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Sample records for capocaccia manuela merli

  1. MER SPICE Interface

    NASA Technical Reports Server (NTRS)

    Sayfi, Elias

    2004-01-01

    MER SPICE Interface is a software module for use in conjunction with the Mars Exploration Rover (MER) mission and the SPICE software system of the Navigation and Ancillary Information Facility (NAIF) at NASA's Jet Propulsion Laboratory. (SPICE is used to acquire, record, and disseminate engineering, navigational, and other ancillary data describing circumstances under which data were acquired by spaceborne scientific instruments.) Given a Spacecraft Clock value, MER SPICE Interface extracts MER-specific data from SPICE kernels (essentially, raw data files) and calculates values for Planet Day Number, Local Solar Longitude, Local Solar Elevation, Local Solar Azimuth, and Local Solar Time (UTC). MER SPICE Interface was adapted from a subroutine, denoted m98SpiceIF written by Payam Zamani, that was intended to calculate SPICE values for the Mars Polar Lander. The main difference between MER SPICE Interface and m98SpiceIf is that MER SPICE Interface does not explicitly call CHRONOS, a time-conversion program that is part of a library of utility subprograms within SPICE. Instead, MER SPICE Interface mimics some portions of the CHRONOS code, the advantage being that it executes much faster and can efficiently be called from a pipeline of events in a parallel processing environment.

  2. MERS and SARS

    MedlinePlus

    ... transmission Therapeutics & Vaccines NIAID-funded researchers at the University of Washington are searching for MERS-CoV therapeutics ... Aureus Biocontainment Research Facilities Biosafety Laboratory Sites Rutgers University University of Alabama George Mason University Tufts University ...

  3. MER Telemetry Processor

    NASA Technical Reports Server (NTRS)

    Lee, Hyun H.

    2012-01-01

    MERTELEMPROC processes telemetered data in data product format and generates Experiment Data Records (EDRs) for many instruments (HAZCAM, NAVCAM, PANCAM, microscopic imager, Moessbauer spectrometer, APXS, RAT, and EDLCAM) on the Mars Exploration Rover (MER). If the data is compressed, then MERTELEMPROC decompresses the data with an appropriate decompression algorithm. There are two compression algorithms (ICER and LOCO) used in MER. This program fulfills a MER specific need to generate Level 1 products within a 60-second time requirement. EDRs generated by this program are used by merinverter, marscahv, marsrad, and marsjplstereo to generate higher-level products for the mission operations. MERTELEPROC was the first GDS program to process the data product. Metadata of the data product is in XML format. The software allows user-configurable input parameters, per-product processing (not streambased processing), and fail-over is allowed if the leading image header is corrupted. It is used within the MER automated pipeline. MERTELEMPROC is part of the OPGS (Operational Product Generation Subsystem) automated pipeline, which analyzes images returned by in situ spacecraft and creates level 1 products to assist in operations, science, and outreach.

  4. MER ARA pyroshock test results

    NASA Technical Reports Server (NTRS)

    Chang, Kurng Y.

    2004-01-01

    This paper presents the shock test results achieved in the MER ARA/brush motor pyroshock qualification. The results of MER flight system pyrofiring tests in comparison with the ARA shock test requirements are discussed herein. Alternate test methods were developed in an effort to qualify the critical MER equipment for adequate performance in the actual flight pyroshock condition.

  5. Learning Cultures in Travel and Tourism: A Critique of Manuela du Bois-Reymond's Trendsetter Learner Thesis

    ERIC Educational Resources Information Center

    Morrison, Andrew

    2011-01-01

    This article aims to contribute to the discussion surrounding Manuela du Bois-Reymond's important "trendsetter learner" thesis and, in so doing, to join the wider debate about post-compulsory learning cultures. The article outlines the trendsetter learner thesis and then considers recent criticisms that it has attracted. While the author…

  6. Alone You Are Nobody, Together We Float: The Manuela Ramos Movement. Quality/Calidad/Qualite Number 10.

    ERIC Educational Resources Information Center

    Rogow, Debbie

    The Manuela Ramos Movement began in the 1970s when seven women in Lima, Peru, started meeting each Tuesday to reconsider their assumptions about everyday life. By 1980, the group formed a nongovernmental organization whose strategy was to train women community leaders in Lima's barrios through workshops focusing on the following themes: identity…

  7. Analyzing MER Uplink Reports

    NASA Technical Reports Server (NTRS)

    Savin, Stephen C.

    2005-01-01

    The MER project includes two rovers working simultaneously on opposite sides of Mars each receiving commands only once a day. Creating this uplink is critical, since a failed uplink means a lost day and a waste of money. Examining the process of creating this uplink, I tracked the use of the system developed for requesting observations as well as the development, from stage to stage, in forming an activity plan. I found the system for requesting observations was commonly misused, if used at all. There are half a dozen reports to document the creation of the uplink plan and often there are discrepancies among them. Despite this, the uplink process worked very well and MER has been one of the most successful missions for NASA in recent memory. Still it is clear there is room for improvement.

  8. Middle East Respiratory Syndrome (MERS)

    MedlinePlus

    ... also been found in camels and in one bat. While it is believed to come from animals, ... Prevention. Middle East Respiratory Syndrome (MERS): Frequently Asked Questions and Answers. Updated December 2, 2015. www.cdc. ...

  9. Middle East Respiratory Syndrome (MERS)

    MedlinePlus

    ... United Kingdom (UK), and United States of America (USA). CDC Commentary: Be on the Lookout for MERS- ... OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO (800-232-4636) , TTY: 888- ...

  10. Role of MerC, MerE, MerF, MerT, and/or MerP in resistance to mercurials and the transport of mercurials in Escherichia coli.

    PubMed

    Sone, Yuka; Nakamura, Ryosuke; Pan-Hou, Hidemitsu; Itoh, Tomoo; Kiyono, Masako

    2013-01-01

    The characteristics of bacteria take up mercury into cells via membrane potential-dependent sequence-divergent members of the mercuric ion (Mer) superfamily, i.e., a periplasmic mercuric ion scavenging protein (MerP) and one or more inner membrane-spanning proteins (MerC, MerE, MerF, and MerT), which transport mercuric ions into the cytoplasm, have been applied in engineering of bioreactor used for mercurial bioremediation. We engineered bacteria to express MerC, MerE, MerF, or MerT with or without MerP to clarify their individual role and potential in transport of mercurial. By immunoblot analysis using specific polyclonal antibody, the proteins encoded by merC, merE, merF, merT or merP, were certainly expressed and identified in the membrane fraction. Bacteria expressing MerC, MerE, MerF or MerT in the absence of MerP transported significantly more C6H5Hg(I) and Hg(II) across bacterial membrane than their isogenic strain. In vivo expression of MerP in the presence of all the transporters did not cause apparent difference to the C6H5Hg(I) transport, but gives an apparently higher Hg(II) transport than that did by MerE, MerF or MerT but not by MerC. Among the four transporters studied, MerC showed more potential to transport Hg(II) across bacterial membrane than MerE, MerF and MerT. Together these findings, we demonstrated for the first time that in addition to MerE and MerT, MerF and MerC are broad-spectrum mercury transporters that mediate both Hg(II) and phenylmercury transport into cells. Our results suggested that MerC is the most efficient tool for designing mercurial bioremediation systems, because MerC is sufficient for mercurial transport into cells.

  11. First record of Loricifera from the Iberian Peninsula, with the description of Rugiloricus manuelae sp. nov., (Loricifera, Pliciloricidae)

    NASA Astrophysics Data System (ADS)

    Pardos, Fernando; Kristensen, Reinhardt Møbjerg

    2013-12-01

    Sediment samples were taken along the Cantabric platform (Northern Spain) from 200 to 600 meters depth in October 1990. Forty specimens of loriciferans were sorted out of the samples, of which 38 specimens belong to a new species of Rugiloricus. The new species, R. manuelae sp. nov., was investigated with both light (DIC) and electron microscopy (SEM). Complete descriptions of both adult and larval stages are provided, including mapping of the introvert scalids for both stages. Information from a molting stage with an adult male inside confirms conspecificity of larvae and adults. The presence of a highly reduced postlarval stage leaded to the suggestion of a new modified life cycle for the family Pliciloricidae.

  12. Robust k-mer frequency estimation using gapped k-mers

    PubMed Central

    Ghandi, Mahmoud; Mohammad-Noori, Morteza

    2013-01-01

    Oligomers of fixed length, k, commonly known as k-mers, are often used as fundamental elements in the description of DNA sequence features of diverse biological function, or as intermediate elements in the constuction of more complex descriptors of sequence features such as position weight matrices. k-mers are very useful as general sequence features because they constitute a complete and unbiased feature set, and do not require parameterization based on incomplete knowledge of biological mechanisms. However, a fundamental limitation in the use of k-mers as sequence features is that as k is increased, larger spatial correlations in DNA sequence elements can be described, but the frequency of observing any specific k-mer becomes very small, and rapidly approaches a sparse matrix of binary counts. Thus any statistical learning approach using k-mers will be susceptible to noisy estimation of k-mer frequencies once k becomes large. Because all molecular DNA interactions have limited spatial extent, gapped k-mers often carry the relevant biological signal. Here we use gapped k-mer counts to more robustly estimate the ungapped k-mer frequencies, by deriving an equation for the minimum norm estimate of k-mer frequencies given an observed set of gapped k-mer frequencies. We demonstrate that this approach provides a more accurate estimate of the k-mer frequencies in real biological sequences using a sample of CTCF binding sites in the human genome. PMID:23861010

  13. MER EDL: Overview and Reconstruction Status

    NASA Technical Reports Server (NTRS)

    Desai, Prasun N.; Lee, Wayne J.

    2005-01-01

    An overview and reconstruction of the Mars Exploration Rover (MER) Entry Descent and Landing (EDL) is shown. The topics include: 1) Background; 2) MER Candidate Landing Sites; 3) MER Entry Heritage w/Viking & Mars Pathfinder; 4) MER EDL Animation; 5) MER Entry, Descent, and Landing (EDL) Sequence; 6) Pre-Entry Spirit Entry Atmosphere Models; 7) Spirit Landing Ellipse at Final OD, & Updated Estimate Differenced 1-way Doppler; 8) Spirit Landing Ellipse at Final OD and Final Location Estimates; 9) Monte Carlo Results for Spirit ; 10) Reconstructed and refined Spirit Entry Density Profile; 11) Mars Pathfinder Attitude Reconstruction; 12) Spirit Attitude Reconstruction; 13) Spirit Entry Ground Track; 14) Reconstructed Spirit Terminal Descent Dynamics (Side View); 15) Opportunity Landing Ellipse at Final OD, & Updated Estimate Differenced 1-way Doppler; 16) Spirit Landing Ellipse at Final OD and Final Location Estimates; 17) Monte Carlo Results for Opportunity; 18) Reconstructed Opportunity Entry Density Profile; and 19) Opportunity Attitude Reconstruction.

  14. MERS-CoV spike nanoparticles protect mice from MERS-CoV infection.

    PubMed

    Coleman, Christopher M; Venkataraman, Thiagarajan; Liu, Ye V; Glenn, Gregory M; Smith, Gale E; Flyer, David C; Frieman, Matthew B

    2017-03-14

    The Middle East respiratory syndrome coronavirus (MERS-CoV) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. There are currently no approved therapeutics or vaccinations for MERS-CoV. The MERS-CoV spike (S) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the S protein an ideal target for anti-MERS-CoV vaccines. In this study, we demonstrate protection induced by vaccination with a recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination in mice. The MERS-CoV S nanoparticle vaccine produced high titer anti-S neutralizing antibody and protected mice from MERS-CoV infection in vivo.

  15. Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27

    PubMed Central

    Yu, Xiaojuan; Zhang, Senyan; Jiang, Liwei; Cui, Ye; Li, Dongxia; Wang, Dongli; Wang, Nianshuang; Fu, Lili; Shi, Xuanlin; Li, Ziqiang; Zhang, Linqi; Wang, Xinquan

    2015-01-01

    The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion, and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry, and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection. PMID:26281793

  16. Design and Synthesis of Novel Macrocyclic Mer Tyrosine Kinase Inhibitors.

    PubMed

    Wang, Xiaodong; Liu, Jing; Zhang, Weihe; Stashko, Michael A; Nichols, James; Miley, Michael J; Norris-Drouin, Jacqueline; Chen, Zhilong; Machius, Mischa; DeRyckere, Deborah; Wood, Edgar; Graham, Douglas K; Earp, H Shelton; Kireev, Dmitri; Frye, Stephen V

    2016-12-08

    Mer tyrosine kinase (MerTK) is aberrantly elevated in various tumor cells and has a normal anti-inflammatory role in the innate immune system. Inhibition of MerTK may provide dual effects against these MerTK-expressing tumors through reducing cancer cell survival and redirecting the innate immune response. Recently, we have designed novel and potent macrocyclic pyrrolopyrimidines as MerTK inhibitors using a structure-based approach. The most active macrocycles had an EC50 below 40 nM in a cell-based MerTK phosphor-protein ELISA assay. The X-ray structure of macrocyclic analogue 3 complexed with MerTK was also resolved and demonstrated macrocycles binding in the ATP binding pocket of the MerTK protein as anticipated. In addition, the lead compound 16 (UNC3133) had a 1.6 h half-life and 16% oral bioavailability in a mouse PK study.

  17. MER Caching Rover for 2018 Exploration of Ancient Mars

    NASA Astrophysics Data System (ADS)

    Ehlmann, B. L.; Grotzinger, J. P.; Manning, R. M.; Rivellini, T. P.; Backes, P. G.; Ganino, A. J.; Shiraishi, L. R.; Klein, K. J.; Allen, W. C.; Kahn, C. L.; Ziemer, J. K.; Sherwood, B.; Eisen, H. J.

    2012-06-01

    A modern, minimally updated MER rover can begin sample return in 2018. We demonstrate MER accommodates a caching system and robust science payload. A guided entry airbag landing system enables exploration and sample collection at high priority sites.

  18. Potential MER Landing Site in Melas Chasma

    NASA Technical Reports Server (NTRS)

    Weitz, C. M.; Parker, Timothy J.; Anderson, F. Scott

    2001-01-01

    We have selected one area in Valles Marineris as a potential landing site for the Mars Exploration Rover (MER) mission. After 30 years of analyses, the formation of the Valles Marineris system of troughs and its associated deposits still remains an enigma. Understanding all aspects of the Valles Marineris would significantly contribute to deciphering the internal and external history of Mars. A landing site within Melas Chasma could provide insight into both the formation of Valles Marineris and the composition and origin of the interior layered deposits (ILDs). The ILDs have been proposed as: (1) sedimentary deposits formed in lakes mass wasted material from the walls; (3) remnants of the wall rock; (4) carbonate deposits; (5) aeolian deposits; and (6) volcanic. More recently, Malin and Edgett suggest that the fine-scale, rhythmic layering seen in the interior deposits, as well as other layered deposits in craters, supports a sedimentary origin. Because an understanding of the formation of Valles Marineris and its interior deposits is so important to deciphering the history of Mars, we have proposed a landing site for the MER mission on an exposure of interior deposits in western Melas Chasma. Either MER-A and MER-B could land at this same location.

  19. The MER/CIP Portal for Ground Operations

    NASA Technical Reports Server (NTRS)

    Chan, Louise; Desai, Sanjay; DOrtenzio, Matthew; Filman, Robtert E.; Heher, Dennis M.; Hubbard, Kim; Johan, Sandra; Keely, Leslie; Magapu, Vish; Mak, Ronald

    2003-01-01

    We developed the Mars Exploration Rover/Collaborative Information Portal (MER/CIP) to facilitate MER operations. MER/CIP provides a centralized, one-stop delivery platform integrating science and engineering data from several distributed heterogeneous data sources. Key issues for MER/CIP include: 1) Scheduling and schedule reminders; 2) Tracking the status of daily predicted outputs; 3) Finding and analyzing data products; 4) Collaboration; 5) Announcements; 6) Personalization.

  20. Human Centered Design and Development for NASA's MerBoard

    NASA Technical Reports Server (NTRS)

    Trimble, Jay

    2003-01-01

    This viewgraph presentation provides an overview of the design and development process for NASA's MerBoard. These devices are large interactive display screens which can be shown on the user's computer, which will allow scientists in many locations to interpret and evaluate mission data in real-time. These tools are scheduled to be used during the 2003 Mars Exploration Rover (MER) expeditions. Topics covered include: mission overview, Mer Human Centered Computers, FIDO 2001 observations and MerBoard prototypes.

  1. Deciphering MERS-CoV Evolution in Dromedary Camels.

    PubMed

    Du, Lin; Han, Guan-Zhu

    2016-02-01

    The emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) poses a potential threat to global public health. Many aspects of the evolution and transmission of MERS-CoV in its animal reservoir remain unclear. A recent study provides new insights into the evolution and transmission of MERS-CoV in dromedary camels.

  2. Generation of a tamoxifen inducible Tnnt2MerCreMer knock-in mouse model for cardiac studies.

    PubMed

    Yan, Jianyun; Sultana, Nishat; Zhang, Lu; Park, David S; Shekhar, Akshay; Hu, Jun; Bu, Lei; Cai, Chen-Leng

    2015-06-01

    Tnnt2, encoding thin-filament sarcomeric protein cardiac troponin T, plays critical roles in heart development and function in mammals. To develop an inducible genetic deletion strategy in myocardial cells, we generated a new Tnnt2:MerCreMer (Tnnt2(MerCreMer/+)) knock-in mouse. Rosa26 reporter lines were used to examine the specificity and efficiency of the inducible Cre recombinase. We found that Cre was specifically and robustly expressed in the cardiomyocytes at embryonic and adult stages following tamoxifen induction. The knock-in allele on Tnnt2 locus does not impact cardiac function. These results suggest that this new Tnnt2(MerCreMer/+) mouse could be applied towards the temporal genetic deletion of genes of interests in cardiomyocytes with Cre-LoxP technology. The Tnnt2(MerCreMer/+) mouse model also provides a useful tool to trace myocardial lineage during development and repair after cardiac injury.

  3. Animal models for SARS and MERS coronaviruses

    PubMed Central

    Gretebeck, Lisa M; Subbarao, Kanta

    2015-01-01

    The emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. We can expect to see other novel coronaviruses emerge in the future. An ideal animal model should reflect the clinical signs, viral replication and pathology seen in humans. In this review, we present factors to consider in establishing an animal model for the study of novel coronaviruses and compare the different animal models that have been employed to study SARS-CoV and MERS-CoV. PMID:26184451

  4. Two Years Onboard the MER Opportunity Rover

    NASA Technical Reports Server (NTRS)

    Estlin, Tara; Anderson, Robert C.; Bornstein, Benjamin; Burl, Michael; Castano, Rebecca; Gaines, Daniel; Judd, Michele; Thompson, David R.

    2012-01-01

    The Autonomous Exploration for Gathering Increased Science (AEGIS) system provides automated data collection for planetary rovers. AEGIS is currently being used onboard the Mars Exploration Rover (MER) mission's Opportunity to provide autonomous targeting of the MER Panoramic camera. Prior to AEGIS, targeted data was collected in a manual fashion where targets were manually identified in images transmitted to Earth and the rover had to remain in the same location for one to several communication cycles. AEGIS enables targeted data to be rapidly acquired with no delays for ground communication. Targets are selected by AEGIS through the use of onboard data analysis techniques that are guided by scientist-specified objectives. This paper provides an overview of the how AEGIS has been used on the Opportunity rover, focusing on usage that occurred during a 21 kilometer historic trek to the Mars Endeavour crater.

  5. Animal models for SARS and MERS coronaviruses.

    PubMed

    Gretebeck, Lisa M; Subbarao, Kanta

    2015-08-01

    The emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. We can expect to see other novel coronaviruses emerge in the future. An ideal animal model should reflect the clinical signs, viral replication and pathology seen in humans. In this review, we present factors to consider in establishing an animal model for the study of novel coronaviruses and compare the different animal models that have been employed to study SARS-CoV and MERS-CoV.

  6. Automated Targeting for the MER Rovers

    NASA Technical Reports Server (NTRS)

    Estlin, Tara; Castano, Rebecca; Anderson, Robert C.; Bornstein, Benjamin; Gaines, Daniel; de Granville, Charles; Thompson, David; Burl, Michael; Chien, Steve; Judd, Michele

    2009-01-01

    The Autonomous Exploration for Gathering Increased Science System (AEGIS) will soon provide automated targeting for remote sensing instruments on the Mars Exploration Rover (MER) mission, which currently which currently has two rovers exploring the surface of Mars. Currently, targets for rover remote-sensing instruments, especially narrow field-of-view instruments (such as the MER Mini- TES spectrometer or the 2011 Mars Science Laboratory (MSL) Mission ChemCam Spectrometer), must be selected manually based on imagery already on the ground with the operations team. AEGIS enables the rover flight software to analyze imagery onboard in order to autonomously select and sequence targeted remote-sensing observations in an opportunistic fashion. In this paper, we first provide some background information on the larger autonomous science framework in which AEGIS was developed. We then describe how AEGIS was specifically developed and tested on the JPL FIDO rover. Finally we discuss how AEGIS will be uploaded and used on the Mars Exploration Rover (MER) mission in early 2009.

  7. Cleavage of Mer tyrosine kinase (MerTK) from the cell surface contributes to the regulation of retinal phagocytosis.

    PubMed

    Law, Ah-Lai; Parinot, Célia; Chatagnon, Jonathan; Gravez, Basile; Sahel, José-Alain; Bhattacharya, Shomi S; Nandrot, Emeline F

    2015-02-20

    Phagocytosis of apoptotic cells by macrophages and spent photoreceptor outer segments (POS) by retinal pigment epithelial (RPE) cells requires several proteins, including MerTK receptors and associated Gas6 and protein S ligands. In the retina, POS phagocytosis is rhythmic, and MerTK is activated promptly after light onset via the αvβ5 integrin receptor and its ligand MFG-E8, thus generating a phagocytic peak. The phagocytic burst is limited in time, suggesting a down-regulation mechanism that limits its duration. Our previous data showed that MerTK helps control POS binding of integrin receptors at the RPE cell surface as a negative feedback loop. Our present results show that a soluble form of MerTK (sMerTK) is released in the conditioned media of RPE-J cells during phagocytosis and in the interphotoreceptor matrix of the mouse retina during the morning phagocytic peak. In contrast to macrophages, the two cognate MerTK ligands have an opposite effect on phagocytosis and sMerTK release, whereas the integrin ligand MFG-E8 markedly increases both phagocytosis and sMerTK levels. sMerTK acts as a decoy receptor blocking the effect of both MerTK ligands. Interestingly, stimulation of sMerTK release decreases POS binding. Conversely, blocking MerTK cleavage increased mostly POS binding by RPE cells. Therefore, our data suggest that MerTK cleavage contributes to the acute regulation of RPE phagocytosis by limiting POS binding to the cell surface.

  8. UNC1062, a new and potent Mer inhibitor.

    PubMed

    Liu, Jing; Zhang, Weihe; Stashko, Michael A; Deryckere, Deborah; Cummings, Christopher T; Hunter, Debra; Yang, Chao; Jayakody, Chatura N; Cheng, Nancy; Simpson, Catherine; Norris-Drouin, Jacqueline; Sather, Susan; Kireev, Dmitri; Janzen, William P; Earp, H Shelton; Graham, Douglas K; Frye, Stephen V; Wang, Xiaodong

    2013-07-01

    Abnormal activation of Mer kinase has been implicated in the oncogenesis of many human cancers including acute lymphoblastic and myeloid leukemia, non-small cell lung cancer, and glioblastoma. We have discovered a new family of small molecule Mer inhibitors, pyrazolopyrimidine sulfonamides, that potently inhibit the kinase activity of Mer. Importantly, these compounds do not demonstrate significant hERG activity in the PatchXpress assay. Through structure-activity relationship studies, 35 (UNC1062) was identified as a potent (IC50 = 1.1 nM) and selective Mer inhibitor. When applied to live tumor cells, UNC1062 inhibited Mer phosphorylation and colony formation in soft agar. Given the potential of Mer as a therapeutic target, UNC1062 is a promising candidate for further drug development.

  9. UNC1062, a new and potent Mer inhibitor

    PubMed Central

    Liu, Jing; Zhang, Weihe; Stashko, Michael A; DeRyckere, Deborah; Cummings, Christopher T.; Hunter, Debra; Yang, Chao; Jayakody, Chatura N.; Cheng, Nancy; Simpson, Catherine; Norris-Drouin, Jacqueline; Sather, Susan; Kireev, Dmitri; Janzen, William P.; Earp, H Shelton; Graham, Douglas K.; Frye, Stephen V.; Wang, Xiaodong

    2013-01-01

    Abnormal activation of Mer kinase has been implicated in the oncogenesis of many human cancers including acute lymphoblastic and myeloid leukemia, non-small cell lung cancer, and glioblastoma. We have discovered a new family of small molecule Mer inhibitors, pyrazolopyrimidine sulfonamides, that potently inhibit the kinase activity of Mer. Importantly, these compounds do not demonstrate significant hERG activity in the PatchXpress assay. Through structure-activity relationship studies, 35 (UNC1062) was identified as a potent (IC50 = 1.1 nM) and selective Mer inhibitor. When applied to live tumor cells, UNC1062 inhibited Mer phosphorylation and colony formation in soft agar. Given the potential of Mer as a therapeutic target, UNC1062 is a promising candidate for further drug development. PMID:23693152

  10. Managing PV Power on Mars - MER Rovers

    NASA Technical Reports Server (NTRS)

    Stella, Paul M.; Chin, Keith; Wood, Eric; Herman, Jennifer; Ewell, Richard

    2009-01-01

    The MER Rovers have recently completed over 5 years of operation! This is a remarkable demonstration of the capabilities of PV power on the Martian surface. The extended mission required the development of an efficient process to predict the power available to the rovers on a day-to-day basis. The performance of the MER solar arrays is quite unlike that of any other Space array and perhaps more akin to Terrestrial PV operation, although even severe by that comparison. The impact of unpredictable factors, such as atmospheric conditions and dust accumulation (and removal) on the panels limits the accurate prediction of array power to short time spans. Based on the above, it is clear that long term power predictions are not sufficiently accurate to allow for detailed long term planning. Instead, the power assessment is essentially a daily activity, effectively resetting the boundary points for the overall predictive power model. A typical analysis begins with the importing of the telemetry from each rover's previous day's power subsystem activities. This includes the array power generated, battery state-of-charge, rover power loads, and rover orientation, all as functions of time. The predicted performance for that day is compared to the actual performance to identify the extent of any differences. The model is then corrected for these changes. Details of JPL's MER power analysis procedure are presented, including the description of steps needed to provide the final prediction for the mission planners. A dust cleaning event of the solar array is also highlighted to illustrate the impact of Martian weather on solar array performance

  11. MerTK regulates thymic selection of autoreactive T cells.

    PubMed

    Wallet, Mark A; Flores, Rafael R; Wang, Yaming; Yi, Zuoan; Kroger, Charles J; Mathews, Clayton E; Earp, H Shelton; Matsushima, Glenn; Wang, Bo; Tisch, Roland

    2009-03-24

    T cell-mediated autoimmune diseases such as type 1 diabetes (T1D) are believed to be the result in part of inefficient negative selection of self-specific thymocytes. However, the events regulating thymic negative selection are not fully understood. In the current study, we demonstrate that nonobese diabetic (NOD) mice lacking expression of the Mer tyrosine kinase (MerTK) have reduced inflammation of the pancreatic islets and fail to develop diabetes. Furthermore, NOD mice deficient in MerTK expression (Mer(-/-)) exhibit a reduced frequency of beta cell-specific T cells independent of immunoregulatory effectors. The establishment of bone marrow chimeric mice demonstrated that the block in beta cell autoimmunity required hematopoietic-derived cells lacking MerTK expression. Notably, fetal thymic organ cultures and self-peptide administration showed increased thymic negative selection in Mer(-/-) mice. Finally, thymic dendritic cells (DC) prepared from Mer(-/-) mice exhibited an increased capacity to induce thymocyte apoptosis in a peptide-specific manner in vitro. These findings provide evidence for a unique mechanism involving MerTK-mediated regulation of thymocyte negative selection and thymic DC, and suggest a role for MerTK in contributing to beta cell autoimmunity.

  12. Identification of the merR gene of R100 by using mer-lac gene and operon fusions.

    PubMed Central

    Foster, T J; Brown, N L

    1985-01-01

    Transcriptional (operon) and translational (gene) fusions between the R100 merR gene and lacZ were constructed in vitro in a pBR322 plasmid carrying the mer genes derived from plasmid R100. The translational fusions were oriented in the opposite direction to and divergently from the merTCAD genes. This shows that the reading frame previously thought to be merR was incorrect. Expression of the gene fusion was repressed in trans by a compatible plasmid carrying the R100 merR+ gene, as was a similarly oriented transcriptional fusion. In contrast, expression of beta-galactosidase by the lac fragment located at the same site but in the opposite orientation was at a lower level and was not repressed by merR+. Images PMID:2993235

  13. Science Activity Planner for the MER Mission

    NASA Technical Reports Server (NTRS)

    Norris, Jeffrey S.; Crockett, Thomas M.; Fox, Jason M.; Joswig, Joseph C.; Powell, Mark W.; Shams, Khawaja S.; Torres, Recaredo J.; Wallick, Michael N.; Mittman, David S.

    2008-01-01

    The Maestro Science Activity Planner is a computer program that assists human users in planning operations of the Mars Explorer Rover (MER) mission and visualizing scientific data returned from the MER rovers. Relative to its predecessors, this program is more powerful and easier to use. This program is built on the Java Eclipse open-source platform around a Web-browser-based user-interface paradigm to provide an intuitive user interface to Mars rovers and landers. This program affords a combination of advanced display and simulation capabilities. For example, a map view of terrain can be generated from images acquired by the High Resolution Imaging Science Explorer instrument aboard the Mars Reconnaissance Orbiter spacecraft and overlaid with images from a navigation camera (more precisely, a stereoscopic pair of cameras) aboard a rover, and an interactive, annotated rover traverse path can be incorporated into the overlay. It is also possible to construct an overhead perspective mosaic image of terrain from navigation-camera images. This program can be adapted to similar use on other outer-space missions and is potentially adaptable to numerous terrestrial applications involving analysis of data, operations of robots, and planning of such operations for acquisition of scientific data.

  14. Geology of the MER 2003 "Elysium" Candidate Landing Site

    NASA Astrophysics Data System (ADS)

    Tanaka, K. L.; Skinner, J. A., Jr.; Carr, M. H.; Gilmore, M. S.; Hare, T. M.

    2003-03-01

    Although chosen mainly for its safety characteristics, new Mars Global Surveyor and Mars Odyssey data suggest that the MER 2003 "Elysium" candidate landing site in southeastern Utopia Planitia also meets basic science requirements for the MER mission involving the geologic activity of water.

  15. Dust Accumulation on MER Solar Panels

    NASA Astrophysics Data System (ADS)

    Guinness, E. A.; Arvidson, R. E.; McEwen, A. S.; Cull, S.

    2011-12-01

    HiRISE acquired in March 2011 a color image of the Spirit Mars Exploration Rover from orbit that shows an exceptionally bright reflection from the rover solar panels. HiRISE data combined with laboratory measurements of MER solar cell reflectance provide a method for constraining the thickness of dust on the solar panels. Spirit is the brightest object in the HiRISE scene with a reflectance that is about 3 times higher at 500 nm and about 1.5 times higher at 700 and 850 nm than bright outcrop and soil near the rover. The rover is also less red than these nearby materials and less red than a typical Mars dust spectrum modeled with the same geometry and seen through similar atmospheric conditions as the HiRISE image. Lighting and viewing angles for the HiRISE image of Spirit are close to a specular reflection geometry when factoring in the rover orientation, the sun position, and the location of HiRISE during image acquisition. Laboratory photometric measurements of clean and dust-coated MER solar cells show a strong specular reflection for dust coating thicknesses up to at least 45 micrometers. The specular reflection was not present in the laboratory data when the solar cell was covered with about a 135 micrometer thick layer. The dust used in the experiments consisted of less than 10 micrometer sized particles derived from a palagonitic tephra from Mauna Kea that is spectrally similar to Mars dust. A survey of MER Pancam color images acquired by Spirit and Opportunity also shows several examples of specular reflections from the solar panels. These examples correspond to times when the solar cells were moderately clean to dusty as inferred from the amount of power generated by the cells. Specular reflections in Pancam images have been observed when the solar cell output was only 45% that of a dust-free cell. Spirit HiRISE data indicate that the rover was not covered by an optical thick layer of dust because some of the reflected light must have come from the

  16. Engineering MerR for Sequestration and MerA for Reduction of Toxic Metals and Radionuclides

    SciTech Connect

    Anne O. Summers

    2008-12-15

    The objectives of this project were (1) to alter a metalloregulatory protein (MerR) so that it would bind other toxic metals or radionuclides with similar affinity so that the engineered protein itself and/or bacteria expressing it could be deployed in the environment to specifically sequester such metals and (2) to alter the mercuric reductase, MerA, to reduce radionuclides and render them less mobile. Both projects had a basic science component. In the first case, such information about MerR illuminates how proteins discriminate very similar metals/elements. In the second case, information about MerA reveals the criteria for transmission of reducing equivalents from NADPH to redox-active metals. The work involved genetic engineering of all or parts of both proteins and examination of their resultant properties both in vivo and in vitro, the latter with biochemical and biophysical tools including equilibrium and non-equilibrium dialysis, XAFS, NMR, x-ray crystallography, and titration calorimetry. We defined the basis for metal specificity in MerR, devised a bacterial strain that sequesters Hg while growing, characterized gold reduction by MerA and the role of the metallochaperone domain of MerA, and determined the 3-D structure of MerB, the organomercurial lyase.

  17. The Ames MER Microscopic Imager Toolkit

    NASA Technical Reports Server (NTRS)

    Sargent, Randy; Deans, Matthew; Kunz, Clayton; Sims, Michael; Herkenhoff, Ken

    2005-01-01

    The Mars Exploration Rovers, Spirit and Opportunity, have spent several successful months on Mars, returning gigabytes of images and spectral data to scientists on Earth. One of the instruments on the MER rovers, the Athena Microscopic Imager (MI), is a fixed focus, megapixel camera providing a plus or minus mm depth of field and a 3lx31mm field of view at a working distance of 63 mm from the lens to the object being imaged. In order to maximize the science return from this instrument, we developed the Ames MI Toolkit and supported its use during the primary mission. The MI Toolkit is a set of programs that operate on collections of MI images, with the goal of making the data more understandable to the scientists on the ground. Because of the limited depth of field of the camera, and the often highly variable topography of the terrain being imaged, MI images of a given rock are often taken as a stack, with the Instrument Deployment Device (IDD) moving along a computed normal vector, pausing every few millimeters for the MI to acquire an image. The MI Toolkit provides image registration and focal section merging, which combine these images to form a single, maximally in-focus image, while compensating for changes in lighting as well as parallax due to the motion of the camera. The MI Toolkit also provides a 3-D reconstruction of the surface being imaged using stereo and can embed 2-D MI images as texture maps into 3-D meshes produced by other imagers on board the rover to provide context. The 2-D images and 3-D meshes output from the Toolkit are easily viewed by scientists using other mission tools, such as Viz or the MI Browser. This paper describes the MI Toolkit in detail, as well as our experience using it with scientists at JPL during the primary MER mission.

  18. The Ames MER microscopic imager toolkit

    USGS Publications Warehouse

    Sargent, R.; Deans, Matthew; Kunz, C.; Sims, M.; Herkenhoff, K.

    2005-01-01

    12The Mars Exploration Rovers, Spirit and Opportunity, have spent several successful months on Mars, returning gigabytes of images and spectral data to scientists on Earth. One of the instruments on the MER rovers, the Athena Microscopic Imager (MI), is a fixed focus, megapixel camera providing a ??3mm depth of field and a 31??31mm field of view at a working distance of 63 mm from the lens to the object being imaged. In order to maximize the science return from this instrument, we developed the Ames MI Toolkit and supported its use during the primary mission. The MI Toolkit is a set of programs that operate on collections of MI images, with the goal of making the data more understandable to the scientists on the ground. Because of the limited depth of field of the camera, and the often highly variable topography of the terrain being imaged, MI images of a given rock are often taken as a stack, with the Instrument Deployment Device (IDD) moving along a computed normal vector, pausing every few millimeters for the MI to acquire an image. The MI Toolkit provides image registration and focal section merging, which combine these images to form a single, maximally in-focus image, while compensating for changes in lighting as well as parallax due to the motion of the camera. The MI Toolkit also provides a 3-D reconstruction of the surface being imaged using stereo and can embed 2-D MI images as texture maps into 3-D meshes produced by other imagers on board the rover to provide context. The 2-D images and 3-D meshes output from the Toolkit are easily viewed by scientists using other mission tools, such as Viz or the MI Browser.This paper describes the MI Toolkit in detail, as well as our experience using it with scientists at JPL during the primary MER mission. ?? 2005 IEEE.

  19. mer [Römer, Roemer], Ole [Olaf] Christensen (1644-1710)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Born in Aarhus, Denmark, studied at the University of Copenhagen under Thomas and Erasmus Bartholin, who gave him TYCHO BRAHE's manuscripts to edit and his own daughter to wed. Rømer accompanied Bartholin and JEAN PICARD to Hven to measure the position of Tycho's observatory, the better to reduce Tycho's observations. He went on to the Paris Observatory where he made and used instruments for the ...

  20. Recombination spot identification Based on gapped k-mers

    PubMed Central

    Wang, Rong; Xu, Yong; Liu, Bin

    2016-01-01

    Recombination is crucial for biological evolution, which provides many new combinations of genetic diversity. Accurate identification of recombination spots is useful for DNA function study. To improve the prediction accuracy, researchers have proposed several computational methods for recombination spot identification. The k-mer feature is one of the most useful features for modeling the properties and function of DNA sequences. However, it suffers from the inherent limitation. If the value of word length k is large, the occurrences of k-mers are closed to a binary variable, with a few k-mers present once and most k-mers are absent. This usually causes the sparse problem and reduces the classification accuracy. To solve this problem, we add gaps into k-mer and introduce a new feature called gapped k-mer (GKM) for identification of recombination spots. By using this feature, we present a new predictor called SVM-GKM, which combines the gapped k-mers and Support Vector Machine (SVM) for recombination spot identification. Experimental results on a widely used benchmark dataset show that SVM-GKM outperforms other highly related predictors. Therefore, SVM-GKM would be a powerful predictor for computational genomics. PMID:27030570

  1. Monoclonal Antibody Shows Promise as Potential Therapeutic for MERS | Poster

    Cancer.gov

    A monoclonal antibody has proven effective in preventing Middle Eastern Respiratory Syndrome (MERS) in lab animals, suggesting further development as a potential intervention for the deadly disease in humans, according to new research. MERS is a newly emerged coronavirus first detected in humans in 2012. Most cases have occurred in the Middle East, but the disease has appeared elsewhere. In all, MERS has infected more than 1,700 individuals and killed more than 600, according to the World Health Organization. No vaccines or antiviral therapies currently exist. Several candidate vaccines are being developed, and some have been tested in animal models, a prerequisite to human clinical trials.

  2. MGS and Odyssey - relay satellites for the MER mission

    NASA Technical Reports Server (NTRS)

    Esposito, Pasquale B.; Bhat, R.; Demeak, S.; Ardalan, S.; Breeden, J.; Helfrich, C.; Jefferson, D.; Stauch, J.

    2004-01-01

    Both Mars Global Surveyor (MGS) and Odyssey are currently in low altitude, nearly circular and highly inclined orbits about Mars. Thus, they are available adn compartible to serve as relay satellites for the Mars Exploration Rovers (MER) mission. Consequently, the MER project developed requirements for MGS to be overhead for MER-A (Spirit) at Gusev crater, at maximum elevation, mudway between lander separation and initial touchdown; in time, this was specified as 01/04/04. 04:24:55 UTC/SCET with a 30 sec tolerance.

  3. Translating MAPGEN to ASPEN for MER

    NASA Technical Reports Server (NTRS)

    Rabideau, Gregg R.; Knight, Russell L.; Lenda, Matthew; Maldague, Pierre F.

    2013-01-01

    This software translates MAPGEN (Europa and APGEN) domains to ASPEN, and the resulting domain can be used to perform planning for the Mars Exploration Rover (MER). In other words, this is a conversion of two distinct planning languages (both declarative and procedural) to a third (declarative) planning language in order to solve the problem of faithful translation from mixed-domain representations into the ASPEN Modeling Language. The MAPGEN planning system is an example of a hybrid procedural/declarative system where the advantages of each are leveraged to produce an effective planner/scheduler for MER tactical planning. The adaptation of the planning system (ASPEN) was investigated, and, with some translation, much of the procedural knowledge encoding is amenable to declarative knowledge encoding. The approach was to compose translators from the core languages used for adapting MAGPEN, which consists of Europa and APGEN. Europa is a constraint- based planner/scheduler where domains are encoded using a declarative model. APGEN is also constraint-based, in that it tracks constraints on resources and states and other variables. Domains are encoded in both constraints and code snippets that execute according to a forward sweep through the plan. Europa and APGEN communicate to each other using proxy activities in APGEN that represent constraints and/or tokens in Europa. The composition of a translator from Europa to ASPEN was fairly straightforward, as ASPEN is also a declarative planning system, and the specific uses of Europa for the MER domain matched ASPEN s native encoding fairly closely. On the other hand, translating from APGEN to ASPEN was considerably more involved. On the surface, the types of activities and resources one encodes in APGEN appear to match oneto- one to the activities, state variables, and resources in ASPEN. But, when looking into the definitions of how resources are profiled and activities are expanded, one sees code snippets that access

  4. Mars Atmosphere Argon Density Measurement on MER Mission

    NASA Astrophysics Data System (ADS)

    Economou, T. E.

    2008-11-01

    Using the Alpha Particle X-ray Spectrometer (APXS) on board Spirit and Opportunity rovers on MER mission, we were able to measure the argon density variation in the martian atmosphere as a function of seasonal changes.

  5. Characterization of Martian Rock Shape for MER Airbag Drop Tests

    NASA Astrophysics Data System (ADS)

    Dimaggio, E. N.; Schroeder, R. D.; Golombek, M. P.; Haldemann, A.; Castle, N.

    2003-03-01

    To aid in defining the rock distributions for MER airbag tests, images from the Viking Landers 1 and 2 and MPF were used to identify rocks that are >20 cm high and characterize them by their shape and burial.

  6. WATER ON MARS: EVIDENCE FROM MER MISSION RESULTS

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A.

    2006-01-01

    The Mars Exploration Rover (MER) mission landed two rovers on Mars, equipped with a highly-capable suite of science instruments. The Spirit rover landed on the inside Gusev Crater on January 5, 2004, and the Opportunity rover three weeks later on Meridiani Planum. This paper summarizes some of the findings from the MER rovers related to the NASA science strategy of investigating past and present water on Mars.

  7. Discovery of Macrocyclic Pyrimidines as MerTK-Specific Inhibitors.

    PubMed

    McIver, Andrew L; Zhang, Weihe; Liu, Qingyang; Jiang, Xinpeng; Stashko, Michael A; Nichols, James; Miley, Michael J; Norris-Drouin, Jacqueline; Machius, Mischa; DeRyckere, Deborah; Wood, Edgar; Graham, Douglas K; Earp, H Shelton; Kireev, Dmitri; Frye, Stephen V; Wang, Xiaodong

    2017-02-03

    Macrocycles have attracted significant attention in drug discovery recently. In fact, a few de novo designed macrocyclic kinase inhibitors are currently in clinical trials with good potency and selectivity for their intended target. In this study, we successfully engaged a structure-based drug design approach to discover macrocyclic pyrimidines as potent Mer tyrosine kinase (MerTK)-specific inhibitors. An enzyme-linked immunosorbent assay (ELISA) in 384-well format was employed to evaluate the inhibitory activity of macrocycles in a cell-based assay assessing tyrosine phosphorylation of MerTK. Through structure-activity relationship (SAR) studies, analogue 11 [UNC2541; (S)-7-amino-N-(4-fluorobenzyl)-8-oxo-2,9,16-triaza-1(2,4)-pyrimidinacyclohexadecaphane-1-carboxamide] was identified as a potent and MerTK-specific inhibitor that exhibits sub-micromolar inhibitory activity in the cell-based ELISA. In addition, an X-ray structure of MerTK protein in complex with 11 was resolved to show that these macrocycles bind in the MerTK ATP pocket.

  8. Receptor-binding domain-based subunit vaccines against MERS-CoV.

    PubMed

    Zhang, Naru; Tang, Jian; Lu, Lu; Jiang, Shibo; Du, Lanying

    2015-04-16

    Development of effective vaccines, in particular, subunit-based vaccines, against emerging Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) will provide the safest means of preventing the continuous spread of MERS in humans and camels. This review briefly describes the structure of the MERS-CoV spike (S) protein and its receptor-binding domain (RBD), discusses the current status of MERS vaccine development and illustrates the strategies used to develop RBD-based subunit vaccines against MERS. It also summarizes currently available animal models for MERS-CoV and proposes a future direction for MERS vaccines. Taken together, this review will assist researchers working to develop effective and safe subunit vaccines against MERS-CoV and any other emerging coronaviruses that might cause future pandemics.

  9. Predicting the Mars Atmosphere for MER EDL

    NASA Astrophysics Data System (ADS)

    Kass, D.

