELOPMENT CONTRACTING 1835.016-70 Foreign participation under broad agency announcements (BAAs). (a) Policy. (1) NASA seeks the broadest participation in response to broad agency announcements, including...

76 FR 34087 - Broad Stakeholder Survey

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-10

... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2011-0027] Broad Stakeholder Survey AGENCY... Survey. DATES: Comments are encouraged and will be accepted until August 9, 2011. This process is... Stakeholder Survey is designed to gather stakeholder feedback on the effectiveness of OEC services and to...

A Catalog of Broad Absorption Line Quasars from the Sloan Digital Sky Survey Third Data Release

NASA Astrophysics Data System (ADS)

Trump, Jonathan R.; Hall, Patrick B.; Reichard, Timothy A.; Richards, Gordon T.; Schneider, Donald P.; Vanden Berk, Daniel E.; Knapp, Gillian R.; Anderson, Scott F.; Fan, Xiaohui; Brinkman, J.; Kleinman, S. J.; Nitta, Atsuko

2006-07-01

We present a total of 4784 unique broad absorption line quasars from the Sloan Digital Sky Survey Third Data Release. An automated algorithm was used to match a continuum to each quasar and to identify regions of flux at least 10% below the continuum over a velocity range of at least 1000 km s-1 in the C IV and Mg II absorption regions. The model continuum was selected as the best-fit match from a set of template quasar spectra binned in luminosity, emission line width, and redshift, with the power-law spectral index and amount of dust reddening as additional free parameters. We characterize our sample through the traditional ``balnicity'' index and a revised absorption index, as well as through parameters such as the width, outflow velocity, fractional depth, and number of troughs. From a sample of 16,883 quasars at 1.7<=z<=4.38, we identify 4386 (26.0%) quasars with broad C IV absorption, of which 1756 (10.4%) satisfy traditional selection criteria. From a sample of 34,973 quasars at 0.5<=z<=2.15, we identify 457 (1.31%) quasars with broad Mg II absorption, 191 (0.55%) of which satisfy traditional selection criteria. We also provide a supplementary list of 39 visually identified z>4.38 quasars with broad C IV absorption. We find that broad absorption line quasars may have broader emission lines on average than other quasars.

Full term viable secondary broad ligament pregnancy - A rare case.

PubMed

Sheethal, C H; Powar, Akshata

2017-01-01

Broad ligament pregnancy is also known as inter ligamentous pregnancy which is a rare form of ectopic pregnancy. Very few successful live births have been reported in this condition, where such pregnancies reached term and with live birth of a baby. A case of 28 year old primigravida of 35 weeks gestation with oligoamnios was referred to our hospital. A right broad ligament pregnancy was confirmed after an ultrasound and an MRI. She was taken up for surgery and an incision was given on the anterior leaf of the broad ligament and a male live fetus was extracted. Placenta was found on the posterior leaf of the broad ligament and it was removed without any undue haemorrhage. Uterus was lying medial to the sac and was around ten weeks in size. Both mother and baby were discharged on seventh postoperative day in good health condition.

Ecosystem Services Provided by Agricultural Land as Modeled by Broad Scale Geospatial Analysis

NASA Astrophysics Data System (ADS)

Kokkinidis, Ioannis

Agricultural ecosystems provide multiple services including food and fiber provision, nutrient cycling, soil retention and water regulation. Objectives of the study were to identify and quantify a selection of ecosystem services provided by agricultural land, using existing geospatial tools and preferably free and open source data, such as the Virginia Land Use Evaluation System (VALUES), the North Carolina Realistic Yield Expectations (RYE) database, and the land cover datasets NLCD and CDL. Furthermore I sought to model tradeoffs between provisioning and other services. First I assessed the accuracy of agricultural land in NLCD and CDL over a four county area in eastern Virginia using cadastral parcels. I uncovered issues concerning the definition of agricultural land. The area and location of agriculture saw little change in the 19 years studied. Furthermore all datasets have significant errors of omission (11.3 to 95.1%) and commission (0 to 71.3%). Location of agriculture was used with spatial crop yield databases I created and combined with models I adapted to calculate baseline values for plant biomass, nutrient composition and requirements, land suitability for and potential production of biofuels and the economic impact of agriculture for the four counties. The study area was then broadened to cover 97 counties in eastern Virginia and North Carolina, investigating the potential for increased regional grain production through intensification and extensification of agriculture. Predicted yield from geospatial crop models was compared with produced yield from the NASS Survey of Agriculture. Area of most crops in CDL was similar to that in the Survey of Agriculture, but a yield gap is present for most years, partially due to weather, thus indicating potential for yield increase through intensification. Using simple criteria I quantified the potential to extend agriculture in high yield land in other uses and modeled the changes in erosion and runoff should

A systematic literature review of individuals' perspectives on broad consent and data sharing in the United States.

PubMed

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

2016-07-01

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. 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. 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. 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.

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…

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci

PubMed Central

Ju, Jin Hyun; Crystal, Ronald G.

2017-01-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci.

PubMed

Ju, Jin Hyun; Shenoy, Sushila A; Crystal, Ronald G; Mezey, Jason G

2017-05-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In

Do Periodic Plate Reorganisations Control Late-stage Volcanism across a Broad Galápagos Hotspot?

NASA Astrophysics Data System (ADS)

O'Connor, J. M.; Hoernle, K.; Wijbrans, J. R.; Werner, R.; Hauff, S. F.; Stoffers, P.

2010-12-01

Much of the Galápagos Volcanic Province (GVP), consisting of the Cocos, Carnegie, Coiba and Malpelo aseismic ridges and related seamount provinces, remains poorly understood due to a lack of direct age and geochemical data. In recent years reconnaissance dredge/grab sampling of these submerged regions of the GVP provides some new insights that can be re-evaluated in the context of the three new cruises to the region in 2010. The distribution of 40Ar/39Ar basement ages [1-3] suggest that volcanism migrated time-progressively across GVP in broad regions of long-lived, possible concurrent, hotspot volcanism. Development of the GVP via such broad zones of overlapping volcanism leads to multiple phases of volcanism post-dating the onset of hotspot volcanism, similar to rejuvenescent volcanism that occurs million years after the main shield-building phase of mid-plate oceanic volcano, most notably along the Hawaiian-Emperor Seamount Chain. Evidence for rejuvenescent volcanism across the GVP provides an opportunity to evaluate this poorly understood process in a very different physical setting compared to the Hawaiian-Emperor Chain (mid-plate versus on/near spreading axis). Widespread episodes of coeval GVP volcanism show that the Galápagos hotspot influences broad regions of the lithosphere implying relative motion between the Cocos and Nazca plates and a broad Galápagos hotspot. The complex spreading history of the Cocos-Nazca spreading centre likely controlled the relative distribution of GVP volcanism between the Cocos and Nazca plates while creating lithosphere of variable age/thickness across the region [3]. But recent age and geochemical studies of other hotspot systems show that lithosphere influenced in the past by hotspot activity is more likely to generate late-stage volcanism in response to changing patterns of stress in the lithosphere. Late stage volcanism across a broad Galápagos hotspot might therefore reflect periodic reorganisations of the Gal

Massive Broad Ligament Cellular Leiomyoma with Cystic Change: A Diagnostic Dilemma.

PubMed

Sharma, Preeti; Zaheer, Sufian; Yadav, Amit Kumar; Mandal, Ashish Kumar

2016-04-01

Leiomyomas are known to arise from uterus, but rarely from broad ligament. Further, cellular leiomyoma of broad ligament is the least common variant reported in literature. The diagnostic dilemma arises when leiomyomas undergo degenerative changes. This poses both clinical and radiological difficulty in differentiating with an ovarian tumour. We present an unusual case of a huge broad ligament mass measuring 29x19x09cm, mimicking an ovarian tumour both clinically and radiologically. Histopathology revealed cellular leiomyoma of broad ligament with cystic and myxoid degeneration hereby being the second case reported in literature. This case is being presented not only because of the rare incidence but also due to its diagnostic confusion with ovarian malignancy on clinical evaluation and radiological findings.

A broad band X-ray imaging spectrophotometer for astrophysical studies

NASA Technical Reports Server (NTRS)

Lum, Kenneth S. K.; Lee, Dong Hwan; Ku, William H.-M.

1988-01-01

A broadband X-ray imaging spectrophotometer (BBXRIS) has been built for astrophysical studies. The BBXRIS is based on a large-imaging gas scintillation proportional counter (LIGSPC), a combination of a gas scintillation proportional counter and a multiwire proportional counter, which achieves 8 percent (FWHM) energy resolution and 1.5-mm (FWHM) spatial resolution at 5.9 keV. The LIGSPC can be integrated with a grazing incidence mirror and a coded aperture mask to provide imaging over a broad range of X-ray energies. The results of tests involving the LIGSPC and a coded aperture mask are presented, and possible applications of the BBXRIS are discussed.

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.

FirebrowseR: an R client to the Broad Institute's Firehose Pipeline.

PubMed

Deng, Mario; Brägelmann, Johannes; Kryukov, Ivan; Saraiva-Agostinho, Nuno; Perner, Sven

2017-01-01

With its Firebrowse service (http://firebrowse.org/) the Broad Institute is making large-scale multi-platform omics data analysis results publicly available through a Representational State Transfer (REST) Application Programmable Interface (API). Querying this database through an API client from an arbitrary programming environment is an essential task, allowing other developers and researchers to focus on their analysis and avoid data wrangling. Hence, as a first result, we developed a workflow to automatically generate, test and deploy such clients for rapid response to API changes. Its underlying infrastructure, a combination of free and publicly available web services, facilitates the development of API clients. It decouples changes in server software from the client software by reacting to changes in the RESTful service and removing direct dependencies on a specific implementation of an API. As a second result, FirebrowseR, an R client to the Broad Institute's RESTful Firehose Pipeline, is provided as a working example, which is built by the means of the presented workflow. The package's features are demonstrated by an example analysis of cancer gene expression data.Database URL: https://github.com/mariodeng/. © The Author(s) 2017. Published by Oxford University Press.

Construction and Characterization of Broad-Spectrum Promoters for Synthetic Biology.

PubMed

Yang, Sen; Liu, Qingtao; Zhang, Yunfeng; Du, Guocheng; Chen, Jian; Kang, Zhen

2018-01-19

Characterization of genetic circuits and biosynthetic pathways in different hosts always requires promoter substitution and redesigning. Here, a strong, broad-spectrum promoter, P bs , for Escherichia coli, Bacillus subtilis, and Saccharomyces cerevisiae was constructed, and it was incorporated into the minimal E. coli-B. subtilis-S. cerevisiae shuttle plasmid pEBS (5.8 kb). By applying a random mutation strategy, three broad-spectrum promoters P bs1 , P bs2 , and P bs3 , with different strengths were generated and characterized. These broad-spectrum promoters will expand the synthetic biology toolbox for E. coli, B. subtilis, and S. cerevisiae.

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…

Broad ligament hernia successfully repaired by single-incision laparoscopy: A case report.

PubMed

Takeyama, Hiroshi; Kogita, Yuya; Nishigaki, Takahiko; Yamashita, Masafumi; Aikawa, Eriko; Hoshi, Minako; Taniguchi, Hirokazu; Maruyama, Yasuki; Nakajima, Kazuhiro; Yamamoto, Yoshimitsu; Adachi, Kazushige; Yamamoto, Hitoshi; Ikeda, Kimimasa; Kurokawa, Eiji

2017-11-08

A 52-year-old woman with a history of two parturitions presented with lower abdominal pain. Multi-detector CT of the abdomen showed discontinuity of the sigmoid colon near the broad ligament on the left side. We assigned a provisional diagnosis of an internal hernia progressing through a defect in the broad ligament. SILS revealed a total broad ligament defect on the left side but no signs of ischemic, necrotic bowel. We successfully repaired the broad ligament defect with suturing. At the 2-month follow-up, the patient remained well with no signs of recurrence. This case appears to be the first report of a broad ligament hernia successfully diagnosed and repaired by SILS. © 2017 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

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 of...

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 of...

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 of...

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 of...

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 of...

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.

Can Broad Consent be Informed Consent?

PubMed Central

Sheehan, Mark

2011-01-01

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

Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein

DOE PAGES

Chen, Edwin; Salinas, Nichole D.; Huang, Yining; ...

2016-05-18

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 motifsmore » 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. In conclusion, 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.« less

Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Edwin; Salinas, Nichole D.; Huang, Yining

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 motifsmore » 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. In conclusion, 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.« less

Size of nesting female Broad-snouted Caimans (Caiman latirostris Daudin 1802).

PubMed

Leiva, P M L; Simoncini, M S; Portelinha, T C G; Larriera, A; Piña, C I

2018-03-12

The southern distribution of the Broad-snouted Caiman (Caiman latirostris Daudin 1802) in Argentina occurs in Santa Fe Province, where its population has been under management by "Proyecto Yacaré" since 1990. From 1997 to 2016, we captured 77 nesting female Broad-snouted Caimans in Santa Fe Province. Our results suggest that previously defined size classes for Broad-snouted Caiman do not adequately describe the reproductively mature female segment of the population. Here we propose to change size ranges for general size classes for Broad-snouted Caiman. In addition, we have observed that reintroduced reproductive females by Proyecto Yacaré represent about 32% of captured females. These results indicate that reintroduced females by the management program are surviving and reproducing in the wild at least up to 20 years.

Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

PubMed

Jurgeit, Andreas; McDowell, Robert; Moese, Stefan; Meldrum, Eric; Schwendener, Reto; Greber, Urs F

2012-01-01

Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

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 general—(1)...

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…

Broad Ligament Lipoleiomyoma Masses: Two curious cases masquerading as ovarian carcinomas.

PubMed

Yadav, Surekha; Maheswari, Barkha; Sagar, Nishant; Mallya, Varuna; Khurana, Nita; Gupta, Sangeeta

2017-11-01

Lipoleiomyomas are an extremely rare form of uterine leiomyoma; moreover, the occurrence of this type of tumour on the broad ligament is even rarer. We report two cases of broad ligament lipoleiomyomas in 15- and 38-year-old female patients who presented to the Lok Nayak Jai Prakash Hospital in New Delhi, India, between 2016 and 2017. In both cases, the preoperative diagnosis was of a solid ovarian malignancy. Most broad ligament tumours are mistaken for ovarian masses as they are difficult to diagnose radiologically.

Surface defect assisted broad spectra emission from CdSe quantum dots for white LED application

NASA Astrophysics Data System (ADS)

Samuel, Boni; Mathew, S.; Anand, V. R.; Correya, Adrine Antony; Nampoori, V. P. N.; Mujeeb, A.

2018-02-01

This paper reports, broadband photoluminescence from CdSe quantum dots (QDs) under the excitation of 403 nm using fluorimeter and 403 nm CW laser excitation. The broad spectrum obtained from the colloidal quantum dots was ranges from 450 nm to 800 nm. The broadness of the spectra was attributed to the merging of band edge and defect driven emissions from the QDs. Six different sizes of particles were prepared via kinetic growth method by using CdO and elemental Se as sources of Cd and Se respectively. The particle sizes were measured from TEM images. The size dependent effect on broad emission was also studied and the defect state emission was found to be predominant in very small QDs. The defect driven emission was also observed to be redshifted, similar to the band edge emission, due to quantum confinement effect. The emission corresponding to different laser power was also studied and a linear relation was obtained. In order to study the colour characteristics of the emission, CIE chromaticity coordinate, CRI and CCT of the prepared samples were measured. It is observed that, these values were tunable by the addition of suitable intensity of blue light from the excitation source to yield white light of various colour temperatures. The broad photoluminescence spectrum of the QDs, were compared with that of a commercially available white LED. It was found that the prepared QDs are good alternatives for the phosphor in phosphor converted white LEDs, to provide good spectral tunability.

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.

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.

Leiomyoma of broad ligament mimicking ovarian malignancy- report of a unique case.

PubMed

Mallick, D; Saha, M; Chakrabarti, S; Chakraborty, J

2014-01-01

Tumors of the broad ligament are uncommon. Leiomyoma, which is the commonest female genital neoplasm, is also the most common solid tumor of the broad ligament. Leiomyomas affect 30% of all women of reproductive age but the incidence of broad-ligament leiomyoma is <1%. These benign tumors are usually asymptomatic. A case is being described where a 52 year old presented with gradual abdominal swelling which was clinically and radiologically diagnosed as ovarian malignancy. On abdominal and bimanual palpation a soft cystic mass was noted in the right pelvic region. CA 125 was mildly raised. CEA, CA 19.9 levels were within normal limit. The radiological diagnosis was ovarian cyst with possibility of malignant changes. Staging laparotomy and histopathological examination of the resected specimen revealed a right sided broad ligament leiomyoma with cystic changes. The degenerative changes in the leiomyoma lead to the clinical and radiological diagnostic confusion. Thus, though uncommon, broad ligament leiomyoma should be considered during evaluation of adnexal masses for optimal patient management. The above description of leiomyoma in the broad ligament is a highly unique case and thus deserves appropriate attention.

The RF Probe: providing space situational awareness through broad-spectrum detection and characterization

NASA Astrophysics Data System (ADS)

Zenick, Raymond; Kohlhepp, Kimberly; Partch, Russell

2004-09-01

AeroAstro's patented RF Probe is a system designed to address the needs of spacecraft developers and operators interested in measuring and analyzing near-field RF emissions emanating from a nearby spacecraft of interest. The RF Probe consists of an intelligent spectrum analyzer with digital signal processing capabilities combined with a calibrated, wide-bandwidth antenna and RF front end that covers the 50 kHz to 18 GHz spectrum. It is capable of acquiring signal level and signal vector information, classifying signals, assessing the quality of a satellite"s transponders, and characterizing near-field electromagnetic emissions. The RF Probe is intended for either incorporation as part of a suite of spacecraft sensors, or as a stand-alone sensor on spacecraft or other platforms such as Unmanned Aerial Vehicles (UAVs). The RF Probe was initially conceived as a tool to detect and aid in diagnosis of malfunctions in a spacecraft of interest. However, the utility of the RF Probe goes far beyond this initial concept, spanning a wide range of military applications. Most importantly, the RF Probe can provide space situational awareness for critical on-orbit assets by detecting externally induced RF fields, aiding in protection against potentially devastating attacks.

Discovery of potent broad spectrum antivirals derived from marine actinobacteria.

PubMed

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

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

Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hargrove, Tatiana Y.; Garvey, Edward P.; Hoekstra, William J.

ABSTRACT Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungusAspergillus fumigatus. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole,more » ketoconazole, and posaconazole. The X-ray structure of the VT-1598/A. fumigatusCYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis ofA. fumigatusCYP51/voriconazole andCandida albicansCYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using twoA. fumigatusstrains (strains 32820 and 1022) displayed a direct correlation between the effects of the drugs on CYP51B activity and fungal growth inhibition, indicating the noteworthy anti-A. fumigatuspotency of VT-1598 and confirming its promise as a broad-spectrum antifungal agent.« less

Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity

PubMed Central

Hargrove, Tatiana Y.; Garvey, Edward P.; Hoekstra, William J.; Yates, Christopher M.; Wawrzak, Zdzislaw; Rachakonda, Girish; Villalta, Fernando

2017-01-01

ABSTRACT Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungus Aspergillus fumigatus. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole, ketoconazole, and posaconazole. The X-ray structure of the VT-1598/A. fumigatus CYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis of A. fumigatus CYP51/voriconazole and Candida albicans CYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using two A. fumigatus strains (strains 32820 and 1022) displayed a direct correlation between the effects of the drugs on CYP51B activity and fungal growth inhibition, indicating the noteworthy anti-A. fumigatus potency of VT-1598 and confirming its promise as a broad-spectrum antifungal agent. PMID:28461309

Potential Adverse Effects of Broad-Spectrum Antimicrobial Exposure in the Intensive Care Unit.

PubMed

Wiens, Jenna; Snyder, Graham M; Finlayson, Samuel; Mahoney, Monica V; Celi, Leo Anthony

2018-02-01

The potential adverse effects of empiric broad-spectrum antimicrobial use among patients with suspected but subsequently excluded infection have not been fully characterized. We sought novel methods to quantify the risk of adverse effects of broad-spectrum antimicrobial exposure among patients admitted to an intensive care unit (ICU). Among all adult patients admitted to ICUs at a single institution, we selected patients with negative blood cultures who also received ≥1 broad-spectrum antimicrobials. Broad-spectrum antimicrobials were categorized in ≥1 of 5 categories based on their spectrum of activity against potential pathogens. We performed, in serial, 5 cohort studies to measure the effect of each broad-spectrum category on patient outcomes. Exposed patients were defined as those receiving a specific category of broad-spectrum antimicrobial; nonexposed were all other patients in the cohort. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay and nosocomial acquisition of antimicrobial-resistant bacteria (ARB) or Clostridium difficile within 30 days of admission. Among the study cohort of 1918 patients, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay >7 days or an ICU length of stay >3 days, and 106 (5.5%) acquired either a nosocomial ARB or C. difficile . The short-term use of broad-spectrum antimicrobials in any of the defined broad-spectrum categories was not significantly associated with either primary or secondary outcomes. The prompt and brief empiric use of defined categories of broad-spectrum antimicrobials could not be associated with additional patient harm.

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

Viral Hemorrhagic Fevers

MedlinePlus

... Controls Cancel Submit Search the CDC Viral Hemorrhagic Fevers (VHFs) Note: Javascript is disabled or is not ... visit this page: About CDC.gov . Viral Hemorrhagic Fevers (VHFs) Virus Families Arenaviruses Old World/New World ...

Genistein, a general kinase inhibitor, as a potential antiviral for arenaviral hemorrhagic fever as described in the Pirital virus-Syrian golden hamster model.

PubMed

Vela, Eric M; Knostman, Katherine A; Mott, Jason M; Warren, Richard L; Garver, Jennifer N; Vela, Lela Johnson; Stammen, Rachelle L

2010-09-01

Arenaviruses are rodent-borne negative strand RNA viruses and infection of these viruses in humans may result in disease and hemorrhagic fever. To date, supportive care, ribavirin, and in some cases immune plasma remain the foremost treatment options for arenaviral hemorrhagic fever. Research with the hemorrhagic fever causing-arenaviruses usually requires a Biosafety level (BSL)-4 environment; however, surrogate animal model systems have been developed to preliminarily study and screen various vaccines and antivirals. The Syrian golden hamster-Pirital virus (PIRV) surrogate model of hemorrhagic fever provides an opportunity to test new antivirals in an ABSL-3 setting. Thus, we challenged hamsters, implanted with telemetry, with PIRV and observed viremia and tissue viral titers, and changes in core body temperature, hematology, clinical chemistry, and coagulation parameters. Physical signs of disease of the PIRV-infected hamsters included weight loss, lethargy, petechial rashes, epistaxis, ocular orbital and rectal hemorrhage, and visible signs of neurologic disorders. However, treating animals with genistein, a plant derived isoflavone and general kinase inhibitor, resulted in increased survival rates and led to an improved clinical profile. In all, the results from this study demonstrate the potential of a general kinase inhibitor genistein as an antiviral against arenaviral hemorrhagic fever. 2010 Elsevier B.V. All rights reserved.

Conserved residues in Lassa fever virus Z protein modulate viral infectivity at the level of the ribonucleoprotein.

PubMed

Capul, Althea A; de la Torre, Juan Carlos; Buchmeier, Michael J

2011-04-01

Arenaviruses are negative-strand RNA viruses that cause human diseases such as lymphocytic choriomeningitis, Bolivian hemorrhagic fever, and Lassa hemorrhagic fever. No licensed vaccines exist, and current treatment is limited to ribavirin. The prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is a model for dissecting virus-host interactions in persistent and acute disease. The RING finger protein Z has been identified as the driving force of arenaviral budding and acts as the viral matrix protein. While residues in Z required for viral budding have been described, residues that govern the Z matrix function(s) have yet to be fully elucidated. Because this matrix function is integral to viral assembly, we reasoned that this would be reflected in sequence conservation. Using sequence alignment, we identified several conserved residues in Z outside the RING and late domains. Nine residues were each mutated to alanine in Lassa fever virus Z. All of the mutations affected the expression of an LCMV minigenome and the infectivity of virus-like particles, but to greatly varying degrees. Interestingly, no mutations appeared to affect Z-mediated budding or association with viral GP. Our findings provide direct experimental evidence supporting a role for Z in the modulation of the activity of the viral ribonucleoprotein (RNP) complex and its packaging into mature infectious viral particles.

Reduction of Broad-Spectrum Antimicrobial Use in a Tertiary Children's Hospital Post Antimicrobial Stewardship Program Guideline Implementation.

PubMed

Lee, Kelley R; Bagga, Bindiya; Arnold, Sandra R

2016-03-01

broad-spectrum antibiotic use and acquisition cost. Programs with very limited resources may find similar implementation of guidelines effective to provide initial success, so that putting into practice one of the more resource intensive core strategies, such as prospective audit and feedback, may be feasible.

Finance issue brief: any willing provider: year end report-2002.

PubMed

Morgan, Rachel; MacEachern, Lillian

2002-12-31

Today, almost half the states have laws obligating managed care organizations (MCOs) such as health maintenance organizations (HMOs) and preferred provider organizations (PPOs) to contract with any willing health care provider. Although most provisions are limited to pharmacies or pharmacists, several states have adopted broad provisions applying to hospitals, physicians, chiropractors, pharmacists, podiatrists, therapists and nurses.

Finance issue brief: any willing provider: year end report-2003.

PubMed

MacEachern, Lillian

2003-12-31

Today, almost half the states have laws obligating managed care organizations (MCOs) such as health maintenance organizations (HMOs) and preferred provider organizations (PPOs) to contract with any willing health care provider. Although most provisions are limited to pharmacies or pharmacists, several states have adopted broad provisions applying to hospitals, physicians, chiropractors, pharmacists, podiatrists, therapists and nurses.

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

2008-11-03

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.

Investigating broad absorption line quasars with SDSS and UKIDSS .

NASA Astrophysics Data System (ADS)

Maddox, Natasha; Hewett, P. C.

The SDSS contains the largest set of spectroscopically confirmed broad line quasars ever compiled. Upon its completion, the UKIDSS LAS will provide a near-infrared counterpart to the SDSS, reaching 3 magnitudes deeper than 2MASS over a 4000 square degree area within the SDSS footprint. Combining the SDSS optical and UKIDSS near-infrared data, allows a new insight into the photometric and spectroscopic properties of broad absorption line quasars (BALQSOs) relative to the quasar population as a whole. An accurate estimate of the intrinsic BALQSO fraction is essential for determining the BAL cloud covering fraction and the implications for the co-evolution of accreting supermassive black holes and their host galaxies. Defining a K-band limited sample of quasars makes clear the significantly redder distribution of i-K colours of the BALQSOs. The BALQSO i-K colour distribution enables us to estimate a lower limit to the intrinsic BALQSO fraction, computed to be ˜ 30 percent, significantly larger than the optical fraction of 15-20 percent found by several authors. We combined the high-quality SDSS spectra of the quasar sample to make several composite spectra based on i-K colour, and the properties of these composites are compared to a composite spectrum of unreddened quasars. If the origin of the wavelength dependent differences between the red and unreddened objects is ascribed to attenuation by dust, we find that the extinction curve of the material is intermediate in form between the steep SMC-like extinction curve and the recent, empirically determined, extinction curve presented by Gaskell & Benker (2007).