    2005-05-01

    As the two Mars Exploration Rovers (MER) approached Mars, Mars Global Surveyor (MGS) detected a regional dust storm. The storm developed as a local storm descending the Chryse storm track but instead of dying out near the equator, it crossed over the Meridiani landing site into the southern hemisphere and started growing. It eventually became a planet encircling storm, with a global impact on atmospheric temperatures. The storm peaked (in terms of dust loading) around December 18th. While the storm was already decaying, it was still expected to change the atmosphere from baseline "clear" atmosphere used for planning Entry Descent and Landing (EDL). To help insure the successful landing, an attempt was made to model and then predict the atmosphere as the dust from the storm (and associated warming) cleared. Two types of data analyses were performed. The first was to rapidly look at MGS-TES daily global maps and MOC weekly reports. This gave a good qualitative assessment of the activity and help give a global view of the activity. The daily global atmospheric temperature maps from TES were particularly useful in showing where there were atmospheric changes but little measurable dust. The second analysis was to use vertical temperature profiles retrieved from the TES data. An effort was made to minimize the turnaround on the analysis and a 3 day latency was achieved. The retrieved profiles from the orbit nearest to the landing site were averaged over a ~ 10 degree latitude bin. They were then incorporated into an engineering model based on the one described in Golombek et al. [2003]. This is an interpolation scheme/Monte-Carlo distribution generator and not an actual dynamical model. It basically uses the TES data as a mean and applies a variability. For Spirit, there was no attempt to make predictions (the storm was too close to landing), so the most recent profiles were just used as a best guess. This turned out to be adequate, resulting in the final model being

  10. Role of MerH in mercury resistance in the archaeon Sulfolobus solfataricus

    PubMed Central

    Schelert, James; Rudrappa, Deepak; Johnson, Tyler

    2013-01-01

    Crenarchaeota include extremely thermoacidophilic organisms that thrive in geothermal environments dominated by sulfidic ores and heavy metals such as mercury. Mercuric ion, Hg(II), inactivates transcription in the crenarchaeote Sulfolobus solfataricus and simultaneously derepresses transcription of a resistance operon, merHAI, through interaction with the MerR transcription factor. While mercuric reductase (MerA) is required for metal resistance, the role of MerH, an adjacent small and predicted product of an ORF, has not been explored. Inactivation of MerH either by nonsense mutation or by in-frame deletion diminished Hg(II) resistance of mutant cells. Promoter mapping studies indicated that Hg(II) sensitivity of the merH nonsense mutant arose through transcriptional polarity, and its metal resistance was restored partially by single copy merH complementation. Since MerH was not required in vitro for MerA-catalysed Hg(II) reduction, MerH may play an alternative role in metal resistance. Inductively coupled plasma-mass spectrometry analysis of the MerH deletion strain following metal challenge indicated that there was prolonged retention of intracellular Hg(II). Finally, a reduced rate of mer operon induction in the merH deletion mutant suggested that the requirement for MerH could result from metal trafficking to the MerR transcription factor. PMID:23619003

  11. Evaluation of candidate vaccine approaches for MERS-CoV

    SciTech Connect

    Wang, Lingshu; Shi, Wei; Joyce, M. Gordon; Modjarrad, Kayvon; Zhang, Yi; Leung, Kwanyee; Lees, Christopher R.; Zhou, Tongqing; Yassine, Hadi M.; Kanekiyo, Masaru; Yang, Zhi-yong; Chen, Xuejun; Becker, Michelle M.; Freeman, Megan; Vogel, Leatrice; Johnson, Joshua C.; Olinger, Gene; Todd, John P.; Bagci, Ulas; Solomon, Jeffrey; Mollura, Daniel J.; Hensley, Lisa; Jahrling, Peter; Denison, Mark R.; Rao, Srinivas S.; Subbarao, Kanta; Kwong, Peter D.; Mascola, John R.; Kong, Wing-Pui; Graham, Barney S.

    2015-07-28

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

  12. Evaluation of candidate vaccine approaches for MERS-CoV

    DOE PAGES

    Wang, Lingshu; Shi, Wei; Joyce, M. Gordon; ...

    2015-07-28

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanismsmore » were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.« less

  13. Potential Noachian-Aged Sites for MER-B

    NASA Astrophysics Data System (ADS)

    Gilmore, M. S.; Tanaka, K. L.

    2001-01-01

    Two Mars Exploration Rovers (MER) are slated for launch in 2003 and will land in the equatorial region of Mars. These rovers are More formidable in both size and instrument complement than the Sojourner rover, potentially allowing greater range. For landing, they will be housed in an airbag system nearly identical to Pathfinder allowing them to land in an area with elevation below 1.3 km, Root Mean Square (RMS) slopes less than 6 degrees, rock abundance less than 20%, and fine component thermal inertia greater than 3-4 cgs units. MER-A may land between 15 S to 5 N and MER-B between 10 S and 10 N. Numerous sites have been identified by the JPL team as meeting the above engineering requirements for the landing of the rovers. Here we focus on a subset of these that lie in Noachian-aged terrain, as defined by Viking-era geologic mapping. This subset is further reduced by the first author's support of the selection (if possible) of a site in the Valles Marineris which can only be reached by MER-A, this study therefore focuses on those Noachian-aged sites that can be reached by MER-B.

  14. Mars Exploration Rover (MER) Project Environmental Assurance Program

    NASA Astrophysics Data System (ADS)

    Man, Kin F.; Farguson, Christine T.; Hoffman, Alan R.

    2004-08-01

    A comprehensive prelaunch environmental assurance program was planned and implemented on NASA's Mars Exploration Rover (MER) project. This project consisted of two rovers/spacecraft launched on two separate launch vehicles. The environmental assurance program included assembly/subsystem and system-level testing in the areas of dynamics, thermal, and electromagnetic (EMC), as well as venting/pressure, dust, radiation, and micrometeoroid analyses. Due to the Martian diurnal cycles, the susceptible hardware also underwent thermal cycling qualification of their packaging designs and manufacturing processes. This paper presents a comprehensive summary of the environmental assurance program for the MER project. A series of test and analysis metrics are generated. Selections of the numerous lessons that have been learned from implementation of the MER environmental assurance program are documented in this paper. They include both technical and programmatic lessons that would be helpful in improving implementation of the environmental program for future projects.

  15. A stable mercury-containing complex of the organomercurial lyase MerB: catalysis, product release, and direct transfer to MerA.

    PubMed

    Benison, Gregory C; Di Lello, Paola; Shokes, Jacob E; Cosper, Nathaniel J; Scott, Robert A; Legault, Pascale; Omichinski, James G

    2004-07-06

    Bacteria isolated from organic mercury-contaminated sites have developed a system of two enzymes that allows them to efficiently convert both ionic and organic mercury compounds to the less toxic elemental mercury. Both enzymes are encoded on the mer operon and require sulfhydryl-bound substrates. The first enzyme is an organomercurial lyase (MerB), and the second enzyme is a mercuric ion reductase (MerA). MerB catalyzes the protonolysis of the carbon-mercury bond, resulting in the formation of a reduced carbon compound and inorganic ionic mercury. Of several mercury-containing MerB complexes that we attempted to prepare, the most stable was a complex consisting of the organomercurial lyase (MerB), a mercuric ion, and a molecule of the MerB inhibitor dithiothreitol (DTT). Nuclear magnetic resonance (NMR) spectroscopy and extended X-ray absorption fine structure spectroscopy of the MerB/Hg/DTT complex have shown that the ligands to the mercuric ion in the complex consist of both sulfurs from the DTT molecule and one cysteine ligand, C96, from the protein. The stability of the MerB/Hg/DTT complex, even in the presence of a large excess of competing cysteine, has been demonstrated by NMR and dialysis. We used an enzyme buffering test to determine that the MerB/Hg/DTT complex acts as a substrate for the mercuric reductase MerA. The observed MerA activity is higher than the expected activity assuming free diffusion of the mercuric ion from MerB to MerA. This suggests that the mercuric ion can be transferred between the two enzymes by a direct transfer mechanism.

  16. The Ballerina Experiment on the Rømer Mission

    NASA Astrophysics Data System (ADS)

    Brandt, Soren

    The Rømer mission has recently been approved as the next mission within the Danish Small Satellite Program. The scientific payload will consist of two separate experiments, the MONS and the Ballerina payloads. The primary objective of Ballerina is to provide accurate, real-time positions relayed to ground for ~ 70 Gamma Ray Bursts (GRBs) per year, and to study the temporal and spectral evolution of the early GRB X-ray afterglow. As an additional goal, Ballerina will detect and study bright X-ray transients, in particular X-ray novae and micro-quasar systems. R{\\o}mer is currently scheduled for launch in late 2003.

  17. Cassini, Rømer, and the velocity of light

    NASA Astrophysics Data System (ADS)

    Bobis, Laurence; Lequeux, James

    2008-07-01

    The discovery of the finite nature of the velocity of light is usually attributed to Rømer. However, a text at the Paris Observatory confirms the minority opinion according to which Cassini was first to propose the ‘successive motion’ of light, while giving a rather correct order of magnitude for the duration of its propagation from the Sun to the Earth. We examine this question, and discuss why, in spite of the criticisms of Halley, Cassini abandoned this hypothesis while leaving Rømer free to publish it.

  18. Current advancements and potential strategies in the development of MERS-CoV vaccines.

    PubMed

    Zhang, Naru; Jiang, Shibo; Du, Lanying

    2014-06-01

    Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future.

  19. Current advancements and potential strategies in the development of MERS-CoV vaccines

    PubMed Central

    Zhang, Naru; Jiang, Shibo; Du, Lanying

    2014-01-01

    Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future. PMID:24766432

  20. Unraveling the drivers of MERS-CoV transmission

    PubMed Central

    Cauchemez, Simon; Nouvellet, Pierre; Cori, Anne; Jombart, Thibaut; Clapham, Hannah; Moore, Sean; Mills, Harriet Linden; Salje, Henrik; Collins, Caitlin; Rodriquez-Barraquer, Isabel; Riley, Steven; Truelove, Shaun; Algarni, Homoud; Alhakeem, Rafat; AlHarbi, Khalid; Turkistani, Abdulhafiz; Aguas, Ricardo J.; Cummings, Derek A. T.; Van Kerkhove, Maria D.; Donnelly, Christl A.; Lessler, Justin; Fraser, Christophe; Al-Barrak, Ali; Ferguson, Neil M.

    2016-01-01

    With more than 1,700 laboratory-confirmed infections, Middle East respiratory syndrome coronavirus (MERS-CoV) remains a significant threat for public health. However, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of MERS-CoV epidemics remain poorly characterized. Here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 MERS-CoV cases detected in the Kingdom of Saudi Arabia (KSA) between January 2013 and July 2014. We assess how infections from the animal reservoir, the different levels of mixing, and heterogeneities in transmission have contributed to the buildup of MERS-CoV epidemics in KSA. We estimate that 12% [95% credible interval (CI): 9%, 15%] of cases were infected from the reservoir, the rest via human-to-human transmission in clusters (60%; CI: 57%, 63%), within (23%; CI: 20%, 27%), or between (5%; CI: 2%, 8%) regions. The reproduction number at the start of a cluster was 0.45 (CI: 0.33, 0.58) on average, but with large SD (0.53; CI: 0.35, 0.78). It was >1 in 12% (CI: 6%, 18%) of clusters but fell by approximately one-half (47% CI: 34%, 63%) its original value after 10 cases on average. The ongoing exposure of humans to MERS-CoV from the reservoir is of major concern, given the continued risk of substantial outbreaks in health care systems. The approach we present allows the study of infectious disease transmission when data linking cases to each other remain limited and uncertain. PMID:27457935

  1. Unraveling the drivers of MERS-CoV transmission.

    PubMed

    Cauchemez, Simon; Nouvellet, Pierre; Cori, Anne; Jombart, Thibaut; Garske, Tini; Clapham, Hannah; Moore, Sean; Mills, Harriet Linden; Salje, Henrik; Collins, Caitlin; Rodriquez-Barraquer, Isabel; Riley, Steven; Truelove, Shaun; Algarni, Homoud; Alhakeem, Rafat; AlHarbi, Khalid; Turkistani, Abdulhafiz; Aguas, Ricardo J; Cummings, Derek A T; Van Kerkhove, Maria D; Donnelly, Christl A; Lessler, Justin; Fraser, Christophe; Al-Barrak, Ali; Ferguson, Neil M

    2016-08-09

    With more than 1,700 laboratory-confirmed infections, Middle East respiratory syndrome coronavirus (MERS-CoV) remains a significant threat for public health. However, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of MERS-CoV epidemics remain poorly characterized. Here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 MERS-CoV cases detected in the Kingdom of Saudi Arabia (KSA) between January 2013 and July 2014. We assess how infections from the animal reservoir, the different levels of mixing, and heterogeneities in transmission have contributed to the buildup of MERS-CoV epidemics in KSA. We estimate that 12% [95% credible interval (CI): 9%, 15%] of cases were infected from the reservoir, the rest via human-to-human transmission in clusters (60%; CI: 57%, 63%), within (23%; CI: 20%, 27%), or between (5%; CI: 2%, 8%) regions. The reproduction number at the start of a cluster was 0.45 (CI: 0.33, 0.58) on average, but with large SD (0.53; CI: 0.35, 0.78). It was >1 in 12% (CI: 6%, 18%) of clusters but fell by approximately one-half (47% CI: 34%, 63%) its original value after 10 cases on average. The ongoing exposure of humans to MERS-CoV from the reservoir is of major concern, given the continued risk of substantial outbreaks in health care systems. The approach we present allows the study of infectious disease transmission when data linking cases to each other remain limited and uncertain.

  2. MGS and Odyssey - Relay Satellites for the MER Mission

    NASA Technical Reports Server (NTRS)

    Esposito, Pasquale B.; Bhat, R.; Demcak, S.; Ardakab, S.; Breeden, J.; Helfrich, C.; Jefferson, D.; Stauch, J.

    2004-01-01

    Both Mars Global Surveyor (MGS) and Mars Odyssey are currently in low altitude, nearly circular and highly inclined orbits about Mars. Thus, they are available and compatible to serve as relay satellites for the Mars Exploration Rover (MER) mission. Consequently, the MER project developed requirements for MGS to be overhead, at a specific time with a 30 second tolerance, during the atmospheric entry, descent and landing (EDL) phase of both MER vehicles. The result, after execution of a single orbit synchronization maneuver (OSM) on 10/03/03, 92.4 days or 1130 orbits before Spirit's EDL, was that MGS was over Spirit 8 seconds past the required time. This maneuver, with a delta-velocity of 0.534 m/s, caused the orbital period to change by 3.34 s and resulted in a time-phasing change of 62 min 19 s in order to achieve the EDL overflight. Based on the navigation and execution of an OSM on 01/04/04, MGS was overhead for the Opportunity EDL on 01/25/04,3.5 seconds after the required epoch. Requirements also existed for the Odyssey over-flight of the MER rovers after landing and various equipment deployments had been completed. Thus, these requirements were that Odyssey should rise no earlier than specified times with respect to each of the landing sites. The Odyssey over-flights of both Spirit and Opportunity on sol 1 were equally successful. This paper will present the navigation plan, trajectory propagation accuracy and maneuver execution for the successful MGS and Odyssey over-flights of both the MER rovers.

  3. MERS-CoV Antibodies in Humans, Africa, 2013–2014

    PubMed Central

    Liljander, Anne; Meyer, Benjamin; Jores, Joerg; Müller, Marcel A.; Lattwein, Erik; Njeru, Ian; Bett, Bernard; Corman, Victor Max

    2016-01-01

    Dromedaries in Africa and elsewhere carry the Middle East respiratory syndrome coronavirus (MERS-CoV). To search for evidence of autochthonous MERS-CoV infection in humans, we tested archived serum from livestock handlers in Kenya for MERS-CoV antibodies. Serologic evidence of infection was confirmed for 2 persons sampled in 2013 and 2014. PMID:27071076

  4. Antenna Designs for the Mars Exploration Rovers (MER) Spacecraft, Lander, and Rover

    NASA Technical Reports Server (NTRS)

    Vacchione, Joseph; Thelen, Michael; Brown, Paula; Huang, John; Kelly, Ken; Krishnan, Satish

    2001-01-01

    This presentation focuses on the design of antennas for the Mars Exploration Rovers (MER). Specific topics covered include: MER spacecraft architecture, the evolution of an antenna system, MER cruise stage antennas, antenna stacks, the heat-shield/back shell antenna, and lander and rover antennas. Additionally, the mission's science objectives are reviewed.

  5. Demonstration of Mer-Cure Technology for Enhanced Mercury Control

    SciTech Connect

    John Marion; Dave O'Neill; Kevin Taugher; Shin Kang; Mark Johnson; Gerald Pargac; Jane Luedecke; Randy Gardiner; Mike Silvertooth; Jim Hicks; Carl Edberg; Ray Cournoyer; Stanley Bohdanowicz; Ken Peterson; Kurt Johnson; Steve Benson; Richard Schulz; Don McCollor; Mike Wuitshick

    2008-06-01

    Alstom Power Inc. has completed a DOE/NETL-sponsored program (under DOE Cooperative Agreement No. De-FC26-07NT42776) to demonstrate Mer-Cure{trademark}, one of Alstom's mercury control technologies for coal-fired boilers. The Mer-Cure{trademark}system utilizes a small amount of Mer-Clean{trademark} sorbent that is injected into the flue gas stream for oxidation and adsorption of gaseous mercury. Mer-Clean{trademark} sorbents are carbon-based and prepared with chemical additives that promote oxidation and capture of mercury. The Mer-Cure{trademark} system is unique in that the sorbent is injected into an environment where the mercury capture kinetics is accelerated. The full-scale demonstration program originally included test campaigns at two host sites: LCRA's 480-MW{sub e} Fayette Unit No.3 and Reliant Energy's 190-MW{sub e} Shawville Unit No.3. The only demonstration tests actually done were the short-term tests at LCRA due to budget constraints. This report gives a summary of the demonstration testing at Fayette Unit No.3. The goals for this Mercury Round 3 program, established by DOE/NETL under the original solicitation, were to reduce the uncontrolled mercury emissions by 90% at a cost significantly less than 50% of the previous target of $60,000/lb mercury removed. The results indicated that Mer-Cure{trademark} technology could achieve mercury removal of 90% based on uncontrolled stack emissions. The estimated costs for 90% mercury control, at a sorbent cost of $0.75 to $2.00/lb respectively, were $13,400 to $18,700/lb Hg removed. In summary, the results from demonstration testing show that the goals established by DOE/NETL were met during this test program. The goal of 90% mercury reduction was achieved. Estimated mercury removal costs were 69-78% lower than the benchmark of $60,000/lb mercury removed, significantly less than 50% of the baseline removal cost.

  6. Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice

    SciTech Connect

    Lee, Ye-Ji; Lee, Seung-Hae; Youn, Young-So; Choi, Ji-Yeon; Song, Keung-Sub; Cho, Min-Sun; Kang, Jihee Lee

    2012-08-15

    Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ►Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ►Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ►TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

  7. Characterization of anti-MERS-CoV antibodies against various recombinant structural antigens of MERS-CoV in an imported case in China.

    PubMed

    Wang, Wenling; Wang, Huijuan; Deng, Yao; Song, Tie; Lan, Jiaming; Wu, Guizhen; Ke, Changwen; Tan, Wenjie

    2016-11-09

    The first imported case of Middle East respiratory syndrome (MERS) in China recently occurred, allowing for the characterization of antibody titers in a series of the patient's sera using the following methods based on recombinant viral structural antigens: inactivated MERS coronavirus (MERS-CoV) enzyme-linked immunosorbent assay (ELISA), recombinant MERS-CoV spike (S, or fragments of S) ELISA, nucleoprotein (NP) ELISA and MERS S pseudovirus particle-based neutralization test (ppNT). A longitudinal profile of the infection showed that seroconversion detected by ELISAs based on the recombinant extracellular domain, S, S1 and receptor-binding domain (RBD) antigens occurred as early as neutralizing antibodies were detected by the ppNT and earlier than antibodies were detected by the inactivated MERS-CoV and N-terminal domain (NTD) ELISAs. Antibodies detected by the NP ELISA occurred last. Strong correlations were found between the S1, RBD and NP ELISAs and the inactivated MERS-CoV ELISA. The S and RBD ELISAs were highly correlated with the commercial S1 ELISA. The S ELISA strongly correlated with the ppNT, although the MERS-CoV, S1, NTD and RBD ELISAs were also significantly correlated with the ppNT (P<0.001).

  8. Characterization of anti-MERS-CoV antibodies against various recombinant structural antigens of MERS-CoV in an imported case in China

    PubMed Central

    Wang, Wenling; Wang, Huijuan; Deng, Yao; Song, Tie; Lan, Jiaming; Wu, Guizhen; Ke, Changwen; Tan, Wenjie

    2016-01-01

    The first imported case of Middle East respiratory syndrome (MERS) in China recently occurred, allowing for the characterization of antibody titers in a series of the patient's sera using the following methods based on recombinant viral structural antigens: inactivated MERS coronavirus (MERS-CoV) enzyme-linked immunosorbent assay (ELISA), recombinant MERS-CoV spike (S, or fragments of S) ELISA, nucleoprotein (NP) ELISA and MERS S pseudovirus particle-based neutralization test (ppNT). A longitudinal profile of the infection showed that seroconversion detected by ELISAs based on the recombinant extracellular domain, S, S1 and receptor-binding domain (RBD) antigens occurred as early as neutralizing antibodies were detected by the ppNT and earlier than antibodies were detected by the inactivated MERS-CoV and N-terminal domain (NTD) ELISAs. Antibodies detected by the NP ELISA occurred last. Strong correlations were found between the S1, RBD and NP ELISAs and the inactivated MERS-CoV ELISA. The S and RBD ELISAs were highly correlated with the commercial S1 ELISA. The S ELISA strongly correlated with the ppNT, although the MERS-CoV, S1, NTD and RBD ELISAs were also significantly correlated with the ppNT (P<0.001). PMID:27826140

  9. Evaluation of MerCAP for Power Plant Mercury Control

    SciTech Connect

    Carl Richardson

    2008-09-30

    This report is submitted to the U.S. Department of Energy National Energy Technology Laboratory (DOE-NETL) as part of Cooperative Agreement DE-FC26-03NT41993, 'Evaluation of EPRI's MerCAP{trademark} Technology for Power Plant Mercury Control'. This project has investigated the mercury removal performance of EPRI's Mercury Capture by Amalgamation Process (MerCAP{trademark}) technology. Test programs were conducted to evaluate gold-based MerCAP{trademark} at Great River Energy's Stanton Station Unit 10 (Site 1), which fired both North Dakota lignite (NDL) and Power River Basin (PRB) coal during the testing period, and at Georgia Power's Plant Yates Unit 1 (Site 2) [Georgia Power is a subsidiary of The Southern Company] which fires a low sulfur Eastern bituminous coal. Additional tests were carried out at Alabama Power's Plant Miller, which fires Powder River Basin Coal, to evaluate a carbon-based MerCAP{trademark} process for removing mercury from flue gas downstream of an electrostatic precipitator [Alabama Power is a subsidiary of The Southern Company]. A full-scale gold-based sorbent array was installed in the clean-air plenum of a single baghouse compartment at GRE's Stanton Station Unit 10, thereby treating 1/10th of the unit's exhaust gas flow. The substrates that were installed were electroplated gold screens oriented parallel to the flue gas flow. The sorbent array was initially installed in late August of 2004, operating continuously until its removal in July 2006, after nearly 23 months. The initial 4 months of operation were conducted while the host unit was burning North Dakota lignite (NDL). In November 2004, the host unit switched fuel to burn Powder River Basin (PRB) subbituminous coal and continued to burn the PRB fuel for the final 19 months of this program. Tests were conducted at Site 1 to evaluate the impacts of flue gas flow rate, sorbent plate spacing, sorbent pre-cleaning and regeneration, and spray dryer operation on Mer

  10. Segmented K-mer and its application on similarity analysis of mitochondrial genome sequences.

    PubMed

    Yu, Hong-Jie

    2013-04-15

    K-mer-based approach has been widely used in similarity analyses so as to discover similarity/dissimilarity among different biological sequences. In this study, we have improved the traditional K-mer method, and introduce a segmented K-mer approach (s-K-mer). After each primary sequence is divided into several segments, we simultaneously transform all these segments into corresponding K-mer-based vectors. In this approach, it is vital how to determine the optimal combination of distance metric with the number of K and the number of segments, i.e., (K(⁎), s(⁎), and d(⁎)). Based on the cascaded feature vectors transformed from s(⁎) segmented sequences, we analyze 34 mammalian genome sequences using the proposed s-K-mer approach. Meanwhile, we compare the results of s-K-mer with those of traditional K-mer. The contrastive analysis results demonstrate that s-K-mer approach outperforms the traditionally K-mer method on similarity analysis among different species.

  11. Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis).

    PubMed

    Munster, Vincent J; Adney, Danielle R; van Doremalen, Neeltje; Brown, Vienna R; Miazgowicz, Kerri L; Milne-Price, Shauna; Bushmaker, Trenton; Rosenke, Rebecca; Scott, Dana; Hawkinson, Ann; de Wit, Emmie; Schountz, Tony; Bowen, Richard A

    2016-02-22

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.

  12. Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis)

    PubMed Central

    Munster, Vincent J.; Adney, Danielle R.; van Doremalen, Neeltje; Brown, Vienna R.; Miazgowicz, Kerri L.; Milne-Price, Shauna; Bushmaker, Trenton; Rosenke, Rebecca; Scott, Dana; Hawkinson, Ann; de Wit, Emmie; Schountz, Tony; Bowen, Richard A.

    2016-01-01

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV. PMID:26899616

  13. K-mer natural vector and its application to the phylogenetic analysis of genetic sequences

    PubMed Central

    Wen, Jia; Chan, Raymond H.; Yau, Shek-Chung; He, Rong L.; Yau, Stephen S. T.

    2014-01-01

    Based on the well-known k-mer model, we propose a k-mer natural vector model for representing a genetic sequence based on the numbers and distributions of k-mers in the sequence. We show that there exists a one-to-one correspondence between a genetic sequence and its associated k-mer natural vector. The k-mer natural vector method can be easily and quickly used to perform phylogenetic analysis of genetic sequences without requiring evolutionary models or human intervention. Whole or partial genomes can be handled more effective with our proposed method. It is applied to the phylogenetic analysis of genetic sequences, and the obtaining results fully demonstrate that the k-mer natural vector method is a very powerful tool for analysing and annotating genetic sequences and determining evolutionary relationships both in terms of accuracy and efficiency. PMID:24858075

  14. Characterization of Martian Rock Shape for MER Airbag Drop Tests

    NASA Astrophysics Data System (ADS)

    Dimaggio, E. N.; Schroeder, R.; Castle, N.; Golombek, M.

    2002-12-01

    Rock distributions for the final platforms used in airbag drop tests are currently being designed for the Mars Exploration Rovers (MER) scheduled to launch in 2003. Like Mars Pathfinder (MPF), launched in 1996, MER will use a series of airbags to cushion its landing on the surface of Mars. Previous MER airbag drop tests have shown that sharp, angular (triangular) rocks >20 cm high may be hazardous. To aid in defining the rock distributions for the final airbag tests, images from the Viking Landers 1 and 2 and MPF were used to identify rocks that are >20 cm high, and characterize them as triangular, square or round. Approximately 33% of all rocks analyzed are triangular. Of the rocks analyzed that are ~20-60 cm high, ~14% are triangular. Most of these triangular rocks are small, ~20-30 cm high. Rock distributions of previous airbag platforms were similarly classified and show a greater percentage of triangular and square rocks that are ~20-60 cm high than at the landing sites. The burial of a rock (perched, partially buried or buried) was also considered because perched rocks may pose less of a threat to the airbags than those buried because perched rocks can be dislodged and roll during impact. Approximately 19% of all rocks analyzed, and ~19% of rocks that are ~20-60 cm high, are triangular and partially buried or buried. These data suggest that the platform rock distributions appropriately represented the risks to the airbags associated with triangular rocks. A similar percentage of >20 cm high triangular rocks will be added to the drop test platforms to represent landing site rock distributions.

  15. Indexing Arbitrary-Length k-Mers in Sequencing Reads.

    PubMed

    Kowalski, Tomasz; Grabowski, Szymon; Deorowicz, Sebastian

    2015-01-01

    We propose a lightweight data structure for indexing and querying collections of NGS reads data in main memory. The data structure supports the interface proposed in the pioneering work by Philippe et al. for counting and locating k-mers in sequencing reads. Our solution, PgSA (pseudogenome suffix array), based on finding overlapping reads, is competitive to the existing algorithms in the space use, query times, or both. The main applications of our index include variant calling, error correction and analysis of reads from RNA-seq experiments.

  16. Indexing Arbitrary-Length k-Mers in Sequencing Reads

    PubMed Central

    Kowalski, Tomasz; Grabowski, Szymon; Deorowicz, Sebastian

    2015-01-01

    We propose a lightweight data structure for indexing and querying collections of NGS reads data in main memory. The data structure supports the interface proposed in the pioneering work by Philippe et al. for counting and locating k-mers in sequencing reads. Our solution, PgSA (pseudogenome suffix array), based on finding overlapping reads, is competitive to the existing algorithms in the space use, query times, or both. The main applications of our index include variant calling, error correction and analysis of reads from RNA-seq experiments. PMID:26182400

  17. A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.

    PubMed

    Cockrell, Adam S; Yount, Boyd L; Scobey, Trevor; Jensen, Kara; Douglas, Madeline; Beall, Anne; Tang, Xian-Chun; Marasco, Wayne A; Heise, Mark T; Baric, Ralph S

    2016-11-28

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR-Cas9 gene editing to modify the mouse genome to encode two amino acids (positions 288 and 330) that match the human sequence in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs and evoked symptoms indicative of severe ARDS, including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary haemorrhage and pathological signs indicative of end-stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the engineered mice against MERS-CoV-induced ARDS.

  18. Debate on MERS-CoV respiratory precautions: surgical mask or N95 respirators?

    PubMed Central

    Chung, Jasmine Shimin; Ling, Moi Lin; Seto, Wing Hong; Ang, Brenda Sze Peng; Tambyah, Paul Anantharajah

    2014-01-01

    Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in mid-2012, there has been controversy over the respiratory precaution recommendations in different guidelines from various international bodies. Our understanding of MERS-CoV is still evolving. Current recommendations on infection control practices are heavily influenced by the lessons learnt from severe acute respiratory syndrome. A debate on respiratory precautions for MERS-CoV was organised by Infection Control Association (Singapore) and the Society of Infectious Disease (Singapore). We herein discuss and present the evidence for surgical masks for the protection of healthcare workers from MERS-CoV. PMID:25017402

  19. Improving Bloom Filter Performance on Sequence Data Using k-mer Bloom Filters.

    PubMed

    Pellow, David; Filippova, Darya; Kingsford, Carl

    2016-11-09

    Using a sequence's k-mer content rather than the full sequence directly has enabled significant performance improvements in several sequencing applications, such as metagenomic species identification, estimation of transcript abundances, and alignment-free comparison of sequencing data. As k-mer sets often reach hundreds of millions of elements, traditional data structures are often impractical for k-mer set storage, and Bloom filters (BFs) and their variants are used instead. BFs reduce the memory footprint required to store millions of k-mers while allowing for fast set containment queries, at the cost of a low false positive rate (FPR). We show that, because k-mers are derived from sequencing reads, the information about k-mer overlap in the original sequence can be used to reduce the FPR up to 30 × with little or no additional memory and with set containment queries that are only 1.3 - 1.6 times slower. Alternatively, we can leverage k-mer overlap information to store k-mer sets in about half the space while maintaining the original FPR. We consider several variants of such k-mer Bloom filters (kBFs), derive theoretical upper bounds for their FPR, and discuss their range of applications and limitations.

  20. Mercuric reductase genes (merA) and mercury resistance plasmids in High Arctic snow, freshwater and sea-ice brine.

    PubMed

    Møller, Annette K; Barkay, Tamar; Hansen, Martin A; Norman, Anders; Hansen, Lars H; Sørensen, Søren J; Boyd, Eric S; Kroer, Niels

    2014-01-01

    Bacterial reduction in Hg(2+) to Hg(0) , mediated by the mercuric reductase (MerA), is important in the biogeochemical cycling of Hg in temperate environments. Little is known about the occurrence and diversity of merA in the Arctic. Seven merA determinants were identified among bacterial isolates from High Arctic snow, freshwater and sea-ice brine. Three determinants in Bacteriodetes, Firmicutes and Actinobacteria showed < 92% (amino acid) sequence similarity to known merA, while one merA homologue in Alphaproteobacteria and 3 homologues from Betaproteobacteria and Gammaproteobacteria were > 99% similar to known merA's. Phylogenetic analysis showed the Bacteroidetes merA to be part of an early lineage in the mer phylogeny, whereas the Betaproteobacteria and Gammaproteobacteria merA appeared to have evolved recently. Several isolates, in which merA was not detected, were able to reduce Hg(2+) , suggesting presence of unidentified merA genes. About 25% of the isolates contained plasmids, two of which encoded mer operons. One plasmid was a broad host-range IncP-α plasmid. No known incompatibility group could be assigned to the others. The presence of conjugative plasmids, and an incongruent distribution of merA within the taxonomic groups, suggests horizontal transfer of merA as a likely mechanism for High Arctic microbial communities to adapt to changing mercury concentration.

  1. mer and fac isomerism in tris chelate diimine metal complexes.

    PubMed

    Dabb, Serin L; Fletcher, Nicholas C

    2015-03-14

    In this perspective, we highlight the issue of meridional (mer) and facial (fac) orientation of asymmetrical diimines in tris-chelate transition metal complexes. Diimine ligands have long been the workhorse of coordination chemistry, and whilst there are now good strategies to isolate materials where the inherent metal centered chirality is under almost complete control, and systematic methodologies to isolate heteroleptic complexes, the conceptually simple geometrical isomerism has not been widely investigated. In systems where the two donor atoms are significantly different in terms of the σ-donor and π-accepting ability, the fac isomer is likely to be the thermodynamic product. For the diimine complexes with two trigonal planar nitrogen atoms there is much more subtlety to the system, and external factors such as the solvent, lattice packing and the various steric considerations play a delicate role in determining the observed and isolable product. In this article we discuss the possibilities to control the isomeric ratio in labile systems, consider the opportunities to separate inert complexes and discuss the observed differences in their spectroscopic properties. Finally we report on the ligand orientation in supramolecular systems where facial coordination leads to simple regular structures such as helicates and tetrahedra, but the ability of the ligand system to adopt a mer orientation enables self-assembled structures of considerable beauty and complexity.

  2. Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction

    PubMed Central

    Omrani, Ali S.; Al-Tawfiq, Jaffar A.

    2015-01-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel enzootic betacoronavirus that was first described in September 2012. The clinical spectrum of MERS-CoV infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. Bats harbour several betacoronaviruses that are closely related to MERS-CoV but more research is needed to establish the relationship between bats and MERS-CoV. The seroprevalence of MERS-CoV antibodies is very high in dromedary camels in Eastern Africa and the Arabian Peninsula. MERS-CoV RNA and viable virus have been isolated from dromedary camels, including some with respiratory symptoms. Furthermore, near-identical strains of MERS-CoV have been isolated from epidemiologically linked humans and camels, confirming inter-transmission, most probably from camels to humans. Though inter-human spread within health care settings is responsible for the majority of reported MERS-CoV cases, the virus is incapable at present of causing sustained human-to-human transmission. Clusters can be readily controlled with implementation of appropriate infection control procedures. Phylogenetic and sequencing data strongly suggest that MERS-CoV originated from bat ancestors after undergoing a recombination event in the spike protein, possibly in dromedary camels in Africa, before its exportation to the Arabian Peninsula along the camel trading routes. MERS-CoV serosurveys are needed to investigate possible unrecognized human infections in Africa. Amongst the important measures to control MERS-CoV spread are strict regulation of camel movement, regular herd screening and isolation of infected camels, use of personal protective equipment by camel handlers and enforcing rules banning all consumption of unpasteurized camel milk and urine. PMID:26924345

  3. Structural basis of the mercury(II)-mediated conformational switching of the dual-function transcriptional regulator MerR

    PubMed Central

    Chang, Chih-Chiang; Lin, Li-Ying; Zou, Xiao-Wei; Huang, Chieh-Chen; Chan, Nei-Li

    2015-01-01

    The mer operon confers bacterial resistance to inorganic mercury (Hg2+) and organomercurials by encoding proteins involved in sensing, transport and detoxification of these cytotoxic agents. Expression of the mer operon is under tight control by the dual-function transcriptional regulator MerR. The metal-free, apo MerR binds to the mer operator/promoter region as a repressor to block transcription initiation, but is converted into an activator upon Hg2+-binding. To understand how MerR interacts with Hg2+ and how Hg2+-binding modulates MerR function, we report here the crystal structures of apo and Hg2+-bound MerR from Bacillus megaterium, corresponding respectively to the repressor and activator conformation of MerR. To our knowledge, the apo-MerR structure represents the first visualization of a MerR family member in its intact and inducer-free form. And the Hg2+-MerR structure offers the first view of a triligated Hg2+-thiolate center in a metalloprotein, confirming that MerR binds Hg2+ via trigonal planar coordination geometry. Structural comparison revealed the conformational transition of MerR is coupled to the assembly/disassembly of a buried Hg2+ binding site, thereby providing a structural basis for the Hg2+-mediated functional switching of MerR. The pronounced Hg2+-induced repositioning of the MerR DNA-binding domains suggests a plausible mechanism for the transcriptional regulation of the mer operon. PMID:26150423

  4. Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission

    PubMed Central

    Zhang, Zhao; Shen, Libing; Gu, Xun

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV’s evolutionary history and the positive selection sites in MERS-CoV’s S protein might enable it to infect human. PMID:27142087

  5. Serologic Evidence for MERS-CoV Infection in Dromedary Camels, Punjab, Pakistan, 2012–2015

    PubMed Central

    Saqib, Muhammad; Sieberg, Andrea; Hussain, Muhammad Hammad; Mansoor, Muhammad Khalid; Zohaib, Ali; Lattwein, Erik; Müller, Marcel Alexander; Corman, Victor Max

    2017-01-01

    Dromedary camels from Africa and Arabia are an established source for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infection among humans. In Pakistan, we found specific neutralizing antibodies in samples from 39.5% of 565 dromedaries, documenting significant expansion of the enzootic range of MERS-CoV to Asia. PMID:28221127

  6. Knowledge and Apprehension of Dental Patients about MERS-A Questionnaire Survey

    PubMed Central

    Ashok, Nipun; Rodrigues, Jean Clare; Azouni, Khalid; Darwish, Shorouk; Abuderman, Abdulwahab; Alkaabba, Abdul Aziz Fahad

    2016-01-01

    Introduction Middle East Respiratory Syndrome (MERS) is a disease caused by beta corona virus. From April 11th to 9th June 2014, World Health Organization (WHO) reported a total of 402 laboratory confirmed cases of MERS from KSA, out of which 132 cases were reported from Riyadh alone. Aim The aim of this study was to assess the knowledge and apprehension of patients about MERS visiting Al Farabi College of Dentistry, Riyadh, Saudi Arabia. Materials and Methods A cross-sectional questionnaire based survey was conducted which consisted of 10 self-prepared questions. A total of 404 patients participated in this study. Results Three hundred and forty patients had heard about MERS. Nearly a quarter of the patients (25.74%) were apprehensive about undergoing dental treatment because of MERS. A little more than half of the patients (50.99%) knew that camel was a source of Middle East Respiratory Syndrome-Corona virus. Most of the patients (80.72%) were aware of the infection control measures to be followed by dentist and 138 patients claimed they took some precaution when present inside the dental college. Conclusion Majority of the patients had heard about MERS and was aware of the infection control measures. However, some patients were apprehensive about undergoing dental treatment because of MERS. Further steps need to be taken to educate the patient’s about transmission of MERS and infection control measures in a dental hospital. PMID:27437361

  7. Exportations of Symptomatic Cases of MERS-CoV Infection to Countries outside the Middle East

    PubMed Central

    O’Hagan, Justin J.; Jewett, Amy; Gambhir, Manoj; Cohen, Nicole J.; Haber, Yoni; Pesik, Nicki; Swerdlow, David L.

    2016-01-01

    In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region. PMID:27358972

  8. Time Course of MERS-CoV Infection and Immunity in Dromedary Camels

    PubMed Central

    Meyer, Benjamin; Juhasz, Judit; Barua, Rajib; Das Gupta, Aungshuman; Hakimuddin, Fatima; Corman, Victor M.; Müller, Marcel A.; Wernery, Ulrich; Nagy, Peter

    2016-01-01

    Knowledge about immunity to Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels is essential for infection control and vaccination. A longitudinal study of 11 dam–calf pairs showed that calves lose maternal MERS-CoV antibodies 5–6 months postparturition and are left susceptible to infection, indicating a short window of opportunity for vaccination. PMID:27224315

  9. Nordic Winter and Cold: Their Correspondence with Tomas Tranströmer's Poetry

    ERIC Educational Resources Information Center

    Hosian, Mohammad Akbar

    2015-01-01

    The Nobel Prize winning poet Tomas Tranströmer was born and bred in Sweden, a remarkably Scandinavian country. Topographically, Scandinavian countries are locations of extreme cold and snowing. This distinguishing climatic condition has had a dominant influence and impact on almost all Scandinavian art and literature, including Tomas Tranströmer's…

  10. Exportations of Symptomatic Cases of MERS-CoV Infection to Countries outside the Middle East.

    PubMed

    Carias, Cristina; O'Hagan, Justin J; Jewett, Amy; Gambhir, Manoj; Cohen, Nicole J; Haber, Yoni; Pesik, Nicki; Swerdlow, David L

    2016-04-01

    In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region.

  11. Discovery of Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia

    PubMed Central

    2012-01-01

    Ectopic Mer expression promotes pro-survival signaling and contributes to leukemogenesis and chemoresistance in childhood acute lymphoblastic leukemia (ALL). Consequently, Mer kinase inhibitors may promote leukemic cell death and further act as chemosensitizers increasing efficacy and reducing toxicities of current ALL regimens. We have applied a structure-based design approach to discover novel small molecule Mer kinase inhibitors. Several pyrazolopyrimidine derivatives effectively inhibit Mer kinase activity at subnanomolar concentrations. Furthermore, the lead compound shows a promising selectivity profile against a panel of 72 kinases and has excellent pharmacokinetic properties. We also describe the crystal structure of the complex between the lead compound and Mer, opening new opportunities for further optimization and new template design. PMID:22662287

  12. Discovery of Novel Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia.

    PubMed

    Liu, Jing; Yang, Chao; Simpson, Catherine; Deryckere, Deborah; Van Deusen, Amy; Miley, Michael J; Kireev, Dmitri; Norris-Drouin, Jacqueline; Sather, Susan; Hunter, Debra; Korboukh, Victoria K; Patel, Hari S; Janzen, William P; Machius, Mischa; Johnson, Gary L; Earp, H Shelton; Graham, Douglas K; Frye, Stephen V; Wang, Xiaodong

    2012-02-09

    Ectopic Mer expression promotes pro-survival signaling and contributes to leukemogenesis and chemoresistance in childhood acute lymphoblastic leukemia (ALL). Consequently, Mer kinase inhibitors may promote leukemic cell death and further act as chemosensitizers increasing efficacy and reducing toxicities of current ALL regimens. We have applied a structure-based design approach to discover novel small molecule Mer kinase inhibitors. Several pyrazolopyrimidine derivatives effectively inhibit Mer kinase activity at sub-nanomolar concentrations. Furthermore, the lead compound shows a promising selectivity profile against a panel of 72 kinases and has excellent pharmacokinetic properties. We also describe the crystal structure of the complex between the lead compound and Mer, opening new opportunities for further optimization and new template design.

  13. MERS-CoV spike protein: Targets for vaccines and therapeutics.

    PubMed

    Wang, Qihui; Wong, Gary; Lu, Guangwen; Yan, Jinghua; Gao, George F

    2016-09-01

    The disease outbreak caused by Middle East respiratory syndrome coronavirus (MERS-CoV) is still ongoing in the Middle East. Over 1700 people have been infected since it was first reported in September 2012. Despite great efforts, licensed vaccines or therapeutics against MERS-CoV remain unavailable. The MERS-CoV spike (S) protein is an important viral antigen known to mediate host-receptor binding and virus entry, as well as induce robust humoral and cell-mediated responses in humans during infection. In this review, we highlight the importance of the S protein in the MERS-CoV life cycle, summarize recent advances in the development of vaccines and therapeutics based on the S protein, and discuss strategies that can be explored to develop new medical countermeasures against MERS-CoV.

  14. MerTK inhibition in tumor leukocytes decreases tumor growth and metastasis

    PubMed Central

    Cook, Rebecca S.; Jacobsen, Kristen M.; Wofford, Anne M.; DeRyckere, Deborah; Stanford, Jamie; Prieto, Anne L.; Redente, Elizabeth; Sandahl, Melissa; Hunter, Debra M.; Strunk, Karen E.; Graham, Douglas K.; Earp, H. Shelton

    2013-01-01

    MerTK, a receptor tyrosine kinase (RTK) of the TYRO3/AXL/MerTK family, is expressed in myeloid lineage cells in which it acts to suppress proinflammatory cytokines following ingestion of apoptotic material. Using syngeneic mouse models of breast cancer, melanoma, and colon cancer, we found that tumors grew slowly and were poorly metastatic in MerTK–/– mice. Transplantation of MerTK–/– bone marrow, but not wild-type bone marrow, into lethally irradiated MMTV-PyVmT mice (a model of metastatic breast cancer) decreased tumor growth and altered cytokine production by tumor CD11b+ cells. Although MerTK expression was not required for tumor infiltration by leukocytes, MerTK–/– leukocytes exhibited lower tumor cell–induced expression of wound healing cytokines, e.g., IL-10 and growth arrest-specific 6 (GAS6), and enhanced expression of acute inflammatory cytokines, e.g., IL-12 and IL-6. Intratumoral CD8+ T lymphocyte numbers were higher and lymphocyte proliferation was increased in tumor-bearing MerTK–/– mice compared with tumor-bearing wild-type mice. Antibody-mediated CD8+ T lymphocyte depletion restored tumor growth in MerTK–/– mice. These data demonstrate that MerTK signaling in tumor-associated CD11b+ leukocytes promotes tumor growth by dampening acute inflammatory cytokines while inducing wound healing cytokines. These results suggest that inhibition of MerTK in the tumor microenvironment may have clinical benefit, stimulating antitumor immune responses or enhancing immunotherapeutic strategies. PMID:23867499

  15. MerTK inhibition in tumor leukocytes decreases tumor growth and metastasis.

    PubMed

    Cook, Rebecca S; Jacobsen, Kristen M; Wofford, Anne M; DeRyckere, Deborah; Stanford, Jamie; Prieto, Anne L; Redente, Elizabeth; Sandahl, Melissa; Hunter, Debra M; Strunk, Karen E; Graham, Douglas K; Earp, H Shelton

    2013-08-01

    MerTK, a receptor tyrosine kinase (RTK) of the TYRO3/AXL/MerTK family, is expressed in myeloid lineage cells in which it acts to suppress proinflammatory cytokines following ingestion of apoptotic material. Using syngeneic mouse models of breast cancer, melanoma, and colon cancer, we found that tumors grew slowly and were poorly metastatic in MerTK-/- mice. Transplantation of MerTK-/- bone marrow, but not wild-type bone marrow, into lethally irradiated MMTV-PyVmT mice (a model of metastatic breast cancer) decreased tumor growth and altered cytokine production by tumor CD11b+ cells. Although MerTK expression was not required for tumor infiltration by leukocytes, MerTK-/- leukocytes exhibited lower tumor cell-induced expression of wound healing cytokines, e.g., IL-10 and growth arrest-specific 6 (GAS6), and enhanced expression of acute inflammatory cytokines, e.g., IL-12 and IL-6. Intratumoral CD8+ T lymphocyte numbers were higher and lymphocyte proliferation was increased in tumor-bearing MerTK-/- mice compared with tumor-bearing wild-type mice. Antibody-mediated CD8+ T lymphocyte depletion restored tumor growth in MerTK-/- mice. These data demonstrate that MerTK signaling in tumor-associated CD11b+ leukocytes promotes tumor growth by dampening acute inflammatory cytokines while inducing wound healing cytokines. These results suggest that inhibition of MerTK in the tumor microenvironment may have clinical benefit, stimulating antitumor immune responses or enhancing immunotherapeutic strategies.

  16. Dust Accumulation and Cleaning of the MER Opportunity Solar Array

    NASA Astrophysics Data System (ADS)

    Herman, J.

    2015-12-01

    The solar array of the NASA Mars Exploration Rover (MER) Opportunity was expected to accumulate a sufficient quantity of dust after ninety Martian days (sols) such that it could no longer provide enough energy to guarantee continued surface operations. Instead, due in part to low dust accumulation rates and numerous dust cleaning events, Opportunity continues to operate on the Martian surface for over 4000 sols (over six Mars years). During this time period, the rover experienced six Martian winters and several dust storms. Because the sources of solar energy loss are known, the solar array energy output offers a method to scientifically estimate the loading and aeolian removal of dust from the solar array each sol. We will discuss the accumulation of dust on the solar panels as a proxy for dust movement at Meridiani Planum over the course of the entire mission to date.

  17. Dust Accumulation and Cleaning of the MER Spirit Solar Array

    NASA Astrophysics Data System (ADS)

    Herman, J. A.; Lemmon, M. T.; Johnson, J. R.; Cantor, B. A.; Stella, P. M.; Chin, K. B.; Wood, E. G.

    2012-12-01

    The solar array of the NASA Mars Exploration Rover (MER) Spirit was expected to accumulate so much dust after ninety Martian days (sols) that it could no longer provide enough energy to guarantee continued surface operations. Instead, due in part to low dust accumulation rates and numerous dust cleaning events, Spirit carried out surface operations for over 2200 sols (over three Mars years). During this time period, the rover experienced four Martian winters and several dust storms. Because the sources of solar energy loss are known, the solar array energy output offers a tool to quantitatively estimate the loading and aeolian removal of dust from the solar array each sol. We will discuss the accumulation of dust on the solar panels as a proxy for dust movement at Gusev Crater over the course of the entire mission.

  18. Molecular identification of Lodoicea maldivica (coco de mer) seeds

    PubMed Central

    2011-01-01

    Background The edible endosperm of Lodoicea maldivica with the common name of coco de mer is used in Chinese medicine for treating cough. Native to Seychelles, Lodoicea maldivica seeds have commanded high prices for centuries due to its scarcity. This study aims to develop a molecular identification method for the authentication of Lodoicea maldivica seeds. Methods DNA was extracted from the sample. Two polymerase chain reaction (PCR) systems were developed to amplify a region of the chloroplast DNA and the nuclear phosphoribulokinase (PRK) region specific to Lodoicea maldivica respectively. DNA sequence of a sample was determined and compared with that of the Lodoicea maldivica reference material. Results The PRK gene of Lodoicea maldivica was successfully amplified and sequenced for identification. Conclusion A new molecular method for the identification of Lodoicea maldivica seeds in fresh, frozen or dried forms was developed. PMID:21961930

  19. MER-DIMES : a planetary landing application of computer vision

    NASA Technical Reports Server (NTRS)

    Cheng, Yang; Johnson, Andrew; Matthies, Larry

    2005-01-01

    During the Mars Exploration Rovers (MER) landings, the Descent Image Motion Estimation System (DIMES) was used for horizontal velocity estimation. The DIMES algorithm combines measurements from a descent camera, a radar altimeter and an inertial measurement unit. To deal with large changes in scale and orientation between descent images, the algorithm uses altitude and attitude measurements to rectify image data to level ground plane. Feature selection and tracking is employed in the rectified data to compute the horizontal motion between images. Differences of motion estimates are then compared to inertial measurements to verify correct feature tracking. DIMES combines sensor data from multiple sources in a novel way to create a low-cost, robust and computationally efficient velocity estimation solution, and DIMES is the first use of computer vision to control a spacecraft during planetary landing. In this paper, the detailed implementation of the DIMES algorithm and the results from the two landings on Mars are presented.

  20. Recapitulating phylogenies using k-mers: from trees to networks

    PubMed Central

    Bernard, Guillaume; Ragan, Mark A.; Chan, Cheong Xin

    2016-01-01

    Ernst Haeckel based his landmark Tree of Life on the supposed ontogenic recapitulation of phylogeny, i.e. that successive embryonic stages during the development of an organism re-trace the morphological forms of its ancestors over the course of evolution. Much of this idea has since been discredited. Today, phylogenies are often based on families of molecular sequences. The standard approach starts with a multiple sequence alignment, in which the sequences are arranged relative to each other in a way that maximises a measure of similarity position-by-position along their entire length. A tree (or sometimes a network) is then inferred. Rigorous multiple sequence alignment is computationally demanding, and evolutionary processes that shape the genomes of many microbes (bacteria, archaea and some morphologically simple eukaryotes) can add further complications. In particular, recombination, genome rearrangement and lateral genetic transfer undermine the assumptions that underlie multiple sequence alignment, and imply that a tree-like structure may be too simplistic. Here, using genome sequences of 143 bacterial and archaeal genomes, we construct a network of phylogenetic relatedness based on the number of shared k-mers (subsequences at fixed length k). Our findings suggest that the network captures not only key aspects of microbial genome evolution as inferred from a tree, but also features that are not treelike. The method is highly scalable, allowing for investigation of genome evolution across a large number of genomes. Instead of using specific regions or sequences from genome sequences, or indeed Haeckel’s idea of ontogeny, we argue that genome phylogenies can be inferred using k-mers from whole-genome sequences. Representing these networks dynamically allows biological questions of interest to be formulated and addressed quickly and in a visually intuitive manner. PMID:28105314

  1. Successful recovery of MERS CoV pneumonia in a patient with acquired immunodeficiency syndrome: a case report.

    PubMed

    Shalhoub, Sarah; AlZahrani, Abdulwahab; Simhairi, Raed; Mushtaq, Adnan

    2015-01-01

    Middle East Respiratory Syndrome Coronavirus (MERS CoV) may cause severe pneumonia with significant morbidity and mortality, particularly in patients with multiple comorbid condition. MERS CoV pneumonia has not been previously reported in patients with Human Immunodeficiency Virus (HIV). Herein, we report a case of MERS CoV pneumonia with a successful outcome in a patient recently diagnosed with HIV.

  2. MERS and the dromedary camel trade between Africa and the Middle East.

    PubMed

    Younan, M; Bornstein, S; Gluecks, I V

    2016-08-01

    Dromedary camels are the most likely source for the coronavirus that sporadically causes Middle East respiratory syndrome (MERS) in humans. Serological results from archived camel sera provide evidence for circulation of MERS coronavirus (MERS-CoV) among dromedary camels in the Greater Horn of Africa as far back as 1983 and in Saudi Arabia as far back as 1992. High seroprevalences of MERS-CoV antibodies and the high virus prevalence in Saudi Arabian dromedary camels indicate an endemicity of the virus in the Arabian Peninsula, which predates the 2012 human MERS index case. Saudi Arabian dromedary camels show significantly higher MERS-CoV carrier rates than dromedary camels imported from Africa. Two MERS-CoV lineages identified in Nigerian camels were found to be genetically distinct from those found in camels and humans in the Middle East. This supports the hypothesis that camel imports from Africa are not of significance for circulation of the virus in camel populations of the Arabian Peninsula.

  3. NMR assignments of the macro domain from Middle East respiratory syndrome coronavirus (MERS-CoV).

    PubMed

    Huang, Yi-Ping; Cho, Chao-Cheng; Chang, Chi-Fon; Hsu, Chun-Hua

    2016-10-01

    The newly emerging human pathogen, Middle East respiratory syndrome coronavirus (MERS-CoV), contains a macro domain in the highly conserved N-terminal region of non-structural protein 3. Intense research has shown that macro domains bind ADP-ribose and other derivatives, but it still remains intangible about their exact function. In this study we report the preliminary structural analysis through solution NMR spectroscopy of the MERS-CoV macro domain. The near complete NMR assignments of MERS-CoV macro domain provide the basis for subsequent structural and biochemical investigation in the context of protein function.

  4. Improvement in Engine Generator Characteristics by Using a Series Compensator Named MERS

    NASA Astrophysics Data System (ADS)

    Kashiwagi, Kouhei; Isobe, Takanori; Shimada, Ryuichi

    Terminal voltage of a synchronous generator drops with an increase in the generator current because of the large inductance in the generator, called synchronous reactance. This paper proposes the use of an active series compensation device named magnetic energy recovery switch (MERS) for improving engine generator performance. The MERS can compensate for the voltage drop caused by the synchronous reactance and it can control the load voltage more quickly than the auto voltage regulator can control the excitation current. Thus, the MERS can improve the generator efficiency and transient over power characteristics.

  5. Water on Mars: Evidence from MER Mission Results

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A.

    2004-01-01

    The Viking and the Mars Exploration Rover missions observed that the surface of Mars is encrusted by a thinly cemented layer, or "duricrust". Elemental analyzes at five sites on Mars show that these soils have sulfur content and chlorine content consistent with the presence of sulfates and halides as mineral cements. The soil is highly enriched in the salt-forming elements compared with rock. Analysis of the soil cementation indicates some features which may be evidence of liquid water. At both MER sites, duricrust textures revealed by the Microscopic Imager show features including the presence of fine sand-sized grains, some of which may be aggregates of fine silt and clay, surrounded by a pervasive light colored material that is associated with microtubular structures and networks of microfractures. Stereo views of undisturbed duricrust surfaces reveal rugged microrelief between 2-3 mm and minimal loose material. Comparisons of microscopic images of duricrust soils obtain before and after placement of the Mossbauer spectrometer indicate differing degrees of compaction and cementation. Two models of a transient water hypothesis are offered, a "top down" hypothesis that emphasizes the surface deposition of frost, melting and downward migration of liquid water and a "bottom up" alternative that proposes the presence of interstitial ice/brine, with the upward capillary migration of liquid water. The viability of both of these models ultimately hinges on the availability of seasonally transient liquid water for brief periods.

  6. Autonomous Navigation Results from the Mars Exploration Rover (MER) Mission

    NASA Technical Reports Server (NTRS)

    Maimone, Mark; Johnson, Andrew; Cheng, Yang; Willson, Reg; Matthies, Larry H.

    2004-01-01

    In January, 2004, the Mars Exploration Rover (MER) mission landed two rovers, Spirit and Opportunity, on the surface of Mars. Several autonomous navigation capabilities were employed in space for the first time in this mission. ]n the Entry, Descent, and Landing (EDL) phase, both landers used a vision system called the, Descent Image Motion Estimation System (DIMES) to estimate horizontal velocity during the last 2000 meters (m) of descent, by tracking features on the ground with a downlooking camera, in order to control retro-rocket firing to reduce horizontal velocity before impact. During surface operations, the rovers navigate autonomously using stereo vision for local terrain mapping and a local, reactive planning algorithm called Grid-based Estimation of Surface Traversability Applied to Local Terrain (GESTALT) for obstacle avoidance. ]n areas of high slip, stereo vision-based visual odometry has been used to estimate rover motion, As of mid-June, Spirit had traversed 3405 m, of which 1253 m were done autonomously; Opportunity had traversed 1264 m, of which 224 m were autonomous. These results have contributed substantially to the success of the mission and paved the way for increased levels of autonomy in future missions.

  7. Nutrient availability at Mer Bleue bog measured by PRSTM probes

    NASA Astrophysics Data System (ADS)

    Wang, M.; Moore, T. R.; Talbot, J.

    2015-12-01

    Bogs, covering ~0.7 million km2 in Canada, store a large amount of C and N. As nutrient deficient ecosystems, it's critical to examine the nutrient availabilities and seasonal dynamics. We used Plant Root Simulators (PRSTM) at Mer Bleue bog to provide some baseline data on nutrient availability and its variability. In particular, we focused on ammonium, nitrate, phosphate, calcium, magnesium and potassium, iron, sulphate and aluminum. We placed PRS probes at a depth of 5 - 15 cm in pristine plots and plots with long term N, P and K fertilization for 4 weeks and determined the availability of these nutrients, from spring through to fall. Probes were also placed beneath the water table in hummock and hollow microtopography and along a transect including part of the bog which had been drained through the creation of a ditch 80 years ago. The result showed that there was limited available ammonium, nitrate and phosphate in the bog, the seasonal variation of nutrient availabilities probably due to mineralization, an increase in the availability of some nutrients between different water table depths or as a result of drainage, and the relative availability of nutrients compared to the input from fertilization. We suggest that PRS probes could be a useful tool to examine nutrient availability and dynamics in wetlands, with careful consideration of installing condition, for example, proper exposure period, depth relative to water table etc.

  8. Metagenome Fragment Classification Using N-Mer Frequency Profiles

    PubMed Central

    Rosen, Gail; Garbarine, Elaine; Caseiro, Diamantino; Polikar, Robi; Sokhansanj, Bahrad

    2008-01-01

    A vast amount of microbial sequencing data is being generated through large-scale projects in ecology, agriculture, and human health. Efficient high-throughput methods are needed to analyze the mass amounts of metagenomic data, all DNA present in an environmental sample. A major obstacle in metagenomics is the inability to obtain accuracy using technology that yields short reads. We construct the unique N-mer frequency profiles of 635 microbial genomes publicly available as of February 2008. These profiles are used to train a naive Bayes classifier (NBC) that can be used to identify the genome of any fragment. We show that our method is comparable to BLAST for small 25 bp fragments but does not have the ambiguity of BLAST's tied top scores. We demonstrate that this approach is scalable to identify any fragment from hundreds of genomes. It also performs quite well at the strain, species, and genera levels and achieves strain resolution despite classifying ubiquitous genomic fragments (gene and nongene regions). Cross-validation analysis demonstrates that species-accuracy achieves 90% for highly-represented species containing an average of 8 strains. We demonstrate that such a tool can be used on the Sargasso Sea dataset, and our analysis shows that NBC can be further enhanced. PMID:19956701

  9. Metagenome fragment classification using N-mer frequency profiles.

    PubMed

    Rosen, Gail; Garbarine, Elaine; Caseiro, Diamantino; Polikar, Robi; Sokhansanj, Bahrad

    2008-01-01

    A vast amount of microbial sequencing data is being generated through large-scale projects in ecology, agriculture, and human health. Efficient high-throughput methods are needed to analyze the mass amounts of metagenomic data, all DNA present in an environmental sample. A major obstacle in metagenomics is the inability to obtain accuracy using technology that yields short reads. We construct the unique N-mer frequency profiles of 635 microbial genomes publicly available as of February 2008. These profiles are used to train a naive Bayes classifier (NBC) that can be used to identify the genome of any fragment. We show that our method is comparable to BLAST for small 25 bp fragments but does not have the ambiguity of BLAST's tied top scores. We demonstrate that this approach is scalable to identify any fragment from hundreds of genomes. It also performs quite well at the strain, species, and genera levels and achieves strain resolution despite classifying ubiquitous genomic fragments (gene and nongene regions). Cross-validation analysis demonstrates that species-accuracy achieves 90% for highly-represented species containing an average of 8 strains. We demonstrate that such a tool can be used on the Sargasso Sea dataset, and our analysis shows that NBC can be further enhanced.

  10. Planning Mars Memory: Learning from the Mer Mission

    NASA Technical Reports Server (NTRS)

    Linde, Charlotte

    2004-01-01

    Knowledge management for space exploration is part of a multi-generational effort at recognizing, preserving and transmitting learning. Each mission should be built on the learning, of both successes and failures, derived from previous missions. Knowledge management begins with learning, and the recognition that this learning has produced knowledge. The Mars Exploration Rover mission provides us with an opportunity to track how learning occurs, how it is recorded, and whether the representations of this learning will be optimally useful for subsequent missions. This paper focuses on the MER science and engineering teams during Rover operations. A NASA team conducted an observational study of the ongoing work and learning of the these teams. Learning occurred in a wide variety of areas: how to run two teams on Mars time for three months; how to use the instruments within the constraints of the martian environment, the deep space network and the mission requirements; how to plan science strategy; how best to use the available software tools. This learning is preserved in many ways. Primarily it resides in peoples memories, to be carried on to the next mission. It is also encoded in stones, in programming sequences, in published reports, and in lessons learned activities, Studying learning and knowledge development as it happens allows us to suggest proactive ways of capturing and using it across multiple missions and generations.

  11. Redefining Tactical Operations for MER Using Cloud Computing

    NASA Technical Reports Server (NTRS)

    Joswig, Joseph C.; Shams, Khawaja S.

    2011-01-01

    The Mars Exploration Rover Mission (MER) includes the twin rovers, Spirit and Opportunity, which have been performing geological research and surface exploration since early 2004. The rovers' durability well beyond their original prime mission (90 sols or Martian days) has allowed them to be a valuable platform for scientific research for well over 2000 sols, but as a by-product it has produced new challenges in providing efficient and cost-effective tactical operational planning. An early stage process adaptation was the move to distributed operations as mission scientists returned to their places of work in the summer of 2004, but they would still came together via teleconference and connected software to plan rover activities a few times a week. This distributed model has worked well since, but it requires the purchase, operation, and maintenance of a dedicated infrastructure at the Jet Propulsion Laboratory. This server infrastructure is costly to operate and the periodic nature of its usage (typically heavy usage for 8 hours every 2 days) has made moving to a cloud based tactical infrastructure an extremely tempting proposition. In this paper we will review both past and current implementations of the tactical planning application focusing on remote plan saving and discuss the unique challenges present with long-latency, distributed operations. We then detail the motivations behind our move to cloud based computing services and as well as our system design and implementation. We will discuss security and reliability concerns and how they were addressed

  12. UNC2025, a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor

    PubMed Central

    2015-01-01

    We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable of inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse bone marrow. Kinome profiling versus more than 300 kinases in vitro and cellular selectivity assessments demonstrate that 11 has similar subnanomolar activity against Flt3, an additional important target in acute myelogenous leukemia (AML), with pharmacologically useful selectivity versus other kinases examined. PMID:25068800

  13. UNC2025, a potent and orally bioavailable MER/FLT3 dual inhibitor.

    PubMed

    Zhang, Weihe; DeRyckere, Deborah; Hunter, Debra; Liu, Jing; Stashko, Michael A; Minson, Katherine A; Cummings, Christopher T; Lee, Minjung; Glaros, Trevor G; Newton, Dianne L; Sather, Susan; Zhang, Dehui; Kireev, Dmitri; Janzen, William P; Earp, H Shelton; Graham, Douglas K; Frye, Stephen V; Wang, Xiaodong

    2014-08-28

    We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable of inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse bone marrow. Kinome profiling versus more than 300 kinases in vitro and cellular selectivity assessments demonstrate that 11 has similar subnanomolar activity against Flt3, an additional important target in acute myelogenous leukemia (AML), with pharmacologically useful selectivity versus other kinases examined.

  14. Unanswered questions about the Middle East respiratory syndrome coronavirus (MERS-CoV)

    PubMed Central

    2014-01-01

    Background The Middle East respiratory syndrome coronavirus (MERS-CoV) represents a current threat to the Arabian Peninsula, and potential pandemic disease. As of June 3, 2014, MERS CoV has reportedly infected 688 people and killed 282. We briefly summarize the state of the outbreak, and highlight unanswered questions and various explanations for the observed epidemiology. Findings The continuing but infrequent cases of MERS-CoV reported over the past two years have been puzzling and difficult to explain. The epidemiology of MERS-CoV, with many sporadic cases and a few hospital outbreaks, yet no sustained epidemic, suggests a low reproductive number. Furthermore, a clear source of infection to humans remains unknown. Also puzzling is the fact that MERS-CoV has been present in Saudi Arabia over several mass gatherings, including the 2012 and 2013 Hajj and Umrah pilgrimages, which predispose to epidemics, without an epidemic arising. Conclusions The observed epidemiology of MERS-CoV is quite distinct and does not clearly fit either a sporadic or epidemic pattern. Possible explanations of the unusual features of the epidemiology of MERS-CoV include sporadic ongoing infections from a non-human source; human to human transmission with a large proportion of undetected cases; or a combination of both. The virus has been identified in camels; however the mode of transmission of the virus to humans remains unknown, and many cases have no history of animal contact. In order to gain a better understanding of the epidemiology of MERS CoV, further investigation is warranted. PMID:24920393

  15. Genetic analysis of transcriptional activation and repression in the Tn21 mer operon. [Bacteria

    SciTech Connect

    Ross, W.; Park, S.J.; Summers, A.O. )

    1989-07-01

    Transcription of the Tn21 mercury resistance operon (mer) is controlled by the toxic metal cation Hg(II). This control is mediated by the product of the merR gene, a 144-amino-acid protein which represses transcription of the structural genes (merTPCAD) in the absence of Hg(II) and activates transcription in the presence of Hg(II). We have used a mer-lac transcriptional fusion to obtain regulatory mutants in this metal-responsive system. Some mutants were defective in Hg(II)-induced activation while retaining repression function, others were defective in repression but not activation, and some had lost both functions. Mutations in three of the four cysteine residues of merR resulted in complete loss of Hg(II)-inducible activation but retention of the repressor function. Other lesions adjacent to or very near these cysteines exhibited severely reduced activation and also retained repressor function. There were two putative helix-turn-helix (HTH) domains in merR, and mutants in each had very different phenotypes. A partially dominant mutation in the more amino-terminal region of the two putative HTH regions resulted in loss of both activation and repression, consistent with a role for this region in DNA binding. Mutations in the more centrally located HTH region resulted only in loss of Hg(II)-induced activation. Lesions in the central and in the carboxy-terminal regions of merR exhibited both Hg(II)-independent and Hg(II)-dependent transcriptional activation. The sole cis-acting mutant obtained with this operon fusion strategy, a down-promoter mutation, lies in a highly conserved base in the -35 region of the merTPCAD promoter.

  16. A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines.

    PubMed

    Du, Lanying; Kou, Zhihua; Ma, Cuiqing; Tao, Xinrong; Wang, Lili; Zhao, Guangyu; Chen, Yaoqing; Yu, Fei; Tseng, Chien-Te K; Zhou, Yusen; Jiang, Shibo

    2013-01-01

    An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367-606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients' lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.

  17. Discovery of Mer specific tyrosine kinase inhibitors for the treatment and prevention of thrombosis.

    PubMed

    Zhang, Weihe; McIver, Andrew L; Stashko, Michael A; DeRyckere, Deborah; Branchford, Brian R; Hunter, Debra; Kireev, Dmitri; Miley, Michael J; Norris-Drouin, Jacqueline; Stewart, Wendy M; Lee, Minjung; Sather, Susan; Zhou, Yingqiu; Di Paola, Jorge A; Machius, Mischa; Janzen, William P; Earp, H Shelton; Graham, Douglas K; Frye, Stephen V; Wang, Xiaodong

    2013-12-12

    The role of Mer kinase in regulating the second phase of platelet activation generates an opportunity to use Mer inhibitors for preventing thrombosis with diminished likelihood for bleeding as compared to current therapies. Toward this end, we have discovered a novel, Mer kinase specific substituted-pyrimidine scaffold using a structure-based drug design and a pseudo ring replacement strategy. The cocrystal structure of Mer with two compounds (7 and 22) possessing distinct activity have been determined. Subsequent SAR studies identified compound 23 (UNC2881) as a lead compound for in vivo evaluation. When applied to live cells, 23 inhibits steady-state Mer kinase phosphorylation with an IC50 value of 22 nM. Treatment with 23 is also sufficient to block EGF-mediated stimulation of a chimeric receptor containing the intracellular domain of Mer fused to the extracellular domain of EGFR. In addition, 23 potently inhibits collagen-induced platelet aggregation, suggesting that this class of inhibitors may have utility for prevention and/or treatment of pathologic thrombosis.

  18. Discovery of Mer Specific Tyrosine Kinase Inhibitors for the Treatment and Prevention of Thrombosis

    PubMed Central

    Zhang, Weihe; McIver, Andrew L.; Stashko, Michael A.; DeRyckere, Deborah; Branchford, Brian R.; Hunter, Debra; Kireev, Dmitri; Miley, Michael J.; Norris-Drouin, Jacqueline; Stewart, Wendy M.; Lee, Minjung; Sather, Susan; Zhou, Yingqiu; Di Paola, Jorge A.; Machius, Mischa; Janzen, William P.; Earp, H. Shelton; Graham, Douglas K.; Frye, Stephen V.; Wang, Xiaodong

    2014-01-01

    The role of Mer kinase in regulating the second phase of platelet activation generates an opportunity to use Mer inhibitors for preventing thrombosis with diminished likelihood for bleeding as compared to current therapies. Toward this end, we have discovered a novel, Mer kinase specific substituted-pyrimidine scaffold using a structure-based drug design and a pseudo-ring replacement strategy. The co-crystal structure of Mer with two compounds (7 & 22) possessing distinct activity have been determined. Subsequent SAR studies identified compound 23 (UNC2881) as a lead compound for in vivo evaluation. When applied to live cells, 23 inhibits steady-state Mer kinase phosphorylation with an IC50 value of 22 nM. Treatment with 23 is also sufficient to block EGF-mediated stimulation of a chimeric receptor containing the intracellular domain of Mer fused to the extracellular domain of EGFR. In addition, 23 potently inhibits collagen-induced platelet aggregation, suggesting that this class of inhibitors may have utility for prevention and/or treatment of pathologic thrombosis. PMID:24219778

  19. Antibodies against MERS coronavirus in dromedary camels, United Arab Emirates, 2003 and 2013.

    PubMed

    Meyer, Benjamin; Müller, Marcel A; Corman, Victor M; Reusken, Chantal B E M; Ritz, Daniel; Godeke, Gert-Jan; Lattwein, Erik; Kallies, Stephan; Siemens, Artem; van Beek, Janko; Drexler, Jan F; Muth, Doreen; Bosch, Berend-Jan; Wernery, Ulrich; Koopmans, Marion P G; Wernery, Renate; Drosten, Christian

    2014-04-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) has caused an ongoing outbreak of severe acute respiratory tract infection in humans in the Arabian Peninsula since 2012. Dromedary camels have been implicated as possible viral reservoirs. We used serologic assays to analyze 651 dromedary camel serum samples from the United Arab Emirates; 151 of 651 samples were obtained in 2003, well before onset of the current epidemic, and 500 serum samples were obtained in 2013. Recombinant spike protein-specific immunofluorescence and virus neutralization tests enabled clear discrimination between MERS-CoV and bovine CoV infections. Most (632/651, 97.1%) camels had antibodies against MERS-CoV. This result included all 151 serum samples obtained in 2003. Most (389/651, 59.8%) serum samples had MERS-CoV-neutralizing antibody titers >1,280. Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases.

  20. MERS-CoV recombination: implications about the reservoir and potential for adaptation

    PubMed Central

    Dudas, Gytis; Rambaut, Andrew

    2016-01-01

    Recombination is a process that unlinks neighboring loci allowing for independent evolutionary trajectories within genomes of many organisms. If not properly accounted for, recombination can compromise many evolutionary analyses. In addition, when dealing with organisms that are not obligately sexually reproducing, recombination gives insight into the rate at which distinct genetic lineages come into contact. Since June 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 1,106 laboratory-confirmed infections, with 421 MERS-CoV-associated deaths as of 16 April 2015. Although bats are considered as the likely ultimate source of zoonotic betacoronaviruses, dromedary camels have been consistently implicated as the source of current human infections in the Middle East. In this article, we use phylogenetic methods and simulations to show that MERS-CoV genome has likely undergone numerous recombinations recently. Recombination in MERS-CoV implies frequent co-infection with distinct lineages of MERS-CoV, probably in camels given the current understanding of MERS-CoV epidemiology. PMID:27774293

  1. Challenges presented by MERS corona virus, and SARS corona virus to global health.

    PubMed

    Al-Hazmi, Ali

    2016-07-01

    Numerous viral infections have arisen and affected global healthcare facilities. Millions of people are at severe risk of acquiring several evolving viral infections through several factors. In the present article we have described about risk factors, chance of infection, and prevention methods of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV), human coronaviruses (CoVs) frequently cause a normal cold which is mild and self-restricting. Zoonotic transmission of CoVs such as the newly discovered MERS-CoV and SARS-CoV, may be associated with severe lower respiratory tract infection. The present review provides the recent clinical and pathological information on MERS and SARS. The task is to transform these discoveries about MERS and SARS pathogenesis and to develop intervention methods that will eventually allow the effective control of these recently arising severe viral infections. Global health sector has learnt many lessons through the recent outbreak of MERS and SARS, but the need for identifying new antiviral treatment was not learned. In the present article we have reviewed the literature on the several facets like transmission, precautions and effectiveness of treatments used in patients with MERS-CoV and SARS infections.

  2. Development of animal models against emerging coronaviruses: From SARS to MERS coronavirus.

    PubMed

    Sutton, Troy C; Subbarao, Kanta

    2015-05-01

    Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV.

  3. Mice lacking Axl and Mer tyrosine kinase receptors are susceptible to experimental autoimmune orchitis induction.

    PubMed

    Li, Nan; Liu, Zhenghui; Zhang, Yue; Chen, Qiaoyuan; Liu, Peng; Cheng, C Yan; Lee, Will M; Chen, Yongmei; Han, Daishu

    2015-03-01

    The mammalian testis is an immunoprivileged organ where male germ cell autoantigens are immunologically ignored. Both systemic immune tolerance to autoantigens and local immunosuppressive milieu contribute to the testicular immune privilege. Testicular immunosuppression has been intensively studied, but information on systemic immune tolerance to autoantigens is lacking. In the present study, we aimed to determine the role of Axl and Mer receptor tyrosine kinases in maintaining the systemic tolerance to male germ cell antigens using the experimental autoimmune orchitis (EAO) model. Axl and Mer double-knockout (Axl(-/-)Mer(-/-)) mice developed evident EAO after a single immunization with germ cell homogenates emulsified with complete Freund's adjuvant. EAO was characterized by the accumulation of macrophages and T lymphocytes in the testis. Damage to the seminiferous epithelium was also observed. EAO induction was associated with pro-inflammatory cytokine upregulation in the testes, impaired permeability of the blood-testis barrier and generation of autoantibodies against germ cell antigens in Axl(-/-)Mer(-/-) mice. Immunization also induced mild EAO in Axl or Mer single-gene-knockout mice. By contrast, a single immunization failed to induce EAO in wild-type mice. The results indicate that Axl and Mer receptors cooperatively regulate the systemic immune tolerance to male germ cell antigens.

  4. DNA sequence analysis by hybridization with oligonucleotide microchips: MALDI mass spectrometry identification of 5mers contiguously stacked to microchip oligonucleotides

    PubMed Central

    Stomakhin, Andrey A.; Vasiliskov, Vadim A.; Timofeev, Edward; Schulga, Dennis; Cotter, Richard J.; Mirzabekov, Andrei D.

    2000-01-01

    Matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) has been applied to increase the informational output from DNA sequence analysis. It has been used to analyze DNA by hybridization with microarrays of gel-immobilized oligonucleotides extended with stacked 5mers. In model experiments, a 28 nt long DNA fragment was hybridized with 10 immobilized, overlapping 8mers. Then, in a second round of hybridization DNA–8mer duplexes were hybridized with a mixture of 10 5mers. The stability of the 5mer complex with DNA was increased to raise the melting temperature of the duplex by 10–15°C as a result of stacking interaction with 8mers. Contiguous 13 bp duplexes containing an internal break were formed. MALDI MS identified one or, in some cases, two 5mers contiguously stacked to each DNA–8mer duplex formed on the microchip. Incorporating a mass label into 5mers optimized MALDI MS monitoring. This procedure enabled us to reconstitute the sequence of a model DNA fragment and identify polymorphic nucleotides. The application of MALDI MS identification of contiguously stacked 5mers to increase the length of DNA for sequence analysis is discussed. PMID:10666462

  5. Analysis of common k-mers for whole genome sequences using SSB-tree.

    PubMed

    Choi, Jeong-Hyeon; Cho, Hwan-Gue

    2002-01-01

    As sequenced genomes become larger and sequencing process becomes faster, there is a need to develop a tool to analyze sequences in the whole genomic scale. However, on-memory algorithms such as suffix tree and suffix array are not applicable to the analysis of whole genome sequence set, since the size of individual whole genome ranges from several million base pairs to hundreds billion base pairs. In order to effectively manipulate the huge sequence data, it is necessary to use the indexed data structure for external memory. In this paper, we introduce a workbench called SequeX for the analysis and visualization of whole genome sequences using SSB-tree (Static SB-tree). It consists of two parts: the analysis query subsystem and the visualization subsystem. The query subsystem supports various transactions such as pattern matching, k-occurrence, and k-mer analysis. The visualization subsystem helps biologists to easily understand whole genome structure and feature by sequence viewer, annotation viewer, CGR (Chaos Game Representation) viewer, and k-mer viewer. The system also supports a user-friendly programming interface based on Java script for batch processing and the extension for a specific purpose of a user. SequeX can be used to identify conserved genes or sequences by the analysis of the common k-mers and annotation. We analyze the common k-mer for 72 microbial genomes announced by Entrez, and find an interesting biological fact that the longest common k-mer for 72 sequences is 11-mer, and only 11 such sequences exist. Finally we note that many common k-mers occur in conserved region such as CDS, rRNA, and tRNA.

  6. Biomolecular Mechanisms of Mercury Transfers and Transformations by Proteins of the Mer Operon

    NASA Astrophysics Data System (ADS)

    Miller, S. M.; Hong, B.; Nauss, R.; Momany, C.; Summers, A. O.; Feng, X.; Harwood, I.; Stroud, R.

    2008-12-01

    Aerobic bacteria exhibiting resistance to the toxic effects of Hg(II) and organomercurials [RHg(I), e.g. MeHg(I)] and are widely found in both pristine and mercury contaminated environments. Resistance, afforded by a plasmid- or transposon-associated mer operon, involves an unusual pathway where Hg(II) and organomercurials [RHg(I)] undergo facilitated entry into the bacterial cytoplasm via an integral membrane transport protein (MerT) and are then "detoxified" by the concerted effort of two enzymes, organomercurial lyase (MerB), which catalyzes dealkylation (i.e., demethylation) of RHg(I) to Hg(II) and a hydrocarbon, and mercuric ion reductase (MerA), which catalyzes reduction of Hg(II) to Hg(0) as the ultimate detoxification for the organism. With a widespread distribution, these bacterial transformations play a significant role in the fate of mercury in the environment. Our focus is on elucidation of the molecular mechanisms for the transport and catalytic transformations of RHg(I) and Hg(II) by these proteins and the factors that influence the overall efficiency of the process. Current efforts are focused primarily on elucidating details of RHg(I) binding and dealkylation by MerB as well as the mechanism for transfer of the Hg(II) product to MerA. Key findings include the demonstration of a non-cysteine residue as essential for the catalytic activity and demonstration that direct transfer of Hg(II) to MerA proceeds more rapidly and more completely than transfer to small MW thiols such as cysteines or glutathione. Reuslts of these studies as well as an overview of our current understanding of the whole system will be presented.

  7. Characterizing the empirical distribution of prokaryotic genome n-mers in the presence of nullomers.

    PubMed

    Tabb, Loni Philip; Zhao, Wei; Huang, Jingyu; Rosen, Gail L

    2014-10-01

    Characterizing the empirical distribution of the frequency of n-mers is a vital step in understanding the entire genome. This will allow for researchers to examine how complex the genome really is, and move beyond simple, traditional modeling frameworks that are often biased in the presence of abundant and/or extremely rare words. We hypothesize that models based on the negative binomial distribution and its zero-inflated counterpart will characterize the n-mer distributions of genomes better than the Poisson. Our study examined the empirical distribution of the frequency of n-mers (6 ≤ n ≤ 11) in 2,199 genomes. We considered four distributions: Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial (ZINB). The number of genomes that have nullomers in 6-, 7-, and 8-mers was 150, 602 and 2,012, respectively, whereas all of the genomes for the 9-, 10-, and 11-mers had nullomers. In each n-mer considered, the negative binomial model performed the best for at least 93% of the 2,199 genomes; however, a small percentage (i.e., <7%) of the genomes did prefer the ZINB. The negative binomial and zero-inflation distributions extend the traditional Poisson setting and are more flexible in handling overdispersion that can be caused by an increase in nullomers. In an effort to characterize the distribution of the frequency of n-mers, researchers should also consider other discrete distributions that are more flexible and adjust for possible overdispersion.

  8. Worry experienced during the 2015 Middle East Respiratory Syndrome (MERS) pandemic in Korea

    PubMed Central

    Ro, Jun-Soo; Lee, Jin-Seok; Kang, Sung-Chan; Jung, Hye-Min

    2017-01-01

    Background Korea failed in its risk communication during the early stage of the Middle East Respiratory Syndrome (MERS) outbreak; consequently, it faced difficulties in managing MERS, while disease-related worry increased. Disease-related worry can help disease prevention and management, but can also have a detrimental effect. This study measured the overall level of disease-related worry during the MERS outbreak period in Korea and the influencing factors and levels of disease-related worry during key outbreak periods. Methods The cross-sectional survey included 1,000 adults who resided in Korea. An ordinal logistic regression was performed for the overall level of MERS-related worry, and influencing factors of worry were analyzed. A reliability test was performed on the levels of MERS-related worry during key outbreak periods. Results The overall level of MERS-related worry was 2.44. Multivariate analysis revealed that women and respondents w very poor subjective health status had higher levels of worry. Respondents with very high stress in daily life had higher levels of worry than those who reported having little stress. The reliability test results on MERS-related worry scores during key outbreak periods showed consistent scores during each period. Conclusion Level of worry increased in cases having higher perceived susceptibility and greater trust in informal information, while initial stage of outbreak was closely associated with that at later stages. These findings suggest the importance of managing the level of worry by providing timely and accurate disease-related information during the initial stage of disease outbreak. PMID:28273131

  9. An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels.

    PubMed

    Haagmans, Bart L; van den Brand, Judith M A; Raj, V Stalin; Volz, Asisa; Wohlsein, Peter; Smits, Saskia L; Schipper, Debby; Bestebroer, Theo M; Okba, Nisreen; Fux, Robert; Bensaid, Albert; Solanes Foz, David; Kuiken, Thijs; Baumgärtner, Wolfgang; Segalés, Joaquim; Sutter, Gerd; Osterhaus, Albert D M E

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) infections have led to an ongoing outbreak in humans, which was fueled by multiple zoonotic MERS-CoV introductions from dromedary camels. In addition to the implementation of hygiene measures to limit further camel-to-human and human-to-human transmissions, vaccine-mediated reduction of MERS-CoV spread from the animal reservoir may be envisaged. Here we show that a modified vaccinia virus Ankara (MVA) vaccine expressing the MERS-CoV spike protein confers mucosal immunity in dromedary camels. Compared with results for control animals, we observed a significant reduction of excreted infectious virus and viral RNA transcripts in vaccinated animals upon MERS-CoV challenge. Protection correlated with the presence of serum neutralizing antibodies to MERS-CoV. Induction of MVA-specific antibodies that cross-neutralize camelpox virus would also provide protection against camelpox.

  10. Comparison of De Novo Transcriptome Assemblers and k-mer Strategies Using the Killifish, Fundulus heteroclitus

    PubMed Central

    Rana, Satshil B.; Zadlock, Frank J.; Zhang, Ziping; Murphy, Wyatt R.; Bentivegna, Carolyn S.

    2016-01-01

    Background De novo assembly of non-model organism’s transcriptomes has recently been on the rise in concert with the number of de novo transcriptome assembly software programs. There is a knowledge gap as to what assembler software or k-mer strategy is best for construction of an optimal de novo assembly. Additionally, there is a lack of consensus on which evaluation metrics should be used to assess the quality of de novo transcriptome assemblies. Result Six different assembly strategies were evaluated from four different assemblers. The Trinity assembly was used in its default 25 single k-mer value while Bridger, Oases, and SOAPdenovo-Trans were performed with multiple k-mer strategies. Bridger, Oases, and SOAPdenovo-Trans used a small multiple k-mer (SMK) strategy consisting of the k-mer lengths of 21, 25, 27, 29, 31, and 33. Additionally, Oases and SOAPdenovo-Trans were performed using a large multiple k-mer (LMK) strategy consisting of k-mer lengths of 25, 35, 45, 55, 65, 75, and 85. Eleven metrics were used to evaluate each assembly strategy including three genome related evaluation metrics (contig number, N50 length, Contigs >1 kb, reads) and eight transcriptome evaluation metrics (mapped back to transcripts (RMBT), number of full length transcripts, number of open reading frames, Detonate RSEM-EVAL score, and percent alignment to the southern platyfish, Amazon molly, BUSCO and CEGMA databases). The assembly strategy that performed the best, that is it was within the top three of each evaluation metric, was the Bridger assembly (10 of 11) followed by the Oases SMK assembly (8 of 11), the Oases LMK assembly (6 of 11), the Trinity assembly (4 of 11), the SOAP LMK assembly (4 of 11), and the SOAP SMK assembly (3 of 11). Conclusion This study provides an in-depth multi k-mer strategy investigation concluding that the assembler itself had a greater impact than k-mer size regardless of the strategy employed. Additionally, the comprehensive performance

  11. Serological Evidence of MERS-CoV Antibodies in Dromedary Camels (Camelus dromedaries) in Laikipia County, Kenya.

    PubMed

    Deem, Sharon L; Fèvre, Eric M; Kinnaird, Margaret; Browne, A Springer; Muloi, Dishon; Godeke, Gert-Jan; Koopmans, Marion; Reusken, Chantal B

    2015-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently identified virus causing severe viral respiratory illness in people. Little is known about the reservoir in the Horn of Africa. In Kenya, where no human MERS cases have been reported, our survey of 335 dromedary camels, representing nine herds in Laikipia County, showed a high seroprevalence (46.9%) to MERS-CoV antibodies. Between herd differences were present (14.3%- 82.9%), but was not related to management type or herd isolation. Further research should focus on identifying similarity between MERS-CoV viral isolates in Kenya and clinical isolates from the Middle East and elsewhere.

  12. Evolutionary mechanism and biological functions of 8-mers containing CG dinucleotide in yeast.

    PubMed

    Zheng, Yan; Li, Hong; Wang, Yue; Meng, Hu; Zhang, Qiang; Zhao, Xiaoqing

    2017-02-09

    The rules of k-mer non-random usage and the biological functions are worthy of special attention. Firstly, the article studied human 8-mer spectra and found that only the spectra of cytosine-guanine (CG) dinucleotide classification formed independent unimodal distributions when the 8-mers were classified into three subsets under 16 dinucleotide classifications. Secondly, the distribution rules were reproduced by other seven species including yeast, which showed that the evolution phenomenon had species universality. It followed that we proposed two theoretical conjectures: (1) CG1 motifs (8-mers including 1 CG) are the nucleosome-binding motifs. (2) CG2 motifs (8-mers including two or more than two CG) are the modular units of CpG islands. Our conjectures were confirmed in yeast by the following results: a maximum of average area under the receiver operating characteristic (AUC) resulted from CG1 information during nucleosome core sequences, and linker sequences were distinguished by three CG subsets; there was a one-to-one relationship between abundant CG1 signal regions and histone positions; the sequence changing of squeezed nucleosomes was relevant with the strength of CG1 signals; and the AUC value of 0.986 was based on CG2 information when CpG islands and non-CpG islands were distinguished by the three CG subsets.

  13. Tomas Tranströmer's stroke of genius: language but no words.

    PubMed

    Iniesta, Iván

    2013-01-01

    In 1990, the widely acclaimed Swedish poet Tomas Tranströmer lost his speech and the ability to use his right hand as a result of a stroke. As if anticipating his own fate, in 1974, he referred in his longest poem Baltics the story of the Russian composer Vissarion Shebalin who suffered the same symptoms as Tranströmer following a brain bleed: "Then, cerebral hemorrhage: paralysis on the right side with aphasia." An amateur pianist himself, Tranströmer carried on playing left-handed piano pieces after the stroke. In spite of a severe nonfluent dysphasia with dysgraphia, Tranströmer kept producing a poetic language of the highest caliber in accordance with his 1979 no less prophetic verse "language but no words." And through music and poetry, overcame the great communication barriers imposed by a large dominant hemispheric stroke. A nonprolific writer before the stroke, after it Tranströmer became disproportionately brief compared to his prestroke production, confining most of his poetry to the agrammatical and telegraphic haiku style.