Potential Adverse Effects of Broad-Spectrum Antimicrobial Exposure in the Intensive Care Unit

PubMed Central

Wiens, Jenna; Finlayson, Samuel; Mahoney, Monica V; Celi, Leo Anthony

2018-01-01

Abstract Background The potential adverse effects of empiric broad-spectrum antimicrobial use among patients with suspected but subsequently excluded infection have not been fully characterized. We sought novel methods to quantify the risk of adverse effects of broad-spectrum antimicrobial exposure among patients admitted to an intensive care unit (ICU). Methods Among all adult patients admitted to ICUs at a single institution, we selected patients with negative blood cultures who also received ≥1 broad-spectrum antimicrobials. Broad-spectrum antimicrobials were categorized in ≥1 of 5 categories based on their spectrum of activity against potential pathogens. We performed, in serial, 5 cohort studies to measure the effect of each broad-spectrum category on patient outcomes. Exposed patients were defined as those receiving a specific category of broad-spectrum antimicrobial; nonexposed were all other patients in the cohort. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay and nosocomial acquisition of antimicrobial-resistant bacteria (ARB) or Clostridium difficile within 30 days of admission. Results Among the study cohort of 1918 patients, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay >7 days or an ICU length of stay >3 days, and 106 (5.5%) acquired either a nosocomial ARB or C. difficile. The short-term use of broad-spectrum antimicrobials in any of the defined broad-spectrum categories was not significantly associated with either primary or secondary outcomes. Conclusions The prompt and brief empiric use of defined categories of broad-spectrum antimicrobials could not be associated with additional patient harm. PMID:29479546

Incorporating remotely sensed tree canopy cover data into broad scale assessments of wildlife habitat distribution and conservation

Treesearch

Sebastian Martinuzzi; Lee A. Vierling; William A. Gould; Kerri T. Vierling; Andrew T. Hudak

2009-01-01

Remote sensing provides critical information for broad scale assessments of wildlife habitat distribution and conservation. However, such efforts have been typically unable to incorporate information about vegetation structure, a variable important for explaining the distribution of many wildlife species. We evaluated the consequences of incorporating remotely sensed...

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…

10 CFR 35.15 - Exemptions regarding Type A specific licenses of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Exemptions regarding Type A specific licenses of broad... General Information § 35.15 Exemptions regarding Type A specific licenses of broad scope. A licensee possessing a Type A specific license of broad scope for medical use, issued under Part 33 of this chapter, is...

10 CFR 35.15 - Exemptions regarding Type A specific licenses of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Exemptions regarding Type A specific licenses of broad... General Information § 35.15 Exemptions regarding Type A specific licenses of broad scope. A licensee possessing a Type A specific license of broad scope for medical use, issued under part 33 of this chapter, is...

10 CFR 35.15 - Exemptions regarding Type A specific licenses of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Exemptions regarding Type A specific licenses of broad... General Information § 35.15 Exemptions regarding Type A specific licenses of broad scope. A licensee possessing a Type A specific license of broad scope for medical use, issued under Part 33 of this chapter, is...

10 CFR 35.15 - Exemptions regarding Type A specific licenses of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Exemptions regarding Type A specific licenses of broad... General Information § 35.15 Exemptions regarding Type A specific licenses of broad scope. A licensee possessing a Type A specific license of broad scope for medical use, issued under Part 33 of this chapter, is...

10 CFR 35.15 - Exemptions regarding Type A specific licenses of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Exemptions regarding Type A specific licenses of broad... General Information § 35.15 Exemptions regarding Type A specific licenses of broad scope. A licensee possessing a Type A specific license of broad scope for medical use, issued under Part 33 of this chapter, is...

FirebrowseR: an R client to the Broad Institute’s Firehose Pipeline

PubMed Central

Deng, Mario; Brägelmann, Johannes; Kryukov, Ivan; Saraiva-Agostinho, Nuno; Perner, Sven

2017-01-01

With its Firebrowse service (http://firebrowse.org/) the Broad Institute is making large-scale multi-platform omics data analysis results publicly available through a Representational State Transfer (REST) Application Programmable Interface (API). Querying this database through an API client from an arbitrary programming environment is an essential task, allowing other developers and researchers to focus on their analysis and avoid data wrangling. Hence, as a first result, we developed a workflow to automatically generate, test and deploy such clients for rapid response to API changes. Its underlying infrastructure, a combination of free and publicly available web services, facilitates the development of API clients. It decouples changes in server software from the client software by reacting to changes in the RESTful service and removing direct dependencies on a specific implementation of an API. As a second result, FirebrowseR, an R client to the Broad Institute’s RESTful Firehose Pipeline, is provided as a working example, which is built by the means of the presented workflow. The package’s features are demonstrated by an example analysis of cancer gene expression data. Database URL: https://github.com/mariodeng/ PMID:28062517

Dangertalk: Voices of abortion providers.

PubMed

Martin, Lisa A; Hassinger, Jane A; Debbink, Michelle; Harris, Lisa H

2017-07-01

Researchers have described the difficulties of doing abortion work, including the psychosocial costs to individual providers. Some have discussed the self-censorship in which providers engage in to protect themselves and the pro-choice movement. However, few have examined the costs of this self-censorship to public discourse and social movements in the US. Using qualitative data collected during abortion providers' discussions of their work, we explore the tensions between their narratives and pro-choice discourse, and examine the types of stories that are routinely silenced - narratives we name "dangertalk". Using these data, we theorize about the ways in which giving voice to these tensions might transform current abortion discourse by disrupting false dichotomies and better reflecting the complex realities of abortion. We present a conceptual model for dangertalk in abortion discourse, connecting it to functions of dangertalk in social movements more broadly. Copyright © 2017 Elsevier Ltd. All rights reserved.

A postmenopausal woman with sciatica from broad ligament leiomyoma: a case report.

PubMed

Tsai, Ya-Chu May

2016-10-31

Unilateral lower abdominal pain and/or sciatic nerve pain is a common presentation in the elderly population. The prevalence of broad ligament leiomyoma is <1 % with the prevalence declining after the menopause and it is rare for broad ligament leiomyomas to be clinically significant. Thus, we highlight a case of symptomatic broad ligament leiomyoma in a postmenopausal woman whose symptoms improved after definitive treatment. A 62-year-old postmenopausal Macedonian woman was referred to our gynecological department with unexplained pain in her left leg and left iliac fossa region on walking. There was minimal relief with increasing analgesia use prescribed by the family physician. Investigations revealed an ipsilateral adnexal mass and subsequent treatment with laparoscopic broad ligament myomectomy helped to alleviate her symptoms. Our case highlights the importance of staying mindful of alternate diagnoses when presented with a common presentation of iliac fossa pain and pain in the leg. Although broad ligament leiomyomas are benign tumors, the uncommon symptomatic presentation led us to report and focus some attention on this type of tumor.

The National Occupational Research Agenda: a model of broad stakeholder input into priority setting.

PubMed Central

Rosenstock, L; Olenec, C; Wagner, G R

1998-01-01

OBJECTIVES: No single organization has the resources necessary to conduct occupational safety and health research to adequately serve the needs of workers in the United States. The National Institute for Occupational Safety and Health (NIOSH) undertook the task of setting research priorities in response to a broadly perceived need to systematically address those topics most pressing and most likely to yield gains to workers and to the nation. METHODS: NIOSH and its public and private partners used a consensus-building process to set priorities for the next decade for occupational safety and health research--the National Occupational Research Agenda. RESULTS: The process resulted in the identification of 21 research priorities grouped into 3 categories: disease and injury, work environment and workforce, and research tools and approaches. CONCLUSIONS: Although the field of occupational safety and health is often contentious and adversarial, these research priorities reflect a remarkable degree of concurrence among a broad range of stakeholders who provided input into a clearly defined and open process. PMID:9518963

Weaknesses in Awarding Fees for the Broad Area Maritime Surveillance Contract

DTIC Science & Technology

2010-11-02

Table of Contents Introduction 1 Audit Objectives 1 Background on Broad Area Maritime Surveillance 1...24 Mangement Comments The Assistant Secretary of the Navy for Research, Development, and Acquisition 25... Introduction Audit Objectives This is the first in a series of reports on the contract supporting the Broad Area Maritime

48 CFR 35.016 - Broad agency announcement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Scientific Review (see 6.102(d)(2)) for the acquisition of basic and applied research and that part of... CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 35.016 Broad agency announcement. (a) General... documents, shall— (1) Describe the agency's research interest, either for an individual program requirement...

Broad absorption-line time variability in the QSO CSO 203

NASA Technical Reports Server (NTRS)

Barlow, Thomas A.; Junkkarinen, Vesa T.; Burbidge, E. M.; Weymann, Ray J.; Morris, Simon L.; Korista, Kirk T.

1992-01-01

We present spectroscopy of the BALQSO CSO 203 during four epochs over a 17-month time span. These data show three distinct levels in the broad absorption lines (BALs) of Si IV 1397A and C IV 1549A. We also note possible variations in the N V 1240A and Al III 1857A absorption troughs. A broad-band monitoring effort during this period shows that the continuum level remained constant to within 10 percent. We argue that the triggering mechanism for the absorption-line changes is most likely synchronous with the continuum source photons; however, no correlation with the central source has yet been found. The observed variations are consistent with changes in the ionization level in the broad absorption-line region (BALR). We discuss possible mechanisms for these changes and the implications for the structure of the BALR.

Leiomyosarcoma of the broad ligament: a case report with CT and MRI images.

PubMed

Makihara, N; Maeda, T; Ebina, Y; Kitajima, K; Kawakami, F; Hara, S; Yamada, H

2014-01-01

Primary leiomyosarcoma of the broad ligament is a very rare and highly malignant gynecological tumor. The authors report a 61-year-old postmenopausal woman with signs and symptoms of malignant ovarian tumor. Preoperative magnetic resonance imaging (MRI) was interpreted as being suspicious for malignant tumors, such as an ovarian cancer or a leiomyosarcoma of the broad ligament, so laparotomy was performed. Macroscopically, the tumor was revealed with a 18 x 13.7 x 9.5 cm degenerated, multiple cystic part and solid whitish part arising from broad ligament which on histopathology proved to be leiomyosarcoma. To the best of the authors' knowledge, primary leiomyosarcoma of the broad ligament has been documented in 21 reports or so, and no imaging findings are available. Here the authors present the MRI findings of primary leiomyosarcoma of the broad ligament.

Ablation centration after active eye tracker-assisted LASIK and comparison of flying-spot and broad-beam laser.

PubMed

Lin, Jane-Ming; Chen, Wen-Lu; Chiang, Chun-Chi; Tsai, Yi-Yu

2008-04-01

To evaluate ablation centration of flying-spot LASIK, investigate the effect of patient- and surgeon-related factors on centration, and compare flying-spot and broad-beam laser results. This retrospective study comprised 173 eyes of 94 patients who underwent LASIK with the Alcon LADARVision4000 with an active eye-tracking system. The effective tracking rate of the system is 100 Hz. The amount of decentration was analyzed by corneal topography. Patient- (low, high, and extreme myopia; effect of learning) and surgeon-related (learning curve) factors influencing centration were identified. Centration was compared to the SCHWIND Multiscan broad-beam laser with a 50-Hz tracker from a previous study. Mean decentration was 0.36+/-0.18 mm (range: 0 to 0.9 mm). Centration did not differ in low, high, and extreme myopia or in patients' first and second eyes. There were no significant differences in centration between the first 50 LASIK procedures and the last 50 procedures. Comparing flying-spot and broad-beam laser results, there were no differences in centration in low myopia. However, the LADARVision4000 yielded better centration results in high and extreme myopia. The Alcon LADARVision4000 active eye tracking system provides good centration for all levels of myopic correction and better centration than the Schwind broad-beam Multiscan in eyes with high and extreme myopia.

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.

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.

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.

33 CFR 334.475 - Brickyard Creek and tributaries and the Broad River at Beaufort, SC.

Code of Federal Regulations, 2014 CFR

2014-07-01

... and the Broad River at Beaufort, SC. 334.475 Section 334.475 Navigation and Navigable Waters CORPS OF....475 Brickyard Creek and tributaries and the Broad River at Beaufort, SC. (a) The areas: (1) That...°. (9) (Laurel Bay Military Family Housing Area, Broad River). That section of the Broad River...

33 CFR 334.475 - Brickyard Creek and tributaries and the Broad River at Beaufort, SC.

Code of Federal Regulations, 2012 CFR

2012-07-01

... and the Broad River at Beaufort, SC. 334.475 Section 334.475 Navigation and Navigable Waters CORPS OF....475 Brickyard Creek and tributaries and the Broad River at Beaufort, SC. (a) The areas: (1) That...°. (9) (Laurel Bay Military Family Housing Area, Broad River). That section of the Broad River...

33 CFR 334.475 - Brickyard Creek and tributaries and the Broad River at Beaufort, SC.

Code of Federal Regulations, 2013 CFR

2013-07-01

... and the Broad River at Beaufort, SC. 334.475 Section 334.475 Navigation and Navigable Waters CORPS OF....475 Brickyard Creek and tributaries and the Broad River at Beaufort, SC. (a) The areas: (1) That...°. (9) (Laurel Bay Military Family Housing Area, Broad River). That section of the Broad River...

33 CFR 334.475 - Brickyard Creek and tributaries and the Broad River at Beaufort, SC.

Code of Federal Regulations, 2011 CFR

2011-07-01

... and the Broad River at Beaufort, SC. 334.475 Section 334.475 Navigation and Navigable Waters CORPS OF....475 Brickyard Creek and tributaries and the Broad River at Beaufort, SC. (a) The areas: (1) That...°. (9) (Laurel Bay Military Family Housing Area, Broad River). That section of the Broad River...

33 CFR 334.475 - Brickyard Creek and tributaries and the Broad River at Beaufort, SC.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and the Broad River at Beaufort, SC. 334.475 Section 334.475 Navigation and Navigable Waters CORPS OF....475 Brickyard Creek and tributaries and the Broad River at Beaufort, SC. (a) The areas: (1) That...°. (9) (Laurel Bay Military Family Housing Area, Broad River). That section of the Broad River...

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…

Double-peaked broad line emission from the LINER nucleus of NGC 1097

NASA Technical Reports Server (NTRS)

Storchi-Bergmann, Thaisa; Baldwin, Jack A.; Wilson, Andrew S.

1993-01-01

We report the recent appearance of a very broad component in the H-alpha and H-beta emission lines of the weakly active nucleus of the Sersic-Pastoriza galaxy NGC 1097. The FWZI of the broad component is about 21,000 km/s, and its profile is double-peaked; the presence of a blue, featureless continuum in the nucleus is also suggested. The broad component was first observed in H-alpha in November 2, 1991, and confirmed 11 months later. The H-alpha profile and flux did not change in this time interval. Comparison with previously published spectral data indicates that the broad lines have only recently appeared. Together with the relatively high X-ray luminosity and the compact nuclear radio source, our results characterize the presence of a Seyfert 1 nucleus in a galaxy which had previously shown only LINER characteristics. Obscuring material along our line of sight to the nucleus appears to have recently cleared, permitting a direct view of the active nucleus. We discuss two possible structures for the broad line region, biconical outflow and an accretion disk, that could give rise to the observed profile.

A role for the C terminus of Mopeia virus nucleoprotein in its incorporation into Z protein-induced virus-like particles.

PubMed

Shtanko, Olena; Imai, Masaki; Goto, Hideo; Lukashevich, Igor S; Neumann, Gabriele; Watanabe, Tokiko; Kawaoka, Yoshihiro

2010-05-01

Arenaviruses are enveloped, negative-strand RNA viruses. For several arenaviruses, virus-like particle (VLP) formation requires the viral matrix Z protein. However, the mechanism by which viral ribonucleoprotein complexes are incorporated into virions is poorly understood. Here, we show that the expression of the Z protein and nucleoprotein (NP) of Mopeia virus, a close relative of the pathogenic Lassa virus, resulted in the highly selective incorporation of the NP protein into Z protein-induced VLPs. Moreover, the Z protein promoted the association of NP with cellular membranes, suggesting that the association of NP, Z, and the cellular membranes may facilitate the efficient incorporation of NP into VLPs. By employing a series of NP deletion constructs and testing their VLP incorporation, we further demonstrated an important role for the C-terminal half of NP in its incorporation into VLPs.

Quasars with P v broad absorption in BOSS data release 9

NASA Astrophysics Data System (ADS)

Capellupo, D. M.; Hamann, F.; Herbst, H.; Brandt, W. N.; Ge, J.; Pâris, I.; Petitjean, P.; Schneider, D. P.; Streblyanska, A.; York, D.

2017-07-01

Broad absorption lines (BALs) found in a significant fraction of quasar spectra identify high-velocity outflows that might be present in all quasars and could be a major factor in feedback to galaxy evolution. Understanding the nature of these flows requires further constraints on their physical properties, including their column densities, for which well-studied BALs, such as C IV λλ1548,1551, typically provide only a lower limit because of saturation effects. Low-abundance lines, such as P v λλ1118,1128, indicate large column densities, implying that outflows more powerful than measurements of C IV alone would indicate. We search through a sample of 2694 BAL quasars from the Sloan Digital Sky Survey III/Baryon Oscillation Spectroscopic Survey data release 9 quasar catalogue for such absorption, and we identify 81 'definite' and 86 'probable' detections of P v broad absorption, yielding a firm lower limit of 3.0-6.2 per cent for the incidence of such absorption among BAL quasars. The P v-detected quasars tend to have stronger C IV and Si IV absorption, as well as a higher incidence of LoBAL absorption, than the overall BAL quasar population. Many of the P v-detected quasars have C IV troughs that do not reach zero intensity (at velocities where P v is detected), confirming that the outflow gas only partially covers the UV continuum source. P v appears significantly in a composite spectrum of non-P v-detected BAL quasars, indicating that P v absorption (and large column densities) is much more common than indicated by our search results. Our sample of P v detections significantly increases the number of known P v detections, providing opportunities for follow-up studies to better understand BAL outflow energetics.

Hints of correlation between broad-line and radio variations for 3C 120

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, H. T.; Bai, J. M.; Li, S. K.

2014-01-01

In this paper, we investigate the correlation between broad-line and radio variations for the broad-line radio galaxy 3C 120. By the z-transformed discrete correlation function method and the model-independent flux randomization/random subset selection (FR/RSS) Monte Carlo method, we find that broad Hβ line variations lead the 15 GHz variations. The FR/RSS method shows that the Hβ line variations lead the radio variations by a factor of τ{sub ob} = 0.34 ± 0.01 yr. This time lag can be used to locate the position of the emitting region of radio outbursts in the jet, on the order of ∼5 lt-yr frommore » the central engine. This distance is much larger than the size of the broad-line region. The large separation of the radio outburst emitting region from the broad-line region will observably influence the gamma-ray emission in 3C 120.« less

48 CFR 1335.016-70 - DOC procedures for the use of broad agency announcements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false DOC procedures for the use of broad agency announcements. 1335.016-70 Section 1335.016-70 Federal Acquisition Regulations System... procedures for the use of broad agency announcements. Procedures for the use of broad agency announcements...

48 CFR 1335.016-70 - DOC procedures for the use of broad agency announcements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false DOC procedures for the use of broad agency announcements. 1335.016-70 Section 1335.016-70 Federal Acquisition Regulations System... procedures for the use of broad agency announcements. Procedures for the use of broad agency announcements...

48 CFR 1335.016-70 - DOC procedures for the use of broad agency announcements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false DOC procedures for the use of broad agency announcements. 1335.016-70 Section 1335.016-70 Federal Acquisition Regulations System... procedures for the use of broad agency announcements. Procedures for the use of broad agency announcements...

48 CFR 1335.016-70 - DOC procedures for the use of broad agency announcements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false DOC procedures for the use of broad agency announcements. 1335.016-70 Section 1335.016-70 Federal Acquisition Regulations System... procedures for the use of broad agency announcements. Procedures for the use of broad agency announcements...

48 CFR 1335.016-70 - DOC procedures for the use of broad agency announcements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false DOC procedures for the use of broad agency announcements. 1335.016-70 Section 1335.016-70 Federal Acquisition Regulations System... procedures for the use of broad agency announcements. Procedures for the use of broad agency announcements...

Designing for Broad Understanding of Science.

PubMed

Hristov, Nickolay; Strohecker, Carol; Allen, Louise; Merson, Martha

2018-06-04

With the acceleration and increasing complexity of macro-scale problems such as climate change, the need for scientists to ensure that their work is understood has become urgent. As citizens and recipients of public funds for research, scientists have an obligation to communicate their findings in ways many people can understand. However, developing translations that are broadly accessible without being "dumbed down" can be challenging. Fortunately, tenets of visual literacy, combined with narrative methods, can help to convey scientific knowledge with fidelity, while sustaining viewers' interest. Here we outline strategies for such translating, with an emphasis on visual approaches. Among the examples is an innovative, NSF-funded professional development initiative in which National Park rangers use scientists' imagery to create compelling explanations for the visiting public. Thoughtful visualizations based on interpretive images, motion pictures, 3D animations and augmented, immersive experiences complement the impact of the natural resource and enhance the role of the park ranger. The visualizations become scaffolds for participatory exchanges in which the ranger transcends the traditional roles of information-holder and presenter, to facilitate provocative conversations that provide members of the public with enjoyable experiences and well-founded bases for reflection and ultimately understanding. The process of generating the supporting visualizations benefits from partnerships with design professionals, who develop opportunities for engaging the public by translating important scientific findings and messages in compelling and memorable ways.

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.

Establishing Normative Reference Values for Standing Broad Jump among Hungarian Youth

ERIC Educational Resources Information Center

Saint-Maurice, Pedro F.; Laurson, Kelly R.; Kaj, Mónika; Csányi, Tamás

2015-01-01

Purpose: The purpose of this study was to examine age and sex trends in anaerobic power assessed by a standing broad jump and to determine norm-referenced values for youth in Hungary. Method: A sample of 2,427 Hungarian youth (1,360 boys and 1,067 girls) completed the standing broad jump twice, and the highest distance score was recorded. Quantile…

Strategies to induce broadly protective antibody responses to viral glycoproteins.

PubMed

Krammer, F

2017-05-01

Currently, several universal/broadly protective influenza virus vaccine candidates are under development. Many of these vaccines are based on strategies to induce protective antibody responses against the surface glycoproteins of antigenically and genetically diverse influenza viruses. These strategies might also be applicable to surface glycoproteins of a broad range of other important viral pathogens. Areas covered: Common strategies include sequential vaccination with divergent antigens, multivalent approaches, vaccination with glycan-modified antigens, vaccination with minimal antigens and vaccination with antigens that have centralized/optimized sequences. Here we review these strategies and the underlying concepts. Furthermore, challenges, feasibility and applicability to other viral pathogens are discussed. Expert commentary: Several broadly protective/universal influenza virus vaccine strategies will be tested in humans in the coming years. If successful in terms of safety and immunological readouts, they will move forward into efficacy trials. In the meantime, successful vaccine strategies might also be applied to other antigenically diverse viruses of concern.

Aerosol Absorption Retrievals from the PACE Broad Spectrum Ocean Color Instrument (OCI)

NASA Technical Reports Server (NTRS)

Mattoo, Shana; Remer, Lorraine A.; Levy, Robert C.; Gupta, Pawan; Ahmad, Ziauddin; Martins, J. Vanderlei; Lima, Adriana Rocha; Torres, Omar

2016-01-01

The PACE (Pre-­Aerosol, Clouds and ocean Ecosystem) mission, anticipated for launch in the early 2020s, is designed to characterize oceanic and atmospheric properties. The primary instrument on-­-board will be a moderate resolution (approximately 1 km nadir) radiometer, called the Ocean Color Instrument (OCI). OCI will provide high spectral resolution (5 nm) from the UV to NIR (350 - 800 nm), with additional spectral bands in the NIR and SWIR. The OCI itself is an excellent instrument for atmospheric objectives, providing measurements across a broad spectral range that in essence combines the capabilities of MODIS and OMI, but with the UV channels from OMI to be available at moderate resolution. (Image credit: PACE Science Definition Team Report). Objective: Can we make use of the UV-­SWIR measurements to derive information about aerosol absorption when aerosol loading is high?

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,…

MIPPA: First Broad Changes to Medicare Part D Plan Operations.

PubMed

LeMasurier, Jean D; Edgar, Babette

2009-04-01

In July 2008, as part of broad Medicare reform, Congress passed the first major legislative changes to Medicare Part D since its enactment in 2003-the Medicare Improvements for Patients and Providers Act. This new legislation has significant implications for how Part D plans can market and enroll Medicare beneficiaries. The new legislation also strengthened beneficiary protections, expanded the low-income subsidy provisions originally included in Part D, and expanded Part D coverage. These changes have significant implications for the operation of Part D plans and can affect those involved in benefit design, including specialty pharmacy coverage. This article discusses the major changes that took effect on January 1, 2009, and have immediate implications for Part D plan sponsors, including Medicare Advantage plans and stand-alone prescription drug plans.

MIPPA: First Broad Changes to Medicare Part D Plan Operations

PubMed Central

LeMasurier, Jean D.; Edgar, Babette

2009-01-01

In July 2008, as part of broad Medicare reform, Congress passed the first major legislative changes to Medicare Part D since its enactment in 2003—the Medicare Improvements for Patients and Providers Act. This new legislation has significant implications for how Part D plans can market and enroll Medicare beneficiaries. The new legislation also strengthened beneficiary protections, expanded the low-income subsidy provisions originally included in Part D, and expanded Part D coverage. These changes have significant implications for the operation of Part D plans and can affect those involved in benefit design, including specialty pharmacy coverage. This article discusses the major changes that took effect on January 1, 2009, and have immediate implications for Part D plan sponsors, including Medicare Advantage plans and stand-alone prescription drug plans. PMID:25126279

Broad photoelectron spectrum and lowered electron affinity due to hydrogen in ZnOH: A joint experimental and theoretical study

NASA Astrophysics Data System (ADS)

Iordanov, I.; Gunaratne, K. D. D.; Harmon, C. L.; Sofo, J. O.; Castleman, A. W.

2012-06-01

We report a combined experimental and theoretical photoelectron spectroscopy study of ZnOH-. We find that the electron binding energy spectrum of ZnOH- reveals a broad and featureless peak between 1.4 and 2.4 eV in energy. The vertical detachment energy (VDE) of ZnOH- is determined to be 1.78 eV, which is lower than the 2.08 eV VDE of ZnO-. Our theoretical calculations match the VDE of ZnOH- accurately, but we find that the broadness of the peak cannot be explained by rotational or vibrational state excitation. The broadness of this peak is in strong contrast to the narrow and easily understood first peak of the ZnO spectrum, which features a well-resolved vibrational progression that can be readily explained by calculating the Franck-Condon transition factors. This study provides spectroscopic evidence of the effect of hydrogen on diatomic ZnO.

Broad photoelectron spectrum and lowered electron affinity due to hydrogen in ZnOH: a joint experimental and theoretical study.