  14. Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants.

    PubMed

    Tai, Wanbo; Wang, Yufei; Fett, Craig A; Zhao, Guangyu; Li, Fang; Perlman, Stanley; Jiang, Shibo; Zhou, Yusen; Du, Lanying

    2017-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via the spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014, and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains. Like the RBD of prototype EMC2012 (EMC-RBD), all five RBDs maintained good antigenicity and functionality, the ability to bind RBD-specific neutralizing monoclonal antibodies (MAbs) and the DPP4 receptor, and high immunogenicity, able to elicit S-specific antibodies. They induced potent neutralizing antibodies cross-neutralizing 17 MERS pseudoviruses expressing S proteins of representative human and camel MERS-CoV strains identified during the 2012-2015 outbreaks, 5 MAb escape MERS-CoV mutants, and 2 live human MERS-CoV strains. We then constructed two RBDs mutated in multiple key residues in the receptor-binding motif (RBM) of RBD and demonstrated their strong cross-reactivity with anti-EMC-RBD antibodies. These RBD mutants with diminished DPP4 binding also led to virus attenuation, suggesting that immunoevasion after RBD immunization is accompanied by loss of viral fitness. Therefore, this study demonstrates that MERS-CoV RBD is an important vaccine target able to induce highly potent and broad-spectrum neutralizing antibodies against infection by divergent circulating human and camel MERS-CoV strains.

  15. Dynamical transmission model of MERS-CoV in two areas

    NASA Astrophysics Data System (ADS)

    Yong, Benny; Owen, Livia

    2016-02-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a disease first reported in Saudi Arabia in 2012 and it can be transmitted from human to human. This disease has spread to several other countries, most confirmed cases have displayed symptoms of severe acute respiratory illness and many of these patients have died. This research is aimed to construct a mathematical model for the transmission of MERS-CoV in two areas by separating the human population into two groups; susceptible and infectious groups. The dynamics of the disease is studied by a compartmental model involving ordinary differrential equations. The basic reproductive number of this disease is discussed to control the outbreak of this disease. Sensitivity analysis of this model is performed to determine the relative importance of the model parameters to the MERS-CoV transmission.

  16. Simrank: Rapid and sensitive general-purpose k-mer search tool

    SciTech Connect

    DeSantis, T.Z.; Keller, K.; Karaoz, U.; Alekseyenko, A.V; Singh, N.N.S.; Brodie, E.L; Pei, Z.; Andersen, G.L; Larsen, N.

    2011-04-01

    Terabyte-scale collections of string-encoded data are expected from consortia efforts such as the Human Microbiome Project (http://nihroadmap.nih.gov/hmp). Intra- and inter-project data similarity searches are enabled by rapid k-mer matching strategies. Software applications for sequence database partitioning, guide tree estimation, molecular classification and alignment acceleration have benefited from embedded k-mer searches as sub-routines. However, a rapid, general-purpose, open-source, flexible, stand-alone k-mer tool has not been available. Here we present a stand-alone utility, Simrank, which allows users to rapidly identify database strings the most similar to query strings. Performance testing of Simrank and related tools against DNA, RNA, protein and human-languages found Simrank 10X to 928X faster depending on the dataset. Simrank provides molecular ecologists with a high-throughput, open source choice for comparing large sequence sets to find similarity.

  17. MerTK cleavage limits proresolving mediator biosynthesis and exacerbates tissue inflammation

    PubMed Central

    Cai, Bishuang; Thorp, Edward B.; Doran, Amanda C.; Subramanian, Manikandan; Sansbury, Brian E.; Lin, Chyuan-Sheng; Spite, Matthew; Fredman, Gabrielle; Tabas, Ira

    2016-01-01

    The acute inflammatory response requires a coordinated resolution program to prevent excessive inflammation, repair collateral damage, and restore tissue homeostasis, and failure of this response contributes to the pathology of numerous chronic inflammatory diseases. Resolution is mediated in part by long-chain fatty acid-derived lipid mediators called specialized proresolving mediators (SPMs). However, how SPMs are regulated during the inflammatory response, and how this process goes awry in inflammatory diseases, are poorly understood. We now show that signaling through the Mer proto-oncogene tyrosine kinase (MerTK) receptor in cultured macrophages and in sterile inflammation in vivo promotes SPM biosynthesis by a mechanism involving an increase in the cytoplasmic:nuclear ratio of a key SPM biosynthetic enzyme, 5-lipoxygenase. This action of MerTK is linked to the resolution of sterile peritonitis and, after ischemia–reperfusion (I/R) injury, to increased circulating SPMs and decreased remote organ inflammation. MerTK is susceptible to ADAM metallopeptidase domain 17 (ADAM17)-mediated cell-surface cleavage under inflammatory conditions, but the functional significance is not known. We show here that SPM biosynthesis is increased and inflammation resolution is improved in a new mouse model in which endogenous MerTK was replaced with a genetically engineered variant that is cleavage-resistant (MertkCR). MertkCR mice also have increased circulating levels of SPMs and less lung injury after I/R. Thus, MerTK cleavage during inflammation limits SPM biosynthesis and the resolution response. These findings contribute to our understanding of how SPM synthesis is regulated during the inflammatory response and suggest new therapeutic avenues to boost resolution in settings where defective resolution promotes disease progression. PMID:27199481

  18. Value, Market Preferences and Trade of Beche-De-Mer from Pacific Island Sea Cucumbers

    PubMed Central

    Purcell, Steven W.

    2014-01-01

    Market preferences of natural resources contribute to shape their exploitation and production. Beche-de-mer, the product after gutting, cooking, salting and drying sea cucumbers, is exported worldwide to Asian dried seafood markets. A better understanding of the trade, value and market preferences of Pacific island beche-de-mer could identify critical postharvest processing techniques and management strategies for fisheries and aquaculture. Data were collected on export prices and trade of beche-de-mer from Kiribati, Fiji, Tonga and New Caledonia, and the selling prices, respective sizes and organoleptic properties of the products in stores in China. Export prices varied considerably within and among the four countries and low-value species were the most exported by volume. Most of the beche-de-mer from the four Pacific islands is exported to Hong Kong, where quality products are sold and others are distributed to mainland China. Prices of the beche-de-mer in Chinese stores varied up to ten-fold and were mostly influenced by species, body size and, to a lesser extent, physical damage to the products. Market prices across species (averaging US$15–385 kg−1) appear to have mostly increased six- to twelve-fold over the past decade. The data allude that fisheries for Holothuria scabra, H. lessoni, H. fuscogilva, H. whitmaei and Thelenota ananas should be most carefully managed because they were the highest-value species and under greatest demand. The relationships between size of beche-de-mer and sale price were species specific and highly varied. This study also highlights the need for better regulations and/or enforcement of minimum size limits in sea cucumber fisheries, which can help to maximise economic benefits of wild stocks. PMID:24736374

  19. Compact representation of k-mer de Bruijn graphs for genome read assembly

    PubMed Central

    2013-01-01

    Background Processing of reads from high throughput sequencing is often done in terms of edges in the de Bruijn graph representing all k-mers from the reads. The memory requirements for storing all k-mers in a lookup table can be demanding, even after removal of read errors, but can be alleviated by using a memory efficient data structure. Results The FM-index, which is based on the Burrows–Wheeler transform, provides an efficient data structure providing a searchable index of all substrings from a set of strings, and is used to compactly represent full genomes for use in mapping reads to a genome: the memory required to store this is in the same order of magnitude as the strings themselves. However, reads from high throughput sequences mostly have high coverage and so contain the same substrings multiple times from different reads. I here present a modification of the FM-index, which I call the kFM-index, for indexing the set of k-mers from the reads. For DNA sequences, this requires 5 bit of information for each vertex of the corresponding de Bruijn subgraph, i.e. for each different k−1-mer, plus some additional overhead, typically 0.5 to 1 bit per vertex, for storing the equivalent of the FM-index for walking the underlying de Bruijn graph and reproducing the actual k-mers efficiently. Conclusions The kFM-index could replace more memory demanding data structures for storing the de Bruijn k-mer graph representation of sequence reads. A Java implementation with additional technical documentation is provided which demonstrates the applicability of the data structure (http://folk.uio.no/einarro/Projects/KFM-index/). PMID:24152242

  20. MerTK cleavage limits proresolving mediator biosynthesis and exacerbates tissue inflammation.

    PubMed

    Cai, Bishuang; Thorp, Edward B; Doran, Amanda C; Subramanian, Manikandan; Sansbury, Brian E; Lin, Chyuan-Sheng; Spite, Matthew; Fredman, Gabrielle; Tabas, Ira

    2016-06-07

    The acute inflammatory response requires a coordinated resolution program to prevent excessive inflammation, repair collateral damage, and restore tissue homeostasis, and failure of this response contributes to the pathology of numerous chronic inflammatory diseases. Resolution is mediated in part by long-chain fatty acid-derived lipid mediators called specialized proresolving mediators (SPMs). However, how SPMs are regulated during the inflammatory response, and how this process goes awry in inflammatory diseases, are poorly understood. We now show that signaling through the Mer proto-oncogene tyrosine kinase (MerTK) receptor in cultured macrophages and in sterile inflammation in vivo promotes SPM biosynthesis by a mechanism involving an increase in the cytoplasmic:nuclear ratio of a key SPM biosynthetic enzyme, 5-lipoxygenase. This action of MerTK is linked to the resolution of sterile peritonitis and, after ischemia-reperfusion (I/R) injury, to increased circulating SPMs and decreased remote organ inflammation. MerTK is susceptible to ADAM metallopeptidase domain 17 (ADAM17)-mediated cell-surface cleavage under inflammatory conditions, but the functional significance is not known. We show here that SPM biosynthesis is increased and inflammation resolution is improved in a new mouse model in which endogenous MerTK was replaced with a genetically engineered variant that is cleavage-resistant (Mertk(CR)). Mertk(CR) mice also have increased circulating levels of SPMs and less lung injury after I/R. Thus, MerTK cleavage during inflammation limits SPM biosynthesis and the resolution response. These findings contribute to our understanding of how SPM synthesis is regulated during the inflammatory response and suggest new therapeutic avenues to boost resolution in settings where defective resolution promotes disease progression.

  1. Healthcare Workers Emotions, Perceived Stressors and Coping Strategies During a MERS-CoV Outbreak

    PubMed Central

    Khalid, Imran; Khalid, Tabindeh J.; Qabajah, Mohammed R.; Barnard, Aletta G.; Qushmaq, Ismael A.

    2016-01-01

    Objective Healthcare workers (HCWs) are at high risk of contracting Middle East respiratory syndrome coronavirus (MERS-CoV) during an epidemic. We explored the emotions, perceived stressors, and coping strategies of healthcare workers who worked during a MERS-CoV outbreak in our hospital. Design A cross-sectional descriptive survey design. Setting A tertiary care hospital. Participants HCWs (150) who worked in high risk areas during the April–May 2014 MERS-CoV outbreak that occurred in Jeddah, Saudi Arabia. Methods We developed and administered a “MERS-CoV staff questionnaire” to study participants. The questionnaire consisted of 5 sections with 72 questions. The sections evaluated hospital staffs emotions, perceived stressors, factors that reduced their stress, coping strategies, and motivators to work during future outbreaks. Responses were scored on a scale from 0–3. The varying levels of stress or effectiveness of measures were reported as mean and standard deviation, as appropriate. Results Completed questionnaires were returned by 117 (78%) of the participants. The results had many unique elements. HCWs ethical obligation to their profession pushed them to continue with their jobs. The main sentiments centered upon fear of personal safety and well-being of colleagues and family. Positive attitudes in the workplace, clinical improvement of infected colleagues, and stoppage of disease transmission among HCWs after adopting strict protective measures alleviated their fear and drove them through the epidemic. They appreciated recognition of their efforts by hospital management and expected similar acknowledgment, infection control guidance, and equipment would entice them to work during future epidemics. Conclusion The MERS-CoV outbreak was a distressing time for our staff. Hospitals can enhance HCWs experiences during any future MERS-CoV outbreak by focusing on the above mentioned aspects. PMID:26847480

  2. Value, market preferences and trade of Beche-de-mer from Pacific Island sea cucumbers.

    PubMed

    Purcell, Steven W

    2014-01-01

    Market preferences of natural resources contribute to shape their exploitation and production. Beche-de-mer, the product after gutting, cooking, salting and drying sea cucumbers, is exported worldwide to Asian dried seafood markets. A better understanding of the trade, value and market preferences of Pacific island beche-de-mer could identify critical postharvest processing techniques and management strategies for fisheries and aquaculture. Data were collected on export prices and trade of beche-de-mer from Kiribati, Fiji, Tonga and New Caledonia, and the selling prices, respective sizes and organoleptic properties of the products in stores in China. Export prices varied considerably within and among the four countries and low-value species were the most exported by volume. Most of the beche-de-mer from the four Pacific islands is exported to Hong Kong, where quality products are sold and others are distributed to mainland China. Prices of the beche-de-mer in Chinese stores varied up to ten-fold and were mostly influenced by species, body size and, to a lesser extent, physical damage to the products. Market prices across species (averaging US$15-385 kg-1) appear to have mostly increased six- to twelve-fold over the past decade. The data allude that fisheries for Holothuria scabra, H. lessoni, H. fuscogilva, H. whitmaei and Thelenota ananas should be most carefully managed because they were the highest-value species and under greatest demand. The relationships between size of beche-de-mer and sale price were species specific and highly varied. This study also highlights the need for better regulations and/or enforcement of minimum size limits in sea cucumber fisheries, which can help to maximise economic benefits of wild stocks.

  3. Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

    SciTech Connect

    Johnson, Reed F.; Via, Laura E.; Kumar, Mia R.; Cornish, Joseph P.; Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R.; Solomon, Jeffrey; Johnson, Joshua C.; Pickel, James; Hensley, Lisa E.; Jahrling, Peter B.

    2015-11-15

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.

  4. 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012

    SciTech Connect

    Johnson, Reed F.; Bagci, Ulas; Keith, Lauren; Tang, Xianchun; Mollura, Daniel J.; Zeitlin, Larry; Qin, Jing; Huzella, Louis; Bartos, Christopher J.; Bohorova, Natasha; Bohorov, Ognian; Goodman, Charles; Kim, Do H.; Paulty, Michael H.; Velasco, Jesus; Whaley, Kevin J.; Johnson, Joshua C.; Pettitt, James; Ork, Britini L.; Solomon, Jeffrey [Clinical Research Directorate and others

    2016-03-15

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×10{sup 6} PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment. - Highlights: • MERS-CoV Jordan-n3/2012 challenge of rhesus monkeys results in a mild disease. • CT can be used to monitor disease progression to aid models of human disease. • Treatment with the human monoclonal antibody 3B11-N resulted in decreased disease.

  5. The MER Mossbauer Spectrometers: 40 Months of Operation on the Martian Surface

    NASA Technical Reports Server (NTRS)

    Fleischer, Iris; Rodionov, D.; Schroeder, C.; Morris, R.; Yen, A.; Ming, D.; McCoy, T.; Mittlefehldt, D.; Gellert, R.; Cohen, B.; Schmidt, M.; Klingelhoefer, Goestar

    2007-01-01

    The primary MER objectives have been successfully completed. The total integration time of all MB measurements exceeds the duration of the primary 90-sols-mission for Spirit's MB spectrometer, and approaches this value for Opportunity's MB spectrometer. Both MB spectrometers continue to accumulate valuable scientific data after three years of operation (data is available for download [13]) The identification of aqueous minerals such as goethite in Gusev crater and jarosite at Meridiani Planum by the MER Mossbauer spectrometers is strong evidence for past water activity at the two landing sites.

  6. 77 FR 49059 - Requested Administrative Waiver of the Coastwise Trade Laws: Vessel CHAT DE MER; Invitation for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Maritime Administration Requested Administrative Waiver of the Coastwise Trade Laws: Vessel CHAT DE MER... of the vessel CHAT DE MER is: Intended Commercial Use of Vessel: Primarily carrying passengers...

  7. Toward Bioremediation of Methylmercury Using Silica Encapsulated Escherichia coli Harboring the mer Operon.

    PubMed

    Kane, Aunica L; Al-Shayeb, Basem; Holec, Patrick V; Rajan, Srijay; Le Mieux, Nicholas E; Heinsch, Stephen C; Psarska, Sona; Aukema, Kelly G; Sarkar, Casim A; Nater, Edward A; Gralnick, Jeffrey A

    2016-01-01

    Mercury is a highly toxic heavy metal and the ability of the neurotoxin methylmercury to biomagnify in the food chain is a serious concern for both public and environmental health globally. Because thousands of tons of mercury are released into the environment each year, remediation strategies are urgently needed and prompted this study. To facilitate remediation of both organic and inorganic forms of mercury, Escherichia coli was engineered to harbor a subset of genes (merRTPAB) from the mercury resistance operon. Protein products of the mer operon enable transport of mercury into the cell, cleavage of organic C-Hg bonds, and subsequent reduction of ionic mercury to the less toxic elemental form, Hg(0). E. coli containing merRTPAB was then encapsulated in silica beads resulting in a biological-based filtration material. Performing encapsulation in aerated mineral oil yielded silica beads that were smooth, spherical, and similar in diameter. Following encapsulation, E. coli containing merRTPAB retained the ability to degrade methylmercury and performed similarly to non-encapsulated cells. Due to the versatility of both the engineered mercury resistant strain and silica bead technology, this study provides a strong foundation for use of the resulting biological-based filtration material for methylmercury remediation.

  8. Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines

    PubMed Central

    Du, Lanying; Tai, Wanbo; Yang, Yang; Zhao, Guangyu; Zhu, Qing; Sun, Shihui; Liu, Chang; Tao, Xinrong; Tseng, Chien-Te K.; Perlman, Stanley; Jiang, Shibo; Zhou, Yusen; Li, Fang

    2016-01-01

    Viral subunit vaccines often contain immunodominant non-neutralizing epitopes that divert host immune responses. These epitopes should be eliminated in vaccine design, but there is no reliable method for evaluating an epitope's capacity to elicit neutralizing immune responses. Here we introduce a new concept ‘neutralizing immunogenicity index' (NII) to evaluate an epitope's neutralizing immunogenicity. To determine the NII, we mask the epitope with a glycan probe and then assess the epitope's contribution to the vaccine's overall neutralizing immunogenicity. As proof-of-concept, we measure the NII for different epitopes on an immunogen comprised of the receptor-binding domain from MERS coronavirus (MERS-CoV). Further, we design a variant form of this vaccine by masking an epitope that has a negative NII score. This engineered vaccine demonstrates significantly enhanced efficacy in protecting transgenic mice from lethal MERS-CoV challenge. Our study may guide the rational design of highly effective subunit vaccines to combat MERS-CoV and other life-threatening viruses. PMID:27874853

  9. Estimating Potential Incidence of MERS-CoV Associated with Hajj Pilgrims to Saudi Arabia, 2014.

    PubMed

    Lessler, Justin; Rodriguez-Barraquer, Isabel; Cummings, Derek A T; Garske, Tini; Van Kerkhove, Maria; Mills, Harriet; Truelove, Shaun; Hakeem, Rafat; Albarrak, Ali; Ferguson, Neil M

    2014-11-24

    Between March and June 2014 the Kingdom of Saudi Arabia (KSA) had a large outbreak of MERS-CoV, renewing fears of a major outbreak during the Hajj this October. Using KSA Ministry of Health data, the MERS-CoV Scenario and Modeling Working Group forecast incidence under three scenarios. In the expected incidence scenario, we estimate 6.2 (95% Prediction Interval [PI]: 1-17) pilgrims will develop MERS-CoV symptoms during the Hajj, and 4.0 (95% PI: 0-12) foreign pilgrims will be infected but return home before developing symptoms. In the most pessimistic scenario, 47.6 (95% PI: 32-66) cases will develop symptoms during the Hajj, and 29.0 (95% PI: 17-43) will be infected but return home asymptomatic. Large numbers of MERS-CoV cases are unlikely to occur during the 2014 Hajj even under pessimistic assumptions, but careful monitoring is still needed to detect possible mass infection events and minimize introductions into other countries.

  10. Discovery of Mer kinase inhibitors by Virtual Screening using Structural Protein-Ligand Interaction Fingerprints

    PubMed Central

    Da, C.; Stashko, M.; Jayakody, C.; Wang, X.; Janzen, W.; Frye, S.; Kireev, D.

    2015-01-01

    Mer is a receptor tyrosine kinase implicated in acute lymphoblastic leukemia (ALL), the most common malignancy in children. The currently available data provide a rationale for development of Mer kinase inhibitors as cancer therapeutics that can target both cell autologous and immune-modulatory anti-tumor effects. We have previously reported several series of potent Mer inhibitors and the objective of the current report is to identify a chemically dissimilar back-up series that might circumvent potential, but currently unknown, flaws inherent to the lead series. To this end, we virtually screened a database of ∼3.8 million commercially available compounds using high-throughput docking followed by a filter involving Structural Protein-Ligand Interaction Fingerprints (SPLIF). SPLIF permits a quantitative assessment of whether a docking pose interacts with the protein target similarly to an endogenous or known synthetic ligand, and therefore helps to improve both sensitivity and specificity with respect to the docking score alone. Of the total of 62 experimentally tested compounds, 15 demonstrated reliable dose-dependent responses in the Mer in vitro kinase activity assay with inhibitory potencies ranging from 0.46 μM to 9.9 μM. PMID:25638502

  11. Discovery of Mer kinase inhibitors by virtual screening using Structural Protein-Ligand Interaction Fingerprints.

    PubMed

    Da, C; Stashko, M; Jayakody, C; Wang, X; Janzen, W; Frye, S; Kireev, D

    2015-03-01

    Mer is a receptor tyrosine kinase implicated in acute lymphoblastic leukemia (ALL), the most common malignancy in children. The currently available data provide a rationale for development of Mer kinase inhibitors as cancer therapeutics that can target both cell autologous and immune-modulatory anti-tumor effects. We have previously reported several series of potent Mer inhibitors and the objective of the current report is to identify a chemically dissimilar back-up series that might circumvent potential, but currently unknown, flaws inherent to the lead series. To this end, we virtually screened a database of ∼3.8million commercially available compounds using high-throughput docking followed by a filter involving Structural Protein-Ligand Interaction Fingerprints (SPLIF). SPLIF permits a quantitative assessment of whether a docking pose interacts with the protein target similarly to an endogenous or known synthetic ligand, and therefore helps to improve both sensitivity and specificity with respect to the docking score alone. Of the total of 62 experimentally tested compounds, 15 demonstrated reliable dose-dependent responses in the Mer in vitro kinase activity assay with inhibitory potencies ranging from 0.46μM to 9.9μM.

  12. Toward Bioremediation of Methylmercury Using Silica Encapsulated Escherichia coli Harboring the mer Operon

    PubMed Central

    Kane, Aunica L.; Al-Shayeb, Basem; Holec, Patrick V.; Rajan, Srijay; Le Mieux, Nicholas E.; Heinsch, Stephen C.; Psarska, Sona; Aukema, Kelly G.; Sarkar, Casim A.; Nater, Edward A.; Gralnick, Jeffrey A.

    2016-01-01

    Mercury is a highly toxic heavy metal and the ability of the neurotoxin methylmercury to biomagnify in the food chain is a serious concern for both public and environmental health globally. Because thousands of tons of mercury are released into the environment each year, remediation strategies are urgently needed and prompted this study. To facilitate remediation of both organic and inorganic forms of mercury, Escherichia coli was engineered to harbor a subset of genes (merRTPAB) from the mercury resistance operon. Protein products of the mer operon enable transport of mercury into the cell, cleavage of organic C-Hg bonds, and subsequent reduction of ionic mercury to the less toxic elemental form, Hg(0). E. coli containing merRTPAB was then encapsulated in silica beads resulting in a biological-based filtration material. Performing encapsulation in aerated mineral oil yielded silica beads that were smooth, spherical, and similar in diameter. Following encapsulation, E. coli containing merRTPAB retained the ability to degrade methylmercury and performed similarly to non-encapsulated cells. Due to the versatility of both the engineered mercury resistant strain and silica bead technology, this study provides a strong foundation for use of the resulting biological-based filtration material for methylmercury remediation. PMID:26761437

  13. Enhanced MERS coronavirus surveillance of travelers from the Middle East to England.

    PubMed

    Thomas, Helen Lucy; Zhao, Hongxin; Green, Helen K; Boddington, Nicola L; Carvalho, Carlos F A; Osman, Husam K; Sadler, Carol; Zambon, Maria; Bermingham, Alison; Pebody, Richard G

    2014-09-01

    During the first year of enhanced MERS coronavirus surveillance in England, 77 persons traveling from the Middle East had acute respiratory illness and were tested for the virus. Infection was confirmed in 2 travelers with acute respiratory distress syndrome and 2 of their contacts. Patients with less severe manifestations tested negative.

  14. Multi-Agent Modeling and Simulation Approach for Design and Analysis of MER Mission Operations

    NASA Technical Reports Server (NTRS)

    Seah, Chin; Sierhuis, Maarten; Clancey, William J.

    2005-01-01

    A space mission operations system is a complex network of human organizations, information and deep-space network systems and spacecraft hardware. As in other organizations, one of the problems in mission operations is managing the relationship of the mission information systems related to how people actually work (practices). Brahms, a multi-agent modeling and simulation tool, was used to model and simulate NASA's Mars Exploration Rover (MER) mission work practice. The objective was to investigate the value of work practice modeling for mission operations design. From spring 2002 until winter 2003, a Brahms modeler participated in mission systems design sessions and operations testing for the MER mission held at Jet Propulsion Laboratory (JPL). He observed how designers interacted with the Brahms tool. This paper discussed mission system designers' reactions to the simulation output during model validation and the presentation of generated work procedures. This project spurred JPL's interest in the Brahms model, but it was never included as part of the formal mission design process. We discuss why this occurred. Subsequently, we used the MER model to develop a future mission operations concept. Team members were reluctant to use the MER model, even though it appeared to be highly relevant to their effort. We describe some of the tool issues we encountered.

  15. Geology of a Proposed MER Landing Site in Western Melas Chasma

    NASA Technical Reports Server (NTRS)

    Weitz, C. M.; Parker, T. J.; Anderson, F. S.; Grant, J. A.

    2002-01-01

    A proposed landing site for the Mars Exploration Rover (MER) has been identified in western Melas Chasma. The landing ellipse contains a blocky, bright deposit which we propose formed as a landslide, perhaps beneath a former lake. Additional information is contained in the original extended abstract.

  16. Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow

    PubMed Central

    Jung, Younghun; Decker, Ann M.; Wang, Jingcheng; Lee, Eunsohl; Kana, Lulia A.; Yumoto, Kenji; Cackowski, Frank C.; Rhee, James; Carmeliet, Peter; Buttitta, Laura; Morgan, Todd M.; Taichman, Russell S.

    2016-01-01

    GAS6 and its receptors (Tryo 3, Axl, Mer or “TAM”) are known to play a role in regulating tumor progression in a number of settings. Previously we have demonstrated that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells. We have also demonstrated that GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy. Here we investigated the role that endogenous GAS6 and Mer receptor signaling plays in establishing prostate cancer stem cells in the bone marrow microenvironment. We first observed that high levels of endogenous GAS6 are expressed by disseminated tumor cells (DTCs) in the bone marrow, whereas relatively low levels of endogenous GAS6 are expressed in PCa tumors grown in a s.c. setting. Interestingly, elevated levels of endogenous GAS6 were identified in putative cancer stem cells (CSCs, CD133+/CD44+) compared to non-CSCs (CD133–/CD44–) isolated from PCa/osteoblast cocultures in vitro and in DTCs isolated from the bone marrow 24 hours after intracardiac injection. Moreover, we found that endogenous GAS6 expression is associated with Mer receptor expression in growth arrested (G1) PCa cells, which correlates with the increase of the CSC populations. Importantly, we found that overexpression of GAS6 activates phosphorylation of Mer receptor signaling and subsequent induction of the CSC phenotype in vitro and in vivo. Together these data suggest that endogenous GAS6 and Mer receptor signaling contribute to the establishment of PCa CSCs in the bone marrow microenvironment, which may have important implications for targeting metastatic disease. PMID:27028863

  17. Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: Implication for designing novel mucosal MERS vaccines.

    PubMed

    Ma, Cuiqing; Li, Ye; Wang, Lili; Zhao, Guangyu; Tao, Xinrong; Tseng, Chien-Te K; Zhou, Yusen; Du, Lanying; Jiang, Shibo

    2014-04-11

    Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was originally identified in Saudi Arabia in 2012. It has caused MERS outbreaks with high mortality in the Middle East and Europe, raising a serious concern about its pandemic potential. Therefore, development of effective vaccines is crucial for preventing its further spread and future pandemic. Our previous study has shown that subcutaneous (s.c.) vaccination of a recombinant protein containing receptor-binding domain (RBD) of MERS-CoV S fused with Fc of human IgG (RBD-Fc) induced strong systemic neutralizing antibody responses in vaccinated mice. Here, we compared local and systemic immune responses induced by RBD-Fc via intranasal (i.n.) and s.c. immunization pathways. We found that i.n. vaccination of MERS-CoV RBD-Fc induced systemic humoral immune responses comparable to those induced by s.c. vaccination, including neutralizing antibodies, but more robust systemic cellular immune responses and significantly higher local mucosal immune responses in mouse lungs. This study suggests the potential of developing MERS-CoV RBD protein into an effective and safe mucosal candidate vaccine for prevention of respiratory tract infections caused by MERS-CoV.

  18. Probabilistic differential diagnosis of Middle East respiratory syndrome (MERS) using the time from immigration to illness onset among imported cases.

    PubMed

    Ejima, Keisuke; Aihara, Kazuyuki; Nishiura, Hiroshi

    2014-04-07

    Middle East respiratory syndrome (MERS) has spread worldwide since 2012. As the clinical symptoms of MERS tend to be non-specific, the incubation period has been shown to complement differential diagnosis, especially to rule out influenza. However, because an infection event is seldom directly observable, the present study aims to construct a diagnostic model that predicts the probability of MERS diagnosis given the time from immigration to illness onset among imported cases which are suspected of MERS. Addressing censoring by considering the transmission dynamics in an exporting country, we demonstrate that the illness onset within 2 days from immigration is suggestive of influenza. Two exceptions to suspect MERS even for those with illness onset within 2 days since immigration are (i) when we observe substantial community transmissions of MERS and (ii) when the cases are at high risk of MERS (e.g. cases with close contact in hospital or household). It is vital to collect the information of the incubation period upon emergence of a novel infectious disease, and moreover, in our model, the fundamental transmission dynamics including the initial growth rate has to be explored to differentiate the disease diagnoses with non-specific symptoms.

  19. Quantitation of the immunodominant 33-mer peptide from α-gliadin in wheat flours by liquid chromatography tandem mass spectrometry

    PubMed Central

    Schalk, Kathrin; Lang, Christina; Wieser, Herbert; Koehler, Peter; Scherf, Katharina Anne

    2017-01-01

    Coeliac disease (CD) is triggered by the ingestion of gluten proteins from wheat, rye, and barley. The 33-mer peptide from α2-gliadin has frequently been described as the most important CD-immunogenic sequence within gluten. However, from more than 890 published amino acid sequences of α-gliadins, only 19 sequences contain the 33-mer. In order to make a precise assessment of the importance of the 33-mer, it is necessary to elucidate which wheat species and cultivars contain the peptide and at which concentrations. This paper presents the development of a stable isotope dilution assay followed by liquid chromatography tandem mass spectrometry to quantitate the 33-mer in flours of 23 hexaploid modern and 15 old common (bread) wheat as well as two spelt cultivars. All flours contained the 33-mer peptide at levels ranging from 91–603 μg/g flour. In contrast, the 33-mer was absent (mer in all common wheat and spelt flours analysed here, the special focus in the literature on this most immunodominant peptide seems to be justified. PMID:28327674

  20. Quantitation of the immunodominant 33-mer peptide from α-gliadin in wheat flours by liquid chromatography tandem mass spectrometry.

    PubMed

    Schalk, Kathrin; Lang, Christina; Wieser, Herbert; Koehler, Peter; Scherf, Katharina Anne

    2017-03-22

    Coeliac disease (CD) is triggered by the ingestion of gluten proteins from wheat, rye, and barley. The 33-mer peptide from α2-gliadin has frequently been described as the most important CD-immunogenic sequence within gluten. However, from more than 890 published amino acid sequences of α-gliadins, only 19 sequences contain the 33-mer. In order to make a precise assessment of the importance of the 33-mer, it is necessary to elucidate which wheat species and cultivars contain the peptide and at which concentrations. This paper presents the development of a stable isotope dilution assay followed by liquid chromatography tandem mass spectrometry to quantitate the 33-mer in flours of 23 hexaploid modern and 15 old common (bread) wheat as well as two spelt cultivars. All flours contained the 33-mer peptide at levels ranging from 91-603 μg/g flour. In contrast, the 33-mer was absent (mer in all common wheat and spelt flours analysed here, the special focus in the literature on this most immunodominant peptide seems to be justified.

  1. A Comparative Study of Clinical Presentation and Risk Factors for Adverse Outcome in Patients Hospitalised with Acute Respiratory Disease Due to MERS Coronavirus or Other Causes

    PubMed Central

    Garbati, Musa A.; Fagbo, Shamsudeen F.; Fang, Vicky J.; Skakni, Leila; Joseph, Mercy; Wani, Tariq A.; Cowling, Benjamin J.; Peiris, Malik; Hakawi, Ahmed

    2016-01-01

    Middle East Respiratory syndrome (MERS) first emerged in Saudi Arabia in 2012 and remains a global health concern. The objective of this study was to compare the clinical features and risk factors for adverse outcome in patients with RT-PCR confirmed MERS and in those with acute respiratory disease who were MERS-CoV negative, presenting to the King Fahad Medical City (KFMC) in Riyadh between October 2012 and May 2014. The demographics, clinical and laboratory characteristics and clinical outcomes of patients with RT-PCR confirmed MERS-CoV infection was compared with those testing negative MERS-CoV PCR. Health care workers (HCW) with MERS were compared with MERS patients who were not health care workers. One hundred and fifty nine patients were eligible for inclusion. Forty eight tested positive for MERS CoV, 44 (92%) being hospital acquired infections and 23 were HCW. There were 111 MERS-CoV negative patients with acute respiratory illnesses included in this study as “negative controls”. Patient with confirmed MERS-CoV infection were not clinically distinguishable from those with negative MERS-CoV RT-PCR results although diarrhoea was commoner in MERS patients. A high level of suspicion in initiating laboratory tests for MERS-CoV is therefore indicated. Variables associated with adverse outcome were older age and diabetes as a co-morbid illness. Interestingly, co-morbid illnesses other than diabetes were not significantly associated with poor outcome. Health care workers with MERS had a markedly better clinical outcome compared to non HCW MERS patients. PMID:27812197

  2. UNC569, a novel small molecule Mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo

    PubMed Central

    Christoph, Sandra; DeRyckere, Deborah; Schlegel, Jennifer; Frazer, J. Kimble; Batchelor, Lance A.; Trakhimets, Alesia Y.; Sather, Susan; Hunter, Debra M.; Cummings, Christopher; Liu, Jing; Yang, Chao; Kireev, Dmitri; Simpson, Catherine; Norris-Drouin, Jacqueline; Hull-Ryde, Emily A.; Janzen, William P.; Johnson, Gary L.; Wang, Xiaodong; Frye, Stephen V.; Earp, H. Shelton; Graham, Douglas K.

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although survival rates have improved, patients with certain biological subtypes still have suboptimal outcomes. Current chemotherapeutic regimens are associated with short- and long-term toxicities and novel, less toxic therapeutic strategies are needed. Mer receptor tyrosine kinase is ectopically expressed in ALL patient samples and cell lines. Inhibition of Mer expression reduces pro-survival signaling, increases chemosensitivity, and delays development of leukaemia in vivo suggesting that Mer tyrosine kinase inhibitors are excellent candidates for targeted therapies. Brain and spinal tumors are the second most common malignancies in childhood. Multiple chemotherapy approaches and radiation have been attempted, yet overall survival remains dismal. Mer is also abnormally expressed in atypical teratoid/rhabdoid tumors (ATRT), providing a rationale for targeting Mer as a therapeutic strategy. We have previously described UNC569, the first small molecule Mer inhibitor. This manuscript describes the biochemical and biological effects of UNC569 in ALL and ATRT. UNC569 inhibited Mer activation and downstream signaling through ERK1/2 and AKT, determined by western blot analysis. Treatment with UNC569 reduced proliferation/survival in liquid culture, decreased colony formation in methylcellulose/soft agar, and increased sensitivity to cytotoxic chemotherapies. MYC transgenic zebrafish with T-ALL were treated with UNC569 (4 µM for 2 weeks). Fluorescence was quantified as indicator of the distribution of lymphoblasts, which express Mer and enhanced green fluorescent protein. UNC569 induced >50% reduction in tumor burden compared to vehicle- and mock-treated fish. These data support further development of Mer inhibitors as effective therapies in ALL and ATRT. PMID:23997116

  3. UNC569, a novel small-molecule mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo.

    PubMed

    Christoph, Sandra; Deryckere, Deborah; Schlegel, Jennifer; Frazer, J Kimble; Batchelor, Lance A; Trakhimets, Alesia Y; Sather, Susan; Hunter, Debra M; Cummings, Christopher T; Liu, Jing; Yang, Chao; Kireev, Dmitri; Simpson, Catherine; Norris-Drouin, Jacqueline; Hull-Ryde, Emily A; Janzen, William P; Johnson, Gary L; Wang, Xiaodong; Frye, Stephen V; Earp, H Shelton; Graham, Douglas K

    2013-11-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although survival rates have improved, patients with certain biologic subtypes still have suboptimal outcomes. Current chemotherapeutic regimens are associated with short- and long-term toxicities and novel, less toxic therapeutic strategies are needed. Mer receptor tyrosine kinase is ectopically expressed in ALL patient samples and cell lines. Inhibition of Mer expression reduces prosurvival signaling, increases chemosensitivity, and delays development of leukemia in vivo, suggesting that Mer tyrosine kinase inhibitors are excellent candidates for targeted therapies. Brain and spinal tumors are the second most common malignancies in childhood. Multiple chemotherapy approaches and radiotherapies have been attempted, yet overall survival remains dismal. Mer is also abnormally expressed in atypical teratoid/rhabdoid tumors (AT/RT), providing a rationale for targeting Mer as a therapeutic strategy. We have previously described UNC569, the first small-molecule Mer inhibitor. This article describes the biochemical and biologic effects of UNC569 in ALL and AT/RT. UNC569 inhibited Mer activation and downstream signaling through ERK1/2 and AKT, determined by Western blot analysis. Treatment with UNC569 reduced proliferation/survival in liquid culture, decreased colony formation in methylcellulose/soft agar, and increased sensitivity to cytotoxic chemotherapies. MYC transgenic zebrafish with T-ALL were treated with UNC569 (4 μmol/L for two weeks). Fluorescence was quantified as indicator of the distribution of lymphoblasts, which express Mer and enhanced GFP. UNC569 induced more than 50% reduction in tumor burden compared with vehicle- and mock-treated fish. These data support further development of Mer inhibitors as effective therapies in ALL and AT/RT.

  4. A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein.

    PubMed

    Li, Yan; Wan, Yuhua; Liu, Peipei; Zhao, Jincun; Lu, Guangwen; Qi, Jianxun; Wang, Qihui; Lu, Xuancheng; Wu, Ying; Liu, Wenjun; Zhang, Buchang; Yuen, Kwok-Yung; Perlman, Stanley; Gao, George F; Yan, Jinghua

    2015-11-01

    The newly-emerging Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans. Despite global efforts, the potential for an associated pandemic in the future cannot be excluded. The development of effective counter-measures is urgent. MERS-CoV-specific anti-viral drugs or vaccines are not yet available. Using the spike receptor-binding domain of MERS-CoV (MERS-RBD) to immunize mice, we identified two neutralizing monoclonal antibodies (mAbs) 4C2 and 2E6. Both mAbs potently bind to MERS-RBD and block virus entry in vitro with high efficacy. We further investigated their mechanisms of neutralization by crystallizing the complex between the Fab fragments and the RBD, and solved the structure of the 4C2 Fab/MERS-RBD complex. The structure showed that 4C2 recognizes an epitope that partially overlaps the receptor-binding footprint in MERS-RBD, thereby interfering with the virus/receptor interactions by both steric hindrance and interface-residue competition. 2E6 also blocks receptor binding, and competes with 4C2 for binding to MERS-RBD. Based on the structure, we further humanized 4C2 by preserving only the paratope residues and substituting the remaining amino acids with the counterparts from human immunoglobulins. The humanized 4C2 (4C2h) antibody sustained similar neutralizing activity and biochemical characteristics to the parental mouse antibody. Finally, we showed that 4C2h can significantly abate the virus titers in lungs of Ad5-hCD26-transduced mice infected with MERS-CoV, therefore representing a promising agent for prophylaxis and therapy in clinical settings.

  5. Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction.

    PubMed

    Zizzo, Gaetano; Hilliard, Brendan A; Monestier, Marc; Cohen, Philip L

    2012-10-01

    Mer tyrosine kinase (MerTK) is a major macrophage apoptotic cell (AC) receptor. Its functional impairment promotes autoimmunity and atherosclerosis, whereas overexpression correlates with poor prognosis in cancer. However, little is known about mechanisms regulating MerTK expression in humans. We found that MerTK expression is heterogenous among macrophage subsets, being mostly restricted to anti-inflammatory M2c (CD14(+)CD16(+)CD163(+)CD204(+)CD206(+)CD209(-)) cells, differentiated by M-CSF or glucocorticoids. Small numbers of MerTK(+) "M2c-like" cells are also detectable among circulating CD14(bright)CD16(+) monocytes. MerTK expression levels adapt to changing immunologic environment, being suppressed in M1 and M2a macrophages and in dendritic cells. Remarkably, although glucocorticoid-induced differentiation is IL-10 independent, M-CSF-driven M2c polarization and related MerTK upregulation require IL-10. However, neither IL-10 alone nor TGF-β are sufficient to fully differentiate M2c (CD16(+)CD163(+)MerTK(+)) macrophages. M-CSF and IL-10, both released by T lymphocytes, may thus be required together to promote regulatory T cell-mediated induction of anti-inflammatory monocytes-macrophages. MerTK enables M2c macrophages to clear early ACs more efficiently than other macrophage subsets, and it mediates AC clearance by CD14(bright)CD16(+) monocytes. Moreover, M2c cells release Gas6, which in turn amplifies IL-10 secretion via MerTK. IL-10-dependent induction of the Gas6/MerTK pathway may, therefore, constitute a positive loop for M2c macrophage homeostasis and a critical checkpoint for maintenance of anti-inflammatory conditions. Our findings give new insight into human macrophage polarization and favor a central role for MerTK in regulation of macrophage functions. Eliciting M2c polarization can have therapeutic utility for diseases such as lupus, in which a defective AC clearance contributes to initiate and perpetuate the pathological process.

  6. NCI Researchers Discover Exceptionally Potent Antibodies with Potential for Prophylaxis and Therapy of MERS-Coronavirus Infections | Poster

    Cancer.gov

    By Andrea Frydl, Contributing Writer In a recent article published in the Journal of Virology, Tianlei Ying, Ph.D., Dimiter Dimitrov, Ph.D., and their colleagues in the Laboratory of Experimental Immunology (LEI), Cancer and Inflammation Program, NCI Center for Cancer Research, reported the identification of three human monoclonal antibodies (m336, m337, and m338) that target the part of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) that is responsible for binding to its receptor. These antibodies are exceptionally potent inhibitors of MERS-CoV infection and also provide a basis for creating a future MERS-CoV vaccine.

  7. Application of State Analysis and Goal-Based Operations to a MER Mission Scenario

    NASA Technical Reports Server (NTRS)

    Morris, J. Richard; Ingham, Michel D.; Mishkin, Andrew H.; Rasmussen, Robert D.; Starbird, Thomas W.

    2006-01-01

    State Analysis is a model-based systems engineering methodology employing a rigorous discovery process which articulates operations concepts and operability needs as an integrated part of system design. The process produces requirements on system and software design in the form of explicit models which describe the behavior of states and the relationships among them. By applying State Analysis to an actual MER flight mission scenario, this study addresses the specific real world challenges of complex space operations and explores technologies that can be brought to bear on future missions. The paper describes the tools currently used on a daily basis for MER operations planning and provides an in-depth description of the planning process, in the context of a Martian day's worth of rover engineering activities, resource modeling, flight rules, science observations, and more. It then describes how State Analysis allows for the specification of a corresponding goal-based sequence that accomplishes the same objectives, with several important additional benefits.

  8. MAPGEN : mixed initiative planning and scheduling for the Mars '03 MER mission

    NASA Technical Reports Server (NTRS)

    Ai-Chang, Mitchell; Bresina, John; Charest, Len; Jonsson, Ari; Hsu, Jennifer; Kanefsky, Bob; Maldague, Pierre; Morris, Paul; Rajan, Kanna; Yglesias, Jeffrey

    2003-01-01

    The Mars Exploration Rovers Mars '03 mission is one of NASA's most ambitious science missions to date. The rovers will be launched in the summer of 2003 with each rover carrying instruments to conduct remote and in-situ observation to elucidate the planet's past climate, water activity, and habitability. Science is the primary driver of MER and, as a consequence, making best use of the scientific instruments, within the available resources, is a crucial aspect of the mission. To address this critically, the MER project has selected MAPGEN (Mixed-Initiative Activity Plan GENerator) as an activity planning tool. MAPGEN combines two exiting systems, each with a strong heritage: APGEN the Activity Planning tool from the Jet Propulsion Laboratory and the Europs Planning/Scheduling system from NASA Ames Research Center. This paper discusses the issues arising from combining these tools in the context of this mission.

  9. The Middle East respiratory syndrome coronavirus (MERS-CoV) does not replicate in Syrian hamsters.

    PubMed

    de Wit, Emmie; Prescott, Joseph; Baseler, Laura; Bushmaker, Trenton; Thomas, Tina; Lackemeyer, Matthew G; Martellaro, Cynthia; Milne-Price, Shauna; Haddock, Elaine; Haagmans, Bart L; Feldmann, Heinz; Munster, Vincent J

    2013-01-01

    In 2012 a novel coronavirus, MERS-CoV, associated with severe respiratory disease emerged in the Arabian Peninsula. To date, 55 human cases have been reported, including 31 fatal cases. Several of the cases were likely a result of human-to-human transmission. The emergence of this novel coronavirus prompts the need for a small animal model to study the pathogenesis of this virus and to test the efficacy of potential intervention strategies. In this study we explored the use of Syrian hamsters as a small animal disease model, using intratracheal inoculation and inoculation via aerosol. Clinical signs of disease, virus replication, histological lesions, cytokine upregulation nor seroconversion were observed in any of the inoculated animals, indicating that MERS-CoV does not replicate in Syrian hamsters.

  10. Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response.

    PubMed

    Kindler, E; Thiel, V; Weber, F

    2016-01-01

    Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are the most severe coronavirus (CoV)-associated diseases in humans. The causative agents, SARS-CoV and MERS-CoV, are of zoonotic origin but may be transmitted to humans, causing severe and often fatal respiratory disease in their new host. The two coronaviruses are thought to encode an unusually large number of factors that allow them to thrive and replicate in the presence of efficient host defense mechanisms, especially the antiviral interferon system. Here, we review the recent progress in our understanding of the strategies that highly pathogenic coronaviruses employ to escape, dampen, or block the antiviral interferon response in human cells.

  11. The Merli-Missiroli-Pozzi Two-Slit Electron-Interference Experiment.

    PubMed

    Rosa, Rodolfo

    In 2002 readers of Physics World voted Young's double-slit experiment with single electrons as "the most beautiful experiment in physics" of all time. Pier Giorgio Merli, Gian Franco Missiroli, and Giulio Pozzi carried out this experiment in a collaboration between the Italian Research Council and the University of Bologna almost three decades earlier. I examine their experiment, place it in historical context, and discuss its philosophical implications.

  12. The Merli-Missiroli-Pozzi Two-Slit Electron-Interference Experiment

    NASA Astrophysics Data System (ADS)

    Rosa, Rodolfo

    2012-06-01

    In 2002 readers of Physics World voted Young's double-slit experiment with single electrons as "the most beautiful experiment in physics" of all time. Pier Giorgio Merli, Gian Franco Missiroli, and Giulio Pozzi carried out this experiment in a collaboration between the Italian Research Council and the University of Bologna almost three decades earlier. I examine their experiment, place it in historical context, and discuss its philosophical implications.

  13. TAM receptors Tyro3 and Mer as novel targets in colorectal cancer

    PubMed Central

    Schmitz, Robin; Valls, Aida Freire; Yerbes, Rosario; von Richter, Sophie; Kahlert, Christoph; Loges, Sonja; Weitz, Jürgen; Schneider, Martin; de Almodovar, Carmen Ruiz; Ulrich, Alexis; Schmidt, Thomas

    2016-01-01

    Purpose CRC remains the third most common cancer worldwide with a high 5-year mortality rate in advanced cases. Combined with chemotherapy, targeted therapy is an additional treatment option. However as CRC still escapes targeted therapy the vigorous search for new targets is warranted to increase patients' overall survival. Results In this study we describe a new role for Gas6/protein S-TAM receptor interaction in CRC. Gas6, expressed by tumor-infiltrating M2-like macrophages, enhances malignant properties of tumor cells including proliferation, invasion and colony formation. Upon chemotherapy macrophages increase Gas6 synthesis, which significantly attenuates the cytotoxic effect of 5-FU chemotherapy on tumor cells. The anti-coagulant protein S has similar effects as Gas6. In CRC patient samples Tyro3 was overexpressed within the tumor. In-vitro inhibition of Tyro3 and Mer reduces tumor cell proliferation and sensitizes tumor cells to chemotherapy. Moreover high expression of Tyro3 and Mer in tumor tissue significantly shortens CRC patients' survival. Experimental design Various in vitro models were used to investigate the role of Gas6 and its TAM receptors in human CRC cells, by stimulation (rhGas6) and knockdown (siRNA) of Axl, Tyro3 and Mer. In terms of a translational research, we additionally performed an expression analysis in human CRC tissue and analyzed the medical record of these patients. Conclusions Tyro3 and Mer represent novel therapeutic targets in CRC and warrant further preclinical and clinical investigation in the future. PMID:27486820

  14. NCI Scientists Solve Structure of Protein that Enables MERS Virus to Spread | Poster

    Cancer.gov

    Scientists at the Frederick National Lab have produced three crystal structures that reveal a specific part of a protein that can be targeted to fight the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an emerging viral respiratory illness. Senior Investigator David Waugh, Ph.D., Macromolecular Crystallography Laboratory, has solved the structure of an enzyme known as the 3C-like protease (3CLpro), which, if blocked, can prevent the virus from replicating...

  15. Public response to MERS-CoV in the Middle East: iPhone survey in six countries.

    PubMed

    Alqahtani, Amani S; Rashid, Harunor; Basyouni, Mada H; Alhawassi, Tariq M; BinDhim, Nasser F

    2017-02-06

    Gulf Cooperation Council (GCC) countries bear the heaviest brunt of MERS-CoV. This study aims to compare public awareness and practice around MERS-CoV across GCC countries. A cross-sectional survey was conducted using the Gulf Indicators (GI) smartphone app among people in the six GCC countries, namely Saudi Arabia, Kuwait, the United Arab Emirates, Qatar, Bahrain, and Oman. A total of 1812 participants recruited. All were aware of MERS-CoV, yet the perception and practice around MERS-CoV varied widely between countries. Over two thirds were either "not concerned" or "slightly concerned" about contracting MERS-CoV; believing that they were under Allah's (God's) protection (40%) was the most cited reason. While 79% were aware that the disease can transmit through droplet from infected person, only 12% stated that MERS-CoV transmits via camels; people in Saudi Arabia were better aware of the transmission. Nevertheless, only 22% of respondents believed that camels are the zoonotic reservoir of MERS-CoV. Those who were concerned about contracting MERS-CoV (aOR: 1.6, 95% CI: 1.2-2.1, p<0.01) and those who thought MERS-CoV to be a severe disease only for those with high-risk conditions (aOR: 1.5, 95% CI: 1.1-2.1, p<0.01) were more likely to believe that camels are the zoonotic source. However, residents of KSA (aOR: 0.03, 95% CI: 0.01-0.07, p<0.01), UAE (aOR: 0.01, 95% CI: 0.004-0.02, p<0.01) and Kuwait (aOR: 0.03, 95% CI: 0.01-0.07, p<0.01) were less likely to believe that camels are the main zoonotic source compared to respondents from the other countries. Hygienic measures were more commonly adopted than avoidance of camels or their raw products, yet there was a discrepancy between the countries. This study highlights that despite being aware of the ongoing MERS-CoV epidemic; many people lack accurate understanding about MERS-CoV transmission, prevention, and are not fully compliant with preventive measures.

  16. [Middle East respiratory syndrome (MERS): bats or dromedary, which of them is responsible?].

    PubMed

    Chastel, C

    2014-05-01

    In 2012 a new viral emergent human disease appeared in the Middle East. This entity was named MERS for' Middle East respiratory syndrome'. By January 9, 2014, the disease had already struck 178 persons of whom 75 died from respiratory failure and diarrhoea. As the new disease was very similar to the deadly SARS (2002-2003) and since it was provoked by a Betacoronavirus, chiroptera were first suspected to be at the origin of this infection. Morever, recent studies performed in Saudi Arabia showed that one individual of the bat Taphozous perforatus harbored a short nucleotide segment identical to the homologous segment present in the viral strain isolated from the index-case of the epidemic. In addition, many strains of Betacoronavirus more or less related to those responsible for the MERS disease in man have been isolated from bats in Africa, Asia and Europe. However, another hypothesis was simultaneously proposed incriminating dromedary (Camelus dromedarius L.) as a likely actor in the transmission to human beings of the disease.We then reviewed data relative to other viral zoonosis in which dromedary was possibly implicated. This led to the provisional conclusion that this large mammal might play a role in the dissemination of the MERS-COV, the etiologic agent of the disease. This is based on epidemiological data and results of several serological surveys in animals.

  17. From Prime to Extended Mission: Evolution of the MER Tactical Uplink Process

    NASA Technical Reports Server (NTRS)

    Mishkin, Andrew H.; Laubach, Sharon

    2006-01-01

    To support a 90-day surface mission for two robotic rovers, the Mars Exploration Rover mission designed and implemented an intensive tactical operations process, enabling daily commanding of each rover. Using a combination of new processes, custom software tools, a Mars-time staffing schedule, and seven-day-a-week operations, the MER team was able to compress the traditional weeks-long command-turnaround for a deep space robotic mission to about 18 hours. However, the pace of this process was never intended to be continued indefinitely. Even before the end of the three-month prime mission, MER operations began evolving towards greater sustainability. A combination of continued software tool development, increasing team experience, and availability of reusable sequences first reduced the mean process duration to approximately 11 hours. The number of workshifts required to perform the process dropped, and the team returned to a modified 'Earth-time' schedule. Additional process and tool adaptation eventually provided the option of planning multiple Martian days of activity within a single workshift, making 5-day-a-week operations possible. The vast majority of the science team returned to their home institutions, continuing to participate fully in the tactical operations process remotely. MER has continued to operate for over two Earth-years as many of its key personnel have moved on to other projects, the operations team and budget have shrunk, and the rovers have begun to exhibit symptoms of aging.

  18. Avoiding student infection during a Middle East respiratory syndrome (MERS) outbreak: a single medical school experience

    PubMed Central

    2016-01-01

    Purpose: In outbreaks of infectious disease, medical students are easily overlooked in the management of healthcare personnel protection although they serve in clinical clerkships in hospitals. In the early summer of 2015, Middle East respiratory syndrome (MERS) struck South Korea, and students of Sungkyunkwan University School of Medicine (SKKUSOM) were at risk of contracting the disease. The purpose of this report is to share SKKUSOM’s experience against the MERS outbreak and provide suggestions for medical schools to consider in the face of similar challenges. Methods: Through a process of reflection-on-action, we examined SKKUSOM’s efforts to avoid student infection during the MERS outbreak and derived a few practical guidelines that medical schools can adopt to ensure student safety in outbreaks of infectious disease. Results: The school leadership conducted ongoing risk assessment and developed contingency plans to balance student safety and continuity in medical education. They rearranged the clerkships to another hospital and offered distant lectures and tutorials. Five suggestions are extracted for medical schools to consider in infection outbreaks: instant cessation of clinical clerkships; rational decision making on a school closure; use of information technology; constant communication with hospitals; and open communication with faculty, staff, and students. Conclusion: Medical schools need to take the initiative and actively seek countermeasures against student infection. It is essential that medical schools keep constant communication with their index hospitals and the involved personnel. In order to assure student learning, medical schools may consider offering distant education with online technology. PMID:27240893

  19. From Prime to Extended Mission: Evolution of the MER Tactical Uplink Process

    NASA Technical Reports Server (NTRS)

    Michkin, Andrew H.; Laubach, Sharon

    2006-01-01

    To support a 90-day surface mission for two robotic rovers, the Mars Exploration Rover mission designed and implemented an intensive tactical operations process, enabling daily commanding of each rover. Using a combination of new processes, custom software tools, a Mars-time staffing schedule, and seven-day-a-week operations, the MER team was able to compress the traditional weeks-long command-turnaround for a deep space robotic mission to about 18 hours. However, there was never an intention of maintaining the pace of this process indefinitely. Even before the end of the three-month prime mission, MER operations began evolving towards greater sustainability. A combination of continued software tool development, increasing team experience, and availability of reusable sequences first reduced the mean process duration to approximately 11 hours. The number of workshifts required to perform the process dropped, and the team returned to a modified 'Earth-time' schedule. Additional process and tool adaptation eventually provided the option of planning multiple Martian days of activity within a single workshift, making 5- day-a-week operations possible. The vast majority of the science team returned to their home institutions, continuing to participate fully in the tactical operations process remotely. MER has continued to operate for over two Earth-years as many of its key personnel have moved on to other projects, the operations team and budget have shrunk, and the rovers have begun to exhibit symptoms of aging.

  20. Meter-scale slopes of candidate MER landing sites from point photoclinometry

    USGS Publications Warehouse

    Beyer, R.A.; McEwen, A.S.; Kirk, R.L.

    2003-01-01

    Photoclinometry was used to analyze the small-scale roughness of areas that fall within the proposed Mars Exploration Rover (MER) 2003 landing ellipses. The landing ellipses presented in this study were those in Athabasca Valles, Elysium Planitia, Eos Chasma, Gusev Crater, Isidis Planitia, Melas Chasma, and Meridiani Planum. We were able to constrain surface slopes on length scales comparable to the image resolution (1.5 to 12 m/pixel). The MER 2003 mission has various engineering constraints that each candidate landing ellipse must satisfy. These constraints indicate that the statistical slope values at 5 m baselines are an important criterion. We used our technique to constrain maximum surface slopes across large swaths of each image, and built up slope statistics for the images in each landing ellipse. We are confident that all MER 2003 landing site ellipses in this study, with the exception of the Melas Chasma ellipse, are within the small-scale roughness constraints. Our results have provided input into the landing hazard assessment process. In addition to evaluating the safety of the landing sites, our mapping of small-scale roughnesses can also be used to better define and map morphologic units. The morphology of a surface is characterized by the slope distribution and magnitude of slopes. In looking at how slopes are distributed, we can better define landforms and determine the boundaries of morphologic units. Copyright 2003 by the American Geophysical Union.

  1. Geology of the MER 2003 "Elysium" candidate landing site in southeastern Utopia Planitia, Mars

    USGS Publications Warehouse

    Tanaka, K.L.; Carr, M.H.; Skinner, J.A.; Gilmore, M.S.; Hare, T.M.

    2003-01-01

    The NASA Mars Exploration Rover (MER) Project has been considering a landing-site ellipse designated EP78B2 in southeastern Utopia Planitia, southwest of Elysium Mons. The site appears to be relatively safe for a MER landing site because of its predicted low wind velocities in mesoscale atmospheric circulation models and its low surface roughness at various scales as indicated by topographic and imaging data sets. Previously, the site's surface rocks have been interpreted to be marine sediments or lava flows. In addition, we suggest that Late Noachian to Early Hesperian collapse and mass wasting of Noachian highland rocks contributed to the deposition of detritus in the area of the ellipse. Furthermore, we document partial Late Hesperian to Early Amazonian resurfacing of the ellipse by flows and vents that may be of mud or silicate volcanic origin. A rover investigation of the Utopia landing site using the MER Athena instrument package might address some fundamental aspects of Martian geologic evolution, such as climate change, hydrologic evolution, and magmatic and tectonic history. Copyright 2003 by the American Geophysical Union.

  2. Relationship between the persistence of mer operon sequences in Escherichia coli and their resistance to mercury.

    PubMed

    Murtaza, Imtiyaz; Dutt, Amit; Ali, Arif

    2002-03-01

    Studies related to geographic distribution of E. coli carrying mer operon sequences were carried out on the Indian subcontinent. Out of the 80 E. coli isolates, collected from five geographically distinct regions of India, 68 were found to be resistant to one or the other heavy metal used in the study. Among these isolates, 36 were found to be resistant to the inorganic form (HgCl2) and only 5 to resist both the inorganic and organic forms of mercury. Colony hybridization studies revealed 35 isolates out of 68 to hybridize with the probe. Interestingly, some of the mercury-sensitive isolates (Hgs), especially from the Dal Lake, were found positive in hybridization studies. These findings, supported by mercury volatilization studies, indicate the presence of nonfunctional/vestigial mer sequences in the isolates collected from different environments. On the other hand, few of the mercury-resistant isolates (Hgr) from the Yamuna River did not show any sign of hybridization. Further, volatilization studies also indicated an alternate mode of resistance mechanism operating in them. The studies demonstrate that the mer operon sequences share very high homology among the E. coli isolates collected from different geographical locations, and this metal resistance may be a genetic character that arose from a common ancestral background.

  3. Thermophysical properties of the MER and Beagle II landing site regions on Mars

    NASA Astrophysics Data System (ADS)

    Jakosky, Bruce M.; Hynek, Brian M.; Pelkey, Shannon M.; Mellon, Michael T.; Martínez-Alonso, Sara; Putzig, Nathaniel E.; Murphy, Nate; Christensen, Philip R.

    2006-08-01

    We analyzed remote-sensing observations of the Isidis Basin, Gusev Crater, and Meridiani Planum landing sites for Beagle II, MER-A Spirit, and MER-B Opportunity spacecraft, respectively. We emphasized the thermophysical properties using daytime and nighttime radiance measurements from the Mars Global Surveyor (MGS) Thermal Emission Spectrometer and Mars Odyssey Thermal Emission Imaging System (THEMIS) and thermal inertias derived from nighttime data sets. THEMIS visible images, MGS Mars Orbiter Camera (MOC) narrow-angle images, and MGS Mars Orbiter Laser Altimeter (MOLA) data are incorporated as well. Additionally, the remote-sensing data were compared with ground-truth at the MER sites. The Isidis Basin surface layer has been shaped by aeolian processes and erosion by slope winds coming off of the southern highlands and funneling through notches between massifs. In the Gusev region, surface materials of contrasting thermophysical properties have been interpreted as rocks or bedrock, duricrust, and dust deposits; these are consistent with a complex geological history dominated by volcanic and aeolian processes. At Meridiani Planum the many layers having different thermophysical and erosional properties suggest periodic deposition of differing sedimentological facies possibly related to clast size, grain orientation and packing, or mineralogy.

  4. Understanding M-ligand bonding and mer-/fac-isomerism in tris(8-hydroxyquinolinate) metallic complexes.

    PubMed

    Lima, Carlos F R A C; Taveira, Ricardo J S; Costa, José C S; Fernandes, Ana M; Melo, André; Silva, Artur M S; Santos, Luís M N B F

    2016-06-28

    Tris(8-hydroxyquinolinate) metallic complexes, Mq3, are one of the most important classes of organic semiconductor materials. Herein, the nature of the chemical bond in Mq3 complexes and its implications on their molecular properties were investigated by a combined experimental and computational approach. Various Mq3 complexes, resulting from the alteration of the metal and substitution of the 8-hydroxyquinoline ligand in different positions, were prepared. The mer-/fac-isomerism in Mq3 was explored by FTIR and NMR spectroscopy, evidencing that, irrespective of the substituent, mer- and fac-are the most stable molecular configurations of Al(iii) and In(iii) complexes, respectively. The relative M-ligand bond dissociation energies were evaluated experimentally by electrospray ionization tandem mass spectrometry (ESI-MS-MS), showing a non-monotonous variation along the group (Al > In > Ga). The results reveal a strong covalent character in M-ligand bonding, which allows for through-ligand electron delocalization, and explain the preferred molecular structures of Mq3 complexes as resulting from the interplay between bonding and steric factors. The mer-isomer reduces intraligand repulsions, being preferred for smaller metals, while the fac-isomer is favoured for larger metals where stronger covalent M-ligand bonds can be formed due to more extensive through-ligand conjugation mediated by metal "d" orbitals.

  5. Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein

    PubMed Central

    Al-amri, Sawsan S.; Abbas, Ayman T.; Siddiq, Loai A.; Alghamdi, Abrar; Sanki, Mohammad A.; Al-Muhanna, Muhanna K.; Alhabbab, Rowa Y.; Azhar, Esam I.; Li, Xuguang; Hashem, Anwar M.

    2017-01-01

    MERS-coronavirus is a novel zoonotic pathogen which spread rapidly to >25 countries since 2012. Its apparent endemicity and the wide spread of its reservoir host (dromedary camels) in the Arabian Peninsula highlight the ongoing public health threat of this virus. Therefore, development of effective prophylactic vaccine needs to be urgently explored given that there are no approved prophylactics or therapeutics for humans or animals to date. Different vaccine candidates have been investigated but serious safety concerns remain over protein or full-length spike (S) protein-based vaccines. Here, we investigated the immunogenicity of naked DNA vaccines expressing different fragments of MERS-CoV S protein in mice. We found that plasmids expressing full-length (pS) or S1-subunit (pS1) could induce significant levels of S1-specific antibodies (Abs) but with distinct IgG isotype patterns. Specifically, pS1 immunization elicited a balanced Th1/Th2 response and generally higher levels of all IgG isotypes compared to pS vaccination. Interestingly, only mice immunized with pS1 demonstrated significant S1-specific cellular immune response. Importantly, both constructs induced cross-neutralizing Abs against multiple strains of human and camel origins. These results indicate that vaccines expressing S1-subunit of the MERS-CoV S protein could represent a potential vaccine candidate without the possible safety concerns associated with full-length protein-based vaccines. PMID:28332568

  6. Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution

    PubMed Central

    Tang, Xian-Chun; Agnihothram, Sudhakar S.; Jiao, Yongjun; Stanhope, Jeremy; Graham, Rachel L.; Peterson, Eric C.; Avnir, Yuval; Tallarico, Aimee St. Clair; Sheehan, Jared; Zhu, Quan; Baric, Ralph S.; Marasco, Wayne A.

    2014-01-01

    The newly emerging Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a Severe Acute Respiratory Syndrome-like disease with ∼43% mortality. Given the recent detection of virus in dromedary camels, zoonotic transfer of MERS-CoV to humans is suspected. In addition, little is known about the role of human neutralizing Ab (nAb) pressure as a driving force in MERS-CoV adaptive evolution. Here, we used a well-characterized nonimmune human Ab-phage library and a panning strategy with proteoliposomes and cells to identify seven human nAbs against the receptor-binding domain (RBD) of the MERS-CoV Spike protein. These nAbs bind to three different epitopes in the RBD and human dipeptidyl peptidase 4 (hDPP4) interface with subnanomolar/nanomolar binding affinities and block the binding of MERS-CoV Spike protein with its hDPP4 receptor. Escape mutant assays identified five amino acid residues that are critical for neutralization escape. Despite the close proximity of the three epitopes on the RBD interface, escape from one epitope did not have a major impact on neutralization with Abs directed to a different epitope. Importantly, the majority of escape mutations had negative impacts on hDPP4 receptor binding and viral fitness. To our knowledge, these results provide the first report on human nAbs against MERS-CoV that may contribute to MERS-CoV clearance and evolution. Moreover, in the absence of a licensed vaccine or antiviral for MERS, this panel of nAbs offers the possibility of developing human mAb-based immunotherapy, especially for health-care workers. PMID:24778221

  7. External Store Airloads Prediction Technique. Volume 2. Detailed Data. Book 3. MER Carriage Side Force and Yawing Moment Predictions

    DTIC Science & Technology

    1975-07-01

    STORE.AIRLOADS- PREDICTION TE-CHNIQUE 0: VOLUMEE DETAILED DATA. BOOK 3. MER CARRIAGE SIDE FORCE AND YAWING MOMENT PREDICTIONS, VOUGHT SYSTEMS DIVISION...OF CONTENTS Section Title Page No. IV MER Carriage Airload Prediction ..................... 385 4.1 Side Force...obtain an initial prediction for the side force, yawing moment, normal force, and pitching moment components for the two rack centerline stations (MIR

  8. Molecular cloning of MER-2, a human chromosome-11-encoded red blood cell antigen, using linkage of cotransfected markers.

    PubMed

    Bill, J; Palmer, E; Jones, C

    1987-09-01

    We report the molecular cloning of a human gene MER-2 located on chromosome 11 that encodes a cell surface antigen which is polymorphic on red blood cells. An essential element of the cloning strategy was cotransfection-induced linkage of pSV2-neo, which encodes resistance to the antibiotic G418, to the human MER-2 gene. An important feature of the pSV2-neo construct is that the same gene (the transposon, Tn5) that encodes G418 resistance in eukaryotic cells confers neomycin resistance in bacteria. Chinese hamster ovary (CHO) cells were cotransfected with pSV2-neo and genomic DNA from a CHO X human cell hybrid containing a single human chromosome (chromosome 11). Transfectants expressing both the human MER-2 gene and G418 resistance were isolated by selection in the antibiotic G418, followed by indirect immunofluorescence using the monoclonal antibody 1D12, which recognizes the MER-2 antigen, manual enrichment, and single-cell cloning. Genomic DNA from a primary transfectant positive for MER-2 expression and G418 resistance was used to construct a cosmid library and cosmid clones able to grow in neomycin were isolated. Of 150,000 cosmid clones screened, 90 were resistant to neomycin and of these, 11 contained human repetitive sequences. Five neomycin-resistant cosmid clones containing human repetitive DNA were able to transfect CHO cells for G418 resistance and MER-2 expression.

  9. Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26.

    PubMed

    Wang, Qihui; Qi, Jianxun; Yuan, Yuan; Xuan, Yifang; Han, Pengcheng; Wan, Yuhua; Ji, Wei; Li, Yan; Wu, Ying; Wang, Jianwei; Iwamoto, Aikichi; Woo, Patrick C Y; Yuen, Kwok-Yung; Yan, Jinghua; Lu, Guangwen; Gao, George F

    2014-09-10

    The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) is phylogenetically closely related to the bat coronaviruses (BatCoVs) HKU4 and HKU5. However, the evolutionary pathway of MERS-CoV is still unclear. A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry. The high sequence identity in the viral spike protein prompted us to investigate if HKU4 and HKU5 can recognize hCD26 for cell entry. We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition. The structure of the HKU4-RBD/hCD26 complex revealed a hCD26-binding mode similar overall to that observed for MERS-RBD. HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD, explaining its lower affinity for receptor binding. Our findings support a bat origin for MERS-CoV and indicate the need for surveillance of HKU4-related viruses in bats.

  10. Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

    PubMed Central

    Johnson, Reed F.; Via, Laura E.; Kumar, Mia R.; Cornish, Joseph P.; Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R.; Solomon, Jeffrey; Johnson, Joshua C.; Pickel, James; Hensley, Lisa E.; Jahrling, Peter B.

    2016-01-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. PMID:26342468

  11. Efficient Design of Compact Unstructured RNA Libraries Covering All k-mers

    PubMed Central

    Orenstein, Yaron

    2016-01-01

    Abstract Current microarray technologies to determine RNA structure or measure protein–RNA interactions rely on single-stranded, unstructured RNA probes on a chip covering together all k-mers. Since space on the array is limited, the problem is to efficiently design a compact library of unstructured ℓ-long RNA probes, where each k-mer is covered at least p times. Ray et al. designed such a library for specific values of k, ℓ, and p using ad-hoc rules. To our knowledge, there is no general method to date to solve this problem. Here, we address the problem of finding a minimum-size covering of all k-mers by ℓ-long sequences with the desired properties for any value of k, ℓ, and p. As we prove that the problem is NP-hard, we give two solutions: the first is a greedy algorithm with a logarithmic approximation ratio; the second, a heuristic greedy approach based on random walks in de Bruijn graphs. The heuristic algorithm works well in practice and produces a library of unstructured RNA probes that is only ∼1.1-times greater in size compared to the theoretical lower bound. We present results for typical values of k and probe lengths ℓ and show that our algorithm generates a library that is significantly smaller than the library of Ray et al.; moreover, we show that our algorithm outperforms naive methods. Our approach can be generalized and extended to generate RNA or DNA oligo libraries with other desired properties. The software is freely available online. PMID:26713687

  12. The Amorphous Component in Martian Basaltic Soil in Global Perspective from MSL and MER Missions

    NASA Technical Reports Server (NTRS)

    Morris, R. V.; Ming, D. W.; Blake, D. F.; Vaniman, D. T.; Bish, D. L.; Chipera, S. J.; Downs, R. T.; Gellert, R.; Treiman, A. H.; Yen, A. S.; Achilles, C. N.; Anderson, R. C.; Bristow, T. F.; Crisp, J. A.; Des Marais, D. J.; Farmer, J. D.; Grotzinger, J. P.; Leshin, L. A.; McAdam, A. C.; Morookian, J. M.; Morrison, S. M.; Rampe, E. B.; Sarrazin, P. C.; Spanovich, N.; Stolper, E. M.

    2013-01-01

    The mineralogy instrument CheMin onboard the MSL rover Curiosity analyzed by transmission XRD [1] the <150 microns size fraction of putative global basaltic martian soil from scoops 4 and 5 of the Rocknest aeolian bedform (sol 81-120). Here, we combine chemical (APXS) and mineralogical (Mossbauer; MB) results from the MER rovers with chemical (APXS) and mineralogical (CheMin) results from Curiosity to constrain the relative proportions of amorphous and crystalline components, the bulk chemical composition of those components, and the

  13. Electrical conductivity of a monolayer produced by random sequential adsorption of linear k -mers onto a square lattice

    NASA Astrophysics Data System (ADS)

    Tarasevich, Yuri Yu.; Goltseva, Valeria A.; Laptev, Valeri V.; Lebovka, Nikolai I.

    2016-10-01

    The electrical conductivity of a monolayer produced by the random sequential adsorption (RSA) of linear k -mers (particles occupying k adjacent adsorption sites) onto a square lattice was studied by means of computer simulation. Overlapping with predeposited k -mers and detachment from the surface were forbidden. The RSA process continued until the saturation jamming limit, pj. The isotropic (equiprobable orientations of k -mers along x and y axes) and anisotropic (all k -mers aligned along the y axis) depositions for two different models—of an insulating substrate and conducting k -mers (C model) and of a conducting substrate and insulating k -mers (I model)—were examined. The Frank-Lobb algorithm was applied to calculate the electrical conductivity in both the x and y directions for different lengths (k =1 - 128) and concentrations (p =0 - pj) of the k -mers. The "intrinsic electrical conductivity" and concentration dependence of the relative electrical conductivity Σ (p ) (Σ =σ /σm for the C model and Σ =σm/σ for the I model, where σm is the electrical conductivity of substrate) in different directions were analyzed. At large values of k the Σ (p ) curves became very similar and they almost coincided at k =128 . Moreover, for both models the greater the length of the k -mers the smoother the functions Σx y(p ) ,Σx(p ) and Σy(p ) . For the more practically important C model, the other interesting findings are (i) for large values of k (k =64 ,128 ), the values of Σx y and Σy increase rapidly with the initial increase of p from 0 to 0.1; (ii) for k ≥16 , all the Σx y(p ) and Σx(p ) curves intersect with each other at the same isoconductivity points; (iii) for anisotropic deposition, the percolation concentrations are the same in the x and y directions, whereas, at the percolation point the greater the length of the k -mers the larger the anisotropy of the electrical conductivity, i.e., the ratio σy/σx (>1 ).

  14. 2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) nosocomial outbreak in South Korea: insights from modeling.

    PubMed

    Hsieh, Ying-Hen

    2015-01-01

    Background. Since the emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, more than 1,300 laboratory confirmed cases of MERS-CoV infections have been reported in Asia, North Africa, and Europe by July 2015. The recent MERS-CoV nosocomial outbreak in South Korea quickly became the second largest such outbreak with 186 total cases and 36 deaths in a little more than one month, second only to Saudi Arabia in country-specific number of reported cases. Methods. We use a simple mathematical model, the Richards model, to trace the temporal course of the South Korea MERS-CoV outbreak. We pinpoint its outbreak turning point and its transmissibility via basic reproduction number R 0 in order to ascertain the occurrence of this nosocomial outbreak and how it was quickly brought under control. Results. The estimated outbreak turning point of ti = 23.3 days (95% CI [22.6-24.0]), or 23-24 days after the onset date of the index case on May 11, pinpoints June 3-4 as the time of the turning point or the peak incidence for this outbreak by onset date. R 0 is estimated to range between 7.0 and 19.3. Discussion and Conclusion. The turning point of the South Korea MERS-CoV outbreak occurred around May 27-29, when control measures were quickly implemented after laboratory confirmation of the first cluster of nosocomial infections by the index patient. Furthermore, transmissibility of MERS-CoV in the South Korea outbreak was significantly higher than those reported from past MERS-CoV outbreaks in the Middle East, which is attributable to the nosocomial nature of this outbreak. Our estimate of R 0 for the South Korea MERS-CoV nosocomial outbreak further highlights the importance and the risk involved in cluster infections and superspreading events in crowded settings such as hospitals. Similar to the 2003 SARS epidemic, outbreaks of infectious diseases with low community transmissibility like MERS-CoV could still occur initially with large clusters of nosocomial

  15. Electrical conductivity of a monolayer produced by random sequential adsorption of linear k-mers onto a square lattice.

    PubMed

    Tarasevich, Yuri Yu; Goltseva, Valeria A; Laptev, Valeri V; Lebovka, Nikolai I

    2016-10-01

    The electrical conductivity of a monolayer produced by the random sequential adsorption (RSA) of linear k-mers (particles occupying k adjacent adsorption sites) onto a square lattice was studied by means of computer simulation. Overlapping with predeposited k-mers and detachment from the surface were forbidden. The RSA process continued until the saturation jamming limit, p_{j}. The isotropic (equiprobable orientations of k-mers along x and y axes) and anisotropic (all k-mers aligned along the y axis) depositions for two different models-of an insulating substrate and conducting k-mers (C model) and of a conducting substrate and insulating k-mers (I model)-were examined. The Frank-Lobb algorithm was applied to calculate the electrical conductivity in both the x and y directions for different lengths (k=1 - 128) and concentrations (p=0 - p_{j}) of the k-mers. The "intrinsic electrical conductivity" and concentration dependence of the relative electrical conductivity Σ(p) (Σ=σ/σ_{m} for the C model and Σ=σ_{m}/σ for the I model, where σ_{m} is the electrical conductivity of substrate) in different directions were analyzed. At large values of k the Σ(p) curves became very similar and they almost coincided at k=128. Moreover, for both models the greater the length of the k-mers the smoother the functions Σ_{xy}(p),Σ_{x}(p) and Σ_{y}(p). For the more practically important C model, the other interesting findings are (i) for large values of k (k=64,128), the values of Σ_{xy} and Σ_{y} increase rapidly with the initial increase of p from 0 to 0.1; (ii) for k≥16, all the Σ_{xy}(p) and Σ_{x}(p) curves intersect with each other at the same isoconductivity points; (iii) for anisotropic deposition, the percolation concentrations are the same in the x and y directions, whereas, at the percolation point the greater the length of the k-mers the larger the anisotropy of the electrical conductivity, i.e., the ratio σ_{y}/σ_{x} (>1).

  16. Pseudo Cyclization through Intramolecular Hydrogen Bond Enables Discovery of Pyridine Substituted Pyrimidines as New Mer Kinase Inhibitors

    PubMed Central

    Zhang, Weihe; Zhang, Dehui; Stashko, Michael A; DeRyckere, Deborah; Hunter, Debra; Kireev, Dmitri; Miley, Michael J; Cummings, Christopher; Lee, Minjung; Norris-Drouin, Jacqueline; Stewart, Wendy M.; Sather, Susan; Zhou, Yingqiu; Kirkpatrick, Gregory; Machius, Mischa; Janzen, William P.; Earp, H Shelton; Graham, Douglas K.; Frye, Stephen V.; Wang, Xiaodong

    2014-01-01

    Abnormal activation or overexpression of Mer receptor tyrosine kinase has been implicated in survival signaling and chemoresistance in many human cancers. Consequently, Mer is a promising novel cancer therapeutic target. A structure-based drug design approach using a pseudo-ring replacement strategy was developed and validated to discover a new family of pyridinepyrimidine analogs as potent Mer inhibitors. Through SAR studies, 10 (UNC2250) was identified as the lead compound for further investigation based on high selectivity against other kinases and good pharmacokinetic properties. When applied to live cells, 10 inhibited steady-state phosphorylation of endogenous Mer with an IC50 of 9.8 nM and blocked ligand-stimulated activation of a chimeric EGFR-Mer protein. Treatment with 10 also resulted in decreased colony-forming potential in rhabdoid and NSCLC tumor cells, thereby demonstrating functional anti-tumor activity. The results provide a rationale for further investigation of this compound for therapeutic application in patients with cancer. PMID:24195762

  17. Pseudo-cyclization through intramolecular hydrogen bond enables discovery of pyridine substituted pyrimidines as new Mer kinase inhibitors.

    PubMed

    Zhang, Weihe; Zhang, Dehui; Stashko, Michael A; DeRyckere, Deborah; Hunter, Debra; Kireev, Dmitri; Miley, Michael J; Cummings, Christopher; Lee, Minjung; Norris-Drouin, Jacqueline; Stewart, Wendy M; Sather, Susan; Zhou, Yingqiu; Kirkpatrick, Gregory; Machius, Mischa; Janzen, William P; Earp, H Shelton; Graham, Douglas K; Frye, Stephen V; Wang, Xiaodong

    2013-12-12

    Abnormal activation or overexpression of Mer receptor tyrosine kinase has been implicated in survival signaling and chemoresistance in many human cancers. Consequently, Mer is a promising novel cancer therapeutic target. A structure-based drug design approach using a pseudo-ring replacement strategy was developed and validated to discover a new family of pyridinepyrimidine analogues as potent Mer inhibitors. Through SAR studies, 10 (UNC2250) was identified as the lead compound for further investigation based on high selectivity against other kinases and good pharmacokinetic properties. When applied to live cells, 10 inhibited steady-state phosphorylation of endogenous Mer with an IC50 of 9.8 nM and blocked ligand-stimulated activation of a chimeric EGFR-Mer protein. Treatment with 10 also resulted in decreased colony-forming potential in rhabdoid and NSCLC tumor cells, thereby demonstrating functional antitumor activity. The results provide a rationale for further investigation of this compound for therapeutic application in patients with cancer.

  18. The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses

    PubMed Central

    Forni, Diego; Filippi, Giulia; Cagliani, Rachele; De Gioia, Luca; Pozzoli, Uberto; Al-Daghri, Nasser; Clerici, Mario; Sironi, Manuela

    2015-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of the spike (S) gene in betacoronaviruses (betaCoVs) isolated from different mammals, in bat coronavirus populations, as well as in MERS-CoV strains from the current outbreak. Results indicated several positively selected sites located in the region comprising the two heptad repeats (HR1 and HR2) and their linker. Two sites (R652 and V1060) were positively selected in the betaCoVs phylogeny and correspond to mutations associated with expanded host range in other coronaviruses. During the most recent evolution of MERS-CoV, adaptive mutations in the HR1 (Q/R/H1020) arose in camels or in a previous host and spread to humans. We determined that different residues at position 1020 establish distinct inter- and intra-helical interactions and affect the stability of the six-helix bundle formed by the HRs. A similar effect on stability was observed for a nearby mutation (T1015N) that increases MERS-CoV infection efficiency in vitro. Data herein indicate that the heptad repeat region was a major target of adaptive evolution in MERS-CoV-related viruses; these results are relevant for the design of fusion inhibitor peptides with antiviral function. PMID:26404138

  19. Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CL(Pro) inhibitors.

    PubMed

    Kumar, Vathan; Shin, Jin Soo; Shie, Jiun-Jie; Ku, Keun Bon; Kim, Chonsaeng; Go, Yun Young; Huang, Kai-Fa; Kim, Meehyein; Liang, Po-Huang

    2017-02-17

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory illness with fever, cough and shortness of breath. Up to date, it has resulted in 1826 human infections, including 649 deaths. Analogous to picornavirus 3C protease (3C(pro)), 3C-like protease (3CL(pro)) is critical for initiation of the MERS-CoV replication cycle and is thus regarded as a validated drug target. As presented here, our peptidomimetic inhibitors of enterovirus 3C(pro) (6b, 6c and 6d) inhibited 3CL(pro) of MERS-CoV and severe acute respiratory syndrome coronavirus (SARS-CoV) with IC50 values ranging from 1.7 to 4.7 μM and from 0.2 to 0.7 μM, respectively. In MERS-CoV-infected cells, the inhibitors showed antiviral activity with EC50 values ranging from 0.6 to 1.4 μM, by downregulating the viral protein production in cells as well as reducing secretion of infectious viral particles into culture supernatants. They also suppressed other α- and β-CoVs from human and feline origin. These compounds exhibited good selectivity index (over 70 against MERS-CoV) and could lead to the development of broad-spectrum antiviral drugs against emerging CoVs and picornaviruses.

  20. Application of State Analysis and Goal-based Operations to a MER Mission Scenario

    NASA Technical Reports Server (NTRS)

    Morris, John Richard; Ingham, Michel D.; Mishkin, Andrew H.; Rasmussen, Robert D.; Starbird, Thomas W.

    2006-01-01

    State Analysis is a model-based systems engineering methodology employing a rigorous discovery process which articulates operations concepts and operability needs as an integrated part of system design. The process produces requirements on system and software design in the form of explicit models which describe the system behavior in terms of state variables and the relationships among them. By applying State Analysis to an actual MER flight mission scenario, this study addresses the specific real world challenges of complex space operations and explores technologies that can be brought to bear on future missions. The paper first describes the tools currently used on a daily basis for MER operations planning and provides an in-depth description of the planning process, in the context of a Martian day's worth of rover engineering activities, resource modeling, flight rules, science observations, and more. It then describes how State Analysis allows for the specification of a corresponding goal-based sequence that accomplishes the same objectives, with several important additional benefits.

  1. Molecular phylogenetics before sequences: oligonucleotide catalogs as k-mer spectra.

    PubMed

    Ragan, Mark A; Bernard, Guillaume; Chan, Cheong Xin

    2014-01-01

    From 1971 to 1985, Carl Woese and colleagues generated oligonucleotide catalogs of 16S/18S rRNAs from more than 400 organisms. Using these incomplete and imperfect data, Carl and his colleagues developed unprecedented insights into the structure, function, and evolution of the large RNA components of the translational apparatus. They recognized a third domain of life, revealed the phylogenetic backbone of bacteria (and its limitations), delineated taxa, and explored the tempo and mode of microbial evolution. For these discoveries to have stood the test of time, oligonucleotide catalogs must carry significant phylogenetic signal; they thus bear re-examination in view of the current interest in alignment-free phylogenetics based on k-mers. Here we consider the aims, successes, and limitations of this early phase of molecular phylogenetics. We computationally generate oligonucleotide sets (e-catalogs) from 16S/18S rRNA sequences, calculate pairwise distances between them based on D 2 statistics, compute distance trees, and compare their performance against alignment-based and k-mer trees. Although the catalogs themselves were superseded by full-length sequences, this stage in the development of computational molecular biology remains instructive for us today.

  2. Exploring the GalMer database: bar properties and non-circular motions

    NASA Astrophysics Data System (ADS)

    Randriamampandry, T. H.; Deg, N.; Carignan, C.; Combes, F.; Spekkens, K.

    2016-10-01

    Context. We use Tree-SPH simulations from the GalMer database to characterize and quantify the non-circular motions induced by the presence of bar-like structures on the observed rotation curve of barred galaxies derived from empirical models of their line-of-sight velocity maps. The GalMer database consists of SPH simulations of galaxies spanning a wide range of morphological types and sizes. Aims: The aim is to compare the intrinsic velocities and bar properties from the simulations with those derived from pseudo-observations. This allows us to estimate the amount of non-circularity and to test the various methods used to derive the bar properties and rotation curves. Methods: The intrinsic velocities in the simulations are calculated from the gravitational forces whereas the observed rotation velocities are derived by applying the ROTCUR and DiskFit algorithms to well-resolved observations of intermediate-inclination, strongly barred galaxies. Results: Our results confirm that the tilted ring method implemented in ROTCUR systematically underestimates or overestimates the rotational velocities by up to 40 percent in the inner part of the galaxy when the bar is aligned with one of the symmetry axes for all the models. For the DiskFit analysis, we find that it produces unrealistic values for all the models used in this work when the bar is within approximately ten degrees of the major or minor axis.

  3. Seasonal Variation of Aerosol Particle Size Using MER/Pancam Sky Imaging

    NASA Astrophysics Data System (ADS)

    Smith, M. D.; Wolff, M. J.

    2013-12-01

    Imaging of the sky taken by the Pancam cameras on-board the Mars Exploration Rovers (MER) provide a useful tool for determining the optical depth and physcial properties of aerosols above the rover. Specifically, the brightness of the sky as a function of angle away from the Sun provides a powerful constraint on the size distribution and shape of dust and water ice aerosols. More than 100 Pancam "sky surveys" were taken by each of the two MER rovers covering a time span of several Mars years and a wide range of dust loading conditions including the planet-encirclind dust storm during Mars Year 28 (Earth year 2007). These sky surveys enable the time evolution of aerosol particle size to be determined including its relation to dust loading. Radiative transfer modeling is used to model the observations. Synthetic Pancam sky brightness is computed using a discrete-ordinates radiative transfer code that accounts for multiple scattering from aerosols and spherical geometry by integrating the source functions along curved paths in that coordinate system. We find that Mie scattering from spheres is not a good approximation for describing the angular variation of sky brightness far from the Sun (at scattering angles greater than 45 degrees). Significant seasonal variations are seen in the retrieved effective radius of the aerosols with higher optical depth strongly correlated with larger particle size.