PubMed

Iordanov, I; Gunaratne, K D D; Harmon, C L; Sofo, J O; Castleman, A W

2012-06-07

We report a combined experimental and theoretical photoelectron spectroscopy study of ZnOH(-). We find that the electron binding energy spectrum of ZnOH(-) reveals a broad and featureless peak between 1.4 and 2.4 eV in energy. The vertical detachment energy (VDE) of ZnOH(-) is determined to be 1.78 eV, which is lower than the 2.08 eV VDE of ZnO(-). Our theoretical calculations match the VDE of ZnOH(-) accurately, but we find that the broadness of the peak cannot be explained by rotational or vibrational state excitation. The broadness of this peak is in strong contrast to the narrow and easily understood first peak of the ZnO spectrum, which features a well-resolved vibrational progression that can be readily explained by calculating the Franck-Condon transition factors. This study provides spectroscopic evidence of the effect of hydrogen on diatomic ZnO.

Risk Factors for Emergence of Resistance to Broad-Spectrum Cephalosporins among Enterobacter spp.

PubMed Central

Kaye, Keith S.; Cosgrove, Sara; Harris, Anthony; Eliopoulos, George M.; Carmeli, Yehuda

2001-01-01

Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalosporin-resistant Enterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3, P = 0.01); quinolone therapy was protective (OR = 0.4, P = 0.03). There were trends toward decreased risk for resistance among patients receiving broad-spectrum cephalosporins and either aminoglycosides or imipenem. Of the patients receiving broad-spectrum cephalosporins, 19% developed resistance. PMID:11502540

Extreme Variability in a Broad Absorption Line Quasar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stern, Daniel; Jun, Hyunsung D.; Graham, Matthew J.

CRTS J084133.15+200525.8 is an optically bright quasar at z = 2.345 that has shown extreme spectral variability over the past decade. Photometrically, the source had a visual magnitude of V ∼ 17.3 between 2002 and 2008. Then, over the following five years, the source slowly brightened by approximately one magnitude, to V ∼ 16.2. Only ∼1 in 10,000 quasars show such extreme variability, as quantified by the extreme parameters derived for this quasar assuming a damped random walk model. A combination of archival and newly acquired spectra reveal the source to be an iron low-ionization broad absorption line quasar withmore » extreme changes in its absorption spectrum. Some absorption features completely disappear over the 9 years of optical spectra, while other features remain essentially unchanged. We report the first definitive redshift for this source, based on the detection of broad H α in a Keck/MOSFIRE spectrum. Absorption systems separated by several 1000 km s{sup −1} in velocity show coordinated weakening in the depths of their troughs as the continuum flux increases. We interpret the broad absorption line variability to be due to changes in photoionization, rather than due to motion of material along our line of sight. This source highlights one sort of rare transition object that astronomy will now be finding through dedicated time-domain surveys.« less

Development of a Memory Game to Improve Knowledge Retention in Preparation for Broad Scope Exams in an Introductory Earth Science Course

NASA Astrophysics Data System (ADS)

Cook, H. M.; Bilsley, N. A.

2015-12-01

As the demand for introductory earth science classes rises at educational institutions, large class sizes place strain on the educator's time and ability to offer extensive project-based assignments. As a result, exams covering a broad spectrum of material are more heavily weighted in students' grades. Students often struggle on the first exam, as they attempt to retain a large amount of information from several different topics, while having no exposure to the type of questions that will be asked. This frequently leads to a large dropout rate early in the academic term, or at least a sense of discouragement and stress among struggling students. To better prepare students for a broad scope exam, a review activity modelled after the traditional Milton Bradley "Memory" game was developed to remind students of what would be covered on the exam, prepare them for the style of questions that may be asked, as well as provide a fun, interactive, and educational activity. The Earth Science Memory Game was developed to have interchangeable sets to cover a broad range of topics and thus also be reusable for the duration of the course. Example games sets presented include, but are not limited to, the scientific method, minerals, rocks, topographic maps, tectonics, geologic structures, volcanoes, and weather. The Earth Science Memory Game not only provides an effective review tool to improve success rates on broad scope exams, but is also customizable by the instructor, reusable, and easily constructed by common office supplies.

Provider Opinions Regarding the Development of a Stigma-Reduction Intervention Tailored for Providers.

PubMed

Mittal, Dinesh; Corrigan, Patrick; Drummond, Karen L; Porchia, Sylvia; Sullivan, Greer

2016-10-01

Interventions involving contact with a person who has recovered from mental illness are most effective at reducing stigma. This study sought input from health care providers to inform the design of a contact intervention intended to reduce provider stigma toward persons with serious mental illness. Using a purposive sampling strategy, data were collected from providers at five Veterans Affairs hospitals in the southeastern United States. Seven focus groups were conducted, and 83 health care providers participated. A semistructured interview guide was used to elicit providers' opinions about the target group of a contact intervention for providers, what providers would consider a credible contact, the preferred format for delivery, the usefulness of potentially tailoring the intervention to a specific facility, and how to measure change in clinical behaviors. Focus group data were analyzed using rapid data analysis techniques. Participants uniformly recommended a broad target audience for the stigma-reduction intervention, including all primary care and specialist providers. They suggested that the person providing the "lived experience" for the contact intervention should be either a health care provider or a patient with serious mental illness. Face-to-face presentation was favored, but video presentation was considered more feasible. Participants stated that information about local disparities in care rendered to patients with or without mental illness would convince providers of how stigma may be a contributing factor to these disparities. Multiple training opportunities were favored, while mandatory training was disliked. Standard stigma-reduction interventions with subgroups of the general public (e.g., providers) may need to be modified for optimum subgroup effectiveness. © 2015 Society for Public Health Education.

Testing Event Discrimination over Broad Regions using the Historical Borovoye Observatory Explosion Dataset

NASA Astrophysics Data System (ADS)

Pasyanos, Michael E.; Ford, Sean R.; Walter, William R.

2014-03-01

We test the performance of high-frequency regional P/S discriminants to differentiate between earthquakes and explosions at test sites and over broad regions using a historical dataset of explosions recorded at the Borovoye Observatory in Kazakhstan. We compare these explosions to modern recordings of earthquakes at the same location. We then evaluate the separation of the two types of events using the raw measurements and those where the amplitudes are corrected for 1-D and 2-D attenuation structure. We find that high-frequency P/S amplitudes can reliably identify earthquakes and explosions, and that the discriminant is applicable over broad regions as long as propagation effects are properly accounted for. Lateral attenuation corrections provide the largest improvement in the 2-4 Hz band, the use of which may successfully enable the identification of smaller, distant events that have lower signal-to-noise at higher frequencies. We also find variations in P/S ratios among the three main nuclear testing locations within the Semipalatinsk Test Site which, due to their nearly identical paths to BRVK, must be a function of differing geology and emplacement conditions.

Broad economic benefits of freight transportation infrastructure improvement.

DOT National Transportation Integrated Search

2012-06-01

This project strives to introduce a novel way to quantify the broad re-organization benefits associated with an : improvement in the freight infrastructure. Using the approach based on 1) the technique known as Field of Influence, and : 2) RAS adjust...

Provider satisfaction in army primary care clinics.

PubMed

Byers, V L; Mays, M Z; Mark, D D

1999-02-01

The job satisfaction of physicians, nurse practitioners, and physician assistants was assessed during the course of a multicenter study of Army primary care clinics. All providers in nine clinics at three medical centers who were engaged in adult or family care were invited to participate in the study. Questionnaires on job satisfaction and other practice style variables were completed by 26 physicians, 19 nurse practitioners, and 13 physician assistants (46, 76, and 41% of eligible providers, respectively). Analysis revealed a broad range of job satisfaction in the sample. However, average levels of job satisfaction were not significantly different across the three groups of primary care providers. Autonomy and collaboration were significant predictors of job satisfaction. It is clear that changes in health care systems that reduce, or appear to reduce, the primary care provider's autonomy in clinical matters are likely to reduce provider satisfaction as well.

Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising

DOE PAGES

Luo, Shishi; Perelson, Alan S.

2015-08-31

The past decade has seen the discovery of numerous broad and potent monoclonal antibodies against HIV type 1 (HIV-1). Eliciting these antibodies via vaccination appears to be remarkably difficult, not least because they arise late in infection and are highly mutated relative to germline antibody sequences. Here, using a computational model, we show that broad antibodies could in fact emerge earlier and be less mutated, but that they may be prevented from doing so as a result of competitive exclusion by the autologous antibody response. We further find that this competitive exclusion is weaker in infections founded by multiple distinctmore » strains, with broadly neutralizing antibodies emerging earlier than in infections founded by a single strain. Our computational model simulates coevolving multitype virus and antibody populations. Broadly neutralizing antibodies may therefore be easier for the adaptive immune system to generate than previously thought. As a result, if less mutated broad antibodies exist, it may be possible to elicit them with a vaccine containing a mixture of diverse virus strains.« less

Crx broadly modulates the pineal transcriptome

PubMed Central

Rovsing, Louise; Clokie, Samuel; Bustos, Diego M.; Rohde, Kristian; Coon, Steven L.; Litman, Thomas; Rath, Martin F.; Møller, Morten; Klein, David C.

2011-01-01

Cone-rod homeobox (Crx) encodes Crx, a transcription factor expressed selectively in retinal photoreceptors and pinealocytes, the major cell type of the pineal gland. Here, the influence of Crx on the mammalian pineal gland was studied by light and electron microscopy and by use of microarray and qRTPCR technology, thereby extending previous studies on selected genes (Furukawa et al. 1999). Deletion of Crx was not found to alter pineal morphology, but was found to broadly modulate the mouse pineal transcriptome, characterized by a >2-fold downregulation of 543 genes and a >2-fold upregulation of 745 genes (p < 0.05). Of these, one of the most highly upregulated (18-fold) is Hoxc4, a member of the Hox gene family, members of which are known to control gene expression cascades. During a 24-hour period, a set of 51 genes exhibited differential day/night expression in pineal glands of wild-type animals; only eight of these were also day/night expressed in the Crx−/− pineal gland. However, in the Crx−/− pineal gland 41 genes exhibit differential night/day expression that is not seen in wild-type animals. These findings indicate that Crx broadly modulates the pineal transcriptome and also influences differential night/day gene expression in this tissue. Some effects of Crx deletion on the pineal transcriptome might be mediated by Hoxc4 upregulation. PMID:21797868

Observations and Simulations of Formation of Broad Plasma Depletions Through Merging Process

NASA Technical Reports Server (NTRS)

Huang, Chao-Song; Retterer, J. M.; Beaujardiere, O. De La; Roddy, P. A.; Hunton, D.E.; Ballenthin, J. O.; Pfaff, Robert F.

2012-01-01

Broad plasma depletions in the equatorial ionosphere near dawn are region in which the plasma density is reduced by 1-3 orders of magnitude over thousands of kilometers in longitude. This phenomenon is observed repeatedly by the Communication/Navigation Outage Forecasting System (C/NOFS) satellite during deep solar minimum. The plasma flow inside the depletion region can be strongly upward. The possible causal mechanism for the formation of broad plasma depletions is that the broad depletions result from merging of multiple equatorial plasma bubbles. The purpose of this study is to demonstrate the feasibility of the merging mechanism with new observations and simulations. We present C/NOFS observations for two cases. A series of plasma bubbles is first detected by C/NOFS over a longitudinal range of 3300-3800 km around midnight. Each of the individual bubbles has a typical width of approx 100 km in longitude, and the upward ion drift velocity inside the bubbles is 200-400 m/s. The plasma bubbles rotate with the Earth to the dawn sector and become broad plasma depletions. The observations clearly show the evolution from multiple plasma bubbles to broad depletions. Large upward plasma flow occurs inside the depletion region over 3800 km in longitude and exists for approx 5 h. We also present the numerical simulations of bubble merging with the physics-based low-latitude ionospheric model. It is found that two separate plasma bubbles join together and form a single, wider bubble. The simulations show that the merging process of plasma bubbles can indeed occur in incompressible ionospheric plasma. The simulation results support the merging mechanism for the formation of broad plasma depletions.

Comprehensive evaluation of broad-beam transmission of patient supports from three fluoroscopy-guided interventional systems.

PubMed

DeLorenzo, Matthew C; Yang, Kai; Li, Xinhua; Liu, Bob

2018-04-01

Trumpf transmission factors were the lowest. The data were successfully fitted to a function of angle, field size, kVp, and added Cu filtration using nine parameters, with an average R 2 value of 0.977 and maximum percentage difference of 4.08%. This study evaluated the broad-beam transmission for three representative fluoroscopy systems and their dependency on angle, kVp, added Cu filter, and field size. The comprehensive data provided for patient support transmission will facilitate accurate calculation of peak skin dose (PSD) and may potentially be integrated into real-time and retrospective dose monitoring with access to Radiation Dose Structured Reports (RDSR) and radiation event data. © 2018 American Association of Physicists in Medicine.

Exploring Broad Area Quantum Cascade Lasers

DTIC Science & Technology

2017-10-01

Research Laboratory AFRL /RDLTD 3550 Aberdeen Ave SE Kirtland AFB, NM 87117-5776 11. SPONSOR/MONITOR’S REPORT NUMBER(S) AFRL -RD-PS-TP-2017-0008 12...LIST DTIC/OCP 8725 John J. Kingman Rd, Suite 0944 Ft Belvoir, VA 22060-6218 1 cy AFRL /RVIL Kirtland AFB, NM 87117-5776 1 cy Chunte Lu... AFRL -RD-PS- AFRL -RD-PS- TP-2017-0008 TP-2017-0008 EXPLORING BROAD AREA QUANTUM CASCADE LASERS Tim Newell, et. al. 1 October 2017 Technical

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.

10 CFR 33.13 - Requirements for the issuance of a Type A specific license of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of broad scope. 33.13 Section 33.13 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.13 Requirements for the issuance of a Type A specific license of broad scope. An application for a Type A specific license of broad...

10 CFR 33.13 - Requirements for the issuance of a Type A specific license of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... of broad scope. 33.13 Section 33.13 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.13 Requirements for the issuance of a Type A specific license of broad scope. An application for a Type A specific license of broad...

10 CFR 33.14 - Requirements for the issuance of a Type B specific license of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of broad scope. 33.14 Section 33.14 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.14 Requirements for the issuance of a Type B specific license of broad scope. An application for a Type B specific license of broad...

10 CFR 33.13 - Requirements for the issuance of a Type A specific license of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of broad scope. 33.13 Section 33.13 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.13 Requirements for the issuance of a Type A specific license of broad scope. An application for a Type A specific license of broad...

10 CFR 33.14 - Requirements for the issuance of a Type B specific license of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... of broad scope. 33.14 Section 33.14 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.14 Requirements for the issuance of a Type B specific license of broad scope. An application for a Type B specific license of broad...

10 CFR 33.14 - Requirements for the issuance of a Type B specific license of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of broad scope. 33.14 Section 33.14 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.14 Requirements for the issuance of a Type B specific license of broad scope. An application for a Type B specific license of broad...

10 CFR 33.14 - Requirements for the issuance of a Type B specific license of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... of broad scope. 33.14 Section 33.14 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.14 Requirements for the issuance of a Type B specific license of broad scope. An application for a Type B specific license of broad...

10 CFR 33.14 - Requirements for the issuance of a Type B specific license of broad scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of broad scope. 33.14 Section 33.14 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.14 Requirements for the issuance of a Type B specific license of broad scope. An application for a Type B specific license of broad...

10 CFR 33.15 - Requirements for the issuance of a Type C specific license of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... of broad scope. 33.15 Section 33.15 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.15 Requirements for the issuance of a Type C specific license of broad scope. An application for a Type C specific license of broad...

10 CFR 33.13 - Requirements for the issuance of a Type A specific license of broad scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of broad scope. 33.13 Section 33.13 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.13 Requirements for the issuance of a Type A specific license of broad scope. An application for a Type A specific license of broad...

10 CFR 33.15 - Requirements for the issuance of a Type C specific license of broad scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of broad scope. 33.15 Section 33.15 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.15 Requirements for the issuance of a Type C specific license of broad scope. An application for a Type C specific license of broad...

10 CFR 33.15 - Requirements for the issuance of a Type C specific license of broad scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... of broad scope. 33.15 Section 33.15 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.15 Requirements for the issuance of a Type C specific license of broad scope. An application for a Type C specific license of broad...

10 CFR 33.13 - Requirements for the issuance of a Type A specific license of broad scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... of broad scope. 33.13 Section 33.13 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES OF BROAD SCOPE FOR BYPRODUCT MATERIAL Specific Licenses of Broad Scope § 33.13 Requirements for the issuance of a Type A specific license of broad scope. An application for a Type A specific license of broad...

Broad-line Type Ic supernova SN 2014ad

NASA Astrophysics Data System (ADS)

Sahu, D. K.; Anupama, G. C.; Chakradhari, N. K.; Srivastav, S.; Tanaka, Masaomi; Maeda, Keiichi; Nomoto, Ken'ichi

2018-04-01

We present optical and ultraviolet photometry and low-resolution optical spectroscopy of the broad-line Type Ic supernova SN 2014ad in the galaxy PGC 37625 (Mrk 1309), covering the evolution of the supernova during -5 to +87 d with respect to the date of maximum in the B band. A late-phase spectrum obtained at +340 d is also presented. With an absolute V-band magnitude at peak of MV = -18.86 ± 0.23 mag, SN 2014ad is fainter than supernovae associated with gamma ray bursts (GRBs), and brighter than most of the normal and broad-line Type Ic supernovae without an associated GRB. The spectral evolution indicates that the expansion velocity of the ejecta, as measured using the Si II line, is as high as ˜33 500 km s-1 around maximum, while during the post-maximum phase it settles at ˜15 000 km s-1. The expansion velocity of SN 2014ad is higher than that of all other well-observed broad-line Type Ic supernovae except for the GRB-associated SN 2010bh. The explosion parameters, determined by applying Arnett's analytical light-curve model to the observed bolometric light-curve, indicate that it was an energetic explosion with a kinetic energy of ˜(1 ± 0.3) × 1052 erg and a total ejected mass of ˜(3.3 ± 0.8) M⊙, and that ˜0.24 M⊙ of 56Ni was synthesized in the explosion. The metallicity of the host galaxy near the supernova region is estimated to be ˜0.5 Z⊙.

Development of a broad-spectrum antiviral with activity against Ebola virus.

PubMed

Aman, M Javad; Kinch, Michael S; Warfield, Kelly; Warren, Travis; Yunus, Abdul; Enterlein, Sven; Stavale, Eric; Wang, Peifang; Chang, Shaojing; Tang, Qingsong; Porter, Kevin; Goldblatt, Michael; Bavari, Sina

2009-09-01

We report herein the identification of a small molecule therapeutic, FGI-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including Ebola, Rift Valley and Dengue Fever viruses, in cell-based assays. Using mouse models of Ebola virus, we further demonstrate that FGI-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. A single treatment, administered 1 day after infection, is sufficient to protect animals from lethal Ebola virus challenge. Cell-based assays also identified inhibitory activity against divergent virus families, which supports a hypothesis that FGI-106 interferes with a common pathway utilized by different viruses. These findings suggest FGI-106 may provide an opportunity for targeting viral diseases.

Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses

PubMed Central

Sheahan, Timothy P.; Sims, Amy C.; Graham, Rachel L.; Menachery, Vineet D.; Gralinski, Lisa E.; Case, James B.; Leist, Sarah R.; Pyrc, Krzysztof; Feng, Joy Y.; Trantcheva, Iva; Bannister, Roy; Park, Yeojin; Babusis, Darius; Clarke, Michael O.; Mackman, Richard L.; Spahn, Jamie E.; Palmiotti, Christopher A.; Siegel, Dustin; Ray, Adrian S.; Cihlar, Tomas; Jordan, Robert; Denison, Mark R.; Baric, Ralph S.

2017-01-01

Emerging viral infections are difficult to control as heterogeneous members periodically cycle in and out of humans and zoonotic hosts, complicating the development of specific antiviral therapies and vaccines. Coronaviruses (CoVs) have a proclivity to spread rapidly into new host species causing severe disease. SARS-CoV and MERS-CoV successively emerged causing severe epidemic respiratory disease in immunologically naïve human populations throughout the globe. Broad-spectrum therapies capable of inhibiting CoV infections would address an immediate unmet medical need and could be invaluable in the treatment of emerging and endemic CoV infections. Here we show that a nucleotide prodrug GS-5734, currently in clinical development for treatment of Ebola virus disease, can inhibit SARS-CoV and MERS-CoV replication in multiple in vitro systems including primary human airway epithelial cell cultures with submicromolar IC50 values. GS-5734 was also effective against bat-CoVs, prepandemic bat-CoVs and circulating contemporary human CoV in primary human lung cells, thus demonstrating broad-spectrum anti-CoV activity. In a mouse model of SARS-CoV pathogenesis, prophylactic and early therapeutic administration of GS-5734 significantly reduced lung viral load and improved clinical signs of disease as well as respiratory functions. These data provide substantive evidence that GS-5734 may prove effective against endemic MERS-CoV in the Middle East, circulating human CoV, and possibly most importantly, emerging CoV of the future. PMID:28659436

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

Drug-nutrient interactions: a broad view with implications for practice.

PubMed

Boullata, Joseph I; Hudson, Lauren M

2012-04-01

The relevance of drug?nutrient interactions in daily practice continues to grow with the widespread use of medication. Interactions can involve a single nutrient, multiple nutrients, food in general, or nutrition status. Mechanistically, drug?nutrient interactions occur because of altered intestinal transport and metabolism, or systemic distribution, metabolism and excretion, as well as additive or antagonistic effects. Optimal patient care includes identifying, evaluating, and managing these interactions. This task can be supported by a systematic approach for categorizing interactions and rating their clinical significance. This review provides such a broad framework using recent examples, as well as some classic drug?nutrient interactions. Pertinent definitions are presented, as is a suggested approach for clinicians. This important and expanding subject will benefit tremendously from further clinician involvement. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Broad autism spectrum and obsessive-compulsive symptoms in adults with the fragile X premutation.

PubMed

Schneider, A; Johnston, C; Tassone, F; Sansone, S; Hagerman, R J; Ferrer, E; Rivera, S M; Hessl, D

2016-08-01

Clinical observations and a limited number of research studies provide evidence that the fragile X premutation may confer risk for autism, executive dysfunction, and psychopathology. The link to autism spectrum symptoms and social cognition deficits with the premutation remains uncertain, and thus was the focus of the present investigation. Our sample included 131 individuals, 42 men/22 women with the FMR1 premutation (mean age = 31.83 ± 8.59 years) with a normal neurological exam, and 48 men/19 women healthy age-matched controls (mean age = 29.48 ± 7.29 years). Individuals completed a comprehensive neuropsychological battery with additional assessments for social cognition, broad autism spectrum, and obsessive-compulsive (OC) symptoms. Premutation carriers self-reported higher rates of autism-related symptoms (Autism Quotient; p = .001). Among males only, premutation carriers showed more atypical social interaction (p < .001) and stereotyped behavior (p = .014) during standardized clinical examination on the Autism Diagnostic Observation Schedule (ADOS) relative to controls. Female premutation carriers reported significantly higher rates of OC symptoms compared to control females (p = .012). Molecular measures defining the expanded premutation (FMR1 CGG repeat length and/or mRNA) were significantly associated with a measure of theory of mind (Reading the Mind in the Eyes Task). The results of this study indicate a higher rate of broad autism spectrum symptoms in some males with the premutation and provide evidence for an obsessive-compulsive subtype in female premutation carriers.

The broad ligament: a review of its anatomy and development in different species and hormonal environments.

PubMed

Miller, Anne; Hong, Matthew K-H; Hutson, John M

2004-04-01

The broad ligament is a double fold of peritoneum forming a mesentery for the human female genital tract. We investigated the anatomy of the broad ligament in different species and its hormonal regulation to determine if it had a role in gonadal positioning. The medical and veterinary literature was reviewed for descriptions of broad ligament anatomy and development. In addition, four adult female rats were dissected to compare the macroscopic anatomy of the broad ligament with any homologous structures in the male (n = 2). Detailed review was made of human males with persistent Müllerian duct syndrome (PMDS) and of bovine freemartin calves to determine the effect of abnormal hormonal environments on broad ligament development. Human and veterinary texts show variable broad ligament development between species, most being consistent with the size and shape of the uterus and uterine tubes. The broad ligament in adult female rats is a simple peritoneal fold and is homologous with the mesentery of the testis and vas deferens in males. Patients with PMDS and bovine freemartins have a broad ligament with intermediate anatomy. In PMDS the broad ligament is elongated and narrow, and not attached to the pelvic wall. The broad ligament is the mesentery of the genital ducts, and its anatomy varies with the degree of Müllerian duct fusion. The absence of a human male homologue is unusual, as the genital mesentery persists in male rodents. Apparent lack of a male homologue in the human may relate to obliteration of the processus vaginalis. The variable development of the broad ligament in pathological conditions is consistent with a role for steroid hormones in its development. Copyright 2004 Wiley-Liss, Inc.

Transcriptome sequencing and annotation for the Jamaican fruit bat (Artibeus jamaicensis).

PubMed

Shaw, Timothy I; Srivastava, Anuj; Chou, Wen-Chi; Liu, Liang; Hawkinson, Ann; Glenn, Travis C; Adams, Rick; Schountz, Tony

2012-01-01

The Jamaican fruit bat (Artibeus jamaicensis) is one of the most common bats in the tropical Americas. It is thought to be a potential reservoir host of Tacaribe virus, an arenavirus closely related to the South American hemorrhagic fever viruses. We performed transcriptome sequencing and annotation from lung, kidney and spleen tissues using 454 and Illumina platforms to develop this species as an animal model. More than 100,000 contigs were assembled, with 25,000 genes that were functionally annotated. Of the remaining unannotated contigs, 80% were found within bat genomes or transcriptomes. Annotated genes are involved in a broad range of activities ranging from cellular metabolism to genome regulation through ncRNAs. Reciprocal BLAST best hits yielded 8,785 sequences that are orthologous to mouse, rat, cattle, horse and human. Species tree analysis of sequences from 2,378 loci was used to achieve 95% bootstrap support for the placement of bat as sister to the clade containing horse, dog, and cattle. Through substitution rate estimation between bat and human, 32 genes were identified with evidence for positive selection. We also identified 466 immune-related genes, which may be useful for studying Tacaribe virus infection of this species. The Jamaican fruit bat transcriptome dataset is a resource that should provide additional candidate markers for studying bat evolution and ecology, and tools for analysis of the host response and pathology of disease.

Selected emerging infectious diseases of squamata.

PubMed

Latney, La'toya V; Wellehan, James

2013-05-01

It is important that reptile clinicians have an appreciation for the epidemiology, clinical signs, pathology, diagnostic options, and prognostic parameters for novel and emerging infectious diseases in squamates. This article provides an update on emerging squamate diseases reported in the primary literature within the past decade. Updates on adenovirus, iridovirus, rhabdovirus, arenavirus, and paramyxovirus epidemiology, divergence, and host fidelity are presented. A new emerging bacterial disease of Uromastyx species, Devriesea agamarum, is reviewed. Chrysosporium ophiodiicola-associated mortality in North American snakes is discussed. Cryptosporidium and pentastomid infections in squamates are highlighted among emerging parasitic infections. Copyright © 2013 Elsevier Inc. All rights reserved.

Hypersensitivity linked to exposure of broad bean protein(s) in allergic patients and BALB/c mice.

PubMed

Kumar, Dinesh; Kumar, Sandeep; Verma, Alok K; Sharma, Akanksha; Tripathi, Anurag; Chaudhari, Bhushan P; Kant, Surya; Das, Mukul; Jain, Swatantra K; Dwivedi, Premendra D

2014-01-01

Broad bean (Vicia faba L.), a common vegetable, belongs to the family Fabaceae and is consumed worldwide. Limited studies have been done on allergenicity of broad beans. The aim of this study was to determine if broad bean proteins have the ability to elicit allergic responses due to the presence of clinically relevant allergenic proteins. Simulated gastric fluid (SGF) assay and immunoglobulin E (IgE) immunoblotting were carried out to identify pepsin-resistant and IgE-binding proteins. The allergenicity of broad beans was assessed in allergic patients, BALB/c mice, splenocytes, and RBL-2H3 cells. Eight broad bean proteins of approximate molecular weight 70, 60, 48, 32, 23, 19, 15, and 10 kDa that remained undigested in SGF, showed IgE-binding capacity as well. Of 127 allergic patients studied, broad bean allergy was evident in 16 (12%). Mice sensitized with broad bean showed increased levels of histamine, total and specific IgE, and severe signs of systemic anaphylaxis compared with controls. Enhanced levels of histamine, prostaglandin D2, cysteinyl leukotriene, and β-hexosaminidase release were observed in the primed RBL-2H3 cells following broad bean exposure. The levels of interleukin IL-4, IL-5, IL-13 and regulated on activation, normal T-cell expressed and secreted were found enhanced in broad bean-treated splenocytes culture supernatant compared with controls. This study inferred that broad bean proteins have the ability to elicit allergic responses due to the presence of clinically relevant allergenic proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

WPVS 007: Dramatic Broad Absorption Line Variability in a Narrow-line Seyfert 1

NASA Astrophysics Data System (ADS)

Cooper, Erin M.; Leighly, K.; Hamann, F. W.; Grupe, D.; Dietrich, M.

2014-01-01

Blue-shifted broad absorption lines are the manifestation of gaseous outflows in astrophysical phenomena. In active galaxies, these outflowing winds may play a key role in the central engine physics by removing angular momentum and in influencing host galaxy evolution by imparting energy and chemically enriched gas to the surrounding medium. AGN wind variability affords us a valuable tool to study this still poorly understood phenomenon. The existence of a high velocity broad line outflow in WPVS007 is especially extraordinary, as Seyfert-luminosity active galaxies are unexpected to produce them. With its lower luminosity and compact size, the NLS1 galaxy WPVS007 (M_V=-19.7, z=0.02882) provides us the ability to study even colossal variability on merely human timescales. Since its 1996 FOS observation, displaying miniBALs but no true broad absorption lines, WPVS007 has experienced a short but rich history of UV BAL variability. By the 2003 FUSE observation, WPVS007 had developed a BAL with v_max ~ 6000km/s, indicating an optically thick, high velocity outflow. We present the 2010 and 2013 June and December HST COS spectra. Between 2003 and 2010, both the maximum and minimum outflow velocity had increased substantially. As of 2013 June, the continuum emission has since dimmed by a factor of ~2 and the BALs have appeared to weaken, with both decreased maximum and minimum velocities. Such dramatic shifts in BAL velocity are unprecedented, as BAL variability is typically confined to changes in optical depth. What is the nature of the variability in this BAL wind? The upcoming (as of the writing of this abstract) December observation should give us more insight into tackling that question, whether it be the transient response of a continuous flow to a fluctuating continuum or perhaps the continued decline of a discrete outflow event.

Holographic injection locking of a broad area laser diode via a photorefractive thin-film device.

PubMed

van Voorst, P D; de Wit, M R; Offerhaus, H L; Tay, S; Thomas, J; Peyghambarian, N; Boller, K-J

2007-12-24

We demonstrate locking of a high power broad area laser diode to a single frequency using holographic feedback from a photorefractive polymer thin-film device for the first time. A four-wave mixing setup is used to generate feedback for the broad area diode at the wavelength of the single frequency source (Ti:Sapphire laser) while the spatial distribution adapts to the preferred profile of the broad area diode. The result is an injection-locked broad area diode emitting with a linewidth comparable to the Ti:Sapphire laser.

Consequences of hot gas in the broad line region of active galactic nuclei

NASA Technical Reports Server (NTRS)

Kallman, T.; Mushotzky, R.

1985-01-01

Models for hot gas in the broad line region of active galactic nuclei are discussed. The results of the two phase equilibrium models for confinement of broad line clouds by Compton heated gas are used to show that high luminosity quasars are expected to show Fe XXVI L alpha line absorption which will be observed with spectrometers such as those planned for the future X-ray spectroscopy experiments. Two phase equilibrium models also predict that the gas in the broad line clouds and the confining medium may be Compton thick. It is shown that the combined effects of Comptonization and photoabsorption can suppress both the broad emission lines and X-rays in the Einstein and HEAO-1 energy bands. The observed properties of such Compton thick active galaxies are expected to be similar to those of Seyfert 2 nuclei. The implications for polarization and variability are also discussed.

Can H2CCC be the Carrier of Broad Diffuse Bands?

NASA Astrophysics Data System (ADS)

Krełowski, J.; Galazutdinov, G.; Kołos, R.

2011-07-01

The recent assignment of two broad diffuse interstellar bands (DIBs) near 4882 and 5450 Å to the propadienylidene (l-C3H2) molecule is examined using a statistically meaningful sample of targets. Our spectra clearly show that the strength ratio of two broad DIBs is strongly variable, contrary to what should be observed if both features are due to l-C3H2, since the proposed transitions are lifetime broadened and start from the same level. Moreover, even in directions where the 4882 DIB and 5450 DIB are strong, the third expected l-C3H2 band, in the 5165-5185 Å region, is absent. Another puzzling characteristic of l-C3H2 as the proposed carrier of both broad diffuse bands is its column density of several 1014 cm-2, inferred from the equivalent width of the 5450 DIB. This value is one order of magnitude higher than N(CH) toward the same objects and two to three orders of magnitude higher than N(H2CCC), measured at radio frequencies in absorption, for comparable samples of the diffuse medium. We conclude that the proposed identification of broad DIBs is unjustified. Based on observations collected at the European Organization for Astronomical Research in the Southern Hemisphere, Chile; programs 073.C-0337(A) and 082.C-0566(A).

The effects of video-game training on broad cognitive transfer in multiple sclerosis: A pilot randomized controlled trial.

PubMed

Janssen, Alisha; Boster, Aaron; Lee, HyunKyu; Patterson, Beth; Prakash, Ruchika Shaurya

2015-01-01

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system that results in diffuse nerve damage and associated physical and cognitive impairments. Of the few comprehensive rehabilitation options that exist for populations with lower baseline cognitive functioning, those that have been successful at eliciting broad cognitive improvements have focused on a multimodal training approach, emphasizing complex cognitive processing that utilizes multiple domains simultaneously. The current study sought to determine the feasibility of an 8-week, hybrid-variable priority training (HVT) program, with a secondary aim to assess the success of this training paradigm at eliciting broad cognitive transfer effects. Capitalizing on the multimodal training modalities offered by the Space Fortress platform, we compared the HVT strategy-based intervention with a waitlist control group, to primarily assess skill acquisition and secondarily determine presence of cognitive transfer. Twenty-eight participants met inclusionary criteria for the study and were randomized to either training or waitlist control groups. To assess broad transfer effects, a battery of neuropsychological tests was administered pre- and post-intervention. The results indicated an overall improvement in skill acquisition and evidence for the feasibility of the intervention, but a lack of broad transfer to tasks of cognitive functioning. Participants in the training group, however, did show improvements on a measure of spatial short-term memory. The current investigation provided support for the feasibility of a multimodal training approach, using the HVT strategy, within the MS population, but lacked broad transfer to multiple domains of cognitive functioning. Future improvements to obtain greater cognitive transfer efficacy would include a larger sample size, a longer course of training to evoke greater game score improvement, the inclusion of only cognitively impaired individuals, and

Broadband and Broad-angle Polarization-independent Metasurface for Radar Cross Section Reduction

PubMed Central

Sun, Hengyi; Gu, Changqing; Chen, Xinlei; Li, Zhuo; Liu, Liangliang; Xu, Bingzheng; Zhou, Zicheng

2017-01-01

In this work, a broadband and broad-angle polarization-independent random coding metasurface structure is proposed for radar cross section (RCS) reduction. An efficient genetic algorithm is utilized to obtain the optimal layout of the unit cells of the metasurface to get a uniform backscattering under normal incidence. Excellent agreement between the simulation and experimental results show that the proposed metasurface structure can significantly reduce the radar cross section more than 10 dB from 17 GHz to 42 GHz when the angle of incident waves varies from 10° to 50°. The proposed coding metasurface provides an efficient scheme to reduce the scattering of the electromagnetic waves. PMID:28106090

Broadband and Broad-angle Polarization-independent Metasurface for Radar Cross Section Reduction.

PubMed

Sun, Hengyi; Gu, Changqing; Chen, Xinlei; Li, Zhuo; Liu, Liangliang; Xu, Bingzheng; Zhou, Zicheng

2017-01-20

In this work, a broadband and broad-angle polarization-independent random coding metasurface structure is proposed for radar cross section (RCS) reduction. An efficient genetic algorithm is utilized to obtain the optimal layout of the unit cells of the metasurface to get a uniform backscattering under normal incidence. Excellent agreement between the simulation and experimental results show that the proposed metasurface structure can significantly reduce the radar cross section more than 10 dB from 17 GHz to 42 GHz when the angle of incident waves varies from 10° to 50°. The proposed coding metasurface provides an efficient scheme to reduce the scattering of the electromagnetic waves.

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...

The Global Evidence Mapping Initiative: scoping research in broad topic areas.

PubMed

Bragge, Peter; Clavisi, Ornella; Turner, Tari; Tavender, Emma; Collie, Alex; Gruen, Russell L

2011-06-17

Evidence mapping describes the quantity, design and characteristics of research in broad topic areas, in contrast to systematic reviews, which usually address narrowly-focused research questions. The breadth of evidence mapping helps to identify evidence gaps, and may guide future research efforts. The Global Evidence Mapping (GEM) Initiative was established in 2007 to create evidence maps providing an overview of existing research in Traumatic Brain Injury (TBI) and Spinal Cord Injury (SCI). The GEM evidence mapping method involved three core tasks:1. Setting the boundaries and context of the map: Definitions for the fields of TBI and SCI were clarified, the prehospital, acute inhospital and rehabilitation phases of care were delineated and relevant stakeholders (patients, carers, clinicians, researchers and policymakers) who could contribute to the mapping were identified. Researchable clinical questions were developed through consultation with key stakeholders and a broad literature search. 2. Searching for and selection of relevant studies: Evidence search and selection involved development of specific search strategies, development of inclusion and exclusion criteria, searching of relevant databases and independent screening and selection by two researchers. 3. Reporting on yield and study characteristics: Data extraction was performed at two levels - 'interventions and study design' and 'detailed study characteristics'. The evidence map and commentary reflected the depth of data extraction. One hundred and twenty-nine researchable clinical questions in TBI and SCI were identified. These questions were then prioritised into high (n = 60) and low (n = 69) importance by the stakeholders involved in question development. Since 2007, 58 263 abstracts have been screened, 3 731 full text articles have been reviewed and 1 644 relevant neurotrauma publications have been mapped, covering fifty-three high priority questions. GEM Initiative evidence maps have a broad

The Global Evidence Mapping Initiative: Scoping research in broad topic areas

PubMed Central

2011-01-01

Background Evidence mapping describes the quantity, design and characteristics of research in broad topic areas, in contrast to systematic reviews, which usually address narrowly-focused research questions. The breadth of evidence mapping helps to identify evidence gaps, and may guide future research efforts. The Global Evidence Mapping (GEM) Initiative was established in 2007 to create evidence maps providing an overview of existing research in Traumatic Brain Injury (TBI) and Spinal Cord Injury (SCI). Methods The GEM evidence mapping method involved three core tasks: 1. Setting the boundaries and context of the map: Definitions for the fields of TBI and SCI were clarified, the prehospital, acute inhospital and rehabilitation phases of care were delineated and relevant stakeholders (patients, carers, clinicians, researchers and policymakers) who could contribute to the mapping were identified. Researchable clinical questions were developed through consultation with key stakeholders and a broad literature search. 2. Searching for and selection of relevant studies: Evidence search and selection involved development of specific search strategies, development of inclusion and exclusion criteria, searching of relevant databases and independent screening and selection by two researchers. 3. Reporting on yield and study characteristics: Data extraction was performed at two levels - 'interventions and study design' and 'detailed study characteristics'. The evidence map and commentary reflected the depth of data extraction. Results One hundred and twenty-nine researchable clinical questions in TBI and SCI were identified. These questions were then prioritised into high (n = 60) and low (n = 69) importance by the stakeholders involved in question development. Since 2007, 58 263 abstracts have been screened, 3 731 full text articles have been reviewed and 1 644 relevant neurotrauma publications have been mapped, covering fifty-three high priority questions. Conclusions GEM

A Broad-Spectrum Inhibitor of CRISPR-Cas9.

PubMed

Harrington, Lucas B; Doxzen, Kevin W; Ma, Enbo; Liu, Jun-Jie; Knott, Gavin J; Edraki, Alireza; Garcia, Bianca; Amrani, Nadia; Chen, Janice S; Cofsky, Joshua C; Kranzusch, Philip J; Sontheimer, Erik J; Davidson, Alan R; Maxwell, Karen L; Doudna, Jennifer A

2017-09-07

CRISPR-Cas9 proteins function within bacterial immune systems to target and destroy invasive DNA and have been harnessed as a robust technology for genome editing. Small bacteriophage-encoded anti-CRISPR proteins (Acrs) can inactivate Cas9, providing an efficient off switch for Cas9-based applications. Here, we show that two Acrs, AcrIIC1 and AcrIIC3, inhibit Cas9 by distinct strategies. AcrIIC1 is a broad-spectrum Cas9 inhibitor that prevents DNA cutting by multiple divergent Cas9 orthologs through direct binding to the conserved HNH catalytic domain of Cas9. A crystal structure of an AcrIIC1-Cas9 HNH domain complex shows how AcrIIC1 traps Cas9 in a DNA-bound but catalytically inactive state. By contrast, AcrIIC3 blocks activity of a single Cas9 ortholog and induces Cas9 dimerization while preventing binding to the target DNA. These two orthogonal mechanisms allow for separate control of Cas9 target binding and cleavage and suggest applications to allow DNA binding while preventing DNA cutting by Cas9. Copyright © 2017 Elsevier Inc. All rights reserved.

Glycolysis-related proteins are broad spectrum vaccine candidates against aquacultural pathogens.

PubMed

Liu, Xiaohong; Sun, Jiamin; Wu, Haizhen

2017-07-05

Reverse vaccinology (RV) has become a popular method for developing vaccines. Although Edwardsiella tarda is deemed to be an important fish pathogen, so far, no reports have used a genome-based approach to screen vaccine candidates against E. tarda. In the current study, protective antigens of E. tarda were screened using RV. Large-scale cloning, expression and purification of potential candidates were carried out, and their immunoprotective potential was evaluated. A candidate fructose-bisphosphate aldolase (FBA) exhibited broad spectrum protection, as did another glycolysis-related protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which we reported previously, indicating the potential of other glycolysis-related proteins of E. tarda as broad spectrum protective antigens. In total, half (5 out 10) of these proteins showed prominent immunoprotective potential. Therefore, we suggest that glycolysis-related proteins are a class of potential broad spectrum protective antigens and that these proteins should be preferentially selected. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lateral modes of broad area semiconductor lasers - Theory and experiment

NASA Technical Reports Server (NTRS)

Lang, Robert J.; Larsson, Anders G.; Cody, Jeffrey G.

1991-01-01

Calculations of the lateral modes of an ideal broad area laser, including the nonlinear interaction between the carriers and the optical field, are made. The results include periodically modulated near fields and single- and double-lobed far fields similar to those previously measured. The unsaturable losses are higher and quantum efficiencies are lower than those determined from plane-wave approximations. Broad area InGaAs-GaAlAs-GaAs quantum-well lasers were fabricated and measured and found to closely agree with the theory in near, far, and spectrally resolved near fields. An occultation experiment on the far field confirms previously predicted unstable resonatorlike modes with V-shaped fronts.

Broadly protective anti-hemagglutinin stalk antibodies induced by live attenuated influenza vaccine expressing chimeric hemagglutinin.

PubMed

Isakova-Sivak, Irina; Korenkov, Daniil; Smolonogina, Tatiana; Kotomina, Tatiana; Donina, Svetlana; Matyushenko, Victoria; Mezhenskaya, Daria; Krammer, Florian; Rudenko, Larisa

2018-05-01

The development of influenza vaccines that can provide broad protection against all drifted seasonal virus variants, zoonotic infections and emerging pandemic strains, has been a priority for two decades. Here we propose a strategy of inducing broadly-reactive anti-stalk antibody by sequential immunizations with live attenuated influenza vaccines (LAIVs) expressing chimeric HAs (cHAs). These vaccines are designed to contain identical hemagglutinin stalk domains from H1N1 virus but antigenically unrelated globular head domains from avian influenza virus subtypes H5, H8 and H9. Mouse experiments demonstrated enhanced cross-protection of cHA-containing LAIVs compared to the relevant vaccine viruses expressing natural HAs, and this enhanced protection was driven by stalk-HA-reactive IgG antibodies. The establishment of fully functional cross-protective immunity after two doses of cHA LAIV vaccination in naïve animals suggests that a similar effect might be expected after a single cHA LAIV dose in primed individuals, or after two to three doses in naïve children. Copyright © 2018 Elsevier Inc. All rights reserved.

Fresh broad (Vicia faba) tissue homogenate-based biosensor for determination of phenolic compounds.

PubMed

Ozcan, Hakki Mevlut; Sagiroglu, Ayten

2014-08-01

In this study, a novel fresh broad (Vicia faba) tissue homogenate-based biosensor for determination of phenolic compounds was developed. The biosensor was constructed by immobilizing tissue homogenate of fresh broad (Vicia faba) on to glassy carbon electrode. For the stability of the biosensor, general immobilization techniques were used to secure the fresh broad tissue homogenate in gelatin-glutaraldehyde cross-linking matrix. In the optimization and characterization studies, the amount of fresh broad tissue homogenate and gelatin, glutaraldehyde percentage, optimum pH, optimum temperature and optimum buffer concentration, thermal stability, interference effects, linear range, storage stability, repeatability and sample applications (Wine, beer, fruit juices) were also investigated. Besides, the detection ranges of thirteen phenolic compounds were obtained with the help of the calibration graphs. A typical calibration curve for the sensor revealed a linear range of 5-60 μM catechol. In reproducibility studies, variation coefficient (CV) and standard deviation (SD) were calculated as 1.59%, 0.64×10(-3) μM, respectively.

Measurements of the UVR protection provided by hats used at school.

PubMed

Gies, Peter; Javorniczky, John; Roy, Colin; Henderson, Stuart

2006-01-01

The importance of protection against solar ultraviolet radiation (UVR) in childhood has lead to SunSmart policies at Australian schools, in particular primary schools, where children are encouraged and in many cases required to wear hats at school. Hat styles change regularly and the UVR protection provided by some of the hat types currently used and recommended for sun protection by the various Australian state cancer councils had not been previously evaluated. The UVR protection of the hats was measured using UVR sensitive polysulphone film badges attached to different facial sites on rotating headforms. The sun protection type hats included in this study were broad-brimmed hats, "bucket hats" and legionnaires hats. Baseball caps, which are very popular, were also included. The broad-brimmed hats and bucket hats provided the most UVR protection for the six different sites about the face and head. Legionnaires hats also provided satisfactory UVR protection, but the caps did not provide UVR protection to many of the facial sites. The highest measured UVR protection factors for facial sites other than the forehead were 8 to 10, indicating that, while some hats can be effective, they need to be used in combination with other forms of UVR protection.

How Germinal Centers Evolve Broadly Neutralizing Antibodies: the Breadth of the Follicular Helper T Cell Response

DOE PAGES

De Boer, Rob J.; Perelson, Alan S.

2017-09-06

Many HIV-1-infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest-affinity receptors tend to acquire the most antigen from the follicular dendritic cell (FDC) network and present the highest density of cognate peptides to follicular helper T (Tfh) cells, which provide survival signals to the B cell. bnAbs are therefore expected to evolve only when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than othermore » lineages of more specific B cells. Here we develop mathematical models of Tfh cells in germinal centers to explicitly define the mechanisms of selection in this complex evolutionary process. Our results suggest that broadly reactive B cells presenting a high density of peptides bound to major histocompatibility complex class II molecules (pMHC) are readily outcompeted by B cells responding to lineages of HIV-1 that transiently dominate the within host viral population. Conversely, if broadly reactive B cells acquire a large variety of several HIV-1 proteins from the FDC network and present a high diversity of several pMHC, they can be rescued by a large fraction of the Tfh cell repertoire in the germinal center. Under such circumstances the evolution of bnAbs is much more consistent. Increasing either the magnitude of the Tfh cell response or the breadth of the Tfh cell repertoire markedly facilitates the evolution of bnAbs. Because both the magnitude and breadth can be increased by vaccination with several HIV-1 proteins, this calls for experimental testing. Many HIV-infected patients slowly evolve antibodies that can neutralize a large variety of viruses. Such broadly neutralizing antibodies (bnAbs) could in the future become therapeutic agents. bnAbs appear very late, and patients are typically

How Germinal Centers Evolve Broadly Neutralizing Antibodies: the Breadth of the Follicular Helper T Cell Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Boer, Rob J.; Perelson, Alan S.

Many HIV-1-infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest-affinity receptors tend to acquire the most antigen from the follicular dendritic cell (FDC) network and present the highest density of cognate peptides to follicular helper T (Tfh) cells, which provide survival signals to the B cell. bnAbs are therefore expected to evolve only when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than othermore » lineages of more specific B cells. Here we develop mathematical models of Tfh cells in germinal centers to explicitly define the mechanisms of selection in this complex evolutionary process. Our results suggest that broadly reactive B cells presenting a high density of peptides bound to major histocompatibility complex class II molecules (pMHC) are readily outcompeted by B cells responding to lineages of HIV-1 that transiently dominate the within host viral population. Conversely, if broadly reactive B cells acquire a large variety of several HIV-1 proteins from the FDC network and present a high diversity of several pMHC, they can be rescued by a large fraction of the Tfh cell repertoire in the germinal center. Under such circumstances the evolution of bnAbs is much more consistent. Increasing either the magnitude of the Tfh cell response or the breadth of the Tfh cell repertoire markedly facilitates the evolution of bnAbs. Because both the magnitude and breadth can be increased by vaccination with several HIV-1 proteins, this calls for experimental testing. Many HIV-infected patients slowly evolve antibodies that can neutralize a large variety of viruses. Such broadly neutralizing antibodies (bnAbs) could in the future become therapeutic agents. bnAbs appear very late, and patients are typically

Mathematical Development: The Role of Broad Cognitive Processes

ERIC Educational Resources Information Center

Calderón-Tena, Carlos O.

2016-01-01

This study investigated the role of broad cognitive processes in the development of mathematics skills among children and adolescents. Four hundred and forty-seven students (age mean [M] = 10.23 years, 73% boys and 27% girls) from an elementary school district in the US southwest participated. Structural equation modelling tests indicated that…

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.

SU-C-204-02: Behavioral and Pathologic Differences in Mice Exposed to Proton Minibeam Arrays Versus Proton Broad Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eley, J; Zhang, C; Wolfe, T

Purpose: Minibeam therapy using protons or light-ions offers a theoretical reduction of biologic damage to tissues upstream of a tumor compared to broad-beam therapy while providing equal tumor control. The purpose of this study was to investigate behavioral and pathologic differences in mice after exposure of healthy brain to proton minibeam arrays versus proton broad beams. Methods: Twenty-four C57BL/6J juvenile mice were divided into 5 study arms: sham irradiation (NoRT), broad-beam 10 Gy (BB10), minibeam 10Gy (MB10), broad-beam 30 Gy (BB30), and minibeam 30 Gy (MB30), approximate integral entrance doses. Circular beams of 100 MeV protons with 7-mm diameter weremore » delivered laterally through the brain, either as broad beams or as planar minibeam arrays having 300-micron beam width and 1-mm spacing on center. Mice were followed for 8 months using standard behavioral tests. Pathologic studies were carried out at 8 months after irradiation. Results: Peak entrance doses were 10.0, 23.8, 30.0, and 71.3 Gy for mice in BB10, MB10, BB30, and MB30, respectively. Despite the high single-fraction doses, no animals showed signs of radiation sickness or neurophysical impairment over the 8-month study duration. The Morris water maze alternate-starting-position trial showed significant evidence of better spatial learning for mice in MB10 versus BB10 (p=0.026), but other behavioral tests showed no significant differences. Glial fibrillary acidic protein stains showed gliosis in arms BB10, BB30, and MB30 but not in NoRT or MB10. A secondary finding was categorically higher epilation in broad-beam arms compared with their minibeam dose counterparts. Conclusion: Our findings indicate trends that, despite the higher peak doses, proton minibeam therapy can reduce radiation side effects in shallow tissue and brain compared to proton broadbeam therapy. As the behavioral findings were mixed, confirmation studies are needed with larger numbers of animals. AAPM Research Seed

Broad ligament hernia successfully treated by laparoscopy: Case report and review of literature.

PubMed

Matsunami, Masatoshi; Kusanagi, Hiroshi; Hayashi, Ken; Yamada, Shigetoshi; Kano, Nobuyasu

2014-11-01

We report a case of a 36-year-old woman with a history of caesarean section who presented with small bowel obstruction. Abdominal multi-detector CT showed discontinuity of the small bowel near the broad ligament on the left. We made a provisional diagnosis of an internal hernia through a defect in the broad ligament and performed laparoscopic exploration, which revealed a viable ileal loop incarcerated by the broad ligament. Multi-detector CT may be useful for diagnosing this type of defect preoperatively, whereby open surgery can be avoided. © 2014 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.

Classifying forest inventory data into species-based forest community types at broad extents: exploring tradeoffs among supervised and unsupervised approaches

Treesearch

Jennifer K. Costanza; Don Faber-Langendoen; John W. Coulston; David N. Wear

2018-01-01

Background: Knowledge of the different kinds of tree communities that currently exist can provide a baseline for assessing the ecological attributes of forests and monitoring future changes. Forest inventory data can facilitate the development of this baseline knowledge across broad extents, but they first must be classified into forest...

Socioeconomic evaluation of broad-scale land management strategies.

Treesearch

Lisa K. Crone; Richard W. Haynes

2001-01-01

This paper examines the socioeconomic effects of alternative management strategies for Forest Service and Bureau of Land Management lands in the interior Columbia basin. From a broad-scale perspective, there is little impact or variation between alternatives in terms of changes in total economic activity or social conditions in the region. However, adopting a finer...