  4. Genome Sizes of Nine Insect Species Determined by Flow Cytometry and k-mer Analysis

    PubMed Central

    He, Kang; Lin, Kejian; Wang, Guirong; Li, Fei

    2016-01-01

    The flow cytometry method was used to estimate the genome sizes of nine agriculturally important insects, including two coleopterans, five Hemipterans, and two hymenopterans. Among which, the coleopteran Lissorhoptrus oryzophilus (Kuschel) had the largest genome of 981 Mb. The average genome size was 504 Mb, suggesting that insects have a moderate-size genome. Compared with the insects in other orders, hymenopterans had small genomes, which were averagely about ~200 Mb. We found that the genome sizes of four insect species were different between male and female, showing the organismal complexity of insects. The largest difference occurred in the coconut leaf beetle Brontispa longissima (Gestro). The male coconut leaf beetle had a 111 Mb larger genome than females, which might be due to the chromosome number difference between the sexes. The results indicated that insect invasiveness was not related to genome size. We also determined the genome sizes of the small brown planthopper Laodelphax striatellus (Fallén) and the parasitic wasp Macrocentrus cingulum (Brischke) using k-mer analysis with Illunima Solexa sequencing data. There were slight differences in the results from the two methods. k-mer analysis indicated that the genome size of L. striatellus was 500–700 Mb and that of M. cingulum was ~150 Mb. In all, the genome sizes information presented here should be helpful for designing the genome sequencing strategy when necessary. PMID:27932995

  5. Acute viral respiratory infections among children in MERS-endemic Riyadh, Saudi Arabia, 2012-2013.

    PubMed

    Fagbo, Shamsudeen F; Garbati, Musa A; Hasan, Rami; AlShahrani, Dayel; Al-Shehri, Mohamed; AlFawaz, Tariq; Hakawi, Ahmed; Wani, Tariq Ahmad; Skakni, Leila

    2017-02-01

    The emergence of the Middle East Respiratory Syndrome (MERS) in Saudi Arabia has intensified focus on Acute Respiratory Infections [ARIs]. This study sought to identify respiratory viruses (RVs) associated with ARIs in children presenting at a tertiary hospital. Children (aged ≤13) presenting with ARI between January 2012 and December 2013 tested for 15 RVs using the Seeplex(R) RV15 kit were retrospectively included. Epidemiological data was retrieved from patient records. Of the 2235 children tested, 61.5% were ≤1 year with a male: female ratio of 3:2. Viruses were detected in 1364 (61.02%) children, 233 (10.4%) having dual infections: these viruses include respiratory syncytial virus (RSV) (24%), human rhinovirus (hRV) (19.7%), adenovirus (5.7%), influenza virus (5.3%), and parainfluenzavirus-3 (4.6%). Children, aged 9-11 months, were most infected (60.9%). Lower respiratory tract infections (55.4%) were significantly more than upper respiratory tract infection (45.3%) (P < 0.001). Seasonal variation of RV was directly and inversely proportional to relative humidity and temperature, respectively, for non MERS coronaviruses (NL63, 229E, and OC43). The study confirms community-acquired RV associated with ARI in children and suggests modulating roles for abiotic factors in RV epidemiology. However, community-based studies are needed to elucidate how these factors locally influence RV epidemiology. J. Med. Virol. 89:195-201, 2017. © 2016 Wiley Periodicals, Inc.

  6. The emergence of the Middle East Respiratory Syndrome coronavirus (MERS-CoV)

    PubMed Central

    Milne-Price, Shauna; Miazgowicz, Kerri L.; Munster, Vincent J.

    2014-01-01

    On September 20, 2012, a Saudi Arabian physician reported the isolation of a novel coronavirus from a patient with pneumonia on ProMED-mail. Within a few days the same virus was detected in a Qatari patient receiving intensive care in a London hospital, a situation reminiscent of the role air travel played in the spread of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2002. SARS-CoV originated in China’s Guangdong Province and affected more than 8000 patients in 26 countries before it was contained six months later. Over a year after the emergence of this novel coronavirus—Middle East Respiratory Syndrome coronavirus (MERS-CoV)—it has caused 178 laboratory confirmed cases and 76 deaths The emergence of a second highly pathogenic coronavirus within a decade highlights the importance of a coordinated global response incorporating reservoir surveillance, high-containment capacity with fundamental and applied research programs, and dependable communication pathways to ensure outbreak containment. Here we review the current state of knowledge on the epidemiology, ecology, molecular biology, clinical features and intervention strategies of the novel coronavirus, MERS-CoV. PMID:24585737

  7. A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells.

    PubMed

    Monteiro, Claudia; Pinheiro, Marina; Fernandes, Mariana; Maia, Sílvia; Seabra, Catarina L; Ferreira-da-Silva, Frederico; Reis, Salette; Gomes, Paula; Martins, M Cristina L

    2015-08-03

    Antimicrobial peptides are widely recognized as an excellent alternative to conventional antibiotics. MSI-78, a highly effective and broad spectrum AMP, is one of the most promising AMPs for clinical application. In this study, we have designed shorter derivatives of MSI-78 with the aim of improving selectivity while maintaining antimicrobial activity. Shorter 17-mer derivatives were created by truncating MSI-78 at the N- and/or C-termini, while spanning MSI-78 sequence. Despite the truncations made, we found a 17-mer peptide, MSI-78(4-20) (KFLKKAKKFGKAFVKIL), which was demonstrated to be as effective as MSI-78 against the Gram-positive Staphylococcus strains tested and the Gram-negative Pseudomonas aeruginosa. This shorter derivative is more selective toward bacterial cells as it was less toxic to erythrocytes than MSI-78, representing an improved version of the lead peptide. Biophysical studies support a mechanism of action for MSI-78(4-20) based on the disruption of the bacterial membrane permeability barrier, which in turn leads to loss of membrane integrity and ultimately to cell death. These features point to a mechanism of action similar to the one described for the lead peptide MSI-78.

  8. Mineralogy at Meridiani Planum, Mars, from the MER Opportunity Mössbauer Spectrometer

    NASA Astrophysics Data System (ADS)

    Klingelhöfer, G.; Morris, R. V.; Rodionov, D.; Schröder, C.; Yen, A.; Ming, D. W.; Fleischer, I.

    The Mars Exploration Rover MER Opportunity landed in Eagle crater Meridiani Planum on 24 January 2004 1 This landing site was chosen on an engineering basis because the region seemed to be flat and smooth favoring a save landing and because hematite alpha -Fe 2 O 3 was detected from orbit by the MGO Thermal Emission Spectrometer TES in significant quantities Hematite can form in different ways including aqueous processes After landing Opportunity with its M o ssbauer MB spectrometer investigated soils and outcrop material present in Eagle crater before exploring the plains and several other craters In contrast to the Spirit landing site at Gusev crater the surface within Eagle crater and the surrounding plains are not heavily covered with large rock fragments The surface is very flat and smooth with some wind ripples on the top and with several craters of different sizes up to sim 200 m diameter where exposed outcrop material similar to Eagle crater is found The scientific objective of the MB spectrometer MIMOS II on MER 3 is to identify the Fe-bearing minerals and phases provide quantitative information about the amount of these minerals and phases present in soils and rocks and the oxidation state and coordination state of Fe In Meridiani Planum MB could identify four main mineralogical components 1 2 i a ferric sulfate called jarosite present in significant amounts in the hematite- and sulfate-rich outcrop rock unit covering the surface and craters of Meridiani Planum along Opportunity s traverse

  9. Cdc7-dependent phosphorylation of Mer2 facilitates initiation of yeast meiotic recombination.

    PubMed

    Sasanuma, Hiroyuki; Hirota, Kouji; Fukuda, Tomoyuki; Kakusho, Naoko; Kugou, Kazuto; Kawasaki, Yasuo; Shibata, Takehiko; Masai, Hisao; Ohta, Kunihiro

    2008-02-01

    Meiosis ensures genetic diversification of gametes and sexual reproduction. For successful meiosis, multiple events such as DNA replication, recombination, and chromosome segregation must occur coordinately in a strict regulated order. We investigated the meiotic roles of Cdc7 kinase in the initiation of meiotic recombination, namely, DNA double-strand breaks (DSBs) mediated by Spo11 and other coactivating proteins. Genetic analysis using bob1-1 cdc7Delta reveals that Cdc7 is essential for meiotic DSBs and meiosis I progression. We also demonstrate that the N-terminal region of Mer2, a Spo11 ancillary protein required for DSB formation and phosphorylated by cyclin-dependent kinase (CDK), contains two types of Cdc7-dependent phosphorylation sites near the CDK site (Ser30): One (Ser29) is essential for meiotic DSB formation, and the others exhibit a cumulative effect to facilitate DSB formation. Importantly, mutations on these sites confer severe defects in DSB formation even when the CDK phosphorylation is present at Ser30. Diploids of cdc7Delta display defects in the chromatin binding of not only Spo11 but also Rec114 and Mei4, other meiotic coactivators that may assist Spo11 binding to DSB hot spots. We thus propose that Cdc7, in concert with CDK, regulates Spo11 loading to DSB sites via Mer2 phosphorylation.

  10. MERS-CoV in Upper Respiratory Tract and Lungs of Dromedary Camels, Saudi Arabia, 2013-2014.

    PubMed

    Khalafalla, Abdelmalik I; Lu, Xiaoyan; Al-Mubarak, Abdullah I A; Dalab, Abdul Hafeed S; Al-Busadah, Khalid A S; Erdman, Dean D

    2015-07-01

    To assess the temporal dynamics of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels, specimens were collected at 1-2 month intervals from 2 independent groups of animals during April 2013-May 2014 in Al-Ahsa Province, Saudi Arabia, and tested for MERS-CoV RNA by reverse transcription PCR. Of 96 live camels, 28 (29.2%) nasal swab samples were positive; of 91 camel carcasses, 56 (61.5%) lung tissue samples were positive. Positive samples were more commonly found among young animals (<4 years of age) than adults (>4 years of age). The proportions of positive samples varied by month for both groups; detection peaked during November 2013 and January 2014 and declined in March and May 2014. These findings further our understanding of MERS-CoV infection in dromedary camels and may help inform intervention strategies to reduce zoonotic infections.

  11. The Effects of the Mars Exploration Rovers (MER) Work Schedule Regime on Locomotor Activity Circadian Rhythms, Sleep and Fatigue

    NASA Technical Reports Server (NTRS)

    DeRoshia, Charles W.; Colletti, Laura C.; Mallis, Melissa M.

    2008-01-01

    This study assessed human adaptation to a Mars sol by evaluating sleep metrics obtained by actigraphy and subjective responses in 22 participants, and circadian rhythmicity in locomotor activity in 9 participants assigned to Mars Exploration Rover (MER) operational work schedules (24.65 hour days) at the Jet Propulsion Laboratory in 2004. During MER operations, increased work shift durations and reduced sleep durations and time in bed were associated with the appearance of pronounced 12-hr (circasemidian) rhythms with reduced activity levels. Sleep duration, workload, and circadian rhythm stability have important implications for adaptability and maintenance of operational performance not only of MER operations personnel but also in space crews exposed to a Mars sol of 24.65 hours during future Mars missions.

  12. Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer.

    PubMed

    Linger, R M A; Cohen, R A; Cummings, C T; Sather, S; Migdall-Wilson, J; Middleton, D H G; Lu, X; Barón, A E; Franklin, W A; Merrick, D T; Jedlicka, P; DeRyckere, D; Heasley, L E; Graham, D K

    2013-07-18

    Non-small cell lung cancer (NSCLC) is a prevalent and devastating disease that claims more lives than breast, prostate, colon and pancreatic cancers combined. Current research suggests that standard chemotherapy regimens have been optimized to maximal efficiency. Promising new treatment strategies involve novel agents targeting molecular aberrations present in subsets of NSCLC. We evaluated 88 human NSCLC tumors of diverse histology and identified Mer and Axl as receptor tyrosine kinases (RTKs) overexpressed in 69% and 93%, respectively, of tumors relative to surrounding normal lung tissue. Mer and Axl were also frequently overexpressed and activated in NSCLC cell lines. Ligand-dependent Mer or Axl activation stimulated MAPK, AKT and FAK signaling pathways indicating roles for these RTKs in multiple oncogenic processes. In addition, we identified a novel pro-survival pathway-involving AKT, CREB, Bcl-xL, survivin, and Bcl-2-downstream of Mer, which is differentially modulated by Axl signaling. We demonstrated that short hairpin RNA (shRNA) knockdown of Mer or Axl significantly reduced NSCLC colony formation and growth of subcutaneous xenografts in nude mice. Mer or Axl knockdown also improved in vitro NSCLC sensitivity to chemotherapeutic agents by promoting apoptosis. When comparing the effects of Mer and Axl knockdown, Mer inhibition exhibited more complete blockade of tumor growth while Axl knockdown more robustly improved chemosensitivity. These results indicate that Mer and Axl have complementary and overlapping roles in NSCLC and suggest that treatment strategies targeting both RTKs may be more effective than singly-targeted agents. Our findings validate Mer and Axl as potential therapeutic targets in NSCLC and provide justification for development of novel therapeutic compounds that selectively inhibit Mer and/or Axl.

  13. Structural Analysis of the Hg(II)-Regulatory Protein Tn501 MerR from Pseudomonas aeruginosa

    NASA Astrophysics Data System (ADS)

    Wang, Dan; Huang, Shanqing; Liu, Pingying; Liu, Xichun; He, Yafeng; Chen, Weizhong; Hu, Qingyuan; Wei, Tianbiao; Gan, Jianhua; Ma, Jing; Chen, Hao

    2016-09-01

    The metalloprotein MerR is a mercury(II)-dependent transcriptional repressor-activator that responds to mercury(II) with extraordinary sensitivity and selectivity. It’s widely distributed in both Gram-negative and Gram-positive bacteria but with barely detectable sequence identities between the two sources. To provide structural basis for the considerable biochemical and biophysical experiments previously performed on Tn501 and Tn21 MerR from Gram-negative bacteria, we analyzed the crystal structure of mercury(II)-bound Tn501 MerR. The structure in the metal-binding domain provides Tn501 MerR with a high affinity for mercury(II) and the ability to distinguish mercury(II) from other metals with its unique planar trigonal coordination geometry, which is adopted by both Gram-negative and Gram-positive bacteria. The mercury(II) coordination state in the C-terminal metal-binding domain is transmitted through the allosteric network across the dimer interface to the N-terminal DNA-binding domain. Together with the previous mutagenesis analyses, the present data indicate that the residues in the allosteric pathway have a central role in maintaining the functions of Tn501 MerR. In addition, the complex structure exhibits significant differences in tertiary and quaternary structural arrangements compared to those of Bacillus MerR from Gram-positive bacteria, which probably enable them to function with specific promoter DNA with different spacers between ‑35 and ‑10 elements.

  14. Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease

    PubMed Central

    Ho, Bo-Lin; Cheng, Shu-Chun; Shi, Lin; Wang, Ting-Yun; Ho, Kuan-I; Chou, Chi-Yuan

    2015-01-01

    Background A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1st October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (Mpro) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. Methods and Results The crystal structure of MERS-CoV Mpro indicates that it shares a similar scaffold to that of other coronaviral Mpro and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV Mpro undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV Mpro is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. Conclusions MERS-CoV Mpro shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral Mpro family. PMID:26658006

  15. Structural Analysis of the Hg(II)-Regulatory Protein Tn501 MerR from Pseudomonas aeruginosa

    PubMed Central

    Wang, Dan; Huang, Shanqing; Liu, Pingying; Liu, Xichun; He, Yafeng; Chen, Weizhong; Hu, Qingyuan; Wei, Tianbiao; Gan, Jianhua; Ma, Jing; Chen, Hao

    2016-01-01

    The metalloprotein MerR is a mercury(II)-dependent transcriptional repressor-activator that responds to mercury(II) with extraordinary sensitivity and selectivity. It’s widely distributed in both Gram-negative and Gram-positive bacteria but with barely detectable sequence identities between the two sources. To provide structural basis for the considerable biochemical and biophysical experiments previously performed on Tn501 and Tn21 MerR from Gram-negative bacteria, we analyzed the crystal structure of mercury(II)-bound Tn501 MerR. The structure in the metal-binding domain provides Tn501 MerR with a high affinity for mercury(II) and the ability to distinguish mercury(II) from other metals with its unique planar trigonal coordination geometry, which is adopted by both Gram-negative and Gram-positive bacteria. The mercury(II) coordination state in the C-terminal metal-binding domain is transmitted through the allosteric network across the dimer interface to the N-terminal DNA-binding domain. Together with the previous mutagenesis analyses, the present data indicate that the residues in the allosteric pathway have a central role in maintaining the functions of Tn501 MerR. In addition, the complex structure exhibits significant differences in tertiary and quaternary structural arrangements compared to those of Bacillus MerR from Gram-positive bacteria, which probably enable them to function with specific promoter DNA with different spacers between −35 and −10 elements. PMID:27641146

  16. Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry

    SciTech Connect

    Song, Wenfei; Wang, Ying; Wang, Nianshuang; Wang, Dongli; Guo, Jianying; Fu, Lili; Shi, Xuanling

    2014-12-15

    Middle East respiratory syndrome coronavirus (MERS-CoV) infects host cells through binding the receptor binding domain (RBD) on its spike glycoprotein to human receptor dipeptidyl peptidase 4 (hDPP4). Here, we report identification of critical residues on hDPP4 for RBD binding and virus entry through analysis of a panel of hDPP4 mutants. Based on the RBD–hDPP4 crystal structure we reported, the mutated residues were located at the interface between RBD and hDPP4, which potentially changed the polarity, hydrophobic or hydrophilic properties of hDPP4, thereby interfering or disrupting their interaction with RBD. Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues in hDPP4–RBD binding interface were important on hDPP4–RBD binding and viral entry. These results provide atomic insights into the features of interactions between hDPP4 and MERS-CoV RBD, and also provide potential explanation for cellular and species tropism of MERS-CoV infection. - Highlights: • It has been demonstrated that MERS-CoV infects host cells through binding its envelope spike (S) glycoprotein to the host cellular receptor dipeptidyl peptidase 4 (DPP4). • To identify the critical residues on hDPP4 for RBD binding and virus entry, we constructed a panel of hDPP4 mutants based on structure-guided mutagenesis. • Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues on hDPP4 had significant impacts on virus/receptor interactions and viral entry. • Our study has provided new insights into the features of interactions between hDPP4 and MERS-CoV RBD, and provides potential explanation for cellular and species tropism of MERS-CoV infection.

  17. Assessing the risk of observing multiple generations of Middle East respiratory syndrome (MERS) cases given an imported case.

    PubMed

    Nishiura, H; Miyamatsu, Y; Chowell, G; Saitoh, M

    2015-07-09

    To guide risk assessment, expected numbers of cases and generations were estimated, assuming a case importation of Middle East respiratory syndrome (MERS). Our analysis of 36 importation events yielded the risk of observing secondary transmission events at 22.7% (95% confidence interval: 19.3–25.1). The risks of observing generations 2, 3 and 4 were estimated at 10.5%, 6.1% and 3.9%, respectively. Countries at risk should be ready for highly variable outcomes following an importation of MERS.

  18. MERS-CoV at the Animal-Human Interface: Inputs on Exposure Pathways from an Expert-Opinion Elicitation.

    PubMed

    Funk, Anna L; Goutard, Flavie Luce; Miguel, Eve; Bourgarel, Mathieu; Chevalier, Veronique; Faye, Bernard; Peiris, J S Malik; Van Kerkhove, Maria D; Roger, Francois Louis

    2016-01-01

    Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert-opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios, e.g., camels-camels, camels-human, bats/other species to camels/humans, and the role of diverse biological substances (milk, urine, etc.) and potential fomites. Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods) on transmission risk. All experts thought that MERS-CoV-infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated "most likely" incidence

  19. MERS-CoV at the Animal–Human Interface: Inputs on Exposure Pathways from an Expert-Opinion Elicitation

    PubMed Central

    Funk, Anna L.; Goutard, Flavie Luce; Miguel, Eve; Bourgarel, Mathieu; Chevalier, Veronique; Faye, Bernard; Peiris, J. S. Malik; Van Kerkhove, Maria D.; Roger, Francois Louis

    2016-01-01

    Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert-opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios, e.g., camels–camels, camels–human, bats/other species to camels/humans, and the role of diverse biological substances (milk, urine, etc.) and potential fomites. Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods) on transmission risk. All experts thought that MERS-CoV-infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated “most likely

  20. MER Field Geologic Traverse in Gusev Crater, Mars: Initial Results From the Perspective of Spirit

    NASA Technical Reports Server (NTRS)

    Crumpler, L.; Cabrol, N.; desMarais, D.; Farmer, J.; Golmbek, M.; Grant, J.; Greely, R.; Grotzinger, J.; Haskin, L.; Arvidson, R.

    2004-01-01

    This report casts the initial results of the traverse and science investigations by the Mars Exploration Rover (MER) Spirit at Gusev crater [1] in terms of data sets commonly used in field geologic investigations: Local mapping of geologic features, analyses of selected samples, and their location within the local map, and the regional context of the field traverse in terms of the larger geologic and physiographic region. These elements of the field method are represented in the MER characterization of the Gusev traverse by perspective-based geologic/morphologic maps, the placement of the results from Mossbauer, APXS, Microscopic Imager, Mini-TES and Pancam multispectral studies in context within this geologic/ morphologic map, and the placement of the overall traverse in the context of narrow-angle MOC (Mars Orbiter Camera) and descent images. A major campaign over a significance fraction of the mission will be the first robotic traverse of the ejecta from a Martian impact crater along an approximate radial from the crater center. The Mars Exploration Rovers have been conceptually described as 'robotic field geologists', that is, a suite of instruments with mobility that enables far-field traverses to multiple sites located within a regional map/image base at which in situ analyses may be done. Initial results from MER, where the field geologic method has been used throughout the initial course of the investigation, confirm that this field geologic model is applicable for remote planetary surface exploration. The field geologic method makes use of near-field geologic characteristics ('outcrops') to develop an understanding of the larger geologic context through continuous loop of rational steps focused on real-time hypothesis identification and testing. This poster equates 'outcrops' with the locations of in situ investigations and 'regional context' with the geology over distance of several kilometers. Using this fundamental field geologic method, we have

  1. mer-Tri-chlorido-tris-(tetra-hydro-thio-phene-κS)iridium(III): preparation and comparison with other mer-tri-chlorido-tris-(tetra-hydro-thio-phene-κS)metal complexes.

    PubMed

    Brown, Loren C; DuChane, Christine M; Merola, Joseph S

    2016-09-01

    The title complex, [IrCl3(C4H8S)3], was prepared according to a literature method. A suitable crystal was obtained by diffusion of pentane into a di-chloro-methane solution and analyzed by single-crystal X-ray diffraction at 100 K. The title complex is isotypic with mer-tri-chlorido-tris-(tetra-hydro-thio-phene-κS)rhodium(III). However, the orientation of the tetra-hydro-thio-phene rings is different from an earlier report of mer-tri-chlorido-tris-(tetra-hydro-thio-phene-κS)iridium(III) deposited in the Cambridge Structural Database. The IrS3Cl3 core shows a nearly octa-hedral structure with various bond angles within 1-2° of the perfect 90 or 180° expected for an octa-hedron. The structure of the title compound is compared with the previous iridium complex as well as the rhodium and other octa-hedral metal tris-tetra-hydro-thio-phene compounds previously structurally characterized. DFT calculations were performed, which indicate the mer isomer is significantly lower in energy than the fac isomer by 50.1 kJ mol(-1), thereby accounting for all compounds in the CSD being of the mer geometry. Powder X-ray diffraction of the bulk material showed that the preparation method yielded only the isomorph reported in this communication.

  2. Reproducible Synthesis and High Porosity of mer-Zn(Im)2 (ZIF-10): Exploitation of an Apparent Double-Eight Ring Template.

    PubMed

    Ramirez, Joseph R; Yang, Haiyang; Kane, Christopher M; Ley, Amanda N; Holman, K Travis

    2016-09-21

    Reproducible synthesis of the elusive merlinoite (mer) topology of zinc imidazolate (mer-Zn(Im)2, or ZIF-10) has been achieved by employing a simple macrocyclic solute-MeMeCH2-as a kinetic template. The corresponding phase-pure material, mer-MeMeCH2@Zn16(Im)32, is confirmed to be porous and exhibits one of the highest experimental surface areas (1893 m(2)/g, BET) yet reported for any ZIF. The X-ray single crystal structure of mer-MeMeCH2@Zn16(Im)32·xsolvent reveals the role of the macrocyle as an 8-fold hydrogen bond acceptor in templating the requisite double-eight rings (d8r) of the mer framework.

  3. Environmental conditions constrain the distribution and diversity of archaeal merA in Yellowstone National Park, Wyoming, U.S.A.

    PubMed

    Wang, Yanping; Boyd, Eric; Crane, Sharron; Lu-Irving, Patricia; Krabbenhoft, David; King, Susan; Dighton, John; Geesey, Gill; Barkay, Tamar

    2011-11-01

    The distribution and phylogeny of extant protein-encoding genes recovered from geochemically diverse environments can provide insight into the physical and chemical parameters that led to the origin and which constrained the evolution of a functional process. Mercuric reductase (MerA) plays an integral role in mercury (Hg) biogeochemistry by catalyzing the transformation of Hg(II) to Hg(0). Putative merA sequences were amplified from DNA extracts of microbial communities associated with mats and sulfur precipitates from physicochemically diverse Hg-containing springs in Yellowstone National Park, Wyoming, using four PCR primer sets that were designed to capture the known diversity of merA. The recovery of novel and deeply rooted MerA lineages from these habitats supports previous evidence that indicates merA originated in a thermophilic environment. Generalized linear models indicate that the distribution of putative archaeal merA lineages was constrained by a combination of pH, dissolved organic carbon, dissolved total mercury and sulfide. The models failed to identify statistically well supported trends for the distribution of putative bacterial merA lineages as a function of these or other measured environmental variables, suggesting that these lineages were either influenced by environmental parameters not considered in the present study, or the bacterial primer sets were designed to target too broad of a class of genes which may have responded differently to environmental stimuli. The widespread occurrence of merA in the geothermal environments implies a prominent role for Hg detoxification in these environments. Moreover, the differences in the distribution of the merA genes amplified with the four merA primer sets suggests that the organisms putatively engaged in this activity have evolved to occupy different ecological niches within the geothermal gradient.

  4. Environmental Conditions Constrain the Distribution and Diversity of Archaeal merA in Yellowstone National Park, Wyoming, U.S.A.

    USGS Publications Warehouse

    Wang, Y.; Boyd, E.; Crane, S.; Lu-Irving, P.; Krabbenhoft, D.; King, S.; Dighton, J.; Geesey, G.; Barkay, T.

    2011-01-01

    The distribution and phylogeny of extant protein-encoding genes recovered from geochemically diverse environments can provide insight into the physical and chemical parameters that led to the origin and which constrained the evolution of a functional process. Mercuric reductase (MerA) plays an integral role in mercury (Hg) biogeochemistry by catalyzing the transformation of Hg(II) to Hg(0). Putative merA sequences were amplified from DNA extracts of microbial communities associated with mats and sulfur precipitates from physicochemically diverse Hg-containing springs in Yellowstone National Park, Wyoming, using four PCR primer sets that were designed to capture the known diversity of merA. The recovery of novel and deeply rooted MerA lineages from these habitats supports previous evidence that indicates merA originated in a thermophilic environment. Generalized linear models indicate that the distribution of putative archaeal merA lineages was constrained by a combination of pH, dissolved organic carbon, dissolved total mercury and sulfide. The models failed to identify statistically well supported trends for the distribution of putative bacterial merA lineages as a function of these or other measured environmental variables, suggesting that these lineages were either influenced by environmental parameters not considered in the present study, or the bacterial primer sets were designed to target too broad of a class of genes which may have responded differently to environmental stimuli. The widespread occurrence of merA in the geothermal environments implies a prominent role for Hg detoxification in these environments. Moreover, the differences in the distribution of the merA genes amplified with the four merA primer sets suggests that the organisms putatively engaged in this activity have evolved to occupy different ecological niches within the geothermal gradient. ?? 2011 Springer Science+Business Media, LLC.

  5. A View from the Cheap Seats: MER and its Implications for Future Mars Exploration

    NASA Astrophysics Data System (ADS)

    Leshin, L. A.; Minitti, M.; Cosarinsky, M.; McAdam, A.; Niles, P.

    2004-12-01

    The spectacular success of the Mars Exploration Rover mission is reflected by the exciting scientific discoveries that Spirit and Opportunity have made concerning habitability potential and geologic history of two sites on Mars. The apparent discovery of strong evidence for the presence of liquid water at the Opportunity site is of historic importance (although at the time of this writing we must note that there is not yet any peer-reviewed publication of this result). But perhaps even more importantly, the success of MER provides key validation of a strategy and approach to Mars exploration. Here, we highlight some of the strategic successes, as well as lessons learned for refining our approach to Mars exploration, and for future exploration endeavors across the solar system and beyond. Almost more than imaginable, MER has validated both the "follow the water" strategy and the "seek-in situ-sample" approach of the Mars Exploration Program developed by a broad, inclusive group of Mars explorers. Seeking interesting, water-relevant sites with remote observations from orbit resulted in one clear success at Meridiani, and in perhaps what is most optimistically termed "delayed success" at Gusev. Three lessons from this are clear. First, it's always better to fly two spacecraft! Second, significant mobility enables greatly enhanced science return. Third, mineralogical evidence appears more reliable than geomorphic evidence if the goal is to seek preserved evidence of aqueous processes (Pathfinder results also support this observation), although the combination of mineralogical information with high-resolution imagery is almost certainly the best way to optimize for success. The 2005 Mars Reconnaissance Orbiter's spectral mapping and imaging capability will thus be critical to future landing site selection. And yet, it is important to note that in spite of mineralogical evidence pointing to Meridiani as a site of "aqueous interest", and the detailed regional geological

  6. Contributions from Particles in Europe (PiE) 2010, Villefranche-sur-Mer, France: an introduction

    NASA Astrophysics Data System (ADS)

    Mikkelsen, Ole A.; Chami, Malik; Doxaran, David

    2012-04-01

    This special issue of Geo-Marine Letters presents selected contributions from the international conference Particles in Europe (PiE) 2010 organized by Sequoia Scientific, Inc., and the Laboratoire d'Océanographie de Villefranche (LOV) on 15-17 November 2010 in Villefranche-sur-Mer, France, and guest-edited by Ole Mikkelsen, Malik Chami and David Doxaran. PiE was initiated in 2008, in order to promote and further our understanding of the importance of suspended particulate matter (SPM) for a very wide range of processes in the aquatic environment—from optics and acoustics, over sediment transport, to the global carbon balance. The papers in this special issue are in particular concerned with the interaction between SPM and water optical properties, as well as how to use optical proxy measurements to understand SPM processes. The next PiE conference is scheduled for 17-19 October 2012 in Barcelona, Spain.

  7. T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV.

    PubMed

    Liu, William J; Zhao, Min; Liu, Kefang; Xu, Kun; Wong, Gary; Tan, Wenjie; Gao, George F

    2017-01-01

    Over 12 years have elapsed since severe acute respiratory syndrome (SARS) triggered the first global alert for coronavirus infections. Virus transmission in humans was quickly halted by public health measures and human infections of SARS coronavirus (SARS-CoV) have not been observed since. However, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of Middle East respiratory syndrome (MERS) in humans. The work on SARS-CoV widens our knowledge on the epidemiology, pathophysiology and immunology of coronaviruses and may shed light on MERS coronavirus (MERS-CoV). It has been confirmed that T-cell immunity plays an important role in recovery from SARS-CoV infection. Herein, we summarize T-cell immunological studies of SARS-CoV and discuss the potential cross-reactivity of the SARS-CoV-specific immunity against MERS-CoV, which may provide useful recommendations for the development of broad-spectrum vaccines against coronavirus infections.

  8. Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion

    PubMed Central

    Duroc, Yann; Kumar, Rajeev; Ranjha, Lepakshi; Adam, Céline; Guérois, Raphaël; Md Muntaz, Khan; Marsolier-Kergoat, Marie-Claude; Dingli, Florent; Laureau, Raphaëlle; Loew, Damarys; Llorente, Bertrand; Charbonnier, Jean-Baptiste; Cejka, Petr; Borde, Valérie

    2017-01-01

    Gene conversions resulting from meiotic recombination are critical in shaping genome diversification and evolution. How the extent of gene conversions is regulated is unknown. Here we show that the budding yeast mismatch repair related MutLβ complex, Mlh1-Mlh2, specifically interacts with the conserved meiotic Mer3 helicase, which recruits it to recombination hotspots, independently of mismatch recognition. This recruitment is essential to limit gene conversion tract lengths genome-wide, without affecting crossover formation. Contrary to expectations, Mer3 helicase activity, proposed to extend the displacement loop (D-loop) recombination intermediate, does not influence the length of gene conversion events, revealing non-catalytical roles of Mer3. In addition, both purified Mer3 and MutLβ preferentially recognize D-loops, providing a mechanism for limiting gene conversion in vivo. These findings show that MutLβ is an integral part of a new regulatory step of meiotic recombination, which has implications to prevent rapid allele fixation and hotspot erosion in populations. DOI: http://dx.doi.org/10.7554/eLife.21900.001 PMID:28051769

  9. A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties

    PubMed Central

    Millet, Jean Kaoru; Goldstein, Monty E; Labitt, Rachael N; Hsu, Hung-Lun; Daniel, Susan; Whittaker, Gary R

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2′ fusion activation site—notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1′ cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell–cell fusion and pseudotyped virus infectivity assays demonstrated that the S2′ substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution. PMID:27999426

  10. Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion.

    PubMed

    Duroc, Yann; Kumar, Rajeev; Ranjha, Lepakshi; Adam, Céline; Guérois, Raphaël; Md Muntaz, Khan; Marsolier-Kergoat, Marie-Claude; Dingli, Florent; Laureau, Raphaëlle; Loew, Damarys; Llorente, Bertrand; Charbonnier, Jean-Baptiste; Cejka, Petr; Borde, Valérie

    2017-01-04

    Gene conversions resulting from meiotic recombination are critical in shaping genome diversification and evolution. How the extent of gene conversions is regulated is unknown. Here we show that the budding yeast mismatch repair related MutLβ complex, Mlh1-Mlh2, specifically interacts with the conserved meiotic Mer3 helicase, which recruits it to recombination hotspots, independently of mismatch recognition. This recruitment is essential to limit gene conversion tract lengths genome-wide, without affecting crossover formation. Contrary to expectations, Mer3 helicase activity, proposed to extend the displacement loop (D-loop) recombination intermediate, does not influence the length of gene conversion events, revealing non-catalytical roles of Mer3. In addition, both purified Mer3 and MutLβ preferentially recognize D-loops, providing a mechanism for limiting gene conversion in vivo. These findings show that MutLβ is an integral part of a new regulatory step of meiotic recombination, which has implications to prevent rapid allele fixation and hotspot erosion in populations.

  11. The Miniaturized Moessbauer Spectrometers MIMOS II on MER: Four Years of Operation - A Summary

    NASA Technical Reports Server (NTRS)

    Fleischer, I.; Klingelhoefer, G.; Morris, R. V.; Rodionov, D.; Blumers, M.; Bernhardt, B.; Schroeder, C.; Ming, D. W.; Yen, A. S.; Cohen, B. A.; McCoy, T. J.; Mittlefehldt, D. W.; Schmidt, M. E.; Girones Lopez, J.; Studlek, G.; Brueckner, J.; Gellert, R.; d'Uston, C.

    2008-01-01

    The two Miniaturized Moessbauer Spectrometers (MIMOS II) on board the two Mars Exploration Rovers Spirit and Opportunity have now been collecting important scientific data for more than four years. The spectrometers provide information about Fe-bearing mineral phases and determine Fe oxidation states. The total amount of targets analized exceeds 600, the total integration time exceeds 260 days for both rovers. Since landing, more than five half-lives of the Co-57 MB sources have past (intensity at the time of landing approx. 150 mCi). Current integration times are about 50 hours in order to achieve reasonable statistics as opposed to 8 hours at the beginning of the mission. In total, 13 different mineral phases were detected: Olivine, pyroxene, hematite, magnetite and nanophase ferric oxide were detected at both landing sites. At Gusev, ilmenite, goethite, a ferric sulfate phase and a yet unassigned phase (in the rock Fuzzy Smith) were detected. At Meridiani, jarosite, metallic iron in meteoritic samples (kamacite), troilite, and an unassigned ferric phase were detected. Jarosite and goethite are of special interest, as these minerals are indicators for water activity. In this abstract, an overview of Moessbauer results will be given, with a focus on data obtained since the last martian winter. The MER mission has proven that Moessbauer spectroscopy is a valuable tool for the in situ exploration of extraterrestrial bodies and for the study of Febearing samples. The experience gained through the MER mission makes MIMOS II a obvious choice for future missions to Mars and other targets. Currently, MIMOS II is on the scientific payload of two approved future missions: Phobos Grunt (Russian Space Agency; 2009) and ExoMars (European Space Agency; 2013).

  12. From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.

    PubMed

    Hilgenfeld, Rolf; Peiris, Malik

    2013-10-01

    This article introduces a series of invited papers in Antiviral Research marking the 10th anniversary of the outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus that emerged in southern China in late 2002. Until that time, coronaviruses had not been recognized as agents causing severe disease in humans, hence, the emergence of the SARS-CoV came as a complete surprise. Research during the past ten years has revealed the existence of a diverse pool of coronaviruses circulating among various bat species and other animals, suggesting that further introductions of highly pathogenic coronaviruses into the human population are not merely probable, but inevitable. The recent emergence of another coronavirus causing severe disease, Middle East respiratory syndrome (MERS), in humans, has made it clear that coronaviruses pose a major threat to human health, and that more research is urgently needed to elucidate their replication mechanisms, identify potential drug targets, and develop effective countermeasures. In this series, experts in many different aspects of coronavirus replication and disease will provide authoritative, up-to-date reviews of the following topics: - clinical management and infection control of SARS; - reservoir hosts of coronaviruses; - receptor recognition and cross-species transmission of SARS-CoV; - SARS-CoV evasion of innate immune responses; - structures and functions of individual coronaviral proteins; - anti-coronavirus drug discovery and development; and - the public health legacy of the SARS outbreak. Each article will be identified in the last line of its abstract as belonging to the series "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses."

  13. Conceptual Design and Architecture of Mars Exploration Rover (MER) for Seismic Experiments Over Martian Surfaces

    NASA Astrophysics Data System (ADS)

    Garg, Akshay; Singh, Amit

    2012-07-01

    Keywords: MER, Mars, Rover, Seismometer Mars has been a subject of human interest for exploration missions for quite some time now. Both rover as well as orbiter missions have been employed to suit mission objectives. Rovers have been preferentially deployed for close range reconnaissance and detailed experimentation with highest accuracy. However, it is essential to strike a balance between the chosen science objectives and the rover operations as a whole. The objective of this proposed mechanism is to design a vehicle (MER) to carry out seismic studies over Martian surface. The conceptual design consists of three units i.e. Mother Rover as a Surrogate (Carrier) and Baby Rovers (two) as seeders for several MEMS-based accelerometer / seismometer units (Nodes). Mother Rover can carry these Baby Rovers, having individual power supply with solar cells and with individual data transmission capabilities, to suitable sites such as Chasma associated with Valles Marineris, Craters or Sand Dunes. Mother rover deploys these rovers in two opposite direction and these rovers follow a triangulation pattern to study shock waves generated through firing tungsten carbide shells into the ground. Till the time of active experiments Mother Rover would act as a guiding unit to control spatial spread of detection instruments. After active shock experimentation, the babies can still act as passive seismometer units to study and record passive shocks from thermal quakes, impact cratering & landslides. Further other experiments / payloads (XPS / GAP / APXS) can also be carried by Mother Rover. Secondary power system consisting of batteries can also be utilized for carrying out further experiments over shallow valley surfaces. The whole arrangement is conceptually expected to increase the accuracy of measurements (through concurrent readings) and prolong life cycle of overall experimentation. The proposed rover can be customised according to the associated scientific objectives and further

  14. Identification and regulation of receptor tyrosine kinases Rse and Mer and their ligand Gas6 in testicular somatic cells.

    PubMed

    Chan, M C; Mather, J P; McCray, G; Lee, W M

    2000-01-01

    Receptor tyrosine kinases act to convey extracellular signals to intracellular signaling pathways and ultimately control cell proliferation and differentiation. Rse, Axl, and Mer belong to a newly identified family of cell adhesion molecule-related receptor tyrosine kinase. They bind the vitamin K-dependent protein growth arrest-specific gene 6 (Gas6), which is also structurally related to the anticoagulation factor Protein S. The aim of this study is to investigate the possible role of Rse/Axl/Mer tyrosine kinase receptors and their ligand in regulating testicular functions. Gene expression of Rse, Axl, Mer, and Gas6 in the testis was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot analysis. The results indicated that receptors Rse and Mer and the ligand Gas6 were expressed in the rat endothelial cell line (TR1), mouse Leydig cell line (TM3), rat peritubular myoid cell line (TRM), mouse Sertoli cell line (TM4), and primary rat Sertoli cells. Axl was not expressed in the testicular somatic cells by RT-PCR or Northern blot analysis. The highest level of expression of Gas6 messenger RNA (mRNA) was observed in the Sertoli cells, and its expression was responsive to the addition of forskolin in vitro. The effects of serum, insulin, and transferrin on Gas6 expression by TM4 cells were examined. It was shown that they all exhibited an up-regulating effect on Gas6 expression. The forskolin-stimulated Gas6 expression was accompanied by an increase in tyrosine phosphorylation of the Rse receptor in vitro, suggesting that Gas6 may exhibit an autocrine effect in the Sertoli cells through multiple tyrosine kinase receptors. Our studies so far have demonstrated that tyrosine kinase receptors Rse and Mer and their ligand Gas6 are widely expressed in the testicular somatic cell lines and may play a marked role in promoting testicular cell survival.

  15. MetaPalette: a k-mer Painting Approach for Metagenomic Taxonomic Profiling and Quantification of Novel Strain Variation

    PubMed Central

    Falush, Daniel

    2016-01-01

    ABSTRACT Metagenomic profiling is challenging in part because of the highly uneven sampling of the tree of life by genome sequencing projects and the limitations imposed by performing phylogenetic inference at fixed taxonomic ranks. We present the algorithm MetaPalette, which uses long k-mer sizes (k = 30, 50) to fit a k-mer “palette” of a given sample to the k-mer palette of reference organisms. By modeling the k-mer palettes of unknown organisms, the method also gives an indication of the presence, abundance, and evolutionary relatedness of novel organisms present in the sample. The method returns a traditional, fixed-rank taxonomic profile which is shown on independently simulated data to be one of the most accurate to date. Tree figures are also returned that quantify the relatedness of novel organisms to reference sequences, and the accuracy of such figures is demonstrated on simulated spike-ins and a metagenomic soil sample. The software implementing MetaPalette is available at: https://github.com/dkoslicki/MetaPalette. Pretrained databases are included for Archaea, Bacteria, Eukaryota, and viruses. IMPORTANCE Taxonomic profiling is a challenging first step when analyzing a metagenomic sample. This work presents a method that facilitates fine-scale characterization of the presence, abundance, and evolutionary relatedness of organisms present in a given sample but absent from the training database. We calculate a “k-mer palette” which summarizes the information from all reads, not just those in conserved genes or containing taxon-specific markers. The compositions of palettes are easy to model, allowing rapid inference of community composition. In addition to providing strain-level information where applicable, our approach provides taxonomic profiles that are more accurate than those of competing methods. Author Video: An author video summary of this article is available. PMID:27822531

  16. PEDF and 34-mer inhibit angiogenesis in the heart by inducing tip cells apoptosis via up-regulating PPAR-γ to increase surface FasL.

    PubMed

    Zhang, Hao; Wei, Tengteng; Jiang, Xia; Li, Zhimin; Cui, Huazhu; Pan, Jiajun; Zhuang, Wei; Sun, Teng; Liu, Zhiwei; Zhang, Zhongming; Dong, Hongyan

    2016-01-01

    Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor whose effects are partially mediated through the induction of endothelial cell apoptosis. However, the underlying mechanism for PEDF and the functional PEDF peptides 34-mer and 44-mer to inhibit angiogenesis in the heart has not been fully established. In the present study, by constructing adult Sprague-Dawley rat models of acute myocardial infarction (AMI) and in vitro myocardial angiogenesis, we showed that PEDF and 34-mer markedly inhibits angiogenesis by selectively inducing tip cells apoptosis rather than quiescent cells. Peptide 44-mer on the other hand exhibits no such effects. Next, we identified Fas death pathway as essential downstream regulators of PEDF and 34-mer activities in inhibiting angiogenesis. By using peroxisome proliferator-activated receptor γ (PPAR-γ) siRNA and PPAR-γ inhibitor, GW9662, we found the effects of PEDF and 34-mer were extensively blocked. These data suggest that PEDF and 34-mer inhibit angiogenesis via inducing tip cells apoptosis at least by means of up-regulating PPAR-γ to increase surface FasL in the ischemic heart, which might be a novel mechanism to understanding cardiac angiogenesis after AMI.

  17. The Synechocystis PCC6803 MerA-Like Enzyme Operates in the Reduction of Both Mercury and Uranium under the Control of the Glutaredoxin 1 Enzyme

    PubMed Central

    Marteyn, Benoit; Sakr, Samer; Farci, Sandrine; Bedhomme, Mariette; Chardonnet, Solenne; Decottignies, Paulette; Lemaire, Stéphane D.; Cassier-Chauvat, Corinne

    2013-01-01

    In a continuing effort to analyze the selectivity/redundancy of the three glutaredoxin (Grx) enzymes of the model cyanobacterium Synechocystis PCC6803, we have characterized an enzyme system that plays a crucial role in protection against two toxic metal pollutants, mercury and uranium. The present data show that Grx1 (Slr1562 in CyanoBase) selectively interacts with the presumptive mercuric reductase protein (Slr1849). This MerA enzyme plays a crucial role in cell defense against both mercuric and uranyl ions, in catalyzing their NADPH-driven reduction. Like MerA, Grx1 operates in cell protection against both mercury and uranium. The Grx1-MerA interaction requires cysteine 86 (C86) of Grx1 and C78 of MerA, which is critical for its reductase activity. MerA can be inhibited by glutathionylation and subsequently reactivated by Grx1, likely through deglutathionylation. The two Grx1 residues C31, which belongs to the redox active site (CX2C), and C86, which operates in MerA interactions, are both required for reactivation of MerA. These novel findings emphasize the role of glutaredoxins in tolerance to metal stress as well as the evolutionary conservation of the glutathionylation process, so far described mostly for eukaryotes. PMID:23852862

  18. Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus.