Saturable nonlinear dielectric waveguide with applications to broad-area semiconductor lasers.

PubMed

Mehuys, D; Mittelstein, M; Salzman, J; Yariv, A

1987-11-01

Self-focusing in a passive dielectric waveguide with a saturable nonlinearity is studied. The eigensolutions constitute a good approximation to the lateral modes of broad-area semiconductor lasers under low-duty-cycle pulsed conditions. The laser modes are predicted to consist of adjacent filaments coupled in phase, leading to a single-lobed far field, and to be stable with increased current injection above saturation intensity. The ultimate filament spacing is inversely proportional to the threshold gain, and thus wider filaments are expected in low-threshold broad-area lasers.

A Haloalkane Dehalogenase from a Marine Microbial Consortium Possessing Exceptionally Broad Substrate Specificity.

PubMed

Buryska, Tomas; Babkova, Petra; Vavra, Ondrej; Damborsky, Jiri; Prokop, Zbynek

2018-01-15

The haloalkane dehalogenase enzyme DmmA was identified by marine metagenomic screening. Determination of its crystal structure revealed an unusually large active site compared to those of previously characterized haloalkane dehalogenases. Here we present a biochemical characterization of this interesting enzyme with emphasis on its structure-function relationships. DmmA exhibited an exceptionally broad substrate specificity and degraded several halogenated environmental pollutants that are resistant to other members of this enzyme family. In addition to having this unique substrate specificity, the enzyme was highly tolerant to organic cosolvents such as dimethyl sulfoxide, methanol, and acetone. Its broad substrate specificity, high overexpression yield (200 mg of protein per liter of cultivation medium; 50% of total protein), good tolerance to organic cosolvents, and a broad pH range make DmmA an attractive biocatalyst for various biotechnological applications. IMPORTANCE We present a thorough biochemical characterization of the haloalkane dehalogenase DmmA from a marine metagenome. This enzyme with an unusually large active site shows remarkably broad substrate specificity, high overexpression, significant tolerance to organic cosolvents, and activity under a broad range of pH conditions. DmmA is an attractive catalyst for sustainable biotechnology applications, e.g., biocatalysis, biosensing, and biodegradation of halogenated pollutants. We also report its ability to convert multiple halogenated compounds to corresponding polyalcohols. Copyright © 2018 American Society for Microbiology.

Approaches to the induction of HIV broadly neutralizing antibodies.

PubMed

Moore, Penny L; Williamson, Carolyn

2016-11-01

A vaccine that elicits antibody responses that can neutralize the diversity of HIV clades has not yet been achieved, and is a major focus of HIV vaccine research. Here, we provide an update on the barriers to eliciting such antibodies, and how advances in immunogen design may circumvent these roadblocks, focusing on data published in the last year. Studies of how broadly neutralizing antibodies (bNAbs) develop in HIV-infected donors continue to produce key insights, suggesting that for some viral targets there are common pathways to developing breadth. Germline-targeting strategies, that aim to recruit rare precursors of bNAbs, have shown promise in immunogenicity studies, and structural biology has led to advances in immunogen design. Mapping of strain-specific tier 2 vaccine responses has highlighted the challenges that remain in driving antibodies toward breadth. Elucidation of the HIV envelope structure, together with an understanding of how bNAbs emerge in vivo has guided the design of new immunogens and vaccine strategies that show promise for eliciting protective antibodies.

High-power broad-area diode lasers optimized for fiber laser pumping

NASA Astrophysics Data System (ADS)

Gilly, J.; Friedmann, P.; Kissel, H.; Biesenbach, J.; Kelemen, M. T.

2012-03-01

In diode laser applications for fibre laser pumping and materials processing high brightness becomes more and more important. At the moment fibre coupled modules benefit from continuous improvement of Broad-Area (BA) lasers on the chip level regarding output power, efficiency and far-field characteristics. To achieve high brightness not only the output power must be increased, but also the far field angles have to be maintained or even decreased because brightness is proportional to output power divided by beam quality. Typically fast axis far fields show mostly a current independent behaviour, for broad-area lasers far-fields in the slow axis suffer from a strong current and temperature dependence, limiting the brightness. These limitations can be overcomed by carefully optimizing epitaxy-design and processing and also thermal management of the mounted device. The easiest way to achieve a good thermal management of BA-Lasers is to increase the resonator length while simultaneously decreasing internal losses of the epitaxy structure. To fulfill these issues, we have realized MBE grown InGaAs/AlGaAs broad-area with resonator lengths between 4mm and 6mm emitting at 976nm. To evaluate the brightness of these broad-area lasers single emitters have been mounted p-side down. Near- and far-fields have been carefully investigated. For a 4mm long broad-area laser with around 100μm emission width a beam parameter product of less than 3.5 mm x mrad has been achieved at 10W with a slope efficiency of more than 1.1W/A and a maximum wall-plug efficiency of more than 67%. For a device with 6mm resonator length we have reached a BPP of less than 3.5mm x mrad at 14W in slow axis direction which results in a brightness around 130MW/cm2 sr, which is to our knowledge the highest brightness reported so far for BA-lasers.

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.

Broad-spectrum non-nucleoside inhibitors for caliciviruses.

PubMed

Netzler, Natalie E; Enosi Tuipulotu, Daniel; Eltahla, Auda A; Lun, Jennifer H; Ferla, Salvatore; Brancale, Andrea; Urakova, Nadya; Frese, Michael; Strive, Tanja; Mackenzie, Jason M; White, Peter A

2017-10-01

Viruses of the Caliciviridae cause significant and sometimes lethal diseases, however despite substantial research efforts, specific antivirals are lacking. Broad-spectrum antivirals could combat multiple viral pathogens, offering a rapid solution when no therapies exist. The RNA-dependent RNA polymerase (RdRp) is an attractive antiviral target as it is essential for viral replication and lacks mammalian homologs. To focus the search for pan-Caliciviridae antivirals, the RdRp was probed with non-nucleoside inhibitors (NNIs) developed against hepatitis C virus (HCV) to reveal both allosteric ligands for structure-activity relationship enhancement, and highly-conserved RdRp pockets for antiviral targeting. The ability of HCV NNIs to inhibit calicivirus RdRp activities was assessed using in vitro enzyme and murine norovirus cell culture assays. Results revealed that three NNIs which bound the HCV RdRp Thumb I (TI) site also inhibited transcriptional activities of six RdRps spanning the Norovirus, Sapovirus and Lagovirus genera of the Caliciviridae. These NNIs included JTK-109 (RdRp inhibition range: IC 50 4.3-16.6 μM), TMC-647055 (IC 50 range: 18.8-45.4 μM) and Beclabuvir (IC 50 range: 23.8->100 μM). In silico studies and site-directed mutagenesis indicated the JTK-109 binding site was within the calicivirus RdRp thumb domain, in a pocket termed Site-B, which is highly-conserved within all calicivirus RdRps. Additionally, RdRp inhibition assays revealed that JTK-109 was antagonistic with the previously reported RdRp inhibitor pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate) tetrasodium salt (PPNDS), that also binds to Site-B. Moreover, like JTK-109, PPNDS was also a potent inhibitor of polymerases from six viruses spanning the three Caliciviridae genera tested (IC 50 range: 0.1-2.3 μM). Together, this study demonstrates the potential for de novo development of broad-spectrum antivirals that target the highly-conserved RdRp thumb pocket

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.

Using the Properties of Broad Absorption Line Quasars to Illuminate Quasar Structure

NASA Astrophysics Data System (ADS)

Yong, Suk Yee; King, Anthea L.; Webster, Rachel L.; Bate, Nicholas F.; O'Dowd, Matthew J.; Labrie, Kathleen

2018-06-01

A key to understanding quasar unification paradigms is the emission properties of broad absorption line quasars (BALQs). The fact that only a small fraction of quasar spectra exhibit deep absorption troughs blueward of the broad permitted emission lines provides a crucial clue to the structure of quasar emitting regions. To learn whether it is possible to discriminate between the BALQ and non-BALQ populations given the observed spectral properties of a quasar, we employ two approaches: one based on statistical methods and the other supervised machine learning classification, applied to quasar samples from the Sloan Digital Sky Survey. The features explored include continuum and emission line properties, in particular the absolute magnitude, redshift, spectral index, line width, asymmetry, strength, and relative velocity offsets of high-ionisation C IV λ1549 and low-ionisation Mg II λ2798 lines. We consider a complete population of quasars, and assume that the statistical distributions of properties represent all angles where the quasar is viewed without obscuration. The distributions of the BALQ and non-BALQ sample properties show few significant differences. None of the observed continuum and emission line features are capable of differentiating between the two samples. Most published narrow disk-wind models are inconsistent with these observations, and an alternative disk-wind model is proposed. The key feature of the proposed model is a disk-wind filling a wide opening angle with multiple radial streams of dense clumps.

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.

Nanoparticles as potential new generation broad spectrum antimicrobial agents.

PubMed

Yah, Clarence S; Simate, Geoffrey S

2015-09-02

The rapid emergence of antimicrobial resistant strains to conventional antimicrobial agents has complicated and prolonged infection treatment and increased mortality risk globally. Furthermore, some of the conventional antimicrobial agents are unable to cross certain cell membranes thus, restricting treatment of intracellular pathogens. Therefore, the disease-causing-organisms tend to persist in these cells. However, the emergence of nanoparticle (NP) technology has come with the promising broad spectrum NP-antimicrobial agents due to their vast physiochemical and functionalization properties. In fact, NP-antimicrobial agents are able to unlock the restrictions experienced by conventional antimicrobial agents. This review discusses the status quo of NP-antimicrobial agents as potent broad spectrum antimicrobial agents, sterilization and wound healing agents, and sustained inhibitors of intracellular pathogens. Indeed, the perspective of developing potent NP-antimicrobial agents that carry multiple-functionality will revolutionize clinical medicine and play a significant role in alleviating disease burden.

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

Broad-band simulation of M7.2 earthquake on the North Tehran fault, considering non-linear soil effects

NASA Astrophysics Data System (ADS)

Majidinejad, A.; Zafarani, H.; Vahdani, S.

2018-05-01

The North Tehran fault (NTF) is known to be one of the most drastic sources of seismic hazard on the city of Tehran. In this study, we provide broad-band (0-10 Hz) ground motions for the city as a consequence of probable M7.2 earthquake on the NTF. Low-frequency motions (0-2 Hz) are provided from spectral element dynamic simulation of 17 scenario models. High-frequency (2-10 Hz) motions are calculated with a physics-based method based on S-to-S backscattering theory. Broad-band ground motions at the bedrock level show amplifications, both at low and high frequencies, due to the existence of deep Tehran basin in the vicinity of the NTF. By employing soil profiles obtained from regional studies, effect of shallow soil layers on broad-band ground motions is investigated by both linear and non-linear analyses. While linear soil response overestimate ground motion prediction equations, non-linear response predicts plausible results within one standard deviation of empirical relationships. Average Peak Ground Accelerations (PGAs) at the northern, central and southern parts of the city are estimated about 0.93, 0.59 and 0.4 g, respectively. Increased damping caused by non-linear soil behaviour, reduces the soil linear responses considerably, in particular at frequencies above 3 Hz. Non-linear deamplification reduces linear spectral accelerations up to 63 per cent at stations above soft thick sediments. By performing more general analyses, which exclude source-to-site effects on stations, a correction function is proposed for typical site classes of Tehran. Parameters for the function which reduces linear soil response in order to take into account non-linear soil deamplification are provided for various frequencies in the range of engineering interest. In addition to fully non-linear analyses, equivalent-linear calculations were also conducted which their comparison revealed appropriateness of the method for large peaks and low frequencies, but its shortage for small to

Development of an anti-HIV vaccine eliciting broadly neutralizing antibodies.

PubMed

Ahmed, Yousuf; Tian, Meijuan; Gao, Yong

2017-09-12

The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response.

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.

Using high spectral resolution spectrophotometry to study broad mineral absorption features on Mars

NASA Technical Reports Server (NTRS)

Blaney, D. L.; Crisp, D.

1993-01-01

Traditionally telescopic measurements of mineralogic absorption features have been made using relatively low to moderate (R=30-300) spectral resolution. Mineralogic absorption features tend to be broad so high resolution spectroscopy (R greater than 10,000) does not provide significant additional compositional information. Low to moderate resolution spectroscopy allows an observer to obtain data over a wide wavelength range (hundreds to thousands of wavenumbers) compared to the several wavenumber intervals that are collected using high resolution spectrometers. However, spectrophotometry at high resolution has major advantages over lower resolution spectroscopy in situations that are applicable to studies of the Martian surface, i.e., at wavelengths where relatively weak surface absorption features and atmospheric gas absorption features both occur.

Broadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteins

PubMed Central

Martinez-Becerra, Francisco J.; Kissmann, Julian M.; Diaz-McNair, Jovita; Choudhari, Shyamal P.; Quick, Amy M.; Mellado-Sanchez, Gabriela; Clements, John D.

2012-01-01

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

Broad targeting of resistance to apoptosis in cancer

PubMed Central

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.

2015-01-01

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

Transmission of broad W/Rh and W/Al (target/filter) x-ray beams operated at 25-49 kVp through common shielding materials.

PubMed

Li, Xinhua; Zhang, Da; Liu, Bob

2012-07-01

To provide transmission data for broad 25-39 kVp (kilovolt peak) W/Rh and 25-49 kVp W/Al (target/filter, W-tungsten, Rh-rhodium, and Al-aluminum) x-ray beams through common shielding materials, such as lead, concrete, gypsum wallboard, wood, steel, and plate glass. The unfiltered W-target x-ray spectra measured on a Selenia Dimensions system (Hologic Inc., Bedford, MA) set at 20-49 kVp were, respectively, filtered using 50-μm Rh and 700-μm Al, and were subsequently used for Monte Carlo calculations. The transmission of broad x-ray beams through shielding materials was simulated using Geant4 low energy electromagnetic physics package with photon- and electron-processes above 250 eV, including photoelectric effect, Compton scattering, and Rayleigh scattering. The calculated transmission data were fitted using Archer equation with a robust fitting algorithm. The transmission of broad x-ray beams through the above-mentioned shielding materials was calculated down to about 10(-5) for 25-39 kVp W/Rh and 25-49 kVp W/Al. The fitted results of α, β, and γ in Archer equation were provided. The α values of kVp ≥ 40 were approximately consistent with those of NCRP Report No. 147. These data provide inputs for the shielding designs of x-ray imaging facilities with W-anode x-ray beams, such as from Selenia Dimensions.

Effect of broad properties fuel on injector performance in a reverse flow combustor

NASA Technical Reports Server (NTRS)

Raddlebaugh, S. M.; Norgren, C. T.

1983-01-01

The effect of fuel type on the performance of various fuel injectors was investigated in a reverse flow combustor. Combustor performance and emissions are documented for simplex pressure atomizing, spill flow, and airblast fuel injectors using a broad properties fuel and compared with performance using Jet A fuel. Test conditions simulated a range of flight conditions including sea level take off, low and high altitude cruise, as well as a parametric evaluation of the effect of increased combustor loading. The baseline simplex injector produced higher emission levels with corresponding lower combustion efficiency with the broad properties fuel. There was little or not loss in performance by the two advanced concept injectors with the broad properties fuel. The airblast injector proved to be especially insensitive to fuel type.

Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein

DOE Office of Scientific and Technical Information (OSTI.GOV)

York, Joanne; Nunberg, Jack H.

2007-03-01

The arenavirus envelope glycoprotein (GP-C) retains a cleaved and stable signal peptide (SSP) as an essential subunit of the mature complex. This 58-amino-acid residue peptide serves as a signal sequence and is additionally required to enable transit of the assembled GP-C complex to the Golgi, and for pH-dependent membrane fusion activity. We have investigated the C-terminal region of the Junin virus SSP to study the role of the cellular signal peptidase (SPase) in generating SSP. Site-directed mutagenesis at the cleavage site (positions - 1 and - 3) reveals a pattern of side-chain preferences consistent with those of SPase. Although positionmore » - 2 is degenerate for SPase cleavage, this residue in the arenavirus SSP is invariably a cysteine. In the Junin virus, this cysteine is not involved in disulfide bonding. We show that replacement with alanine or serine is tolerated for SPase cleavage but prevents the mutant SSP from associating with GP-C and enabling transport to the cell surface. Conversely, an arginine mutation at position - 1 that prevents SPase cleavage is fully compatible with GP-C-mediated membrane fusion activity when the mutant SSP is provided in trans. These results point to distinct roles of SSP sequences in SPase cleavage and GP-C biogenesis. Further studies of the unique structural organization of the GP-C complex will be important in identifying novel opportunities for antiviral intervention against arenaviral hemorrhagic disease.« less

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

Disclosure, Apology, and Offer Programs: Stakeholders' Views of Barriers to and Strategies for Broad Implementation

PubMed Central

Bell, Sigall K; Smulowitz, Peter B; Woodward, Alan C; Mello, Michelle M; Duva, Anjali Mitter; Boothman, Richard C; Sands, Kenneth

2012-01-01

Context The Disclosure, Apology, and Offer (DA&O) model, a response to patient injuries caused by medical care, is an innovative approach receiving national attention for its early success as an alternative to the existing inherently adversarial, inefficient, and inequitable medical liability system. Examples of DA&O programs, however, are few. Methods Through key informant interviews, we investigated the potential for more widespread implementation of this model by provider organizations and liability insurers, defining barriers to implementation and strategies for overcoming them. Our study focused on Massachusetts, but we also explored themes that are broadly generalizable to other states. Findings We found strong support for the DA&O model among key stakeholders, who cited its benefits for both the liability system and patient safety. The respondents did not perceive any insurmountable barriers to broad implementation, and they identified strategies that could be pursued relatively quickly. Such solutions would permit a range of organizations to implement the model without legislative hurdles. Conclusions Although more data are needed about the outcomes of DA&O programs, the model holds considerable promise for transforming the current approach to medical liability and patient safety. PMID:23216427

Disclosure, apology, and offer programs: stakeholders' views of barriers to and strategies for broad implementation.

PubMed

Bell, Sigall K; Smulowitz, Peter B; Woodward, Alan C; Mello, Michelle M; Duva, Anjali Mitter; Boothman, Richard C; Sands, Kenneth

2012-12-01

The Disclosure, Apology, and Offer (DA&O) model, a response to patient injuries caused by medical care, is an innovative approach receiving national attention for its early success as an alternative to the existing inherently adversarial, inefficient, and inequitable medical liability system. Examples of DA&O programs, however, are few. Through key informant interviews, we investigated the potential for more widespread implementation of this model by provider organizations and liability insurers, defining barriers to implementation and strategies for overcoming them. Our study focused on Massachusetts, but we also explored themes that are broadly generalizable to other states. We found strong support for the DA&O model among key stakeholders, who cited its benefits for both the liability system and patient safety. The respondents did not perceive any insurmountable barriers to broad implementation, and they identified strategies that could be pursued relatively quickly. Such solutions would permit a range of organizations to implement the model without legislative hurdles. Although more data are needed about the outcomes of DA&O programs, the model holds considerable promise for transforming the current approach to medical liability and patient safety. © 2012 Milbank Memorial Fund.

Electrically-pumped, broad-area, single-mode photonic crystal lasers.

PubMed

Zhu, Lin; Chak, Philip; Poon, Joyce K S; DeRose, Guy A; Yariv, Amnon; Scherer, Axel

2007-05-14

Planar broad-area single-mode lasers, with modal widths of the order of tens of microns, are technologically important for high-power applications and improved coupling efficiency into optical fibers. They may also find new areas of applications in on-chip integration with devices that are of similar size scales, such as for spectroscopy in microfluidic chambers or optical signal processing with micro-electromechanical systems. An outstanding challenge is that broad-area lasers often require external means of control, such as injection-locking or a frequency/spatial filter to obtain single-mode operation. In this paper, we propose and demonstrate effective index-guided, large-area, edge-emitting photonic crystal lasers driven by pulsed electrical current injection at the optical telecommunication wavelength of 1550 nm. By suitable design of the photonic crystal lattice, our lasers operate in a single mode with a 1/e(2) modal width of 25 microm and a length of 600 microm.

Ultra-wideband and broad-angle linear polarization conversion metasurface

NASA Astrophysics Data System (ADS)

Sun, Hengyi; Gu, Changqing; Chen, Xinlei; Li, Zhuo; Liu, Liangliang; Martín, Ferran

2017-05-01

In this work, a metasurface acting as a linear polarization rotator, that can efficiently convert linearly polarized electromagnetic waves to cross polarized waves within an ultra wide frequency band and with a broad incident angle, is proposed. Based on the electric and magnetic resonant features of the unit cell, composed by a double-head arrow, a cut-wire, and two short V-shaped wire structures, three resonances, which lead to the bandwidth expansion of cross-polarization reflections, are generated. The simulation results show that an average polarization conversion ratio of 90% from 17.3 GHz to 42.2 GHz can be achieved. Furthermore, the designed metasurface exhibits polarization insensitivity within a broad incident angle, from 0° to 50°. The experiments conducted on the fabricated metasurface are in good agreement with the simulations. The proposed metasurface can find potential applications in reflector antennas, imaging systems, and remote sensors operating at microwave frequencies.

Nesting ecology and behavior of Broad-winged Hawks in moist karst forests of Puerto Rico

USGS Publications Warehouse

Hengstenberg, D.W.; Vilella, F.J.

2005-01-01

The Puerto Rican Broad-winged Hawk (Buteo platypterus brunnescens) is an endemic and endangered subspecies inhabiting upland montane forests of Puerto Rico. The reproductive ecology, behavior, and nesting habitat of the Broad-winged Hawk were studied in Ri??o Abajo Forest, Puerto Rico, from 2001-02. We observed 158 courtship displays by Broad-winged Hawks. Also, we recorded 25 territorial interactions between resident Broad-winged Hawks and intruding Red-tailed Hawks (Buteo jamaicensis jamaicensis). Broad-winged Hawks displaced intruding Red-tailed Hawks from occupied territories (P = 0.009). Mayfield nest survival was 0.67 across breeding seasons (0.81 in 2001, N = 6; 0.51 in 2002, N = 4), and pairs averaged 1.1 young per nest (years combined). The birds nested in mixed species timber plantations and mature secondary forest. Nests were placed in the upper reaches of large trees emerging from the canopy. Nest tree DBH, understory stem density, and distance to karst cliff wall correctly classified (77.8%) nest sites. ?? 2005 The Raptor Research Foundation, Inc.

Energy diffusion controlled reaction rate of reacting particle driven by broad-band noise

NASA Astrophysics Data System (ADS)

Deng, M. L.; Zhu, W. Q.

2007-10-01

The energy diffusion controlled reaction rate of a reacting particle with linear weak damping and broad-band noise excitation is studied by using the stochastic averaging method. First, the stochastic averaging method for strongly nonlinear oscillators under broad-band noise excitation using generalized harmonic functions is briefly introduced. Then, the reaction rate of the classical Kramers' reacting model with linear weak damping and broad-band noise excitation is investigated by using the stochastic averaging method. The averaged Itô stochastic differential equation describing the energy diffusion and the Pontryagin equation governing the mean first-passage time (MFPT) are established. The energy diffusion controlled reaction rate is obtained as the inverse of the MFPT by solving the Pontryagin equation. The results of two special cases of broad-band noises, i.e. the harmonic noise and the exponentially corrected noise, are discussed in details. It is demonstrated that the general expression of reaction rate derived by the authors can be reduced to the classical ones via linear approximation and high potential barrier approximation. The good agreement with the results of the Monte Carlo simulation verifies that the reaction rate can be well predicted using the stochastic averaging method.

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.

Approaches to veterinary education--tracking versus a final year broad clinical experience. Part one: effects on career outcome.

PubMed

Klosterman, E S; Kass, P H; Walsh, D A

2009-08-01

This is the first of two papers that provide extensive data and analysis on the two major approaches to clinical veterinary education, which either provide students with experience of a broad range of species (often defined as omni/general clinical competence), or just a few species (sometimes just one), usually termed 'tracking'. Together the two papers provide a detailed analysis of these two approaches for the first time. The responsibilities of veterinary medicine and veterinary education are rapidly increasing throughoutthe globe. It is critical for all in veterinary education to reassess the approaches that have been used, and evaluate on a school-by-school basis which may best meet its expanding and ever-deepening responsibilities.

Successes and challenges from formation to implementation of eleven broad-extent conservation programs.

PubMed

Beever, Erik A; Mattsson, Brady J; Germino, Matthew J; Burg, Max Post Van Der; Bradford, John B; Brunson, Mark W

2014-04-01

Integration of conservation partnerships across geographic, biological, and administrative boundaries is increasingly relevant because drivers of change, such as climate shifts, transcend these boundaries. We explored successes and challenges of established conservation programs that span multiple watersheds and consider both social and ecological concerns. We asked representatives from a diverse set of 11 broad-extent conservation partnerships in 29 countries 17 questions that pertained to launching and maintaining partnerships for broad-extent conservation, specifying ultimate management objectives, and implementation and learning. Partnerships invested more funds in implementing conservation actions than any other aspect of conservation, and a program's context (geographic extent, United States vs. other countries, developed vs. developing nation) appeared to substantially affect program approach. Despite early successes of these organizations and benefits of broad-extent conservation, specific challenges related to uncertainties in scaling up information and to coordination in the face of diverse partner governance structures, conflicting objectives, and vast uncertainties regarding future system dynamics hindered long-term success, as demonstrated by the focal organizations. Engaging stakeholders, developing conservation measures, and implementing adaptive management were dominant challenges. To inform future research on broad-extent conservation, we considered several challenges when we developed detailed questions, such as what qualities of broad-extent partnerships ensure they complement, integrate, and strengthen, rather than replace, local conservation efforts and which adaptive management processes yield actionable conservation strategies that account explicitly for dynamics and uncertainties regarding multiscale governance, environmental conditions, and knowledge of the system? © 2014 Society for Conservation Biology.

The HIV glycan shield as a target for broadly neutralizing antibodies.

PubMed

Doores, Katie J

2015-12-01

The HIV envelope glycoprotein (Env) is the sole target for HIV broadly neutralizing antibodies (bnAbs). HIV Env is one of the most heavily glycosylated proteins known, with approximately half of its mass consisting of host-derived N-linked glycans. The high density of glycans creates a shield that impedes antibody recognition but, critically, some of the most potent and broadly active bnAbs have evolved to recognize epitopes formed by these glycans. Although the virus hijacks the host protein synthesis and glycosylation machinery to generate glycosylated HIV Env, studies have shown that HIV Env glycosylation diverges from that typically observed on host-derived glycoproteins. In particular, the high density of glycans leads to a nonself motif of underprocessed oligomannose-type glycans that forms the target of some of the most broad and potent HIV bnAbs. This review discusses the changing perception of the HIV glycan shield, and summarizes the protein-directed and cell-directed factors controlling HIV Env glycosylation that impact on HIV bnAb recognition and HIV vaccine design strategies. © The Author. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

A novel approach for characterizing broad-band radio spectral energy distributions

NASA Astrophysics Data System (ADS)

Harvey, V. M.; Franzen, T.; Morgan, J.; Seymour, N.

2018-05-01

We present a new broad-band radio frequency catalogue across 0.12 GHz ≤ ν ≤ 20 GHz created by combining data from the Murchison Widefield Array Commissioning Survey, the Australia Telescope 20 GHz survey, and the literature. Our catalogue consists of 1285 sources limited by S20 GHz > 40 mJy at 5σ, and contains flux density measurements (or estimates) and uncertainties at 0.074, 0.080, 0.119, 0.150, 0.180, 0.408, 0.843, 1.4, 4.8, 8.6, and 20 GHz. We fit a second-order polynomial in log-log space to the spectral energy distributions of all these sources in order to characterize their broad-band emission. For the 994 sources that are well described by a linear or quadratic model we present a new diagnostic plot arranging sources by the linear and curvature terms. We demonstrate the advantages of such a plot over the traditional radio colour-colour diagram. We also present astrophysical descriptions of the sources found in each segment of this new parameter space and discuss the utility of these plots in the upcoming era of large area, deep, broad-band radio surveys.

Structural basis of the broad substrate tolerance of the antibody 7B9-catalyzed hydrolysis of p-nitrobenzyl esters.

PubMed

Miyamoto, Naoki; Yoshimura, Miho; Okubo, Yuji; Suzuki-Nagata, Kayo; Tsumuraya, Takeshi; Ito, Nobutoshi; Fujii, Ikuo

2018-05-01

Catalytic antibody 7B9, which was elicited against p-nitrobenzyl phosphonate transition-state analogue (TSA) 1, hydrolyzes a wide range of p-nitrobenzyl monoesters and thus shows broad substrate tolerance. To reveal the molecular basis of this substrate tolerance, the 7B9 Fab fragment complexed with p-nitrobenzyl ethylphosphonate 2 was crystallized and the three-dimensional structure was determined. The crystal structure showed that the strongly antigenic p-nitrobenzyl moiety occupied a relatively shallow antigen-combining site and therefore the alkyl moiety was located outside the pocket. These results support the observed broad substrate tolerance of 7B9 and help rationalize how 7B9 can catalyze various p-nitrobenzyl ester derivatives. The crystal structure also showed that three amino acid residues (Asn H33 , Ser H95 , and Arg L96 ) were placed in key positions to form hydrogen bonds with the phosphonate oxygens of the transitions-state analogue. In addition, the role of these amino acid residues was examined by site-directed mutagenesis to alanine: all mutants (Asn H33 Ala, Ser H95 Ala, and Arg L96 Ala) showed no detectable catalytic activity. Coupling the findings from our structural studies with these mutagenesis results clarified the structural basis of the observed broad substrate tolerance of antibody 7B9-catalyzed hydrolyses. Our findings provide new strategies for the generation of catalytic antibodies that accept a broad range of substrates, aiding their practical application in synthetic organic chemistry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Broad-scale assessments of ecological landscapes: developing methods and applications

USGS Publications Warehouse

Carr, Natasha B.; Wood, David J. A.; Bowen, Zachary H.; Haby, Travis S.

2015-01-01

A major component of the BLM Landscape Approach is the Rapid Ecoregional Assessment (REA) program. REAs identify important ecosystems and wildlife habitats at broad spatial scales and determine where these resources are at risk from environmental stressors that can affect the integrity of ecological systems. Building on the lessons learned from completed or current REAs, the BLM, in partnership with the U.S. Geological Survey, will perform systematic comparisons of REA methods to identify the most promising suite of landscape-level analysis tools. In addition, the BLM and USGS will develop practical applications that demonstrate how to incorporate assessment information to address existing management issues, such as cumulative effects of proposed management actions. The outcome of these efforts will be a set of comprehensive technical guidance documents for conducting and applying broad-scale assessments.

Flavor Compounds in Pixian Broad-Bean Paste: Non-Volatile Organic Acids and Amino Acids.

PubMed

Lin, Hongbin; Yu, Xiaoyu; Fang, Jiaxing; Lu, Yunhao; Liu, Ping; Xing, Yage; Wang, Qin; Che, Zhenming; He, Qiang

2018-05-29

Non-volatile organic acids and amino acids are important flavor compounds in Pixian broad-bean paste, which is a traditional Chinese seasoning product. In this study, non-volatile organic acids, formed in the broad-bean paste due to the metabolism of large molecular compounds, are qualitatively and quantitatively determined by high-performance liquid chromatography (HPLC). Amino acids, mainly produced by hydrolysis of soybean proteins, were determined by the amino acid automatic analyzer. Results indicated that seven common organic acids and eighteen common amino acids were found in six Pixian broad-bean paste samples. The content of citric acid was found to be the highest in each sample, between 4.1 mg/g to 6.3 mg/g, and malic acid were between 2.1 mg/g to 3.6 mg/g ranked as the second. Moreover, fumaric acid was first detected in fermented bean pastes albeit with a low content. For amino acids, savory with lower sour taste including glutamine (Gln), glutamic acid (Glu), aspartic acid (Asp) and asparagines (Asn) were the most abundant, noted to be 6.5 mg/g, 4.0 mg/g, 6.4 mg/g, 4.9 mg/g, 6.2 mg/g and 10.2 mg/g, and bitter taste amino acids followed. More importantly, as important flavor materials in Pixian broad-bean paste, these two groups of substances are expected to be used to evaluate and represent the flavor quality of Pixian broad-bean paste. Moreover, the results revealed that citric acid, glutamic acid, methionine and proline were the most important flavor compounds. These findings are agreat contribution for evaluating the quality and further assessment of Pixian broad-bean paste.

Influenza Virus-Like Particles Containing M2 Induce Broadly Cross Protective Immunity

PubMed Central

Song, Jae-Min; Wang, Bao-Zhong; Park, Kyoung-Mi; Van Rooijen, Nico; Quan, Fu-Shi; Kim, Min-Chul; Jin, Hyun-Tak; Pekosz, Andrew; Compans, Richard W.; Kang, Sang-Moo

2011-01-01

Background Current influenza vaccines based on the hemagglutinin protein are strain specific and do not provide good protection against drifted viruses or emergence of new pandemic strains. An influenza vaccine that can confer cross-protection against antigenically different influenza A strains is highly desirable for improving public health. Methodology/Principal Findings To develop a cross protective vaccine, we generated influenza virus-like particles containing the highly conserved M2 protein in a membrane-anchored form (M2 VLPs), and investigated their immunogenicity and breadth of cross protection. Immunization of mice with M2 VLPs induced anti-M2 antibodies binding to virions of various strains, M2 specific T cell responses, and conferred long-lasting cross protection against heterologous and heterosubtypic influenza viruses. M2 immune sera were found to play an important role in providing cross protection against heterosubtypic virus and an antigenically distinct 2009 pandemic H1N1 virus, and depletion of dendritic and macrophage cells abolished this cross protection, providing new insight into cross-protective immune mechanisms. Conclusions/Significance These results suggest that presenting M2 on VLPs in a membrane-anchored form is a promising approach for developing broadly cross protective influenza vaccines. PMID:21267073

A broad range assay for rapid detection and etiologic characterization of bacterial meningitis: performance testing in samples from sub-Sahara.

PubMed

Won, Helen; Yang, Samuel; Gaydos, Charlotte; Hardick, Justin; Ramachandran, Padmini; Hsieh, Yu-Hsiang; Kecojevic, Alexander; Njanpop-Lafourcade, Berthe-Marie; Mueller, Judith E; Tameklo, Tsidi Agbeko; Badziklou, Kossi; Gessner, Bradford D; Rothman, Richard E

2012-09-01

This study aimed to conduct a pilot evaluation of broad-based multiprobe polymerase chain reaction (PCR) in clinical cerebrospinal fluid (CSF) samples compared to local conventional PCR/culture methods used for bacterial meningitis surveillance. A previously described PCR consisting of initial broad-based detection of Eubacteriales by a universal probe, followed by Gram typing, and pathogen-specific probes was designed targeting variable regions of the 16S rRNA gene. The diagnostic performance of the 16S rRNA assay in "127 CSF samples was evaluated in samples from patients from Togo, Africa, by comparison to conventional PCR/culture methods. Our probes detected Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Uniprobe sensitivity and specificity versus conventional PCR were 100% and 54.6%, respectively. Sensitivity and specificity of uniprobe versus culture methods were 96.5% and 52.5%, respectively. Gram-typing probes correctly typed 98.8% (82/83) and pathogen-specific probes identified 96.4% (80/83) of the positives. This broad-based PCR algorithm successfully detected and provided species level information for multiple bacterial meningitis agents in clinical samples. Copyright © 2012 Elsevier Inc. All rights reserved.

Broad-Range 16S rDNA PCR on Heart Valves in Infective Endocarditis.

PubMed

Müller Premru, Manica; Lejko Zupanc, Tatjana; Klokočovnik, Tomislav; Ruzić Sabljić, Eva; Cerar, Tjaša

2016-03-01

Infective endocarditis (IE) is diagnosed by blood and/or resected valve cultivation and echocardiographic findings, as defined by the Duke criteria. Unfortunately, cultures may be negative due to prior antibiotic therapy or fastidious or slow-growing microorganisms. The study aim was to investigate the value of the broad-range polymerase chain reaction (PCR) in addition to blood and valve culture for the detection of causative microorganisms. Between February 2012 and March 2015, valve samples from 36 patients undergoing cardiac surgery were analyzed; of these patients, 26 had a preoperative diagnosis of IE and 10 served as controls. Multiple blood cultures were obtained from 34 patients before antibiotic therapy was commenced. Valve samples were inoculated on bacteriological media and underwent analysis using broad-range PCR (16S rDNA). IE was confirmed microbiologically in 21 of the 26 patients (80.7%); in 20 cases (76.9%) this was by positive blood cultures and in 16 (61.5%) by positive valves. Valves were positive in 15 blood culturepositive patients, and in one blood-culture negative patient. Broad-range PCR detected a microorganism in valves significantly more frequently (n = 14; 53.8%) compared to valve culture (n = 8; 30.7%) (chisquare 11.5, p <0.001). The predominant microorganisms were Staphylococcus aureus, Streptococcus of the viridans group, coagulasenegative staphylococci and Enterococcus faecalis. Blood, valve cultures and broad-range PCR were negative in five patients (19.3%) with IE, and in all 10 subjects of the control group. Broad-range PCR on valves was more sensitive than valve culture. However, blood culture, if taken before the start of antibiotic therapy, was the best method for detecting IE.

Resistance of nanobacteria isolated from urinary and kidney stones to broad-spectrum antibiotics.

PubMed

Sardarabadi, Hadi; Mashreghi, Mansour; Jamialahmadi, Khadijeh; Dianat, Tahere

2014-08-01

Nanoscopic life forms called Nanobacteria or calcifying nanoparticles (CNP) are unconventional agents. These novel organisms are very small (0.1 to 0.5 microns) and possess unusual properties such as high resistance to heat and routine antimicrobial agents. Nanobacteria are 100 times smaller than bacteria and protected by a shell of apatite, so they could be as candidate for emerging and progress of in vivo pathological calcification. In this study, the inhibitory effect of broad-spectrum antibiotics on growth of these new forms of life has been investigated. Powdered urinary and kidney stones were demineralized with HCl and neutralized with appropriate buffers and became filtered. Finally suspension was incubated in DMEM medium with Fetal Bovine Serum (FBS) and broad-spectrum antibiotics (100U/ml for penicillin and 100μg/ml for streptomycin) for 60 days. In the presence of broad-spectrum antibiotics, Scanning Electron Micrographs (SEM) showed a spherical shape of these nanobacteria. Also, Energy Dispersive X-ray spectroscopy (EDS) showed a pick for calcium and phosphor. Transmission Electron Microscopy (TEM) results illustrated cover around the nanobacteria. The growth of calcifying nanoparticles after adding the broad-spectrum antibiotics may be due to their apatite hard shells supporting them against penetration of the antibiotics.

A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

PubMed Central

Zhao, Hanjun; Zhou, Jie; Zhang, Ke; Chu, Hin; Liu, Dabin; Poon, Vincent Kwok-Man; Chan, Chris Chung-Sing; Leung, Ho-Chuen; Fai, Ng; Lin, Yong-Ping; Zhang, Anna Jin-Xia; Jin, Dong-Yan; Yuen, Kwok-Yung; Zheng, Bo-Jian

2016-01-01

A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities. PMID:26911565

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

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

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.

Broadly wavelength tunable acousto-optically Q-switched Tm:Lu2SiO5 laser.

PubMed

Feng, T; Yang, K; Zhao, S; Zhao, J; Qiao, W; Li, T; Zheng, L; Xu, J

2014-09-20

A broadly wavelength tunable acousto-optically Q-switched Tm:Lu2SiO5 (Tm:LSO) laser is presented for the first time, to our best knowledge. The emission wavelength was tuned in a broad spectral region over 111 nm ranging from 1959 to 2070 nm. A shortest pulse duration of 345 ns with beam quality of M(2)≤1.65 was obtained at pulse repetition frequency (PRF) of 1 kHz, corresponding to a maximum single pulse energy of 0.26 mJ and peak power of 0.75 kW. The experimental results indicated that Tm:LSO crystal has outstanding potential for obtaining broadly wavelength tunable and low-PRF laser pulses at 2 μm.

An optimal proportion of mixing broad-leaved forest for enhancing the effective productivity of moso bamboo.

PubMed

Cheng, Xiao-Fei; Shi, Pei-Jian; Hui, Cang; Wang, Fu-Sheng; Liu, Guo-Hua; Li, Bai-Lian

2015-04-01

Moso bamboos (Phyllostachys edulis) are important forestry plants in southern China, with substantial roles to play in regional economic and ecological systems. Mixing broad-leaved forests and moso bamboos is a common management practice in China, and it is fundamental to elucidate the interactions between broad-leaved trees and moso bamboos for ensuring the sustainable provision of ecosystem services. We examine how the proportion of broad-leaved forest in a mixed managed zone, topology, and soil profile affects the effective productivity of moso bamboos (i.e., those with significant economic value), using linear regression and generalized additive models. Bamboo's diameter at breast height follows a Weibull distribution. The importance of these variables to bamboo productivity is, respectively, slope (25.9%), the proportion of broad-leaved forest (24.8%), elevation (23.3%), gravel content by volume (16.6%), slope location (8.3%), and soil layer thickness (1.2%). Highest productivity is found on the 25° slope, with a 600-m elevation, and 30% broad-leaved forest. As such, broad-leaved forest in the upper slope can have a strong influence on the effective productivity of moso bamboo, ranking only after slope and before elevation. These factors can be considered in future management practice.

Primary malignant lymphoma of the uterus and broad ligament: a case report and review of literature.

PubMed

Chen, Runzhe; Yu, Zhengping; Zhang, Hongming; Ding, Jiahua; Chen, Baoan

2015-01-01

Primary malignant lymphoma of the uterus and broad ligament is rare. Here, we present a rare case of primary diffuse large B-cell lymphoma (DLBCL) of uterus and broad ligament in a 63-year-old female. The patient presenting with lower abdominal distention was referred to our hospital. Subsequent abdominal and pelvic ultrasound revealed the presence of a large mass, which was highly suspected as subserosal uterine leiomyoma. A large tumor was found with unclear boundary with right posterior wall, broad ligament and bilateral adnexa during surgery. Her uterus and the tumor of a broad ligament and bilateral adnexa were all excised as a result. Postoperative pathological examination showed DLBCL in uterus and broad ligament. Further examinations excluded metastatic diseases, which supported the diagnosis of primary DLBCL of the uterus and broad ligament. The patient received six cycles of R-CHOP (21 days) regimen. During the 8 months follow-up, no evidence of disease recurrence was identified. As the prevalence of primary extranodal lymphoma is increasing, the details of this rare case may highlight the importance and facilitate treatment of similar diseases. A summary focusing on the presentation and prognosis as well as a review of current management is also discussed.

Transmission of broad W/Rh and W/Al (target/filter) x-ray beams operated at 25-49 kVp through common shielding materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Xinhua; Zhang Da; Liu, Bob

2012-07-15

Purpose: To provide transmission data for broad 25-39 kVp (kilovolt peak) W/Rh and 25-49 kVp W/Al (target/filter, W-tungsten, Rh-rhodium, and Al-aluminum) x-ray beams through common shielding materials, such as lead, concrete, gypsum wallboard, wood, steel, and plate glass. Methods: The unfiltered W-target x-ray spectra measured on a Selenia Dimensions system (Hologic Inc., Bedford, MA) set at 20-49 kVp were, respectively, filtered using 50-{mu}m Rh and 700-{mu}m Al, and were subsequently used for Monte Carlo calculations. The transmission of broad x-ray beams through shielding materials was simulated using Geant4 low energy electromagnetic physics package with photon- and electron-processes above 250 eV,more » including photoelectric effect, Compton scattering, and Rayleigh scattering. The calculated transmission data were fitted using Archer equation with a robust fitting algorithm. Results: The transmission of broad x-ray beams through the above-mentioned shielding materials was calculated down to about 10{sup -5} for 25-39 kVp W/Rh and 25-49 kVp W/Al. The fitted results of {alpha}, {beta}, and {gamma} in Archer equation were provided. The {alpha} values of kVp Greater-Than-Or-Slanted-Equal-To 40 were approximately consistent with those of NCRP Report No. 147. Conclusions: These data provide inputs for the shielding designs of x-ray imaging facilities with W-anode x-ray beams, such as from Selenia Dimensions.« less

33 CFR 334.480 - Archers Creek, Ribbon Creek, and Broad River; U.S. Marine Corps Recruit Depot, Parris Island...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Broad River; U.S. Marine Corps Recruit Depot, Parris Island, South Carolina; danger zones. 334.480... DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.480 Archers Creek, Ribbon Creek, and Broad River... danger zone on Archers Creek (between the Broad River and Beaufort River), Ribbon Creek, and the Broad...

33 CFR 334.480 - Archers Creek, Ribbon Creek, and Broad River; U.S. Marine Corps Recruit Depot, Parris Island...

Code of Federal Regulations, 2012 CFR

2012-07-01

... Broad River; U.S. Marine Corps Recruit Depot, Parris Island, South Carolina; danger zones. 334.480... DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.480 Archers Creek, Ribbon Creek, and Broad River... danger zone on Archers Creek (between the Broad River and Beaufort River), Ribbon Creek, and the Broad...

33 CFR 334.480 - Archers Creek, Ribbon Creek, and Broad River; U.S. Marine Corps Recruit Depot, Parris Island...

Code of Federal Regulations, 2014 CFR

2014-07-01

... Broad River; U.S. Marine Corps Recruit Depot, Parris Island, South Carolina; danger zones. 334.480... DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.480 Archers Creek, Ribbon Creek, and Broad River... danger zone on Archers Creek (between the Broad River and Beaufort River), Ribbon Creek, and the Broad...

Broad-Scale Genetic Diversity of Cannabis for Forensic Applications.

PubMed

Dufresnes, Christophe; Jan, Catherine; Bienert, Friederike; Goudet, Jérôme; Fumagalli, Luca

2017-01-01

Cannabis (hemp and marijuana) is an iconic yet controversial crop. On the one hand, it represents a growing market for pharmaceutical and agricultural sectors. On the other hand, plants synthesizing the psychoactive THC produce the most widespread illicit drug in the world. Yet, the difficulty to reliably distinguish between Cannabis varieties based on morphological or biochemical criteria impedes the development of promising industrial programs and hinders the fight against narcotrafficking. Genetics offers an appropriate alternative to characterize drug vs. non-drug Cannabis. However, forensic applications require rapid and affordable genotyping of informative and reliable molecular markers for which a broad-scale reference database, representing both intra- and inter-variety variation, is available. Here we provide such a resource for Cannabis, by genotyping 13 microsatellite loci (STRs) in 1 324 samples selected specifically for fibre (24 hemp varieties) and drug (15 marijuana varieties) production. We showed that these loci are sufficient to capture most of the genome-wide diversity patterns recently revealed by NGS data. We recovered strong genetic structure between marijuana and hemp and demonstrated that anonymous samples can be confidently assigned to either plant types. Fibres appear genetically homogeneous whereas drugs show low (often clonal) diversity within varieties, but very high genetic differentiation between them, likely resulting from breeding practices. Based on an additional test dataset including samples from 41 local police seizures, we showed that the genetic signature of marijuana cultivars could be used to trace crime scene evidence. To date, our study provides the most comprehensive genetic resource for Cannabis forensics worldwide.

Broad-Scale Genetic Diversity of Cannabis for Forensic Applications

PubMed Central

Dufresnes, Christophe; Jan, Catherine; Bienert, Friederike; Goudet, Jérôme; Fumagalli, Luca

2017-01-01

Cannabis (hemp and marijuana) is an iconic yet controversial crop. On the one hand, it represents a growing market for pharmaceutical and agricultural sectors. On the other hand, plants synthesizing the psychoactive THC produce the most widespread illicit drug in the world. Yet, the difficulty to reliably distinguish between Cannabis varieties based on morphological or biochemical criteria impedes the development of promising industrial programs and hinders the fight against narcotrafficking. Genetics offers an appropriate alternative to characterize drug vs. non-drug Cannabis. However, forensic applications require rapid and affordable genotyping of informative and reliable molecular markers for which a broad-scale reference database, representing both intra- and inter-variety variation, is available. Here we provide such a resource for Cannabis, by genotyping 13 microsatellite loci (STRs) in 1 324 samples selected specifically for fibre (24 hemp varieties) and drug (15 marijuana varieties) production. We showed that these loci are sufficient to capture most of the genome-wide diversity patterns recently revealed by NGS data. We recovered strong genetic structure between marijuana and hemp and demonstrated that anonymous samples can be confidently assigned to either plant types. Fibres appear genetically homogeneous whereas drugs show low (often clonal) diversity within varieties, but very high genetic differentiation between them, likely resulting from breeding practices. Based on an additional test dataset including samples from 41 local police seizures, we showed that the genetic signature of marijuana cultivars could be used to trace crime scene evidence. To date, our study provides the most comprehensive genetic resource for Cannabis forensics worldwide. PMID:28107530

Broadly tunable terahertz generation in mid-infrared quantum cascade lasers.

PubMed

Vijayraghavan, Karun; Jiang, Yifan; Jang, Min; Jiang, Aiting; Choutagunta, Karthik; Vizbaras, Augustinas; Demmerle, Frederic; Boehm, Gerhard; Amann, Markus C; Belkin, Mikhail A

2013-01-01

Room temperature, broadly tunable, electrically pumped semiconductor sources in the terahertz spectral range, similar in operation simplicity to diode lasers, are highly desired for applications. An emerging technology in this area are sources based on intracavity difference-frequency generation in dual-wavelength mid-infrared quantum cascade lasers. Here we report terahertz quantum cascade laser sources based on an optimized non-collinear Cherenkov difference-frequency generation scheme that demonstrates dramatic improvements in performance. Devices emitting at 4 THz display a mid-infrared-to-terahertz conversion efficiency in excess of 0.6 mW W(-2) and provide nearly 0.12 mW of peak power output. Devices emitting at 2 and 3 THz fabricated on the same chip display 0.09 and 0.4 mW W(-2) conversion efficiencies at room temperature, respectively. High terahertz-generation efficiency and relaxed phase-matching conditions offered by the Cherenkov scheme allowed us to demonstrate, for the first time, an external-cavity terahertz quantum cascade laser source tunable between 1.70 and 5.25 THz.

THE VIEWING ANGLES OF BROAD ABSORPTION LINE VERSUS UNABSORBED QUASARS

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 ofmore » 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.« less

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…

Broad- versus Narrow-Spectrum Oral Antibiotic Transition and Outcomes in Health Care-associated Pneumonia.

PubMed

Buckel, Whitney R; Stenehjem, Edward; Sorensen, Jeff; Dean, Nathan; Webb, Brandon

2017-02-01

Guidelines recommend a switch from intravenous to oral antibiotics once patients who are hospitalized with pneumonia achieve clinical stability. However, little evidence guides the selection of an oral antibiotic for patients with health care-associated pneumonia, especially where no microbiological diagnosis is made. To compare outcomes between patients who were transitioned to broad- versus narrow-spectrum oral antibiotics after initially receiving broad-spectrum intravenous antibiotic coverage. We performed a secondary analysis of an existing database of adults with community-onset pneumonia admitted to seven Utah hospitals. We identified 220 inpatients with microbiology-negative health care-associated pneumonia from 2010 to 2012. After excluding inpatient deaths and treatment failures, 173 patients remained in which broad-spectrum intravenous antibiotics were transitioned to an oral regimen. We classified oral regimens as broad-spectrum (fluoroquinolone) versus narrow-spectrum (usually a β-lactam). We compared demographic and clinical characteristics between groups. Using a multivariable regression model, we adjusted outcomes by severity (electronically calculated CURB-65), comorbidity (Charlson Index), time to clinical stability, and length of intravenous therapy. Age, severity, comorbidity, length of intravenous therapy, and clinical response were similar between the two groups. Observed 30-day readmission (11.9 vs. 21.4%; P = 0.26) and 30-day all-cause mortality (2.3 vs. 5.3%; P = 0.68) were also similar between the narrow and broad oral antibiotic groups. In multivariable analysis, we found no statistically significant differences for adjusted odds of 30-day readmission (adjusted odds ratio, 0.56; 95% confidence interval, 0.06-5.2; P = 0.61) or 30-day all-cause mortality (adjusted odds ratio, 0.55; 95% confidence interval, 0.19-1.6; P = 0.26) between narrow and broad oral antibiotic groups. On the basis of analysis of a limited number of patients

Naturally selected hepatitis C virus polymorphisms confer broad neutralizing antibody resistance.

PubMed

Bailey, Justin R; Wasilewski, Lisa N; Snider, Anna E; El-Diwany, Ramy; Osburn, William O; Keck, Zhenyong; Foung, Steven K H; Ray, Stuart C

2015-01-01

For hepatitis C virus (HCV) and other highly variable viruses, broadly neutralizing mAbs are an important guide for vaccine development. The development of resistance to anti-HCV mAbs is poorly understood, in part due to a lack of neutralization testing against diverse, representative panels of HCV variants. Here, we developed a neutralization panel expressing diverse, naturally occurring HCV envelopes (E1E2s) and used this panel to characterize neutralizing breadth and resistance mechanisms of 18 previously described broadly neutralizing anti-HCV human mAbs. The observed mAb resistance could not be attributed to polymorphisms in E1E2 at known mAb-binding residues. Additionally, hierarchical clustering analysis of neutralization resistance patterns revealed relationships between mAbs that were not predicted by prior epitope mapping, identifying 3 distinct neutralization clusters. Using this clustering analysis and envelope sequence data, we identified polymorphisms in E2 that confer resistance to multiple broadly neutralizing mAbs. These polymorphisms, which are not at mAb contact residues, also conferred resistance to neutralization by plasma from HCV-infected subjects. Together, our method of neutralization clustering with sequence analysis reveals that polymorphisms at noncontact residues may be a major immune evasion mechanism for HCV, facilitating viral persistence and presenting a challenge for HCV vaccine development.

Serving some and serving all: how providers navigate the challenges of providing racially targeted health services.