    PubMed

    Yang, Yang; Du, Lanying; Liu, Chang; Wang, Lili; Ma, Cuiqing; Tang, Jian; Baric, Ralph S; Jiang, Shibo; Li, Fang

    2014-08-26

    Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes ∼ 36% fatality in infected patients. Believed to have originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4 and HKU5. To understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of HKU4 and HKU5. We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS-CoV, is also the receptor for HKU4, but not HKU5. Despite sharing a common receptor, MERS-CoV and HKU4 spikes demonstrated functional differences. First, whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV spike, but not HKU4 spike, mediates pseudovirus entry into human cells. Thus, MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular proteases for efficient human cell entry, contributing to the enhanced pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional receptor for HKU4 and host cellular proteases as a host range determinant for HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human health because of their spikes' capability to adapt to human cells for cross-species transmissions.

  19. Analysis of mer Gene Subclasses within Bacterial Communities in Soils and Sediments Resolved by Fluorescent-PCR-Restriction Fragment Length Polymorphism Profiling

    PubMed Central

    Bruce, K. D.

    1997-01-01

    Bacterial mer (mercury resistance) gene subclasses in mercury-polluted and pristine natural environments have been profiled by Fluorescent-PCR-restriction fragment length polymorphism (FluRFLP). For FluRFLP, PCR products were amplified from individual mer operons in mercury-resistant bacteria and from DNA isolated directly from bacteria in soil and sediment samples. The primers used to amplify DNA were designed from consensus sequences of the major subclasses of archetypal gram-negative mer operons within Tn501, Tn21, pDU1358, and pKLH2. Two independent PCRs were used to amplify two regions of different lengths (merRT(Delta)P [ca. 1 kb] and merR [ca. 0.4 kb]) starting at the same position in merR. The oligonucleotide primer common to both reactions (FluRX) was labelled at the 5(prm1) end with green (TET) fluorescent dye. Analysis of the mer sequences within databases indicated that the major subclasses could be differentiated on the basis of the length from FluRX to the first FokI restriction endonuclease site. The amplified PCR products were digested with FokI restriction endonuclease, with the restriction digest fragments resolved on an automated DNA sequencing machine which detected only those bands labelled with the fluorescent dye. For each of the individual mer operon sources examined, this single peak (in bases) position was observed in separate digests of either amplified region. These peak positions were as predicted on the basis of DNA sequence. mer PCR products amplified from DNA extracted directly from soil and sediment bacteria were studied in order to determine the profiles of the major mer subclasses present in each natural environment. In addition to peaks of the expected sizes, extra peaks were observed which were not predicted on the basis of DNA sequence. Those appearing in the restriction endonuclease digests of both study regions were presumed to be novel mer types. Genetic heterogeneity within and between mercury-polluted and pristine sites

  20. MIMOS II on MER One Year of Mossbauer Spectroscopy on the Surface of Mars: From Jarosite at Meridiani Planum to Goethite at Gusev Crater

    NASA Technical Reports Server (NTRS)

    Klingelhoefer, G.; Rodionov, D. S.; Morris, R. V.; Schroeder, C.; deSouza, P. A.; Ming, D. W.; Yen, A. S.; Bernhardt, B.; Renz, F.; Fleischer, I.

    2005-01-01

    The miniaturized Mossbauer (MB) spectrometer MIMOS II [1] is part of the Athena payload of NASA s twin Mars Exploration Rovers "Spirit" (MER-A) and "Opportunity" (MER-B). It determines the Fe-bearing mineralogy of Martian soils and rocks at the Rovers respective landing sites, Gusev crater and Meridiani Planum. Both spectrometers performed successfully during first year of operation. Total integration time is about 49 days for MERA (79 samples) and 34 days for MER-B (85 samples). For curiosity it might be interesting to mention that the total odometry of the oscillating part of the MB drive exceeds 35 km for both rovers.

  1. Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, Qatar, April 2014.

    PubMed

    Reusken, C B; Farag, E A; Jonges, M; Godeke, G J; El-Sayed, A M; Pas, S D; Raj, V S; Mohran, K A; Moussa, H A; Ghobashy, H; Alhajri, F; Ibrahim, A K; Bosch, B J; Pasha, S K; Al-Romaihi, H E; Al-Thani, M; Al-Marri, S A; AlHajri, M M; Haagmans, B L; Koopmans, M P

    2014-06-12

    Antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV) were detected in serum and milk collected according to local customs from 33 camels in Qatar, April 2014. At one location, evidence for active virus shedding in nasal secretions and/or faeces was observed for 7/12 camels; viral RNA was detected in milk of five of these seven camels. The presence of MERS-CoV RNA in milk of camels actively shedding the virus warrants measures to prevent putative food-borne transmission of MERS-CoV.

  2. Dust Accumulation and Solar Panel Array Performance on the Mars Exploration Rover (MER) Project

    NASA Technical Reports Server (NTRS)

    Turgay, Eren H.

    2004-01-01

    One of the most fundamental design considerations for any space vehicle is its power supply system. Many options exist, including batteries, fuel cells, nuclear reactors, radioisotopic thermal generators (RTGs), and solar panel arrays. Solar arrays have many advantages over other types of power generation. They are lightweight and relatively inexpensive, allowing more mass and funding to be allocated for other important devices, such as scientific instruments. For Mars applications, solar power is an excellent option, especially for long missions. One might think that dust storms would be a problem; however, while dust blocks some solar energy, it also scatters it, making it diffuse rather than beamed. Solar cells are still able to capture this diffuse energy and convert it into substantial electrical power. For these reasons, solar power was chosen to be used on the 1997 Mars Pathfinder mission. The success of this mission set a precedent, as NASA engineers have selected solar power as the energy system of choice for all future Mars missions, including the Mars Exploration Rover (MER) Project. Solar sells have their drawbacks, however. They are difficult to manufacture and are relatively fragile. In addition, solar cells are highly sensitive to different parts of the solar spectrum, and finding the correct balance is crucial to the success of space missions. Another drawback is that the power generated is not a constant with respect to time, but rather changes with the relative angle to the sun. On Mars, dust accumulation also becomes a factor. Over time, dust settles out of the atmosphere and onto solar panels. This dust blocks and shifts the frequency of the incoming light, degrading solar cell performance. My goal is to analyze solar panel telemetry data from the two MERs (Spirit and Opportunity) in an effort to accurately model the effect of dust accumulation on solar panels. This is no easy process due to the large number of factors involved. Changing solar

  3. Extraintestinal manifestations of celiac disease: 33-mer gliadin binding to glutamate receptor GRINA as a new explanation.

    PubMed

    Garcia-Quintanilla, Albert; Miranzo-Navarro, Domingo

    2016-05-01

    We propose a biochemical mechanism for celiac disease and non-celiac gluten sensitivity that may rationalize many of the extradigestive disorders not explained by the current immunogenetic model. Our hypothesis is based on the homology between the 33-mer gliadin peptide and a component of the NMDA glutamate receptor ion channel - the human GRINA protein - using BLASTP software. Based on this homology the 33-mer may act as a natural antagonist interfering with the normal interactions of GRINA and its partners. The theory is supported by numerous independent data from the literature, and provides a mechanistic link with otherwise unrelated disorders, such as cleft lip and palate, thyroid dysfunction, restless legs syndrome, depression, ataxia, hearing loss, fibromyalgia, dermatitis herpetiformis, schizophrenia, toxoplasmosis, anemia, osteopenia, Fabry disease, Barret's adenocarcinoma, neuroblastoma, urinary incontinence, recurrent miscarriage, cardiac anomalies, reduced risk of breast cancer, stiff person syndrome, etc. The hypothesis also anticipates better animal models, and has the potential to open new avenues of research.

  4. Inoculation of Goats, Sheep, and Horses with MERS-CoV Does Not Result in Productive Viral Shedding

    PubMed Central

    Adney, Danielle R.; Brown, Vienna R.; Porter, Stephanie M.; Bielefeldt-Ohmann, Helle; Hartwig, Airn E.; Bowen, Richard A.

    2016-01-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 and can cause severe disease in infected humans. Dromedary camels are the reservoir for the virus, although, other than nasal discharge, these animals do not display any overt clinical disease. Data from in vitro experiments suggest that other livestock such as sheep, goats, and horses might also contribute to viral transmission, although field data has not identified any seropositive animals. In order to understand if these animals could be infected, we challenged young goats and horses and adult sheep with MERS-CoV by intranasal inoculation. Minimal or no virus shedding was detected in all of the animals. During the four weeks following inoculation, neutralizing antibodies were detected in the young goats, but not in sheep or horses. PMID:27548203

  5. Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg-Carbon Bond Cleavage and Metal Binding Specificity.

    PubMed

    Wahba, Haytham M; Lecoq, Lauriane; Stevenson, Michael; Mansour, Ahmed; Cappadocia, Laurent; Lafrance-Vanasse, Julien; Wilkinson, Kevin J; Sygusch, Jurgen; Wilcox, Dean E; Omichinski, James G

    2016-02-23

    In bacterial resistance to mercury, the organomercurial lyase (MerB) plays a key role in the detoxification pathway through its ability to cleave Hg-carbon bonds. Two cysteines (C96 and C159; Escherichia coli MerB numbering) and an aspartic acid (D99) have been identified as the key catalytic residues, and these three residues are conserved in all but four known MerB variants, where the aspartic acid is replaced with a serine. To understand the role of the active site serine, we characterized the structure and metal binding properties of an E. coli MerB mutant with a serine substituted for D99 (MerB D99S) as well as one of the native MerB variants containing a serine residue in the active site (Bacillus megaterium MerB2). Surprisingly, the MerB D99S protein copurified with a bound metal that was determined to be Cu(II) from UV-vis absorption, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, and electron paramagnetic resonance studies. X-ray structural studies revealed that the Cu(II) is bound to the active site cysteine residues of MerB D99S, but that it is displaced following the addition of either an organomercurial substrate or an ionic mercury product. In contrast, the B. megaterium MerB2 protein does not copurify with copper, but the structure of the B. megaterium MerB2-Hg complex is highly similar to the structure of the MerB D99S-Hg complexes. These results demonstrate that the active site aspartic acid is crucial for both the enzymatic activity and metal binding specificity of MerB proteins and suggest a possible functional relationship between MerB and its only known structural homologue, the copper-binding protein NosL.

  6. Leveraging Cloud Computing to Improve Storage Durability, Availability, and Cost for MER Maestro

    NASA Technical Reports Server (NTRS)

    Chang, George W.; Powell, Mark W.; Callas, John L.; Torres, Recaredo J.; Shams, Khawaja S.

    2012-01-01

    The Maestro for MER (Mars Exploration Rover) software is the premiere operation and activity planning software for the Mars rovers, and it is required to deliver all of the processed image products to scientists on demand. These data span multiple storage arrays sized at 2 TB, and a backup scheme ensures data is not lost. In a catastrophe, these data would currently recover at 20 GB/hour, taking several days for a restoration. A seamless solution provides access to highly durable, highly available, scalable, and cost-effective storage capabilities. This approach also employs a novel technique that enables storage of the majority of data on the cloud and some data locally. This feature is used to store the most recent data locally in order to guarantee utmost reliability in case of an outage or disconnect from the Internet. This also obviates any changes to the software that generates the most recent data set as it still has the same interface to the file system as it did before updates

  7. A FASTQ compressor based on integer-mapped k-mer indexing for biologist.

    PubMed

    Zhang, Yeting; Patel, Khyati; Endrawis, Tony; Bowers, Autumn; Sun, Yazhou

    2016-03-15

    Next generation sequencing (NGS) technologies have gained considerable popularity among biologists. For example, RNA-seq, which provides both genomic and functional information, has been widely used by recent functional and evolutionary studies, especially in non-model organisms. However, storing and transmitting these large data sets (primarily in FASTQ format) have become genuine challenges, especially for biologists with little informatics experience. Data compression is thus a necessity. KIC, a FASTQ compressor based on a new integer-mapped k-mer indexing method, was developed (available at http://www.ysunlab.org/kic.jsp). It offers high compression ratio on sequence data, outstanding user-friendliness with graphic user interfaces, and proven reliability. Evaluated on multiple large RNA-seq data sets from both human and plants, it was found that the compression ratio of KIC had exceeded all major generic compressors, and was comparable to those of the latest dedicated compressors. KIC enables researchers with minimal informatics training to take advantage of the latest sequence compression technologies, easily manage large FASTQ data sets, and reduce storage and transmission cost.

  8. Thermal stability and energetics of 15-mer DNA duplex interstrand crosslinked by trans-diamminedichloroplatinum(II).

    PubMed

    Hofr, Ctirad; Brabec, Viktor

    2005-03-01

    The effect of the location of the interstrand cross-link formed by trans-diamminedichloroplatinum(II) (transplatin) on the thermal stability and energetics of 15-mer DNA duplex has been investigated. The duplex containing single, site-specific cross-link, thermodynamically equivalent model structures (hairpins) and nonmodified duplexes were characterized by differential scanning calorimetry, temperature-dependent uv absorption, and circular dichroism. The results demonstrate that the formation of the interstrand cross-link of transplatin does not affect pronouncedly thermodynamic stability of DNA: the cross-link induces no marked changes not only in enthalpy, but also in "reduced" (concentration independent) monomolecular transition entropy. These results are consistent with the previous observations that interstrand cross-links of transplatin structurally perturb DNA only to a relatively small extent. On the other hand, constraining the duplex with the interstrand cross-link of transplatin results in a significant increase in thermal stability that is primarily due to entropic effects: the cross-link reduces the molecularity of the oligomer system from bimolecular to monomolecular. Importantly, the position of the interstrand cross-link within the duplex modulates cooperativity of the melting transition of the duplex and consequently its thermal stability.

  9. Possible Evidence for Iron Sulfates, Iron Sulfides, and Elemental Sulfur at Gusev Crater, Mars, from Mer, Crism, and Analog Data

    NASA Technical Reports Server (NTRS)

    Morris, R. V.; Ming, D. W.; Yen, A.; Arvidson, R. E.; Gruener, J.; Humm, D.; Klingelhoefer, G.; Murchie, S.; Schroeder, C.; Seelos, F., IV; Squyres, S.; Wiseman, S.; Wolff, M.

    2007-01-01

    The Mossbauer (MB) spectrometers on the Mars Exploration Rovers (MER) Spirit (Gusev crater) and Opportunity (Meridiani Planum) have detected 14 Fe-bearing phases, and mineralogical assignments have been made for all except 3. Identified Fe2+-bearing phases are olivine, pyroxene, ilmenite, and troilite. Magnetite and chromite are present as mixed Fe(2+) and Fe(3+) phases. Identified Fe(3+) phase are jarosite, hematite, goethite, and nanophase ferric oxide (npOx). Fe(sup 0) (iron metal) is present as kamacite. Nanophase ferric oxide (npOx) is a generic name for octahedrally coordinated Fe(3+) alteration products that cannot be otherwise mineralogically assigned on the basis of MER data. On the Earth, npOx would include ferrihydrite, iddingsite, schwertmannite, akaganeite, and superparamagnetic hematite and goethite. The Mars Reconnaissance Orbiter CRISM instrument, a visible, near-IR hyperspectral imager (approximately 0.35 to 4 micron) enables mineralogical examination of Mars with a tool that is sensitive to H2O and to M-OH (M = Al, Si, Fe, Mg, etc.) at spatial resolution of about 20 m/pixel. We examined a CRISM image of the MER region of Gusev crater (Columbia Hills and plains to the west), looking for spectral evidence of the aqueous process apparent from the MER analyses. We also searched for spectral constraints for the mineralogical composition of our unidentified Fe-bearing phases and the forms of npOx present on Mars. We also consider evidence from analogue samples that the precursor for the goethite detected by MB in Clovis Class rocks is an iron sulfide. We suggest that there is some indirect evidence that elemental sulfur might be present to different extents in Clovis Class rocks, the Fe3Sulfate-rich soils, and perhaps even typical (Laguna Class) surface soils.

  10. Improved Method for Recovery of mRNA from Aquatic Samples and Its Application to Detection of mer Expression

    PubMed Central

    Jeffrey, Wade H.; Nazaret, Sylvie; Von Haven, Robin

    1994-01-01

    Previously described methods for extraction of mRNA from environmental samples may preclude detecting transcripts from genes that were present in low abundance in aquatic bacterial communities. By combining a boiling sodium dodecyl sulfate-diethylpyrocarbonate lysis step with acid-guanidinium extraction, we improved recovery of target mRNA from both pure cultures and environmental samples. The most significant advantage of the new protocol is that it is easily adapted to yield high recovery of mRNA from 142-mm-diameter flat filters and high-capacity cartridge filters. The lysis and extraction procedures are more rapid than previously described methods, and many samples can be handled at once. RNA extracts have been shown to be free of contaminating DNA. The lysis procedure does not damage target mRNA sequences, and mRNA can be detected from fewer than 106 bacterial cells. We used the new method to examine transcripts of genes responsible for detoxification of mercurial compounds. Induction of merA (specifying mercuric reductase) transcripts in stationary-phase Pseudomonas aeruginosa containing Tn501 occurred within 60 s of HgCl2 addition and was proportional to the amount of Hg(II) added. The new technique also allowed the detection of merA transcripts from the microbial community of a mercury-contaminated pond (Reality Lake, Oak Ridge, Tenn.). Significant differences in merA transcript abundance were observed between different locations associated with the lake. The results indicate that the new method is simple and rapid and can be applied to the study of mer gene expression of aquatic communities in their natural habitats. PMID:16349274

  11. Cultivation of hard-to-culture subsurface mercury-resistant bacteria and discovery of new merA gene sequences.

    PubMed

    Rasmussen, L D; Zawadsky, C; Binnerup, S J; Oregaard, G; Sørensen, S J; Kroer, N

    2008-06-01

    Mercury-resistant bacteria may be important players in mercury biogeochemistry. To assess the potential for mercury reduction by two subsurface microbial communities, resistant subpopulations and their merA genes were characterized by a combined molecular and cultivation-dependent approach. The cultivation method simulated natural conditions by using polycarbonate membranes as a growth support and a nonsterile soil slurry as a culture medium. Resistant bacteria were pregrown to microcolony-forming units (mCFU) before being plated on standard medium. Compared to direct plating, culturability was increased up to 2,800 times and numbers of mCFU were similar to the total number of mercury-resistant bacteria in the soils. Denaturing gradient gel electrophoresis analysis of DNA extracted from membranes suggested stimulation of growth of hard-to-culture bacteria during the preincubation. A total of 25 different 16S rRNA gene sequences were observed, including Alpha-, Beta-, and Gammaproteobacteria; Actinobacteria; Firmicutes; and Bacteroidetes. The diversity of isolates obtained by direct plating included eight different 16S rRNA gene sequences (Alpha- and Betaproteobacteria and Actinobacteria). Partial sequencing of merA of selected isolates led to the discovery of new merA sequences. With phylum-specific merA primers, PCR products were obtained for Alpha- and Betaproteobacteria and Actinobacteria but not for Bacteroidetes and Firmicutes. The similarity to known sequences ranged between 89 and 95%. One of the sequences did not result in a match in the BLAST search. The results illustrate the power of integrating advanced cultivation methodology with molecular techniques for the characterization of the diversity of mercury-resistant populations and assessing the potential for mercury reduction in contaminated environments.

  12. Solfataric Alteration in Hawaii as a Mechanism for Formation of the Sulfates Observed on Mars by OMEGA and the MER Instruments

    NASA Astrophysics Data System (ADS)

    Bishop, J. L.; Schiffman, P.; Lane, M. D.; Dyar, M. D.

    2005-03-01

    Solfataric alteration in the Kilauea caldera, HI, forms sulfates and hydrated phases from volcanic ash. Spectral analyses are presented for detection of these minerals/phases on Mars by OMEGA and for groundtruthing the OMEGA spectra with MER data.

  13. Presence of antibodies but no evidence for circulation of MERS-CoV in dromedaries on the Canary Islands, 2015.

    PubMed

    Gutiérrez, Carlos; Tejedor-Junco, María Teresa; González, Margarita; Lattwein, Erik; Renneker, Stefanie

    2015-01-01

    In 2012, a new betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), was identified in humans. Several studies confirmed dromedary camels to be a potential reservoir and a source for human infection. Camels located on the Canary Islands were included in those studies and ca 10% of them were positive for MERS-CoV-specific antibodies. However, these findings could not be correctly interpreted because epidemiological information was not provided. Thus, further investigations were necessary to clarify these results. A total of 170 camels were investigated in this survey, of which seven (4.1%) were seropositive by ELISA. Epidemiological information revealed that all seropositive camels had been imported from Africa 20 or more years prior. We conclude that seropositive camels had contact with MERS-CoV in Africa and that there is no shedding of the virus among camels or people around the farms on the Canary Islands. However, the presence of antibodies in the camel herds should be monitored.

  14. Flow cytometry and K-mer analysis estimates of the genome sizes of Bemisia tabaci B and Q (Hemiptera: Aleyrodidae)

    PubMed Central

    Guo, Li T.; Wang, Shao L.; Wu, Qing J.; Zhou, Xu G.; Xie, Wen; Zhang, You J.

    2015-01-01

    The genome sizes of the B- and Q-types of the whitefly Bemisia tabaci (Gennnadius) were estimated using flow cytometry (Drosophila melanogaster as the DNA reference standard and propidium iodide (PI) as the fluorochrome) and k-mer analysis. For flow cytometry, the mean nuclear DNA content was 0.686 pg for B-type males, 1.392 pg for B-type females, 0.680 pg for Q-type males, and 1.306 pg for Q-type females. Based on the relationship between DNA content and genome size (1 pg DNA = 980 Mbp), the haploid genome size of B. tabaci ranged from 640 to 682 Mbp. For k-mer analysis, genome size of B-type by two methods were consistent highly, but the k-mer depth distribution graph of Q-type was not enough perfect and the genome size was estimated about 60 M larger than its flow cytometry result. These results corroborate previous reports of genome size based on karyotype analysis and chromosome counting. However, these estimates differ from previous flow cytometry estimates, probably because of differences in the DNA reference standard and dyeing time, which were superior in the current study. For Q-type genome size difference by two method, some discussion were also stated, and all these results represent a useful foundation for B. tabaci genomics research. PMID:26042041

  15. STN area detection using K-NN classifiers for MER recordings in Parkinson patients during neurostimulator implant surgery

    NASA Astrophysics Data System (ADS)

    Schiaffino, L.; Rosado Muñoz, A.; Guerrero Martínez, J.; Francés Villora, J.; Gutiérrez, A.; Martínez Torres, I.; Kohan, y. D. R.

    2016-04-01

    Deep Brain Stimulation (DBS) applies electric pulses into the subthalamic nucleus (STN) improving tremor and other symptoms associated to Parkinson’s disease. Accurate STN detection for proper location and implant of the stimulating electrodes is a complex task and surgeons are not always certain about final location. Signals from the STN acquired during DBS surgery are obtained with microelectrodes, having specific characteristics differing from other brain areas. Using supervised learning, a trained model based on previous microelectrode recordings (MER) can be obtained, being able to successfully classify the STN area for new MER signals. The K Nearest Neighbours (K-NN) algorithm has been successfully applied to STN detection. However, the use of the fuzzy form of the K-NN algorithm (KNN-F) has not been reported. This work compares the STN detection algorithm of K-NN and KNN-F. Real MER recordings from eight patients where previously classified by neurophysiologists, defining 15 features. Sensitivity and specificity for the classifiers are obtained, Wilcoxon signed rank non-parametric test is used as statistical hypothesis validation. We conclude that the performance of KNN-F classifier is higher than K-NN with p<0.01 in STN specificity.

  16. Unbiased K-mer Analysis Reveals Changes in Copy Number of Highly Repetitive Sequences During Maize Domestication and Improvement

    PubMed Central

    Liu, Sanzhen; Zheng, Jun; Migeon, Pierre; Ren, Jie; Hu, Ying; He, Cheng; Liu, Hongjun; Fu, Junjie; White, Frank F.; Toomajian, Christopher; Wang, Guoying

    2017-01-01

    The major component of complex genomes is repetitive elements, which remain recalcitrant to characterization. Using maize as a model system, we analyzed whole genome shotgun (WGS) sequences for the two maize inbred lines B73 and Mo17 using k-mer analysis to quantify the differences between the two genomes. Significant differences were identified in highly repetitive sequences, including centromere, 45S ribosomal DNA (rDNA), knob, and telomere repeats. Genotype specific 45S rDNA sequences were discovered. The B73 and Mo17 polymorphic k-mers were used to examine allele-specific expression of 45S rDNA in the hybrids. Although Mo17 contains higher copy number than B73, equivalent levels of overall 45S rDNA expression indicates that transcriptional or post-transcriptional regulation mechanisms operate for the 45S rDNA in the hybrids. Using WGS sequences of B73xMo17 doubled haploids, genomic locations showing differential repetitive contents were genetically mapped, which displayed different organization of highly repetitive sequences in the two genomes. In an analysis of WGS sequences of HapMap2 lines, including maize wild progenitor, landraces, and improved lines, decreases and increases in abundance of additional sets of k-mers associated with centromere, 45S rDNA, knob, and retrotransposons were found among groups, revealing global evolutionary trends of genomic repeats during maize domestication and improvement. PMID:28186206

  17. Comparison of incubation period distribution of human infections with MERS-CoV in South Korea and Saudi Arabia

    PubMed Central

    Virlogeux, Victor; Fang, Vicky J.; Park, Minah; Wu, Joseph T.; Cowling, Benjamin J.

    2016-01-01

    The incubation period is an important epidemiologic distribution, it is often incorporated in case definitions, used to determine appropriate quarantine periods, and is an input to mathematical modeling studies. Middle East Respiratory Syndrome coronavirus (MERS) is an emerging infectious disease in the Arabian Peninsula. There was a large outbreak of MERS in South Korea in 2015. We examined the incubation period distribution of MERS coronavirus infection for cases in South Korea and in Saudi Arabia. Using parametric and nonparametric methods, we estimated a mean incubation period of 6.9 days (95% credibility interval: 6.3–7.5) for cases in South Korea and 5.0 days (95% credibility interval: 4.0–6.6) among cases in Saudi Arabia. In a log-linear regression model, the mean incubation period was 1.42 times longer (95% credibility interval: 1.18–1.71) among cases in South Korea compared to Saudi Arabia. The variation that we identified in the incubation period distribution between locations could be associated with differences in ascertainment or reporting of exposure dates and illness onset dates, differences in the source or mode of infection, or environmental differences. PMID:27775012

  18. The catalytic core of an archaeal 2-oxoacid dehydrogenase multienzyme complex is a 42-mer protein assembly.

    PubMed

    Marrott, Nia L; Marshall, Jacqueline J T; Svergun, Dmitri I; Crennell, Susan J; Hough, David W; Danson, Michael J; van den Elsen, Jean M H

    2012-03-01

    The dihydrolipoyl acyl-transferase (E2) enzyme forms the structural and catalytic core of the tripartite 2-oxoacid dehydrogenase multienzyme complexes of the central metabolic pathways. Although this family of multienzyme complexes shares a common architecture, their E2 cores form homo-trimers that, depending on the source, further associate into either octahedral (24-mer) or icosahedral (60-mer) assemblies, as predicted by the principles of quasi-equivalence. In the crystal structure of the E2 core from Thermoplasma acidophilum, a thermophilic archaeon, the homo-trimers assemble into a unique 42-mer oblate spheroid. Analytical equilibrium centrifugation and small-angle X-ray scattering analyses confirm that this catalytically active 1.08 MDa assembly exists as a single species in solution, forming a hollow spheroid with a maximum diameter of 220 Å. In this paper we show that a monodisperse macromolecular assembly, built from identical subunits in non-identical environments, forms an irregular protein shell via non-equivalent interactions. This unusually irregular protein shell, combining cubic and dodecahedral geometrical elements, expands on the concept of quasi-equivalence as a basis for understanding macromolecular assemblies by showing that cubic point group symmetry is not a physical requirement in multienzyme assembly. These results extend our basic knowledge of protein assembly and greatly expand the number of possibilities to manipulate self-assembling biological complexes to be utilized in innovative nanotechnology applications.

  19. Knowledge, Attitudes and Behaviours of Healthcare Workers in the Kingdom of Saudi Arabia to MERS Coronavirus and Other Emerging Infectious Diseases

    PubMed Central

    Alsahafi, Abdullah J.; Cheng, Allen C.

    2016-01-01

    Background: The Kingdom of Saudi Arabia has experienced a prolonged outbreak of Middle East Respiratory Syndrome (MERS) coronavirus since 2012. Healthcare workers (HCWs) form a significant risk group for infection. Objectives: The aim of this survey was to assess the knowledge, attitudes, infection control practices and educational needs of HCWs in the Kingdom of Saudi Arabia to MERS coronavirus and other emerging infectious diseases. Methods: 1500 of HCWs from Saudi Ministry of Health were invited to fill a questionnaire developed to cover the survey objectives from 9 September 2015 to 8 November 2015. The response rate was about 81%. Descriptive statistics was used to summarise the responses. Results: 1216 HCWs were included in this survey. A total of 56.5% were nurses and 22% were physicians. The most common sources of MERS-coronavirus (MERS-CoV) information were the Ministry of Health (MOH) memo (74.3%). Only (47.6%) of the physicians, (30.4%) of the nurses and (29.9%) of the other HCWs were aware that asymptomatic MERS-CoV was described. Around half of respondents who having been investigated for MERS-CoV reported that their work performance decreased while they have suspicion of having MERS-CoV and almost two thirds reported having psychological problems during this period. Almost two thirds of the HCWs (61.2%) reported anxiety about contracting MERS-CoV from patients. Conclusions: The knowledge about emerging infectious diseases was poor and there is need for further education and training programs particularly in the use of personal protective equipment, isolation and infection control measures. The self-reported infection control practices were sub-optimal and seem to be overestimated. PMID:27929452

  20. Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Is an Efficient ADP-ribose Binding Module: CRYSTAL STRUCTURE AND BIOCHEMICAL STUDIES.

    PubMed

    Cho, Chao-Cheng; Lin, Meng-Hsuan; Chuang, Chien-Ying; Hsu, Chun-Hua

    2016-03-04

    The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) encodes the conserved macro domain within non-structural protein 3. However, the precise biochemical function and structure of the macro domain is unclear. Using differential scanning fluorimetry and isothermal titration calorimetry, we characterized the MERS-CoV macro domain as a more efficient adenosine diphosphate (ADP)-ribose binding module than macro domains from other CoVs. Furthermore, the crystal structure of the MERS-CoV macro domain was determined at 1.43-Å resolution in complex with ADP-ribose. Comparison of macro domains from MERS-CoV and other human CoVs revealed structural differences in the α1 helix alters how the conserved Asp-20 interacts with ADP-ribose and may explain the efficient binding of the MERS-CoV macro domain to ADP-ribose. This study provides structural and biophysical bases to further evaluate the role of the MERS-CoV macro domain in the host response via ADP-ribose binding but also as a potential target for drug design.

  1. Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice.

    PubMed

    Wang, Chong; Zheng, Xuexing; Gai, Weiwei; Wong, Gary; Wang, Hualei; Jin, Hongli; Feng, Na; Zhao, Yongkun; Zhang, Weijiao; Li, Nan; Zhao, Guoxing; Li, Junfu; Yan, Jinghua; Gao, Yuwei; Hu, Guixue; Yang, Songtao; Xia, Xianzhu

    2017-04-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). sVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphology similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. sVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1: 320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. Furthermore, mice inoculated with sVLP or an adjuvanted sVLP vaccine elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. Our study demonstrates that sVLP displaying the RBD of MERS-CoV are promising prophylactic candidates against MERS-CoV in a potential outbreak situation.

  2. Using Mars and the Mer Mission to Teach Science: A Curriculum Designed for Teachers and Their Students

    NASA Astrophysics Data System (ADS)

    Aubele, J. C.; Stanley, J.; Grochowski, A.; Jones, K.; Aragon, J.

    2006-12-01

    Learning opportunities can be exceptionally successful when linked to national, newsworthy events. Planetary missions are particularly exciting in engaging teachers, and their students, because they combine the human "stories" of scientists and engineers with cutting-edge technology and new science. Planetary suface missions, such as the Mars Exploration Rover (MER) mission, return beautiful and human-scale images that can virtually transport the viewer to another world. The MER mission allows children and adults to participate in the exploration of one of our nearest neighbors in space. New discoveries in the natural history of Mars have been used as the basis of a new integrated curriculum created by Museum and class-room educators designed to serve informal (family learning) and formal (classroom) audiences. The curriculum uses Mars and the MER mission as a "hook" to teach a wide range of topics that relate to all of the sciences, mathematics, social studies (history and exploration), science and society, career readiness, language and literacy, and visual arts. The curriculum, entitled "Making Tracks on Mars: Teacher Resource and Activity Guide," includes the following key features that have contributed to its success and usefulness: (1) basic information about Mars, Mars missions, and the MER mission providing teachers with the knowledge they may lack; (2) activities that follow a standardized format and include necessary information, pre-lesson preparation and post-lesson closure and extensions, and all information and/or images needed; (3) activities that cross the curriculum and can be used to address many different standards; (4) relevant state and national standards listed for each activity; (5) annotated MER image file and PowerPoint presentation for easy classroom use; (6) lists of additional Mars-related resources; (7) emphasis on local connections to the mission to enable teachers and students to feel personally connected; (8) elementary through high

  3. Effect of the antiestrogen ethamoxytriphetol (MER-25) on placental low density lipoprotein uptake and degradation in baboons

    SciTech Connect

    Henson, M.C.; Babischkin, J.S.; Pepe, G.J.; Albrecht, E.D.

    1988-05-01

    The present study determined if the decline in placental progesterone (P4) production that results from administration of the antiestrogen ethamoxytriphetol (MER-25) to pregnant baboons results from a change in placental low density lipoprotein (LDL) uptake and/or degradation. Pregnant baboons (Papio anubis) were untreated (n = 10) or received MER-25 (25 mg/kg BW, orally; n = 10) daily on days 140-170 of gestation (term, 184 days). Placentas were removed by cesarean section on day 170 of gestation, and villous tissue was dispersed with 0.1% collagenase at 37 C for 40 min. Placental cells (10(6)) were incubated in medium 199 (pH 7.2) for 12 h at 37 C with increasing amounts (5-100 micrograms) of (125I)LDL, with or without a 100-fold excess of unlabeled baboon LDL. Mean (+/- SE) peripheral serum P4 concentrations on days 140-170 of gestation were 51% lower (P less than 0.01) in MER-25-treated (5.7 +/- 0.3 ng/ml) than in untreated (11.6 +/- 0.5 ng/ml) baboons. The uptake of LDL was 56% lower (P less than 0.01) in placental cells from antiestrogen-treated (6.3 +/- 1.6 ng/micrograms cell protein) than in those from untreated (14.4 +/- 1.9 ng/micrograms cell protein) baboons. The dissociation constants for placental LDL uptake, as assessed by Scatchard analysis, however, were similar in untreated (0.80 microgram/ml) and MER-25-treated (0.76 microgram/ml) animals. The amount of (125I)LDL concomitantly degraded by cells from baboons that received MER-25 was 54% of that degraded by cells from untreated controls. The relative decline in LDL degradation by cells of antiestrogen-treated baboons was proportionate to the decline in overall LDL uptake. The results indicate, therefore, that antiestrogen treatment decreased the amount of placental LDL uptake, but did not change the affinity for the lipoprotein.

  4. A predictive wheel-soil interaction model for planetary rovers validated in testbeds and against MER Mars rover performance data

    NASA Astrophysics Data System (ADS)

    Richter, L.; Ellery, A.; Gao, Y.; Michaud, S.; Schmitz, N.; Weiss, S.

    Successful designs of vehicles intended for operations on planetary objects outside the Earth demand, just as for terrestrial off-the-road vehicles, a careful assessment of the terrain relevant for the vehicle mission and predictions of the mobility performance to allow rational trade-off's to be made for the choice of the locomotion concept and sizing. Principal issues driving the chassis design for rovers are the stress-strain properties of the planetary surface soil, the distribution of rocks in the terrain representing potential obstacles to movement, and the gravity level on the celestial object in question. Thus far, planetary rovers have been successfully designed and operated for missions to the Earth's moon and to the planet Mars, including NASA's Mars Exploration Rovers (MER's) `Spirit' and `Opportunity' being in operation on Mars since their landings in January 2004. Here we report on the development of a wheel-soil interaction model with application to wheel sizes and wheel loads relevant to current and near-term robotic planetary rovers, i.e. wheel diameters being between about 200 and 500 mm and vertical quasistatic wheel loads in operation of roughly 100 to 200 N. Such a model clearly is indispensable for sizings of future rovers to analyse the aspect of rover mobility concerned with motion across soils. This work is presently funded by the European Space Agency (ESA) as part of the `Rover Chassis Evaluation Tools' (RCET) effort which has developed a set of S/W-implemented models for predictive mobility analysis of rovers in terms of movement on soils and across obstacles, coupled with dedicated testbeds to validate the wheel-soil models. In this paper, we outline the details of the wheel-soil modelling performed within the RCET work and present comparisons of predictions of wheel performance (motion resistance, torque vs. slip and drawbar pull vs. slip) for specific test cases with the corresponding measurements performed in the RCET single wheel

  5. Automated Recognition of Geologically Significant Shapes in MER PANCAM and MI Images

    NASA Technical Reports Server (NTRS)

    Morris, Robert; Shipman, Mark; Roush, Ted L.

    2004-01-01

    Autonomous recognition of scientifically important information provides the capability of: 1) Prioritizing data return; 2) Intelligent data compression; 3) Reactive behavior onboard robotic vehicles. Such capabilities are desirable as mission scenarios include longer durations with decreasing interaction from mission control. To address such issues, we have implemented several computer algorithms, intended to autonomously recognize morphological shapes of scientific interest within a software architecture envisioned for future rover missions. Mars Exploration Rovers (MER) instrument payloads include a Panoramic Camera (PANCAM) and Microscopic Imager (MI). These provide a unique opportunity to evaluate our algorithms when applied to data obtained from the surface of Mars. Early in the mission we applied our algorithms to images available at the mission web site (http://marsrovers.jpl.nasa.gov/gallery/images.html), even though these are not at full resolution. Some algorithms would normally use ancillary information, e.g. camera pointing and position of the sun, but these data were not readily available. The initial results of applying our algorithms to the PANCAM and MI images are encouraging. The horizon is recognized in all images containing it; such information could be used to eliminate unwanted areas from the image prior to data transmission to Earth. Additionally, several rocks were identified that represent targets for the mini-thermal emission spectrometer. Our algorithms also recognize the layers, identified by mission scientists. Such information could be used to prioritize data return or in a decision-making process regarding future rover activities. The spherules seen in MI images were also autonomously recognized. Our results indicate that reliable recognition of scientifically relevant morphologies in images is feasible.

  6. Modeling seasonal to annual carbon balance of Mer Bleue Bog, Ontario, Canada

    NASA Astrophysics Data System (ADS)

    Frolking, Steve; Roulet, Nigel T.; Moore, Tim R.; Lafleur, Peter M.; Bubier, Jill L.; Crill, Patrick M.

    2002-07-01

    Northern peatlands contain enormous quantities of organic carbon within a few meters of the atmosphere and play a significant role in the planetary carbon balance. We have developed a new, process-oriented model of the contemporary carbon balance of northern peatlands, the Peatland Carbon Simulator (PCARS). Components of PCARS are (1) vascular and nonvascular plant photosynthesis and respiration, net aboveground and belowground production, and litterfall; (2) aerobic and anaerobic decomposition of peat; (3) production, oxidation, and emission of methane; and (4) dissolved organic carbon loss with drainage water. PCARS has an hourly time step and requires air and soil temperatures, incoming radiation, water table depth, and horizontal drainage as drivers. Simulations predict a complete peatland C balance for one season to several years. A 3-year simulation was conducted for Mer Bleue Bog, near Ottawa, Ontario, and results were compared with multiyear eddy covariance tower CO2 flux and ancillary measurements from the site. Seasonal patterns and the general magnitude of net ecosystem exchange of CO2 were similar for PCARS and the tower data, though PCARS was generally biased toward net ecosystem respiration (i.e., carbon loss). Gross photosynthesis rates (calculated directly in PCARS, empirically inferred from tower data) were in good accord, so the discrepancy between model and measurement was likely related to autotrophic and/or heterotrophic respiration. Modeled and measured methane emission rates were quite low. PCARS has been designed to link with the Canadian Land Surface Scheme (CLASS) land surface model and a global climate model (GCM) to examine climate-peatland carbon feedbacks at regional scales in future analyses.

  7. Inhibitor recognition specificity of MERS-CoV papain-like protease may differ from that of SARS-CoV.

    PubMed

    Lee, Hyun; Lei, Hao; Santarsiero, Bernard D; Gatuz, Joseph L; Cao, Shuyi; Rice, Amy J; Patel, Kavankumar; Szypulinski, Michael Z; Ojeda, Isabel; Ghosh, Arun K; Johnson, Michael E

    2015-06-19

    The Middle East Respiratory Syndrome coronavirus (MERS-CoV) papain-like protease (PLpro) blocking loop 2 (BL2) structure differs significantly from that of SARS-CoV PLpro, where it has been proven to play a crucial role in SARS-CoV PLpro inhibitor binding. Four SARS-CoV PLpro lead inhibitors were tested against MERS-CoV PLpro, none of which were effective against MERS-CoV PLpro. Structure and sequence alignments revealed that two residues, Y269 and Q270, responsible for inhibitor binding to SARS-CoV PLpro, were replaced by T274 and A275 in MERS-CoV PLpro, making critical binding interactions difficult to form for similar types of inhibitors. High-throughput screening (HTS) of 25 000 compounds against both PLpro enzymes identified a small fragment-like noncovalent dual inhibitor. Mode of inhibition studies by enzyme kinetics and competition surface plasmon resonance (SPR) analyses suggested that this compound acts as a competitive inhibitor with an IC50 of 6 μM against MERS-CoV PLpro, indicating that it binds to the active site, whereas it acts as an allosteric inhibitor against SARS-CoV PLpro with an IC50 of 11 μM. These results raised the possibility that inhibitor recognition specificity of MERS-CoV PLpro may differ from that of SARS-CoV PLpro. In addition, inhibitory activity of this compound was selective for SARS-CoV and MERS-CoV PLpro enzymes over two human homologues, the ubiquitin C-terminal hydrolases 1 and 3 (hUCH-L1 and hUCH-L3).

  8. IFITM Proteins Inhibit Entry Driven by the MERS-Coronavirus Spike Protein: Evidence for Cholesterol-Independent Mechanisms

    PubMed Central

    Wrensch, Florian; Winkler, Michael; Pöhlmann, Stefan

    2014-01-01

    The interferon-inducible transmembrane (IFITM) proteins 1, 2 and 3 inhibit the host cell entry of several enveloped viruses, potentially by promoting the accumulation of cholesterol in endosomal compartments. IFITM3 is essential for control of influenza virus infection in mice and humans. In contrast, the role of IFITM proteins in coronavirus infection is less well defined. Employing a retroviral vector system for analysis of coronavirus entry, we investigated the susceptibility of human-adapted and emerging coronaviruses to inhibition by IFITM proteins. We found that entry of the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is sensitive to inhibition by IFITM proteins. In 293T cells, IFITM-mediated inhibition of cellular entry of the emerging MERS- and SARS-CoV was less efficient than blockade of entry of the globally circulating human coronaviruses 229E and NL63. Similar differences were not observed in A549 cells, suggesting that cellular context and/or IFITM expression levels can impact inhibition efficiency. The differential IFITM-sensitivity of coronaviruses observed in 293T cells afforded the opportunity to investigate whether efficiency of entry inhibition by IFITMs and endosomal cholesterol accumulation correlate. No such correlation was observed. Furthermore, entry mediated by the influenza virus hemagglutinin was robustly inhibited by IFITM3 but was insensitive to accumulation of endosomal cholesterol, indicating that modulation of cholesterol synthesis/transport did not account for the antiviral activity of IFITM3. Collectively, these results show that the emerging MERS-CoV is a target of the antiviral activity of IFITM proteins and demonstrate that mechanisms other than accumulation of endosomal cholesterol can contribute to viral entry inhibition by IFITMs. PMID:25256397

  9. Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination.

    PubMed

    Otter, J A; Donskey, C; Yezli, S; Douthwaite, S; Goldenberg, S D; Weber, D J

    2016-03-01

    Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.

  10. Modelling impacts of offshore wind farms on trophic web: the Courseulles-sur-Mer case study

    NASA Astrophysics Data System (ADS)

    Raoux, Aurore; Pezy, Jean-Philippe; Dauvin, Jean-Claude; Tecchio, samuele; Degraer, Steven; Wilhelmsson, Dan; Niquil, Nathalie

    2016-04-01

    The French government is planning the construction of three offshore wind farms in Normandy. These offshore wind farms will integrate into an ecosystem already subject to a growing number of anthropogenic disturbances such as transportation, fishing, sediment deposit, and sediment extraction. The possible effects of this cumulative stressors on ecosystem functioning are still unknown, but they could impact their resilience, making them susceptible to changes from one stable state to another. Understanding the behaviour of these marine coastal complex systems is essential in order to anticipate potential state changes, and to implement conservation actions in a sustainable manner. Currently, there are no global and integrated studies on the effects of construction and exploitation of offshore wind farms. Moreover, approaches are generally focused on the conservation of some species or groups of species. Here, we develop a holistic and integrated view of ecosystem impacts through the use of trophic webs modelling tools. Trophic models describe the interaction between biological compartments at different trophic levels and are based on the quantification of flow of energy and matter in ecosystems. They allow the application of numerical methods for the characterization of emergent properties of the ecosystem, also called Ecological Network Analysis (ENA). These indices have been proposed as ecosystem health indicators as they have been demonstrated to be sensitive to different impacts on marine ecosystems. We present here in detail the strategy for analysing the potential environmental impacts of the construction of the Courseulles-sur-Mer offshore wind farm (Bay of Seine) such as the reef effect through the use of the Ecopath with Ecosim software. Similar Ecopath simulations will be made in the future on the Le Tréport offshore wind farm site. Results will contribute to a better knowledge of the impacts of the offshore wind farms on ecosystems. They also allow to

  11. An In-Situ Rb-Sr Dating & Organics Characterization Instrument For A MER+ Sized Rover

    NASA Astrophysics Data System (ADS)

    Anderson, F.; Whitaker, T.; Nowicki, K.; Zacny, K.; Pierce, J.