PubMed

Zhou, Amy

2017-10-01

Racially targeted healthcare provides racial minorities with culturally and linguistically appropriate health services. This mandate, however, can conflict with the professional obligation of healthcare providers to serve patients based on their health needs. The dilemma between serving a particular population and serving all is heightened when the patients seeking care are racially diverse. This study examines how providers in a multi-racial context decide whom to include or exclude from health programs. This study draws on 12 months of ethnographic fieldwork at an Asian-specific HIV organization. Fieldwork included participant observation of HIV support groups, community outreach programs, and substance abuse recovery groups, as well as interviews with providers and clients. Providers managed the dilemma in different ways. While some programs in the organization focused on an Asian clientele, others de-emphasized race and served a predominantly Latino and African American clientele. Organizational structures shaped whether services were delivered according to racial categories. When funders examined client documents, providers prioritized finding Asian clients so that their documents reflected program goals to serve the Asian population. In contrast, when funders used qualitative methods, providers could construct an image of a program that targets Asians during evaluations while they included other racial minorities in their everyday practice. Program services were organized more broadly by health needs. Even within racially targeted programs, the meaning of race fluctuates and is contested. Patients' health needs cross cut racial boundaries, and in some circumstances, the boundaries of inclusion can expand beyond specific racial categories to include racial minorities and underserved populations more generally.

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.

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.

[Dust absorption capacities of eight evergreen broad-leaved plants in Beijing, China.

PubMed

Fan, Shu Xin; Cai, Yu; Dong, Li

2017-02-01

Aiming at selecting the evergreen broad-leaved plants with excellent dust capturing capacity that can be applied in Beijing area for improving the urban vegetation dust removal, this study selected 8 evergreen (including semi-evergreen) broad-leaved plants used in urban green-space in Beijing area to measure the dust absorption per unit leaf area by the elution-mass method during winter and early spring in 2014. The dust deposition per leaf and per plant of each species was further calculated for tested species. Based on the dust capturing capacity measured in different units, cluster analysis on the comprehensive dust absorption capacities of different plants was carried out from the corresponding aspect. Results showed that the dust absorption ability differed significantly among the 8 evergreen broad-leaved (including semi-evergreen) species including Buxus sinica, Euonymus japonicus, Ligustrum quihoui, L. vicaryi, E. kiautschovicus, Indocalamus tessellatus, Phyllostachys violascens and Ph. aureosulcata. E. japonicus was best in dust absorption per unit leaf area and per plant, with 1.36 g·m -2 and 59.63 g·plant -1 . I. tessellates (with 1.62 mg·leaf -1 ) had the strongest dust absorption ability per leaf. With different measurement units selected, the ranking changed. The cluster analysis based on the multi index comprehensive dust absorption capacities could roughly divided the 8 evergreen broad-leaved species into 4 categories representing different dust absorption capacity levels. E. japonicus and Ph. sviolascens had the outstanding comprehensive dust capturing capacity, while B. sinica, L. vicaryi and Ph. aureosulcata showed the weak performance.

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…

Broad-band absorbers for reduction of parasitic light: two alternative solutions

NASA Astrophysics Data System (ADS)

Giovannini, Hughes; Lemarquis, F.; Akhouayri, H.; Cathelinaud, Michel; Torchio, Philippe; Amra, C.; Cousin, Bernard; Laubier, D.; Otrio, Georges

2018-04-01

This paper, "Broad-band absorbers for reduction of parasitic light: two alternative solutions," was presented as part of International Conference on Space Optics—ICSO 1997, held in Toulouse, France.

On the origin of gamma-rays in Fermi blazars: beyondthe broad-line region

NASA Astrophysics Data System (ADS)

Costamante, L.; Cutini, S.; Tosti, G.; Antolini, E.; Tramacere, A.

2018-07-01

The gamma-ray emission in broad-line blazars is generally explained as inverse Compton (IC) radiation of relativistic electrons in the jet scattering optical-UV photons from the broad-line region (BLR), the so-called BLR external Compton (EC) scenario. We test this scenario on the Fermi gamma-ray spectra of 106 broad-line blazars detected with the highest significance or largest BLR, by looking for cut-off signatures at high energies compatible with γ-γ interactions with BLR photons. We do not find evidence for the expected BLR absorption. For 2/3 of the sources, we can exclude any significant absorption (τmax < 1), while for the remaining 1/3 the possible absorption is constrained to be 1.5-2 orders of magnitude lower than expected. This result holds also dividing the spectra in high- and low-flux states, and for powerful blazars with large BLR. Only 1 object out of 10 seems compatible with substantial attenuation (τmax > 5). We conclude that for 9 out of 10 objects, the jet does not interact with BLR photons. Gamma-rays seem either produced outside the BLR most of the time, or the BLR is ˜100 × larger than given by reverberation mapping. This means that (i) EC on BLR photons is disfavoured as the main gamma-ray mechanism, versus IC on IR photons from the torus or synchrotron self-Compton; (ii) the Fermi gamma-ray spectrum is mostly intrinsic, determined by the interaction of the particle distribution with the seed-photon spectrum; and (iii) without suppression by the BLR, broad-line blazars can become copious emitters above 100 GeV, as demonstrated by 3C 454.3. We expect the CTA sky to be much richer of broad-line blazars than previously thought.

Origin of the 900 cm{sup −1} broad double-hump OH vibrational feature of strongly hydrogen-bonded carboxylic acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Hoozen, Brian L.; Petersen, Poul B.

2015-03-14

Medium and strong hydrogen bonds are common in biological systems. Here, they provide structural support and can act as proton transfer relays to drive electron and/or energy transfer. Infrared spectroscopy is a sensitive probe of molecular structure and hydrogen bond strength but strongly hydrogen-bonded structures often exhibit very broad and complex vibrational bands. As an example, strong hydrogen bonds between carboxylic acids and nitrogen-containing aromatic bases commonly display a 900 cm{sup −1} broad feature with a remarkable double-hump structure. Although previous studies have assigned this feature to the OH, the exact origin of the shape and width of this unusualmore » feature is not well understood. In this study, we present ab initio calculations of the contributions of the OH stretch and bend vibrational modes to the vibrational spectrum of strongly hydrogen-bonded heterodimers of carboxylic acids and nitrogen-containing aromatic bases, taking the 7-azaindole—acetic acid and pyridine—acetic acid dimers as examples. Our calculations take into account coupling between the OH stretch and bend modes as well as how both of these modes are affected by lower frequency dimer stretch modes, which modulate the distance between the monomers. Our calculations reproduce the broadness and the double-hump structure of the OH vibrational feature. Where the spectral broadness is primarily caused by the dimer stretch modes strongly modulating the frequency of the OH stretch mode, the double-hump structure results from a Fermi resonance between the out of the plane OH bend and the OH stretch modes.« less

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.

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.

Can job redesign interventions influence a broad range of employee outcomes by changing multiple job characteristics? A quasi-experimental study.

PubMed

Holman, David; Axtell, Carolyn

2016-07-01

Many job redesign interventions are based on a multiple mediator-multiple outcome model in which the job redesign intervention indirectly influences a broad range of employee outcomes by changing multiple job characteristics. As this model remains untested, the aim of this study is to test a multiple mediator-multiple outcome model of job redesign. Multilevel analysis of data from a quasi-experimental job redesign intervention in a call center confirmed the hypothesized model and showed that the job redesign intervention affected a broad range of employee outcomes (i.e., employee well-being, psychological contract fulfillment, and supervisor-rated job performance) through changes in 2 job characteristics (i.e., job control and feedback). The results provide further evidence for the efficacy and mechanisms of job redesign interventions. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Personal glucose meters for detection and quantification of a broad range of analytes

DOEpatents

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.

Variable broad lines and outflow in the weak blazar PBC J2333.9-2343

NASA Astrophysics Data System (ADS)

Hernández-García, L.; Vietri, G.; Panessa, F.; Piconcelli, E.; Chavushyan, V.; Jiménez-Andrade, E. F.; Bassani, L.; Bazzano, A.; Cazzoli, S.; Malizia, A.; Masetti, N.; Monaco, L.; Pović, M.; Saviane, I.; Ubertini, P.

2018-05-01

PBC J2333.9-2343 is a peculiar active nucleus with two giant radio lobes and a weak blazar-like nucleus at their center. In the present work we show new optical, UV, and X-ray data taken from the San Pedro Mártir telescope, the New Technology Telescope, NTT/EFOSC2, and the Swift/XRT satellite. The source is highly variable at all frequencies, in particular the strongest variations are found in the broad Hα component with a flux increase of 61±4 per cent between 2009 and 2016, following the X-ray flux increase of 62±6 per cent between 2010 and 2016. We also detected a broad Hβ component in 2016, making the optical classification change from type 1.9 to type 1.8 in one year. We have also detected a broad component of the [OIII]λ5007 line, which is blue-shifted and of high velocity, suggesting an origin from a highly disturbed medium, possibly an outflow. The line flux variability and broad widths are indicative of a jet that is, at least in part, responsible for the ionization of the BLR and NLR.

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…

QSO Broad Emission Line Asymmetries: Evidence of Gravitational Redshift?

NASA Astrophysics Data System (ADS)

Corbin, Michael R.

1995-07-01

The broad optical and ultraviolet emission lines of QSOs and active galactic nuclei (AGNs) display both redward and blueward asymmetries. This result is particularly well established for Hβ and C IV λ1549, and it has been found that Hβ becomes increasingly redward asymmetric with increasing soft X-ray luminosity. Two models for the origin of these asymmetries are investigated: (1) Anisotropic line emission from an ensemble of radially moving clouds, and (2) Two-component profiles consisting of a core of intermediate (˜1000-4000 km s-1) velocity width and a very broad (˜5000-20,000 km s-1) base, in which the asymmetries arise due to a velocity difference between the centroids of the components. The second model is motivated by the evidence that the traditional broad-line region is actually composed of an intermediate-line region (ILR) of optically thick clouds and a very broad line region (VBLR) of optically thin clouds lying closer to the central continuum source. Line profiles produced by model (1) are found to be inconsistent with those observed, being asymmetric mainly in their cores, whereas the asymmetries of actual profiles arise mainly from excess emission in their wings. By contrast, numerical fitting to actual Hβ and C IV λ1549 line profiles reveals that the majority can be accurately modeled by two components, either two Gaussians or the combination of a Gaussian base and a logarithmic core. The profile asymmetries in Hβ can be interpreted as arising from a shift of the base component over a range ˜6300 km s-1 relative to systemic velocity as defined by the position of the [O III] λ5007 line. A similar model appears to apply to C IV λ1549. The correlation between Hβ asymmetry and X-ray luminosity may thus be interpreted as a progressive red- shift of the VBLR velocity centroid relative to systemic velocity with increasing X-ray luminosity. This in turn suggests that the underlying effect is gravitational red shift, as soft X-ray emission

Unusual broad-line Mg II emitters among luminous galaxies in the baryon oscillation spectroscopic survey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roig, Benjamin; Blanton, Michael R.; Ross, Nicholas P.

2014-02-01

Many classes of active galactic nuclei (AGNs) have been observed and recorded since the discovery of Seyfert galaxies. In this paper, we examine the sample of luminous galaxies in the Baryon Oscillation Spectroscopic Survey. We find a potentially new observational class of AGNs, one with strong and broad Mg II λ2799 line emission, but very weak emission in other normal indicators of AGN activity, such as the broad-line Hα, Hβ, and the near-ultraviolet AGN continuum, leading to an extreme ratio of broad Hα/Mg II flux relative to normal quasars. Meanwhile, these objects' narrow-line flux ratios reveal AGN narrow-line regions withmore » levels of activity consistent with the Mg II fluxes and in agreement with that of normal quasars. These AGN may represent an extreme case of the Baldwin effect, with very low continuum and high equivalent width relative to typical quasars, but their ratio of broad Mg II to broad Balmer emission remains very unusual. They may also be representative of a class of AGN where the central engine is observed indirectly with scattered light. These galaxies represent a small fraction of the total population of luminous galaxies (≅ 0.1%), but are more likely (about 3.5 times) to have AGN-like nuclear line emission properties than other luminous galaxies. Because Mg II is usually inaccessible for the population of nearby galaxies, there may exist a related population of broad-line Mg II emitters in the local universe which is currently classified as narrow-line emitters (Seyfert 2 galaxies) or low ionization nuclear emission-line regions.« less

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.

Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes

PubMed Central

Van Dyke, Marley C. Caballero; Chaturvedi, Ashok K.; Hardison, Sarah E.; Leopold Wager, Chrissy M.; Castro-Lopez, Natalia; Hole, Camaron R.; Wozniak, Karen L.; Wormley, Floyd L.

2017-01-01

Cryptococcosis is a fungal disease caused by multiple Cryptococcus serotypes; particularly C. neoformans (serotypes A and D) and C. gattii (serotypes B and C). To date, there is no clinically available vaccine to prevent cryptococcosis. Mice given an experimental pulmonary vaccination with a C. neoformans serotype A strain engineered to produce interferon-γ, denoted H99γ, are protected against a subsequent otherwise lethal experimental infection with C. neoformans serotype A. Thus, we determined the efficacy of immunization with C. neoformans strain H99γ to elicit broad-spectrum protection in BALB/c mice against multiple disparate Cryptococcus serotypes. We observed significantly increased survival rates and significantly decreased pulmonary fungal burden in H99γ immunized mice challenged with Cryptococcus serotypes A, B, or D compared to heat-killed H99γ (HKH99γ) immunized mice. Results indicated that prolonged protection against Cryptococcus serotypes B or D in H99γ immunized mice was CD4+ T cell dependent and associated with the induction of predominantly Th1-type cytokine responses. Interestingly, immunization with H99γ did not elicit greater protection against challenge with the Cryptococcus serotype C tested either due to low overall virulence of this strain or enhanced capacity of this strain to evade host immunity. Altogether, these studies provide “proof-of-concept” for the development of a cryptococcal vaccine that provides cross-protection against multiple disparate serotypes of Cryptococcus. PMID:29163469

Variability of broad and blueshifted component of [OIII]λ5007 in I ZWI

NASA Astrophysics Data System (ADS)

Wang, J.; Wei, J. Y.; He, X. T.

2005-04-01

Although the existence of asymmetrical profile of [OIII]λ5007 has been discovered for ages, its filiation and physics are poorly understood. Two new spectra of I ZWI taken on November 16, 2001 and on December 3, 2002 were compared with the spectra taken by BG92. Following results are obtained. (1) The certain variations of broad [OIII] during about 10 years separating the observations are identified. The inferred length scale of broad [OIII] emitting region ranges from 0.3 to 3 pc. By assuming a Keplerian motion in line emitting region, the material emitting broad [OIII] is likely to be located at the transient emission line region, between BLR and NLR. (2) We find a positive relation between the FeII emission and flux of Hβ (or continuum). On the other hand, the parameter RFe decreases with ionizing continuum marginally. (3) We detect a low ionized NLR in I ZWI, because of the low flux ratios [OIII]n/Hβn (∼1.7).

The dark side of going abroad: How broad foreign experiences increase immoral behavior.

PubMed

Lu, Jackson G; Quoidbach, Jordi; Gino, Francesca; Chakroff, Alek; Maddux, William W; Galinsky, Adam D

2017-01-01

Because of the unprecedented pace of globalization, foreign experiences are increasingly common and valued. Past research has focused on the benefits of foreign experiences, including enhanced creativity and reduced intergroup bias. In contrast, the present work uncovers a potential dark side of foreign experiences: increased immoral behavior. We propose that broad foreign experiences (i.e., experiences in multiple foreign countries) foster not only cognitive flexibility but also moral flexibility. Using multiple methods (longitudinal, correlational, and experimental), 8 studies (N > 2,200) establish that broad foreign experiences can lead to immoral behavior by increasing moral relativism-the belief that morality is relative rather than absolute. The relationship between broad foreign experiences and immoral behavior was robust across a variety of cultural populations (anglophone, francophone), life stages (high school students, university students, MBA students, middle-aged adults), and 7 different measures of immorality. As individuals are exposed to diverse cultures, their moral compass may lose some of its precision. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

T Cell Responses to Arenavirus Infections.

DTIC Science & Technology

1991-11-01

CLASSIFICATION OF THIS PAGE Form AAmWved REPORT DOCUMENTATION PAGE OMB No.O 70O1U ts. REPORT SECURITY CLASSIFICATION lb. RESTRICTIVE MARKINGS Unclassified Za...1991. J. Virol. 65.3001-3006. 23. Ahmed, R., L. D., Butler, and L. Bhatti. 1988. J. Virol. 62: 21 02-21 06. 24. Moskophidis 0, S. P. Cobbold , H. Waldmann

"Still Rather Hazy at Present": Citizens' and Physicians' Views on Returning Results from Biobank Research Using Broad Consent.

PubMed

Barazzetti, Gaia; Cavalli, Samuele; Benaroyo, Lazare; Kaufmann, Alain

2017-03-01

Informed consent and return of research results are among the most debated topics in the biobank literature. We discuss ethical, social, and policy issues associated with returning results in the context of biobanks using a broad consent approach, in the light of data from a qualitative survey of citizens' and physicians' views. Data were collected through interviews and focus groups to investigate stakeholders' perspectives about a large-scale hospital-based biobank designed to foster biomedical research, including prospective genomics research, and "personalized" medicine. Both physicians and citizens considered psychosocial impacts as crucial in the assessment of benefits expected from a return of results to biobank participants. In particular, physicians highlighted the possible consequences on the patient-doctor relationship and discussed implications for the concept of "personalized" medicine. Citizens held ambivalent attitudes toward returning individual research results: they defended the "right not to know," while they also considered a sort of "responsibility to know" because of potential implications of results for family members. Moreover, physicians and citizens raised questions about the broad consent model used for inhospital biobank recruitment and expressed their needs for more training in genomics and more information on the biobank initiative. Stakeholders such as citizens and physicians, who may be concerned as potential biobank participants or as healthcare professionals involved in the management of clinically relevant research results, provide useful insights into several aspects of broad consent and return of results, related in particular to the interface between research and the clinic.

Coherent-subspace array processing based on wavelet covariance: an application to broad-band, seismo-volcanic signals

NASA Astrophysics Data System (ADS)

Saccorotti, G.; Nisii, V.; Del Pezzo, E.

2008-07-01

Long-Period (LP) and Very-Long-Period (VLP) signals are the most characteristic seismic signature of volcano dynamics, and provide important information about the physical processes occurring in magmatic and hydrothermal systems. These events are usually characterized by sharp spectral peaks, which may span several frequency decades, by emergent onsets, and by a lack of clear S-wave arrivals. These two latter features make both signal detection and location a challenging task. In this paper, we propose a processing procedure based on Continuous Wavelet Transform of multichannel, broad-band data to simultaneously solve the signal detection and location problems. Our method consists of two steps. First, we apply a frequency-dependent threshold to the estimates of the array-averaged WCO in order to locate the time-frequency regions spanned by coherent arrivals. For these data, we then use the time-series of the complex wavelet coefficients for deriving the elements of the spatial Cross-Spectral Matrix. From the eigenstructure of this matrix, we eventually estimate the kinematic signals' parameters using the MUltiple SIgnal Characterization (MUSIC) algorithm. The whole procedure greatly facilitates the detection and location of weak, broad-band signals, in turn avoiding the time-frequency resolution trade-off and frequency leakage effects which affect conventional covariance estimates based upon Windowed Fourier Transform. The method is applied to explosion signals recorded at Stromboli volcano by either a short-period, small aperture antenna, or a large-aperture, broad-band network. The LP (0.2 < T < 2s) components of the explosive signals are analysed using data from the small-aperture array and under the plane-wave assumption. In this manner, we obtain a precise time- and frequency-localization of the directional properties for waves impinging at the array. We then extend the wavefield decomposition method using a spherical wave front model, and analyse the VLP

Selection of common bean to broad environmental adaptation in Haiti

USDA-ARS?s Scientific Manuscript database

Common bean (Phaseolus vulgaris L.) cultivars in Haiti need adaptation to a broad range of environments and resistance to the most important diseases such as Bean Golden Yellow Mosaic Virus. The Legume Breeding Program (LBP), a collaborative effort of the AREA project (USAID funded through IFAS/Univ...

Micropatterned Pyramidal Ionic Gels for Sensing Broad-Range Pressures with High Sensitivity.

PubMed

Cho, Sung Hwan; Lee, Seung Won; Yu, Seunggun; Kim, Hyeohn; Chang, Sooho; Kang, Donyoung; Hwang, Ihn; Kang, Han Sol; Jeong, Beomjin; Kim, Eui Hyuk; Cho, Suk Man; Kim, Kang Lib; Lee, Hyungsuk; Shim, Wooyoung; Park, Cheolmin

2017-03-22

The development of pressure sensors that are effective over a broad range of pressures is crucial for the future development of electronic skin applicable to the detection of a wide pressure range from acoustic wave to dynamic human motion. Here, we present flexible capacitive pressure sensors that incorporate micropatterned pyramidal ionic gels to enable ultrasensitive pressure detection. Our devices show superior pressure-sensing performance, with a broad sensing range from a few pascals up to 50 kPa, with fast response times of <20 ms and a low operating voltage of 0.25 V. Since high-dielectric-constant ionic gels were employed as constituent sensing materials, an unprecedented sensitivity of 41 kPa -1 in the low-pressure regime of <400 Pa could be realized in the context of a metal-insulator-metal platform. This broad-range capacitive pressure sensor allows for the efficient detection of pressure from a variety of sources, including sound waves, a lightweight object, jugular venous pulses, radial artery pulses, and human finger touch. This platform offers a simple, robust approach to low-cost, scalable device design, enabling practical applications of electronic skin.

The broad autism phenotype predicts relationship outcomes in newly formed college roommates.

PubMed

Faso, Daniel J; Corretti, Conrad A; Ackerman, Robert A; Sasson, Noah J

2016-05-01

Although previous studies have reported that the broad autism phenotype is associated with reduced relationship quality within established relationships, understanding how this association emerges requires assessment prior to relationship development. In the present longitudinal study, college roommates with minimal familiarity prior to cohabitation (N = 162) completed the broad autism phenotype questionnaire and intermittently reported on their relationship quality and interpersonal behaviors toward their roommate over their first 10 weeks of living together. Actor-Partner Interdependence Models demonstrated that roommates mismatched on aloofness (one high and one low) had lower relationship satisfaction than those matched on it, with the interpersonal behavior of warmth mediating this association. Because relationship satisfaction remained high when both roommates were aloof, satisfaction does not appear predicated upon the presence of aloofness generally but rather reflects a product of dissimilarity in aloof profiles between roommates. In contrast, although participants reported less relationship satisfaction and commitment with roommates higher on pragmatic language abnormalities, mismatches on this broad autism phenotype trait, and on rigid personality, were less consequential. In sum, these findings suggest that complementary profiles of social motivation may facilitate relationship quality during the early course of relationship development. © The Author(s) 2015.

Broad issues to consider for library involvement in bioinformatics*

PubMed Central

Geer, Renata C.

2006-01-01

Background: The information landscape in biological and medical research has grown far beyond literature to include a wide variety of databases generated by research fields such as molecular biology and genomics. The traditional role of libraries to collect, organize, and provide access to information can expand naturally to encompass these new data domains. Methods: This paper discusses the current and potential role of libraries in bioinformatics using empirical evidence and experience from eleven years of work in user services at the National Center for Biotechnology Information. Findings: Medical and science libraries over the last decade have begun to establish educational and support programs to address the challenges users face in the effective and efficient use of a plethora of molecular biology databases and retrieval and analysis tools. As more libraries begin to establish a role in this area, the issues they face include assessment of user needs and skills, identification of existing services, development of plans for new services, recruitment and training of specialized staff, and establishment of collaborations with bioinformatics centers at their institutions. Conclusions: Increasing library involvement in bioinformatics can help address information needs of a broad range of students, researchers, and clinicians and ultimately help realize the power of bioinformatics resources in making new biological discoveries. PMID:16888662

Constraints on the outer radius of the broad emission line region of active galactic nuclei

NASA Astrophysics Data System (ADS)

Landt, Hermine; Ward, Martin J.; Elvis, Martin; Karovska, Margarita

2014-03-01

Here we present observational evidence that the broad emission line region (BELR) of active galactic nuclei (AGN) generally has an outer boundary. This was already clear for sources with an obvious transition between the broad and narrow components of their emission lines. We show that the narrow component of the higher-order Paschen lines is absent in all sources, revealing a broad emission line profile with a broad, flat top. This indicates that the BELR is kinematically separate from the narrow emission line region. We use the virial theorem to estimate the BELR outer radius from the flat top width of the unblended profiles of the strongest Paschen lines, Paα and Paβ, and find that it scales with the ionizing continuum luminosity roughly as expected from photoionization theory. The value of the incident continuum photon flux resulting from this relationship corresponds to that required for dust sublimation. A flat-topped broad emission line profile is produced by both a spherical gas distribution in orbital motion and an accretion disc wind if the ratio between the BELR outer and inner radius is assumed to be less than ˜100-200. On the other hand, a pure Keplerian disc can be largely excluded, since for most orientations and radial extents of the disc the emission line profile is double-horned.

Leiomyosarcoma of the Broad Ligament With Fever Presentation: A Case Report and Review of Literature.

PubMed

Chaichian, Shahla; Mehdizadehkashi, Abolfazl; Tahermanesh, Kobra; Moazzami, Bahram; Jesmi, Fatemeh; Rafiee, Moezedinjavad; Goharimoghaddam, Katayoun

2016-04-01

Leiomyosarcoma is a rare gynecologic malignancy that accounts for less than 1% of gynecological malignancies. Leiomyosarcoma of the broad ligament is an even rarer condition. According to Gardner's criteria, the diagnosis is made when the mass is completely separated from the uterus and adnexa. So far, 23 cases of primary leiomyosarcoma of the broad ligament have been reported in the literature published in English. In September 2014, a 55-year-old, gravida 3, para 3 woman with a BMI of 30 and a chief complaint of fever and dizziness was admitted to the infectious-diseases ward of the Pars general hospital affiliated with Iran University of Medical Sciences in Tehran, Iran. Her symptoms had begun two weeks before. The results of a fever workup and examination for infectious, metabolic, and immunologic problems were all negative. Imaging modalities revealed an endometrial polyp, two calcified myoma in the body of the uterus, and a solid, heterogeneous 70-mm mass in the right para-cervical space, posterior to the broad ligament, and far from the ovary. After surgery, a histologic report revealed leiomyosarcoma. Although a leiomyosarcoma of the broad ligament is rare, practitioners should consider it when dealing with masses in the region of the broad ligament. If there is any suspicion of malignancy, especially in the presence of fever, it is recommended to avoid morcellation during laparoscopy.

Characterization and application of a broad bandwidth oscillator for the HELEN laser facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrew, J.E.; Stevenson, R.M.; Bett, T.H.

1995-12-31

Preliminary investigations of a potential broad band oscillator for the HELEN laser facility and its proposed upgrade are described. The reasons for the need of broad bandwidth and the choice of commercial technology to achieve it are discussed. The characterization of the device and the diagnostics used for the investigations are described. Small signal amplification of the bandwidth by a glass amplifier was also performed along with investigations of the effect of various bandwidths on the far field beam quality when using random phase plates.

Single mode, broad-waveguide ARROW-type semiconductor diode lasers

NASA Astrophysics Data System (ADS)

Al-Muhanna, Abdulrahman Ali

A broad transverse waveguide (low confinement) concept is used to achieve a record-high spatially incoherent cw output power of 11W for InGaAs active devices (λ = 0.97 μm) from 100μm wide-stripe and 2mm-long devices with low internal loss, α1 = 1cm-1, and high characteristic temperatures, T0 = 210K, and T1 = 1800K. A detailed above-threshold analysis reveals that reduction in gain spatial hole burning (GSHB) is possible in ARROW-type structures by using a low transverse confinement factor; consequently, a wider ARROW-core can be utilized. By incorporating both a broad-waveguide concept as well as an asymmetric structure in the transverse direction, and an ARROW-type structure in the lateral direction, a novel single-spatial mode diode laser with improved performance is obtained. Devices with low transverse confinement factor (Γ ~ 1%) and a core-region width of 7.8 μm achieved 510mW single-spatial mode pulsed output power (λ = 0.946 μm) with a full- width at half-maximum (FWHM) of the lateral far-field pattern of 4.7°.

Metabolism of trans-3-hexadecenoic acid in broad bean.

PubMed

Harwood, J L; James, A T

1975-01-02

1. Broad bean (Vicia faba) leaves contain rather high concentrations (about 4% of total fatty acids) of the trans-3-hexadecenoic acid. 2. Amounts of the acid increase with the age of the leaves and are absent from etiolated tissue. 3. Changes in the levels of trans-delta-4-hexadecenoic acid can be produced by subjecting the intact plants to various light/dark periods. 4. Chloroplasts isolated from broad-bean leaves show high rates of fatty acid synthesis from [1-14C]acetate. Synthesis is dependent on coenzyme A and ATP but is insensitive to the addition of exogenous acyl carrier protein. 5. The pattern of acids made includes about 20% palmitic, 5% hexadeconoic, 10% stearic and 60% oleic. trans-3-Hexadecenoic acid synthesis was most active in chloroplasts from plants exposed to the dark for 5 days and light for 3 days. 6. Arsenite addition inhibited stearate formation by isolated chloroplasts but resulted in a two-fold stimulation of overall synthesis. 7. The rate of fatty acid synthesis by isolated chloroplasts paralleled the changes in endogenous trans-3-hexadecenoic acid levels in the leaves from which they were isolated.

The outflow structure of GW170817 from late-time broad-band observations

NASA Astrophysics Data System (ADS)

Troja, E.; Piro, L.; Ryan, G.; van Eerten, H.; Ricci, R.; Wieringa, M. H.; Lotti, S.; Sakamoto, T.; Cenko, S. B.

2018-07-01

We present our broad-band study of GW170817 from radio to hard X-rays, including NuSTAR and Chandra observations up to 165 d after the merger, and a multimessenger analysis including LIGO constraints. The data are compared with predictions from a wide range of models, providing the first detailed comparison between non-trivial cocoon and jet models. Homogeneous and power-law shaped jets, as well as simple cocoon models are ruled out by the data, while both a Gaussian shaped jet and a cocoon with energy injection can describe the current data set for a reasonable range of physical parameters, consistent with the typical values derived from short GRB afterglows. We propose that these models can be unambiguously discriminated by future observations measuring the post-peak behaviour, with Fν ∝ t˜-1.0 for the cocoon and Fν∝ t˜-2.5 for the jet model.

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),…

Huge (9 Kg) Broad Ligament Fibroid Mimicking Sarcoma of Uterus: A Case Report and Review of Literature.

PubMed

Katke, Rajshree Dayanand

2017-01-01

Fibroids are most common benign tumors of the uterus, mostly situated in the body of the uterus. Rarely, they arise from extrauterine sites with broad ligament fibroids being uncommon. We present a case of a 47-year-old female, multipara who presented in outpatient department in CAMA hospital with a history of sudden development of dysuria 10 days back. Intraoperatively, uterus was pushed to side and large broad ligament fibroid of 25 cm × 20 cm × 20 cm seen arising from right-sided broad ligament. The fibroid was densely adherent to bowel and bladder. Exploratory laparotomy with excision of broad ligament fibroid of 9 Kg with total abdominal hysterectomy with right salpingo-oophorectomy was done.

Exploring Metaphors for Making Data Broadly Available.

NASA Astrophysics Data System (ADS)

Parsons, M.; Fox, P.

2012-04-01

As international attention to scientific data continues to grow in today's born digital and Internet age, we take the opportunity to re-visit long-standing approaches to managing data and to critically examine some proposed new capabilities. In this presentation we build on our preliminary exploration of multiple metaphors co-existing in support of a healthy data ecosystem, and discuss what we see as key data ecosystem attributes embedded in modern approaches to data managment across the broad spectrum of geoscientific data and geoscientists. We conclude with a set of suggestions and actions to engage the world wide data and information science community to advance such a discussion.

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…

A broad range assay for rapid detection and etiologic characterization of bacterial meningitis: performance testing in samples from sub-Sahara☆, ☆☆,★

PubMed Central

Won, Helen; Yang, Samuel; Gaydos, Charlotte; Hardick, Justin; Ramachandran, Padmini; Hsieh, Yu-Hsiang; Kecojevic, Alexander; Njanpop-Lafourcade, Berthe-Marie; Mueller, Judith E.; Tameklo, Tsidi Agbeko; Badziklou, Kossi; Gessner, Bradford D.; Rothman, Richard E.

2012-01-01

This study aimed to conduct a pilot evaluation of broad-based multiprobe polymerase chain reaction (PCR) in clinical cerebrospinal fluid (CSF) samples compared to local conventional PCR/culture methods used for bacterial meningitis surveillance. A previously described PCR consisting of initial broad-based detection of Eubacteriales by a universal probe, followed by Gram typing, and pathogen-specific probes was designed targeting variable regions of the 16S rRNA gene. The diagnostic performance of the 16S rRNA assay in “”127 CSF samples was evaluated in samples from patients from Togo, Africa, by comparison to conventional PCR/culture methods. Our probes detected Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Uniprobe sensitivity and specificity versus conventional PCR were 100% and 54.6%, respectively. Sensitivity and specificity of uniprobe versus culture methods were 96.5% and 52.5%, respectively. Gram-typing probes correctly typed 98.8% (82/83) and pathogen-specific probes identified 96.4% (80/83) of the positives. This broad-based PCR algorithm successfully detected and provided species level information for multiple bacterial meningitis agents in clinical samples. PMID:22809694

[Broad ischemic stroke revealing infective endocarditis in a young patient: about a case].

PubMed

Ravelosaona, Fanomezantsoa Noella; Razafimahefa, Julien; Randrianasolo, Rahamefy Odilon; Rakotoarimanana, Solofonirina; Tehindrazanarivelo, Djacoba Alain

2016-01-01

Broad ischemic stroke is mainly due to a cardiac embolus or to an atheromatous plaque. In young subjects, one of the main causes of ischemic stroke (broad ischemic stroke in particolar) is embolic heart disease including infective endocarditis. Infective endocarditis is a contraindication against the anticoagulant therapy (which is indicated for the treatment of embolic heart disease complicated by ischemic stroke). One neurologic complications of infective endocarditis is ischemic stroke which often occurs in multiple sites. We here report the case of a 44-year old man with afebrile acute onset of severe left hemiplegia associated with a sistolic mitral murmur, who had fever in hospital on day 5 with no other obvious source of infection present. Brain CT scan showed full broad ischaemic stroke of the right middle cerebral artery territory and doppler ultrasound, performed after stroke onset, showed infective endocarditis affecting the small mitral valve. He was treated with 4 weeks of antibiotic therapy without anticoagulant therapy ; evolution was marked by the disappearance of mitral valve vegetations and by movement sequelae involving the left side of the body. In practical terms, our problem was the onset of the fever which didn't accompany or pre-exist patient's deficit, leading us to the misdiagnosis of ischemic stroke of cardioembolic origin. This case study underlines the importance of doppler ultrasound, in the diagnosis of all broad ischemic strokes, especially superficial, before starting anticoagulant therapy.

Successes and challenges from formation to implementation of eleven broad-extent conservation programs

USGS Publications Warehouse

Beever, Erik A.; Bradford, John B.; Germino, Matthew J.; Mattsson, Brady J.; Post van der Burg, Max; Brunson, Mark

2014-01-01

Integration of conservation partnerships across geographic, biological, and administrative boundaries is increasingly relevant because drivers of change, such as climate shifts, transcend these boundaries. We explored successes and challenges of established conservation programs that span multiple watersheds and consider both social and ecological concerns. We asked representatives from a diverse set of 11 broadextent conservation partnerships in 29 countries 17 questions that pertained to launching and maintaining partnerships for broad-extent conservation, specifying ultimate management objectives, and implementation and learning. Partnerships invested more funds in implementing conservation actions than any other aspect of conservation, and a program’s context (geographic extent, United States vs. other countries, developed vs. developing nation) appeared to substantially affect program approach. Despite early successes of these organizations and benefits of broad-extent conservation, specific challenges related to uncertainties in scaling up information and to coordination in the face of diverse partner governance structures, conflicting objectives, and vast uncertainties regarding future system dynamics hindered long-term success, as demonstrated by the focal organizations. Engaging stakeholders, developing conservation measures, and implementing adaptive management were dominant challenges. To inform future research on broad-extent conservation, we considered several challenges when we developed detailed questions, such as what qualities of broad-extent partnerships ensure they complement, integrate, and strengthen, rather than replace, local conservation efforts and which adaptive management processes yield actionable conservation strategies that account explicitly for dynamics and uncertainties regarding multiscale governance, environmental conditions, and knowledge of the system?

Intervention to Reduce Broad-Spectrum Antibiotics and Treatment Durations Prescribed at the Time of Hospital Discharge: A Novel Stewardship Approach

PubMed Central

Yogo, Norihiro; Shihadeh, Katherine; Young, Heather; Calcaterra, Susan; Knepper, Bryan C; Burman, William J; Mehler, Philip S; Jenkins, Timothy C

2017-01-01

Objective For most common infections requiring hospitalization, antibiotic treatment is completed after hospital discharge. Post-discharge therapy is often unnecessarily broad-spectrum and prolonged. We developed an intervention to improve antibiotic selection and shorten treatment durations. Design Single center, quasi-experimental retrospective cohort study. Methods Patients prescribed oral antibiotics at hospital discharge before (July 2012 – June 2013) and after (October 2014 – February 2015) an intervention consisting of: 1) institutional guidance for oral step-down antibiotic selection and duration of therapy, and 2) pharmacy audit of discharge prescriptions with real-time prescribing recommendations to providers. The primary outcomes were total prescribed duration of therapy and use of antibiotics with broad gram-negative activity (fluoroquinolones or amoxicillin-clavulanate). Results 300 cases from the pre-intervention period and 200 from the intervention period were included. Compared with the pre-intervention period, use of antibiotics with broad gramnegative activity decreased during the intervention (51% vs 40%, p = 0.02), particularly fluoroquinolones (38% vs 25%, p = 0.002). The difference in total duration of therapy did not reach statistical significance (10 days [interquartile range (IQR) 7–13] vs 9 [IQR 6–13], p = 0.13); however, the duration prescribed at discharge declined from 6 days (IQR 4–10) to 5 (IQR 3–7) (p = 0.003). During the intervention, there was a non-significant increase in the overall appropriateness of discharge prescriptions (52% vs 66%, p = 0.15). Conclusions A multifaceted intervention to optimize antibiotic prescribing at hospital discharge was associated with less frequent use of antibiotics with broad gram-negative activity and shorter post-hospital treatment durations. PMID:28260538

Steps Toward Unveiling the True Population of AGN: Photometric Selection of Broad-Line AGN

NASA Astrophysics Data System (ADS)

Schneider, Evan; Impey, C.

2012-01-01

We present an AGN selection technique that enables identification of broad-line AGN using only photometric data. An extension of infrared selection techniques, our method involves fitting a given spectral energy distribution with a model consisting of three physically motivated components: infrared power law emission, optical accretion disk emission, and host galaxy emission. Each component can be varied in intensity, and a reduced chi-square minimization routine is used to determine the optimum parameters for each object. Using this model, both broad- and narrow-line AGN are seen to fall within discrete ranges of parameter space that have plausible bounds, allowing physical trends with luminosity and redshift to be determined. Based on a fiducial sample of AGN from the catalog of Trump et al. (2009), we find the region occupied by broad-line AGN to be distinct from that of quiescent or star-bursting galaxies. Because this technique relies only on photometry, it will allow us to find AGN at fainter magnitudes than are accessible in spectroscopic surveys, and thus probe a population of less luminous and/or higher redshift objects. With the vast availability of photometric data in large surveys, this technique should have broad applicability and result in large samples that will complement X-ray AGN catalogs.

Bowel obstruction caused by broad ligament hernia sucessfully repaired by laparoscopy.

PubMed

Toolabi, K; Zamanian, A; Parsaei, R

2018-04-01

Internal hernais are rare bowel obstructions. We present a case of small bowel obstruction in a 37-year-old woman caused by internal herniation through a defect in broad ligament, which was managed by laparoscopic surgery.

Broad [C II] Line Wings as Tracer of Molecular and Multi-phase Outflows in Infrared Bright Galaxies

NASA Astrophysics Data System (ADS)

Janssen, A. W.; Christopher, N.; Sturm, E.; Veilleux, S.; Contursi, A.; González-Alfonso, E.; Fischer, J.; Davies, R.; Verma, A.; Graciá-Carpio, J.; Genzel, R.; Lutz, D.; Sternberg, A.; Tacconi, L.; Burtscher, L.; Poglitsch, A.

2016-05-01

We report a tentative correlation between the outflow characteristics derived from OH absorption at 119 μm and [C II] emission at 158 μm in a sample of 22 local and bright ultraluminous infrared galaxies (ULIRGs). For this sample, we investigate whether [C II] broad wings are a good tracer of molecular outflows, and how the two tracers are connected. Fourteen objects in our sample have a broad wing component as traced by [C II], and all of these also show OH119 absorption indicative of an outflow (in one case an inflow). The other eight cases, where no broad [C II] component was found, are predominantly objects with no OH outflow or a low-velocity (≤100 km s-1) OH outflow. The FWHM of the broad [C II] component shows a trend with the OH119 blueshifted velocity, although with significant scatter. Moreover, and despite large uncertainties, the outflow masses derived from OH and broad [C II] show a 1:1 relation. The main conclusion is therefore that broad [C II] wings can be used to trace molecular outflows. This may be particularly relevant at high redshift, where the usual tracers of molecular gas (like low-J CO lines) become hard to observe. Additionally, observations of blueshifted Na I D λλ 5890, 5896 absorption are available for 10 of our sources. Outflow velocities of Na I D show a trend with OH velocity and broad [C II] FWHM. These observations suggest that the atomic and molecular gas phases of the outflow are connected.

Broad-Spectrum Inhibition of the CC-Chemokine Class Improves Wound Healing and Wound Angiogenesis.

PubMed

Ridiandries, Anisyah; Bursill, Christina; Tan, Joanne

2017-01-13

Angiogenesis is involved in the inflammation and proliferation stages of wound healing, to bring inflammatory cells to the wound and provide a microvascular network to maintain new tissue formation. An excess of inflammation, however, leads to prolonged wound healing and scar formation, often resulting in unfavourable outcomes such as amputation. CC-chemokines play key roles in the promotion of inflammation and inflammatory-driven angiogenesis. Therefore, inhibition of the CC-chemokine class may improve wound healing. We aimed to determine if the broad-spectrum CC-chemokine inhibitor "35K" could accelerate wound healing in vivo in mice. In a murine wound healing model, 35K protein or phosphate buffered saline (PBS, control) were added topically daily to wounds. Cohorts of mice were assessed in the early stages (four days post-wounding) and in the later stages of wound repair (10 and 21 days post-wounding). Topical application of the 35K protein inhibited CC-chemokine expression (CCL5, CCL2) in wounds and caused enhanced blood flow recovery and wound closure in early-mid stage wounds. In addition, 35K promoted neovascularisation in the early stages of wound repair. Furthermore, 35K treated wounds had significantly lower expression of the p65 subunit of NF-κB, a key inflammatory transcription factor, and augmented wound expression of the pro-angiogenic and pro-repair cytokine TGF-β. These findings show that broad-spectrum CC-chemokine inhibition may be beneficial for the promotion of wound healing.

A Measure of the Broad Substrate Specificity of Enzymes Based on ‘Duplicate’ Catalytic Residues

PubMed Central

Chakraborty, Sandeep; Ásgeirsson, Bjarni; Rao, Basuthkar J.

2012-01-01

The ability of an enzyme to select and act upon a specific class of compounds with unerring precision and efficiency is an essential feature of life. Simultaneously, these enzymes often catalyze the reaction of a range of similar substrates of the same class, and also have promiscuous activities on unrelated substrates. Previously, we have established a methodology to quantify promiscuous activities in a wide range of proteins. In the current work, we quantitatively characterize the active site for the ability to catalyze distinct, yet related, substrates (BRASS). A protein with known structure and active site residues provides the framework for computing ‘duplicate’ residues, each of which results in slightly modified replicas of the active site scaffold. Such spatial congruence is supplemented by Finite difference Poisson Boltzmann analysis which filters out electrostatically unfavorable configurations. The congruent configurations are used to compute an index (BrassIndex), which reflects the broad substrate profile of the active site. We identify an acetylhydrolase and a methyltransferase as having the lowest and highest BrassIndex, respectively, from a set of non-homologous proteins extracted from the Catalytic Site Atlas. The acetylhydrolase, a regulatory enzyme, is known to be highly specific for platelet-activating factor. In the methyltransferase (PDB: 1QAM), various combinations of glycine (Gly38/40/42), asparagine (Asn101/11) and glutamic acid (Glu59/36) residues having similar spatial and electrostatic profiles with the specified scaffold (Gly38, Asn101 and Glu59) exemplifies the broad substrate profile such an active site may provide. ‘Duplicate’ residues identified by relaxing the spatial and/or electrostatic constraints can be the target of directed evolution methodologies, like saturation mutagenesis, for modulating the substrate specificity of proteins. PMID:23166637

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.

76 FR 9777 - Recent Postings of Broadly Applicable Alternative Test Methods

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

... Applicable Alternative Test Methods AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of availability. SUMMARY: This notice announces the broadly applicable alternative test method approval decisions... technical questions about individual alternative test method decisions, refer to the contact person...

Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-120 interface

PubMed Central

Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark

2014-01-01

The isolation of human monoclonal antibodies (mAbs) is providing important insights regarding the specificities that underlie broad neutralization of HIV-1 (reviewed in1). Here we report a broad and extremely potent HIV-specific mAb, termed 35O22, which binds novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with an IC50<50 μg/ml. The median IC50 of neutralized viruses was 0.033 μg/ml, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed it to bind a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current mAb-based approaches to immunotherapies, prophylaxis, and vaccine design. PMID:25186731

An Atlas of Computed Equivalent Widths of Quasar Broad Emission Lines

NASA Astrophysics Data System (ADS)

Korista, Kirk; Baldwin, Jack; Ferland, Gary; Verner, Dima

We present graphically the results of several thousand photoionization calculations of broad emission-line clouds in quasars, spanning 7 orders of magnitude in hydrogen ionizing flux and particle density. The equivalent widths of 42 quasar emission lines are presented as contours in the particle density-ionizing flux plane for a typical incident continuum shape, solar chemical abundances, and cloud column density of N(H) = 1023 cm-2. Results are similarly given for a small subset of emission lines for two other column densities (1022 and 1024 cm-2), five other incident continuum shapes, and a gas metallicity of 5 Z⊙. These graphs should prove useful in the analysis of quasar emission-line data and in the detailed modeling of quasar broad emission-line regions. The digital results of these emission-line grids and many more are available over the Internet.

Variability of the broad absorption lines in the QSO UM 232

NASA Technical Reports Server (NTRS)

Barlow, Thomas A.; Junkkarinen, Vesa T.; Burbidge, E. Margaret

1989-01-01

Low-resolution spectra of UM 232 taken in 1978, 1979, and 1988 at Lick Observatory are presented. Large changes in the Si IV lambda 1397, CIV lambda 1549, and Al III lambda 1857 broad absorption lines are apparent. The decrease in column density in all three ions and an observed brightening of the QSO suggests that these changes are due to an increase in the ionization level driven by an increase in the central source luminosity. This mechanism has been proposed by Smith and Penston to explain small changes in the absorption spectrum of the QSO 1246-057. The spectra of UM 232 show that the fractional decrease in optical depth is smaller at higher outflow velocies. The structure of the broad absorption-line region (BALR) is investigted by estimating an ionization parameter for each ion species as a function of velocity.

Mapping transmission risk of Lassa fever in West Africa: the importance of quality control, sampling bias, and error weighting.

PubMed

Peterson, A Townsend; Moses, Lina M; Bausch, Daniel G

2014-01-01

Lassa fever is a disease that has been reported from sites across West Africa; it is caused by an arenavirus that is hosted by the rodent M. natalensis. Although it is confined to West Africa, and has been documented in detail in some well-studied areas, the details of the distribution of risk of Lassa virus infection remain poorly known at the level of the broader region. In this paper, we explored the effects of certainty of diagnosis, oversampling in well-studied region, and error balance on results of mapping exercises. Each of the three factors assessed in this study had clear and consistent influences on model results, overestimating risk in southern, humid zones in West Africa, and underestimating risk in drier and more northern areas. The final, adjusted risk map indicates broad risk areas across much of West Africa. Although risk maps are increasingly easy to develop from disease occurrence data and raster data sets summarizing aspects of environments and landscapes, this process is highly sensitive to issues of data quality, sampling design, and design of analysis, with macrogeographic implications of each of these issues and the potential for misrepresenting real patterns of risk.

Broad-spectrum β-lactamases among Enterobacteriaceae of animal origin: molecular aspects, mobility and impact on public health.

PubMed

Smet, Annemieke; Martel, An; Persoons, Davy; Dewulf, Jeroen; Heyndrickx, Marc; Herman, Lieve; Haesebrouck, Freddy; Butaye, Patrick

2010-05-01

Broad-spectrum β-lactamase genes (coding for extended-spectrum β-lactamases and AmpC β-lactamases) have been frequently demonstrated in the microbiota of food-producing animals. This may pose a human health hazard as these genes may be present in zoonotic bacteria, which would cause a direct problem. They can also be present in commensals, which may act as a reservoir of resistance genes for pathogens causing disease both in humans and in animals. Broad-spectrum β-lactamase genes are frequently located on mobile genetic elements, such as plasmids, transposons and integrons, which often also carry additional resistance genes. This could limit treatment options for infections caused by broad-spectrum β-lactam-resistant microorganisms. This review addresses the growing burden of broad-spectrum β-lactam resistance among Enterobacteriaceae isolated from food, companion and wild animals worldwide. To explore the human health hazard, the diversity of broad-spectrum β-lactamases among Enterobacteriaceae derived from animals is compared with respect to their presence in human bacteria. Furthermore, the possibilities of the exchange of genes encoding broad-spectrum β-lactamases - including the exchange of the transposons and plasmids that serve as vehicles for these genes - between different ecosystems (human and animal) are discussed. © 2009 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

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.

MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes.

PubMed

Dhar, Shilpa S; Zhao, Dongyu; Lin, Tao; Gu, Bingnan; Pal, Khusboo; Wu, Sarah J; Alam, Hunain; Lv, Jie; Yun, Kyuson; Gopalakrishnan, Vidya; Flores, Elsa R; Northcott, Paul A; Rajaram, Veena; Li, Wei; Shilatifard, Ali; Sillitoe, Roy V; Chen, Kaifu; Lee, Min Gyu

2018-06-07

Super-enhancers are large clusters of enhancers that activate gene expression. Broad trimethyl histone H3 lysine 4 (H3K4me3) often defines active tumor suppressor genes. However, how these epigenomic signatures are regulated for tumor suppression is little understood. Here we show that brain-specific knockout of the H3K4 methyltransferase MLL4 (a COMPASS-like enzyme, also known as KMT2D) in mice spontaneously induces medulloblastoma. Mll4 loss upregulates oncogenic Ras and Notch pathways while downregulating neuronal gene expression programs. MLL4 enhances DNMT3A-catalyzed DNA methylation and SIRT1/BCL6-mediated H4K16 deacetylation, which antagonize expression of Ras activators and Notch pathway components, respectively. Notably, Mll4 loss downregulates tumor suppressor genes (e.g., Dnmt3a and Bcl6) by diminishing broad H3K4me3 and super-enhancers and also causes widespread impairment of these epigenomic signatures during medulloblastoma genesis. These findings suggest an anti-tumor role for super-enhancers and provide a unique tumor-suppressive mechanism in which MLL4 is necessary to maintain broad H3K4me3 and super-enhancers at tumor suppressor genes. Copyright © 2018 Elsevier Inc. All rights reserved.

Toward broad-band x-ray detected ferromagnetic resonance in longitudinal geometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ollefs, K.; European Synchrotron Radiation Facility; Meckenstock, R.

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 thereforemore » 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.« less

Analyzing extreme sea levels for broad-scale impact and adaptation studies

NASA Astrophysics Data System (ADS)

Wahl, T.; Haigh, I. D.; Nicholls, R. J.; Arns, A.; Dangendorf, S.; Hinkel, J.; Slangen, A.

2017-12-01

. Finally, ESL uncertainties need to be integrated with SLR uncertainties. Otherwise, important improvements in providing more robust SLR projections are of less benefit for broad-scale impact and adaptation studies and decision processes.

On the origin of gamma rays in Fermi blazars: beyond the broad line region.

NASA Astrophysics Data System (ADS)

Costamante, L.; Cutini, S.; Tosti, G.; Antolini, E.; Tramacere, A.

2018-05-01

The gamma-ray emission in broad-line blazars is generally explained as inverse Compton (IC) radiation of relativistic electrons in the jet scattering optical-UV photons from the Broad Line Region (BLR), the so-called BLR External Compton scenario. We test this scenario on the Fermi gamma-ray spectra of 106 broad-line blazars detected with the highest significance or largest BLR, by looking for cut-off signatures at high energies compatible with γ-γ interactions with BLR photons. We do not find evidence for the expected BLR absorption. For 2/3 of the sources, we can exclude any significant absorption (τmax < 1), while for the remaining 1/3 the possible absorption is constrained to be 1.5-2 orders of magnitude lower than expected. This result holds also dividing the spectra in high and low-flux states, and for powerful blazars with large BLR. Only 1 object out of 10 seems compatible with substantial attenuation (τmax > 5). We conclude that for 9 out of 10 objects, the jet does not interact with BLR photons. Gamma-rays seem either produced outside the BLR most of the time, or the BLR is ˜100 × larger than given by reverberation mapping. This means that i) External Compton on BLR photons is disfavoured as the main gamma-ray mechanism, vs IC on IR photons from the torus or synchrotron self-Compton; ii) the Fermi gamma-ray spectrum is mostly intrinsic, determined by the interaction of the particle distribution with the seed-photons spectrum; iii) without suppression by the BLR, broad-line blazars can become copious emitters above 100 GeV, as demonstrated by 3C 454.3. We expect the CTA sky to be much richer of broad-line blazars than previously thought.