    2012-12-01

    We posit that a Mars in-situ geochronology mission that will triage and validate samples for Mars Sample Return (MSR) is technically feasible in the 2018-2022 time frame and addresses the competing scientific, political, and fiscal requirements for flight in this decade.The mission must be responsive to the astrobiological and chronological science goals of the MEPAG, Decadal Survey (DS), and E2E-iSAG, and avoid the MSR appearance of long term political commitment and cost. These requirements can best be accomplished by a rover with a coring drill. JPL has reassessed the MER landing system performance, and determined that the system is capable of significantly higher landed mass (~40-60 kg plus reserve), allowing more sophisticated instruments to be carried. The instrument package is comprised of a time of flight (TOF) mass spectrometer combined with a laser desorption resonance ionization source to sensitively measure isobar free Rb-Sr isotopes for geochronology and organics characterization. The desorption laser is also used with a μRaman/LIBS for mineral characterization, which in combination with the TOF, will additionally provide measurements of K-Ar isotopes for a second form of radiometric dating. The laser desorption resonance ionization mass spectrometry (LDRIMS) technique avoids the interference and mass resolution issues associated with geochronology measurements, and has miniaturization potential. A sample is placed in the TOF mass spectrometer and surface atoms, molecules, and ions are desorbed with a 213 nm laser. Ions are suppressed by an electric field and the plume of expanding particles is present for many μs, during which it is first illuminated with laser light tuned to ionize only Sr, and then 1-3 μs later, for Rb. We have partially miniaturized the instrument, including Sr lasers, ablation laser, and mass spectrometer, and will soon to start using the instrument for field measurements. Our current prototype can measure the isotope ratio of

  12. ROCK AND SOIL PHYSICAL PROPERTIES AT THE MER GUSEV CRATER AND MERIDIANI PLANUM LANDING SITES

    NASA Technical Reports Server (NTRS)

    Ming, Douglas W.; Richter, L.; Arvidson, R.; Bell, J.; Cabrol, N.; Gorevan, S.; Greeley, R.; Herkenhoff, K.

    2006-01-01

    Following the successful landings of both Mars Exploration Rover (MER) vehicles at Gusev Crater and Meridiani Planum, respectively, their Athena suite of instruments is being used to study the geologic history of these two very different landing sites on Mars that had been selected on the basis of showing different types of evidence for aqueous processes in the planet s past. Utilizing the on-board instruments as well as the rovers mobility system, a wide range of physical properties investigations is carried out as well - the subject of this abstract - that provide additional information on the geology and processes at the sites. Results of the mission in general as well as of the physical properties studies thus far greatly exceed expectations in that observations and measurements by both vehicles show a rich variety in materials and processes: the Gusev site in the vicinity of the lander is remarkably flat and generally devoid of large rocks along traverses up to the time of this writing (approx.Sol 50) and suggestive of a deflated surface with generally only thin veneers of bright dust while exhibiting evidence of a widespread occurrence of a crust from cemented fines that has been observed to fail in the form of blocky clods when disturbed by vehicle rolling action; numerous small and shallow depressions - presumably created by impacts - are observed at the site which are infilled with bright, fine-grained material that likewise appears indurated and which was studied by a trenching experiment; small ripple bedforms are scattered across the site and were characterized in terms of particle size distributions. At the Meridiani site, studies so far - up to approx.Sol 33 - have focussed on soils and the rock outcrop encountered within the approx.20 m diameter crater that the spacecraft came to rest in: from a physical properties point of view, a mantle of dark, well-sorted, apparently basaltic sand with small to moderate cohesion has been of interest - and has

  13. Geology and MER target site characteristics along the southern rim of Isidis Planitia, Mars

    NASA Astrophysics Data System (ADS)

    Crumpler, L. S.; Tanaka, K. L.

    2003-12-01

    crustal materials, in the form of rocks within the debris fans, and the weathered condition of the rocky material are potential sources for mineralogical evidence of climatic conditions in earliest Martian geologic history. The absence of alteration within rocks would, on the other hand, support the hypothesis that fluvial runoff during the earliest history of Mars was geologically brief rather than long-term and that long-term saturated groundwater flow was not present. Determination of the presence or absence of alteration would have corresponding implications for hypotheses requiring the long-term presence of aqueous solutions (i.e., complex organic compounds and life). A proposed MER site along the margin addresses realistic field science objectives of the Mars Exploration Rover mission and the current goals of the Mars Exploration Program. In situ measurements may be important in deriving estimates of the longevity and intensity of past wetter climates.

  14. Rock and Soil Physical Properties at the MER Gusev Crater and Meridiani Planum Landing Sites

    NASA Astrophysics Data System (ADS)

    Richter, L.; Arvidson, R.; Bell, J.; Cabrol, N.; Gorevan, S.; Greeley, R.; Herkenhoff, K.; Ming, D.; Sullivan, R.; Mer Athena Science Team

    Following the successful landings of both Mars Exploration Rover (MER) vehicles at Gusev Crater and Meridiani Planum, respectively, their Athena suite of instruments is being used to study the geologic history of these two very different landing sites on Mars that had been selected on the basis of showing different types of evidence for aqueous processes in the planet's past. Utilizing the on-board instruments as well as the rovers' mobility system, a wide range of physical properties investigations is carried out as well -- the subject of this abstract - that provide additional information on the geology and processes at the sites. Results of the mission in general as well as of the physical properties studies thus far greatly exceed expectations in that observations and measurements by both vehicles show a rich variety in materials and processes: the Gusev site in the vicinity of the lander is remarkably flat and generally devoid of large rocks along traverses up to the time of this writing (˜ Sol 50) and suggestive of a deflated surface with generally only thin veneers of bright dust while exhibiting evidence of a widespread occurrence of a crust from cemented fines that has been observed to fail in the form of blocky clods when disturbed by vehicle rolling action; numerous small and shallow depressions -- presumably created by impacts - are observed at the site which are infilled with bright, fine-grained material that likewise appears indurated and which was studied by a trenching experiment; small ripple bedforms are scattered across the site and were characterized in terms of particle size distributions. At the Meridiani site, studies so far -- up to ˜ Sol 33 -- have focussed on soils and the rock outcrop encountered within the ˜ 20 m diameter crater that the spacecraft came to rest in: from a physical properties point of view, a mantle of dark, well-sorted, apparently basaltic sand with small to moderate cohesion has been of interest -- and has been

  15. mer, fac, and Bidentate Coordination of an Alkyl-POP Ligand in the Chemistry of Nonclassical Osmium Hydrides.

    PubMed

    Esteruelas, Miguel A; García-Yebra, Cristina; Martín, Jaime; Oñate, Enrique

    2017-01-03

    Nonclassical and classical osmium polyhydrides containing the diphosphine 9,9-dimethyl-4,5-bis(diisopropylphosphino)xanthene (xant(P(i)Pr2)2), coordinated in κ(3)-mer, κ(3)-fac, and κ(2)-P,P fashions, have been isolated during the cyclic formation of H2 by means of the sequential addition of H(+) and H(-) or H(-) and H(+) to the classical trihydride OsH3Cl{xant(P(i)Pr2)2} (1). This complex adds H(+) to form the compressed dihydride dihydrogen complex [OsCl(H···H)(η(2)-H2){xant(P(i)Pr2)2}](+) (2). Under argon, cation 2 loses H2 and the resulting unsaturated fragment dimerizes to give [(Os(H···H){xant(P(i)Pr2)2})2(μ-Cl)2](2+) (3). During the transformation the phosphine changes its coordination mode from mer to fac. The benzofuran counterpart of 1, OsH3Cl{dbf(P(i)Pr2)2} (4; dbf(P(i)Pr2)2 = 4,6-bis(diisopropylphosphino)dibenzofuran), also adds H(+) to afford the benzofuran counterpart of 2, [OsCl(H···H)(η(2)-H2){xant(P(i)Pr2)2}](+) (5), which in contrast to the latter is stable and does not dimerize. Acetonitrile breaks the chloride bridge of 3 to form the dihydrogen [OsCl(η(2)-H2)(CH3CN){xant(P(i)Pr2)2}](+) (6), regenerating the mer coordination of the diphosphine. The hydride ion also breaks the chloride bridge of 3. The addition of KH to 3 leads to 1, closing a cycle for the formation of H2. Complex 1 reacts with a second hydride ion to give OsH4{xant(P(i)Pr2)2} (7) as consequence of the displacement of the chloride. Similarly to the latter, the oxygen atom of the mer-coordinated diphosphine of 7 has a tendency to be displaced by the hydride ion. Thus, the addition of KH to 7 yields [OsH5{xant(P(i)Pr2)2}](-) (8), containing a κ(2)-P,P-diphosphine. Complex 8 is easily protonated to afford OsH6{xant(P(i)Pr2)2} (9), which releases H2 to regenerate 7, closing a second cycle for the formation of molecular hydrogen.

  16. Mercury-199 NMR of the Metal Receptor Site in MerR and Its Protein-DNA Complex

    NASA Astrophysics Data System (ADS)

    Utschig, Lisa M.; Bryson, James W.; O'Halloran, Thomas V.

    1995-04-01

    Structural insights have been provided by mercury-199 nuclear magnetic resonance (NMR) into the metal receptor site of the MerR metalloregulatory protein alone and in a complex with the regulatory target, DNA. The one- and two-dimensional NMR data are consistent with a trigonal planar Hg-thiolate coordination environment consisting only of Cys side chains and resolve structural aspects of both metal ion recognition and the allosteric mechanism. These studies establish 199Hg NMR techniques as useful probes of the metal coordination environment of regulatory proteins, copper enzymes, and zinc transcription factor complexes as large as 50 kilodaltons.

  17. Proglacial sediment supply and channel evolution of the Arveyron of the Mer de Glace since the early 20th c.

    NASA Astrophysics Data System (ADS)

    Berthet, Johan; Astrade, Laurent; Ravanel, Ludovic; Ployon, Estelle

    2015-04-01

    The Arveyron of the Mer de Glace is the emissary of the most famous and largest French glacier. The latter has dramatically shrunk since the end of the Little Ice Age (LIA), such as every alpine glacier: the front has registered a retreat of 2.7 km since 1820 and a recent modelling showed a likely decrease of an extra km by 2040. The Arveyron and its surroundings are deeply impacted by the retreat. Then, dynamics of proglacial streams and of lateral moraines have been studied at different time and space scales through various methods: airborne and terrestrial Lidar DEM comparisons, mapping from orthophotos, 2D and 3D monoplotting to quantify past events from old terrestrial pictures, etc. By coupling studies on moraines and on stream morphology we wanted to better understand the influence of glacier retreat on sediment supply and transport downstream. Results show the evolution of the stream sediment sources linked to the glacier retreat. Before the middle of the 20th century, till was the main sediment source and was released by major flood events such as GLOFs. Now, geomorphic activity is especially important on the right lateral moraine into the recently deglaciated hanging valley of the Mer de Glace but also in the moraine flanks of the current glacier tongue (many landslides occurred during the Summer 2014). The recent glacier retreat has also formed sediments sinks such as two proglacial lakes which are progressively filling. These lakes work as big sediment traps until they will disappear (around 2017). Fluvial dynamics of the Arveyron depends on the connectivity with potential sediments sources. This is why we crossed upstream studies with the channel evolution on its fan. Arveyron channel has got narrower and incised for at least a century. Such evolution should mean a decreasing sediment yield, but anthropic factors play also an important role on stream morphology. The main anthorpic impact is the complex subglacial harnessing of the Mer de Glace. The

  18. Infectious diseases epidemic threats and mass gatherings: refocusing global attention on the continuing spread of the Middle East Respiratory syndrome coronavirus (MERS-CoV).

    PubMed

    Zumla, Alimuddin; Alagaili, Abdulaziz N; Cotten, Matthew; Azhar, Esam I

    2016-09-07

    Media and World Health Organization (WHO) attention on Zika virus transmission at the 2016 Rio Olympic Games and the 2015 Ebola virus outbreak in West Africa diverted the attention of global public health authorities from other lethal infectious diseases with epidemic potential. Mass gatherings such as the annual Hajj pilgrimage hosted by Kingdom of Saudi Arabia attract huge crowds from all continents, creating high-risk conditions for the rapid global spread of infectious diseases. The highly lethal Middle Eastern respiratory syndrome coronavirus (MERS-CoV) remains in the WHO list of top emerging diseases likely to cause major epidemics. The 2015 MERS-CoV outbreak in South Korea, in which 184 MERS cases including 33 deaths occurred in 2 months, that was imported from the Middle East by a South Korean businessman was a wake-up call for the global community to refocus attention on MERS-CoV and other emerging and re-emerging infectious diseases with epidemic potential. The international donor community and Middle Eastern countries should make available resources for, and make a serious commitment to, taking forward a "One Health" global network for proactive surveillance, rapid detection, and prevention of MERS-CoV and other epidemic infectious diseases threats.

  19. Finding a human telomere DNA-RNA hybrid G-quadruplex formed by human telomeric 6-mer RNA and 16-mer DNA using click chemistry: a protective structure for telomere end.

    PubMed

    Xu, Yan; Suzuki, Yuta; Ishizuka, Takumi; Xiao, Chao-Da; Liu, Xiao; Hayashi, Tetsuya; Komiyama, Makoto

    2014-08-15

    Telomeric repeat-containing RNA is a non-coding RNA molecule newly found in mammalian cells. The telomere RNA has been found to localize to the telomere DNA, but how the newly discovered RNA molecule interacts with telomere DNA is less known. In this study, using the click chemistry we successfully found that a 6-mer human telomere RNA and 16-mer human telomere DNA sequence can form a DNA-RNA hybrid type G-quadruplex structure. Detection of the click-reaction products directly probes DNA-RNA G-quadruplex structures in a complicated solution, whereas traditional methods such as NMR and crystallography may not be suitable. Importantly, we found that formation of DNA-RNA G-quadruplex induced an exonuclease resistance for telomere DNA, indicating that such structures might be important for protecting telomeric DNA from enzyme digestion to avoid telomere DNA shortening. These results provide the direct evidence for formation of DNA-RNA hybrid G-quadruplex structure by human telomere DNA and RNA sequence, suggesting DNA-RNA hybrid G-quadruplex structure associated between telomere DNA and RNA may respond to chromosome end protection and/or present a valuable target for drug design.

  20. Evolution of hut access facing glacier shrinkage in the Mer de Glace basin (Mont Blanc massif, France)

    NASA Astrophysics Data System (ADS)

    Mourey, Jacques; Ravanel, Ludovic

    2016-04-01

    Given the evolution of high mountain environment due to global warming, mountaineering routes and huts accesses are more and more strongly affected by glacial shrinkage and concomitant gravity processes, but almost no studies have been conducted on this relationship. The aim of this research is to describe and explain the evolution over the last century of the access to the five alpine huts around the Mer de Glace glacier (Mont Blanc massif), the larger French glacier (length = 11.5 km, area = 30 km²), a major place for Alpine tourism since 1741 and the birthplace of mountaineering, by using several methods (comparing photographs, surveying, collecting historical documents). While most of the 20th century shows no marked changes, loss of ice thickness and associated erosion of lateral moraines generate numerous and significant changes since the 1990s. Boulder falls, rockfalls and landslides are the main geomorphological processes that affect the access, while the glacier surface lowering makes access much longer and more unstable. The danger is then greatly increased and the access must be relocated and/or equipped more and more frequently (e.g. a total of 520 m of ladders has been added). This questions the future accessibility to the huts, jeopardizing an important part of mountaineering and its linked economy in the Mer de Glace area.

  1. Regulation of placental low-density lipoprotein uptake in baboons by estrogen: Dose-dependent effects of the anti-estrogen ethamoxytriphetol (MER-25)

    SciTech Connect

    Henson, M.C.; Pepe, G.J.; Albrecht, E.D. )

    1991-07-01

    In the present study, increasing amounts of the anti-estrogen 1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenoletha nol (MER-25) were administered to pregnant baboons (Papio anubis) to block the action of endogenous estrogen and to determine effect on placental low-density lipoprotein (LDL) uptake. Pregnant baboons were untreated (n = 8) or received MER-25 orally at a dosage of 25 (n = 10), 50 (n = 8), or 75 (n = 4) mg/kg BW daily on Days 140-170 of gestation (term = 184 days). Placentas were removed on Day 170 of gestation and villous tissue was dispersed with 0.1% collagenase. Placental cells were incubated in Medium 199 for 12 h at 37{degrees} C with increasing amounts of 125I-LDL, with or without a 100-fold excess of unlabeled baboon LDL. Mean ({plus minus} SEM) placental uptake (ng/micrograms cell protein) of 125I-LDL was 55% (6.4 {plus minus} 1.0), 75% (3.6 {plus minus} 0.7), and 81% (2.7 {plus minus} 0.2) lower (p less than 0.001) in baboons that received MER-25 in doses of 25, 50, and 75 mg/kg BW, respectively, than in untreated baboons (14.2 {plus minus} 1.3 ng/micrograms cell protein). Maximal effect occurred with 50 mg MER-25, because LDL uptake was not further decreased with greater levels of MER-25. Dissociation constants for placental LDL uptake, as determined by Scatchard analysis, were unaltered by anti-estrogen treatment. The amount of 125I-LDL degradation by placental cells of untreated and MER-25-treated baboons was proportional to LDL uptake.

  2. Cross-sectional surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels and other mammals in Egypt, August 2015 to January 2016

    PubMed Central

    Ali, Mohamed; El-Shesheny, Rabeh; Kandeil, Ahmed; Shehata, Mahmoud; Elsokary, Basma; Gomaa, Mokhtar; Hassan, Naglaa; El Sayed, Ahmed; El-Taweel, Ahmed; Sobhy, Heba; Oludayo, Fasina Folorunso; Dauphin, Gwenaelle; El Masry, Ihab; Wolde, Abebe Wossene; Daszak, Peter; Miller, Maureen; VonDobschuetz, Sophie; Gardner, Emma; Morzaria, Subhash; Lubroth, Juan; Makonnen, Yilma Jobre

    2017-01-01

    A cross-sectional study was conducted in Egypt to determine the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in imported and resident camels and bats, as well as to assess possible transmission of the virus to domestic ruminants and equines. A total of 1,031 sera, 1,078 nasal swabs, 13 rectal swabs, and 38 milk samples were collected from 1,078 camels in different types of sites. In addition, 145 domestic animals and 109 bats were sampled. Overall, of 1,031 serologically-tested camels, 871 (84.5%) had MERS-CoV neutralising antibodies. Seroprevalence was significantly higher in imported (614/692; 88.7%) than resident camels (257/339; 5.8%) (p < 0.05). Camels from Sudan (543/594; 91.4%) had a higher seroprevalence than those from East Africa (71/98; 72.4%) (p < 0.05). Sampling site and age were also associated with MERS-CoV seroprevalence (p < 0.05). All tested samples from domestic animals and bats were negative for MERS-CoV antibodies except one sheep sample which showed a 1:640 titre. Of 1,078 camels, 41 (3.8%) were positive for MERS-CoV genetic material. Sequences obtained were not found to cluster with clade A or B MERS-CoV sequences and were genetically diverse. The presence of neutralising antibodies in one sheep apparently in contact with seropositive camels calls for further studies on domestic animals in contact with camels. PMID:28333616

  3. Cross-sectional surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels and other mammals in Egypt, August 2015 to January 2016.

    PubMed

    Ali, Mohamed; El-Shesheny, Rabeh; Kandeil, Ahmed; Shehata, Mahmoud; Elsokary, Basma; Gomaa, Mokhtar; Hassan, Naglaa; El Sayed, Ahmed; El-Taweel, Ahmed; Sobhy, Heba; Fasina, Folorunso Oludayo; Dauphin, Gwenaelle; El Masry, Ihab; Wolde, Abebe Wossene; Daszak, Peter; Miller, Maureen; VonDobschuetz, Sophie; Gardner, Emma; Morzaria, Subhash; Lubroth, Juan; Makonnen, Yilma Jobre

    2017-03-16

    A cross-sectional study was conducted in Egypt to determine the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in imported and resident camels and bats, as well as to assess possible transmission of the virus to domestic ruminants and equines. A total of 1,031 sera, 1,078 nasal swabs, 13 rectal swabs, and 38 milk samples were collected from 1,078 camels in different types of sites. In addition, 145 domestic animals and 109 bats were sampled. Overall, of 1,031 serologically-tested camels, 871 (84.5%) had MERS-CoV neutralising antibodies. Seroprevalence was significantly higher in imported (614/692; 88.7%) than resident camels (257/339; 5.8%) (p < 0.05). Camels from Sudan (543/594; 91.4%) had a higher seroprevalence than those from East Africa (71/98; 72.4%) (p < 0.05). Sampling site and age were also associated with MERS-CoV seroprevalence (p < 0.05). All tested samples from domestic animals and bats were negative for MERS-CoV antibodies except one sheep sample which showed a 1:640 titre. Of 1,078 camels, 41 (3.8%) were positive for MERS-CoV genetic material. Sequences obtained were not found to cluster with clade A or B MERS-CoV sequences and were genetically diverse. The presence of neutralising antibodies in one sheep apparently in contact with seropositive camels calls for further studies on domestic animals in contact with camels.

  4. Iron Mineralogy and Aqueous Alteration on Mars from the MER Moessbauer Spectrometers. Chapter 15

    NASA Technical Reports Server (NTRS)

    Morris, Richard V.; Klingelhoefer, Goestar

    2007-01-01

    .05), is relatively uncommon, and occurs as subsurface deposits in the Columbia Hills. Berry Class soil is also heavily altered (SO3 = 5 +/- 1 wt.% and Fe(3+)/Fe(sub T) = 0.60 +/- 0.13) and occurs at Meridiani Planum as lag deposits, at the crests of aeolian bedforms, and as isolated pockets on outcrop surfaces. Magnetite is identified as the strongly magnetic component in martian soil. Jarosite (in the Burns outcrop at Meridiani Planum) and goethite (in Clovis Class rocks at Gusev crater) are mineralogical markers for aqueous processes because they contain the hydroxide anion (OH(-)) as an essential part of their structure. Each yields approx.10 wt.% H2O upon dehydroxylation. The presence of Fe sulfates on opposite sides of Mars is evidence that aqueous processes under acid sulfate conditions are or were common. Except for Independence Class rocks in the Columbia Hills, the overall Fe mineralogical compositions and similar basaltic bulk chemical compositions (calculated with respect to S = Cl = 0) of the population of altered rocks analyzed by MER imply isochemical alteration of basaltic precursors at low water-to-rock ratios.

  5. Geology and MER target site characteristics along the southern rim of Isidis Planitia, Mars

    USGS Publications Warehouse

    Crumpler, L.S.; Tanaka, K.L.

    2003-01-01

    crustal materials, in the form of rocks within the debris fans, and the weathered condition of the rocky material are potential sources for mineralogical evidence of climatic conditions in earliest Martian geologic history. The absence of alteration within rocks would, on the other hand, support the hypothesis that fluvial runoff during the earliest history of Mars was geologically brief rather than long-term and that long-term saturated groundwater flow was not present. Determination of the presence or absence of alteration would have corresponding implications for hypotheses requiring the long-term presence of aqueous solutions (i.e., complex organic compounds and life). A proposed MER site along the margin addresses realistic field science objectives of the Mars Exploration Rover mission and the current goals of the Mars Exploration Program. In situ measurements may be important in deriving estimates of the longevity and intensity of past wetter climates. Copyright 2003 by the American Geophysical Union.

  6. Seasonal variation of Argon in the martian atmosphere as measured by Spirit and Opportunity MER rovers

    NASA Astrophysics Data System (ADS)

    Economou, Thanasis

    Although there were no meteorological devices on any of the 2 rovers of the MER mission, by using the excellent ability of the Alpha Particle X-ray Spectrometer (APXS) to detect even a small amount of the Ar gas in a predominantly CO2 martian atmosphere, we were able to obtain detailed information on the variability of the atmospheric Ar as a function of seasonal changes. The technique is simple and straightforward. In order to increase the accuracy of the technique by eliminating any interference from target elements and minimizing the background from the backscattered Pu-L X-ray lines, dedicated APXS atmospheric Ar measurements were performed over a period of almost 4 martian years. In that mode the only visible peak in the x-ray spectra is the Ar Kα x-ray line at energy Eα=2.96 keV. Polar condensation of CO2 during winter periods, when the temperature falls below the freezing point of CO2, causes massive movement of air masses from the equatorial regions towards the poles. As the CO2 freezes, the remaining air there is enriched in argon (and nitrogen). The GRS experiment on the Odyssey orbiter around Mars has observed a six-fold in the Ar/CO2 mixing ratio in the southern polar region during the winter period. During the summer season, the opposite occurs: sublimating CO2 increases the atmospheric pressure and creates an atmospheric high that pushes the air mass with an enriched Ar fraction towards the equatorial regions where when arrives it is detected by the APXS on the Opportunity and Spirit landing sites. Our results indicate that the variation of the Ar in the martian atmosphere at both landing sites follows generally the variation of the atmospheric pressure, but it is not in phase with it: there is a phase shift of almost one martian season. The measurement of the Ar mixing ratio at the Spirit and Opportunity landing sites is thus a direct probe of the global circulation between the polar CO2 resource/sink and the equatorial regions. This information is

  7. Comparing the Chemistry for the Pathfinder, MER and MSL Martian Landing Sites with APXS

    NASA Astrophysics Data System (ADS)

    Gellert, R.; Arvidson, R. E.; Clark, B. C.; Grotzinger, J. P.; Squyres, S. W.; Yen, A. S.

    2013-12-01

    The Alpha-Particle-X-ray Spectrometer is part of the science payload of all recent NASA Mars rover missions. It allows detailed comparison of the chemical composition and overall findings from rocks and soils at 4 landing sites. It can be even extended to the soil measurements performed with XRF on the two Viking landers. Typical soils at all 6 landing sites are very similar in chemical composition as well as mineralogy from instruments like Moessbauer on MER and CHEMIN on MSL. Beside a dominant basaltic composition the soil contains a significant altered and volatile rich component that is characterized by a constant S/Cl ratio in the APXS data. The overall similarity of the soils as well as the finding that soils around the 30 wt % SO3 rich bedrocks at Meridiani are not elevated in S, indicates the presence of a global distributed or at least large scale homogenized component in the Martian soil. This allows extending the SAM and CHEMIN findings in the altered and volatile components in the Gale Rocknest soils to other landing sites. However, in Gusev Crater anomalous subsurface soils were found - silica and hydrated ferric sulfate rich - that could indicate local fumarole and leaching activities. The sulfate rich Meridiani bedrock, called Burns formations, was documented to be remarkably homogeneous over the ~ 15 miles from the landing site at Eagle Crater to the base of the rim at Endurance Crater. Here for the first time a rover entered an area where evidence for clays is given by orbital CRISM data. With Opportunity's mineralogy instruments out of commission, the APXS was used to document the chemistry of the encountered outcrops. Having a composition close to the average Mars, one main characteristic feature of rocks at the rim is the low sulfur content compared to the younger Meridiani bedrock. The outcrops show post depositional cracks and veins filled with Calciumsulfate and Chlorine rich surface alteration rinds. A smaller outcrop called Esperance has

  8. Paleomagnetic Evidence for the Tectono-Stratigraphic Evolution of the Mt.Galili Area / MER / Ethiopia

    NASA Astrophysics Data System (ADS)

    Popp, F.; Scholger, R.

    2007-12-01

    The Mt.Galili area (N 9,77°, E 040,55°) is the focus of current anthropological studies on early hominid evolution *[4]. The Mount Galili Formation (MGF)*[5] is subdivided into seven Members, each representing a sedimentary cycle, sustaining temporally interruptions by volcanic activity. Our paleomagnetic investigation concentrates on ascertaining primary magnetisation vectors (PMV) of volcanic layers embodied within the MGF, applying alternating field and thermal magnetic cleaning methods. Magnetite and ti-magnetite are the main carriers of the NRM (basalt, ignimbrite). Hematite shares in amounts up to 20%, Goethite occasionally participates up to 30% in magnitude of the NRM components. Two events of magnetic polarity reversals terminate a magnetic inverse period designating the lot of the MGF unit. The amount of the PMV's rotation in respect to an expected paleodirection*[1] of 183°/-13° are in the range of 1°-52° . The resulting mean PMV data provide implications on (A) rift-related block rotation / tilting in relation to the stable African crust since the Pliocene and they also support (B) stratigraphic age determinations of the MGF: A: Rotational movements cluster in 4 sectors: (a) The SE sector demonstrates almost unchanged orientation of the PMVs whereas (b) it's continuation to the NW sector suffered clockwise rotational tilting (up to 12° rot / 19° tilt). (c) The SW sector (Mt.Galili area s.str.) in contrast embrace a unique counterclockwise rotation component of 7°-17°, but the modulus of vector inclination, concerning individual rift blocks, is variable in either direction. (d) The NE sector (Satkawini) sustained the major counterclockwise rotation (41°°-52° rot / 3°- 17° tilt) We consider the Mt.Galili area being the place where trans-tensional tectonics were active during the late Miocene to create the lateral off-set of magmatic segments marking the centre of the MER. This tectonics are considered to belong to a arcuate accommodation

  9. Near infra-red emission from a mer-Ru(II) complex: consequences of strong σ-donation from a neutral, flexible ligand with dual binding modes.

    PubMed

    Pal, Amlan K; Zaccheroni, Nelsi; Campagna, Sebastiano; Hanan, Garry S

    2014-07-04

    A rare example of dual coordination modes by a novel tridentate ligand gives rise to unique fac-and mer-Ru((II/III)) complexes. The mer-Ru(II)-complex displays the farthest red-shift of a triplet metal-to-ligand charge transfer ((3)MLCT) emission with a tridentate ligand for a mononuclear complex. This observation is a consequence of large bite angle and strong σ-donation by the ligand, the combined effect of which helps to separate the energy of the (3)MLCT and (3)MC states.

  10. CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection

    PubMed Central

    Caì, Yíngyún; Yú, Shuǐqìng; Postnikova, Elena N.; Mazur, Steven; Bernbaum, John G.; Burk, Robin; Zhāng, Téngfēi; Radoshitzky, Sheli R.; Müller, Marcel A.; Jordan, Ingo; Bollinger, Laura; Hensley, Lisa E.; Jahrling, Peter B.; Kuhn, Jens H.

    2014-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors. PMID:25409519

  11. Toward Developing a Preventive MERS-CoV Vaccine—Report from a Workshop Organized by the Saudi Arabia Ministry of Health and the International Vaccine Institute, Riyadh, Saudi Arabia, November 14–15, 2015

    PubMed Central

    Delvecchio, Christopher J.; Wiley, Ryan E.; Williams, Marni; Yoon, In-Kyu; Modjarrad, Kayvon; Boujelal, Mohamed; Moorthy, Vasee S.; Hersi, Ahmad Salah; Kim, Jerome H.

    2016-01-01

    Middle East respiratory syndrome (MERS) remains a serious international public health threat. With the goal of accelerating the development of countermeasures against MERS coronavirus (MERS-CoV), funding agencies, nongovernmental organizations, and researchers across the world assembled in Riyadh, Saudi Arabia, on November 14–15, 2015, to discuss vaccine development challenges. The meeting was spearheaded by the Saudi Ministry of Health and co-organized by the International Vaccine Institute, South Korea. Accelerating the development of a preventive vaccine requires a better understanding of MERS epidemiology, transmission, and pathogenesis in humans and animals. A combination of rodent and nonhuman primate models should be considered in evaluating and developing preventive and therapeutic vaccine candidates. Dromedary camels should be considered for the development of veterinary vaccines. Several vaccine technology platforms targeting the MERS-CoV spike protein were discussed. Mechanisms to maximize investment, provide robust data, and affect public health are urgently needed. PMID:27439020

  12. Successful Mars remote sensors, MO THEMIS and MER Mini-TES

    NASA Astrophysics Data System (ADS)

    Silverman, Steven; Christensen, Phil

    2006-10-01

    spectral range 5 29μm at 10cm spectral resolution. Launched in June 2003, one Mini-TES instrument will fly to Mars aboard each of the two missions of NASA's Mars Exploration Rover Project (MER), named Spirit and Opportunity. The first Mini-TES unit was required to meet a two-year development schedule with proven, flight-tested instrumentation. Therefore, SBRS designed Mini-TES based on proven heritage from the successful MGS TES. THEMIS is based on “bolt-together” pushbroom optics and uncooled silicon microbolometer focal plane array (FPA) technology. Sometimes dubbed “Mars Landsat,” THEMIS was launched in 2001 on Mars Odyssey, and provides guidance for future lander missions now in preparation for launch. Advanced materials and optical machining allow THEMIS low-scatter, reflective, wide field-of-view (WFOV) pushbroom optics for relatively long dwell-time compared to narrow FOV optics requiring cross-track scanning for equivalent spatial resolution. This allows uncooled silicon microbolometer FPAs, with less signal sensitivity than cryogenically cooled photo-diode FPAs, to meet the THEMIS sensitivity requirements. Instrument design, performance, integration, as well as details of the calibration are discussed. Full instrument and calibration details are available in the Journal of Geophysical Research Mini-TES and THEMIS papers by Christensen et al.

  13. Discovery of a 9-mer Cationic Peptide (LTX-315) as a Potential First in Class Oncolytic Peptide.

    PubMed

    Haug, Bengt Erik; Camilio, Ketil André; Eliassen, Liv Tone; Stensen, Wenche; Svendsen, John Sigurd; Berg, Kristel; Mortensen, Bjarte; Serin, Guillaume; Mirjolet, Jean-Francois; Bichat, Francis; Rekdal, Øystein

    2016-04-14

    Oncolytic immunotherapies represent a new promising strategy in the treatment of cancer. In our efforts to develop oncolytic peptides, we identified a series of chemically modified 9-mer cationic peptides that were highly effective against both drug-resistant and drug-sensitive cancer cells and with lower toxicity toward normal cells. Among these peptides, LTX-315 displayed superior anticancer activity and was selected as a lead candidate. This peptide showed relative high plasma protein binding abilities and a human plasma half-life of 160 min, resulting in formation of nontoxic metabolites. In addition, the lead candidate demonstrated relatively low ability to inhibit CYP450 enzymes. Collectively these data indicated that this peptide has potential to be developed as a new anticancer agent for intratumoral administration and is currently being evaluated in a phase I/IIa study.

  14. Working on Mars: Understanding How Scientists, Engineers and Rovers Interacted Across Space and Time during the Mars Exploration Rover (MER) Mission

    NASA Technical Reports Server (NTRS)

    Wales, Roxana C.

    2005-01-01

    This viewgraph presentation summarizes the scheduling and planning difficulties inherent in operating the Mars Exploration Rovers (MER) during the overlapping terrestrial day and Martian sol. The presentation gives special empahsis to communication between the teams controlling the rovers from Earth, and keeping track of time on the two planets.

  15. Professional Organizations and the Professionalizing of Practice: The Role of MER, EdCom, and the NAEA Museum Education Division, 1969-2002

    ERIC Educational Resources Information Center

    Kai-Kee, Elliott

    2012-01-01

    The establishment of the Museum Education Roundtable (MER) in 1969, the formation of the Committee on Education of the American Association of Museums (AAM) in 1973, and the creation of the Museum Education Division of the National Art Education Association (NAEA) in 1981 all represent milestones in the professionalization of museum education…

  16. Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti-inflammatory arginase 2 expression in macrophages

    PubMed Central

    Kim, Si-Yoon; Lim, Eun-Jin; Yoon, Young-So; Ahn, Young-Ho; Park, Eun-Mi; Kim, Hee-Sun; Kang, Jihee Lee

    2016-01-01

    Mer signaling increases the transcriptional activity of liver X receptor (LXR) to promote the resolution of acute sterile inflammation. Here, we aimed to understand the pathway downstream of Mer signaling after growth arrest-specific protein 6 (Gas6) treatment that leads to LXR expression and transcriptional activity in mouse bone-marrow derived macrophages (BMDM). Gas6-induced increases in LXRα and LXRβ and expression of their target genes were inhibited in BMDM from STAT1−/− mice or by the STAT1-specific inhibitor fludarabine. Gas6-induced STAT1 phosphorylation, LXR activation, and LXR target gene expression were inhibited in BMDM from Mer−/− mice or by inhibition of PI3K or Akt. Gas6-induced Akt phosphorylation was inhibited in BMDM from STAT1−/− mice or in the presence of fludarabine. Gas6-induced LXR activity was enhanced through an interaction between LXRα and STAT1 on the DNA promoter of Arg2. Additionally, we found that Gas6 inhibited lipopolysaccharide (LPS)-induced nitrite production in a STAT1 and LXR pathway-dependent manner in BMDM. Additionally, Mer-neutralizing antibody reduced LXR and Arg2 expression in lung tissue and enhanced NO production in bronchoalveolar lavage fluid in LPS-induced acute lung injury. Our data suggest the possibility that the Gas6-Mer-PI3K/Akt-STAT1-LXR-Arg2 pathway plays an essential role for resolving inflammatory response in acute lung injury. PMID:27406916

  17. PEDF and PEDF-derived peptide 44mer protect cardiomyocytes against hypoxia-induced apoptosis and necroptosis via anti-oxidative effect.

    PubMed

    Gao, Xiao; Zhang, Hao; Zhuang, Wei; Yuan, Guangda; Sun, Teng; Jiang, Xia; Zhou, Zhongxin; Yuan, Honghua; Zhang, Zhongming; Dong, Hongyan

    2014-07-11

    Pigment epithelium-derived factor (PEDF) has many biological activities. But it's not known whether PEDF and its functional peptides could protect against hypoxia-induced cell death and the mechanisms are still unclear. We used cultured H9c2 cells and primary cardiomyocytes to show that apoptosis and necroptosis were significantly increased after hypoxia. Both PEDF and its fuctional peptides 44mer reduced apoptosis and necroptosis rates and inhibited the expression of cleaved caspase 3 and receptor-interacting protein 3 (RIP3). Furthermore, PEDF and 44mer could up-regulate super oxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, promote clearing of reactive oxygen species (ROS) and malondialdehyde (MDA). While, 34mer, another functional peptides had no effect on cell apoptosis and necroptosis. Hereby this is the first evidence that PEDF and its functional peptide 44mer protect cultured H9c2 cells and primary cardiomyocytes against apoptosis and necroptosis under hypoxic condition via the anti-oxidative mechanism.

  18. mer-[Fe III(bpca)(CN)3]-: a new low-spin iron(III) complex to build heterometallic ladder-like chains.

    PubMed

    Lescouëzec, Rodrigue; Vaissermann, Jacqueline; Toma, Luminita Marilena; Carrasco, Rosa; Lloret, Francesc; Julve, Miguel

    2004-04-05

    The novel mononuclear complex PPh(4)-mer-[Fe(III)(bpca)(3)(CN)(3)].H(2)O (1) [PPh(4)(+) = tetraphenylphosphonium cation and bpca = bis(2-pyridylcarbonyl)amidate anion] and ladder-like chain compound [[Fe(III)(bpca)(micro-CN)(3)Mn(II)(H(2)O)(3)] [Fe(III)(bpca)(CN)(3)

  19. Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

    PubMed Central

    Bhadra, Sanchita; Jiang, Yu Sherry; Kumar, Mia R.; Johnson, Reed F.; Hensley, Lisa E.; Ellington, Andrew D.

    2015-01-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens. PMID:25856093

  20. X-ray Structure and Enzymatic Activity Profile of a Core Papain-like Protease of MERS Coronavirus with utility for structure-based drug design

    PubMed Central

    Clasman, Jozlyn R.; Báez-Santos, Yahira M.; Mettelman, Robert C.; O’Brien, Amornrat; Baker, Susan C.; Mesecar, Andrew D.

    2017-01-01

    Ubiquitin-like domain 2 (Ubl2) is immediately adjacent to the N-terminus of the papain-like protease (PLpro) domain in coronavirus polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection. However, our recent cellular studies reveal that removing the Ubl2 domain from MERS PLpro has no effect on its ability to process the viral polyprotein or act as an interferon antagonist, which involves deubiquitinating and deISGylating cellular proteins. Here, we test the hypothesis that the Ubl2 domain is not required for the catalytic function of MERS PLpro in vitro. The X-ray structure of MERS PLpro-∆Ubl2 was determined to 1.9 Å and compared to PLpro containing the N-terminal Ubl2 domain. While the structures were nearly identical, the PLpro-∆Ubl2 enzyme revealed the intact structure of the substrate-binding loop. Moreover, PLpro-∆Ubl2 catalysis against different substrates and a purported inhibitor revealed no differences in catalytic efficiency, substrate specificity, and inhibition. Further, no changes in thermal stability were observed between enzymes. We conclude that the catalytic core of MERS PLpro, i.e. without the Ubl2 domain, is sufficient for catalysis and stability in vitro with utility to evaluate potential inhibitors as a platform for structure-based drug design. PMID:28079137

  1. CpG oligodeoxynucleotide 5mer-induced apoptosis in MOLT-4 leukaemia cells does not require caspase 3 or new protein synthesis.

    PubMed

    Tidd, David M; Broughton, Caroline M; Clark, Richard E

    2003-05-01

    We have established that CpG oligodeoxynucleotide 5mers, of sequence type CGNNN (N = A, G, C or T), rapidly induce apoptosis/cell cycle arrest in human leukaemia lines. The 5'-CpG is obligatory for these effects. Induction of apoptosis in MOLT-4 cells did not require new protein synthesis and was insensitive to the caspase 3 inhibitor, Ac-DEVD-CHO, although the latter abrogated DNA laddering, phosphatidylserine externalization and collapse of the mitochondrial transmembrane potential. A subline of MOLT-4 cells, MOLT-4CpGR, was selected for acquired resistance to CpG 5mers. Differences in gene expression between MOLT-4 and MOLT-4CpGR cells were identified following three independent reciprocal cDNA subtractions, consensus selection and virtual cloning through targeted display. Several known genes were implicated in the action of or resistance to CpG oligodeoxynucleotide 5mers. Their protein products listed below immediately suggest cell signalling pathways/processes worthy of further investigation in elucidating the mechanism of CpG 5mer activity: caspase 2, the transcription factors Atf4, Hic, HoxB3 and Rqcd1, the splicing factors Rbmx, Sfrs5 and Sfrs7, the DNA replication factors Mcm5 and Brd4, phosphoinositide-3-kinase, annexin A1, mucosa-associated lymphoid tissue lymphoma translocation 1 and three enzymes involved in protein ubiquitylation, Siah1, Gsa7 and Nin283.

  2. High-resolution topomapping of candidate MER landing sites with Mars Orbiter Camera narrow-angle images

    USGS Publications Warehouse

    Kirk, R.L.; Howington-Kraus, E.; Redding, B.; Galuszka, D.; Hare, T.M.; Archinal, B.A.; Soderblom, L.A.; Barrett, J.M.

    2003-01-01

    We analyzed narrow-angle Mars Orbiter Camera (MOC-NA) images to produce high-resolution digital elevation models (DEMs) in order to provide topographic and slope information needed to assess the safety of candidate landing sites for the Mars Exploration Rovers (MER) and to assess the accuracy of our results by a variety of tests. The mapping techniques developed also support geoscientific studies and can be used with all present and planned Mars-orbiting scanner cameras. Photogrammetric analysis of MOC stereopairs yields DEMs with 3-pixel (typically 10 m) horizontal resolution, vertical precision consistent with ???0.22 pixel matching errors (typically a few meters), and slope errors of 1-3??. These DEMs are controlled to the Mars Orbiter Laser Altimeter (MOLA) global data set and consistent with it at the limits of resolution. Photoclinometry yields DEMs with single-pixel (typically ???3 m) horizontal resolution and submeter vertical precision. Where the surface albedo is uniform, the dominant error is 10-20% relative uncertainty in the amplitude of topography and slopes after "calibrating" photoclinometry against a stereo DEM to account for the influence of atmospheric haze. We mapped portions of seven candidate MER sites and the Mars Pathfinder site. Safety of the final four sites (Elysium, Gusev, Isidis, and Meridiani) was assessed by mission engineers by simulating landings on our DEMs of "hazard units" mapped in the sites, with results weighted by the probability of landing on those units; summary slope statistics show that most hazard units are smooth, with only small areas of etched terrain in Gusev crater posing a slope hazard.

  3. A New Capability for Automated Target Selection and Sampling for use with Remote Sensing Instruments on the MER Rovers

    NASA Astrophysics Data System (ADS)

    Castano, R.; Estlin, T.; Anderson, R. C.; Gaines, D.; Bornstein, B.; de Granville, C.; Tang, B.; Thompson, D.; Judd, M.

    2008-12-01

    The Onboard Autonomous Science Investigation System (OASIS) evaluates geologic data gathered by a planetary rover. The system is designed to operate onboard a rover identifying and reacting to serendipitous science opportunities, such as rocks with novel properties. OASIS operates by analyzing data the rover gathers, and then using machine learning techniques, prioritizing the data based on criteria set by the science team. This prioritization can be used to organize data for transmission back to Earth and it can be used to search for specific targets it has been told to find by the science team. If one of these targets is found, it is identified as a new science opportunity and a "science alert" is sent to a planning and scheduling system. After reviewing the rover's current operational status to ensure that it has enough resources to complete its traverse and act on the new science opportunity, OASIS can change the command sequence of the rover in order to obtain additional science measurements. Currently, OASIS is being applied on a new front. OASIS is providing a new rover mission technology that enables targeted remote-sensing science in an automated fashion during or after rover traverses. Currently, targets for remote sensing instruments, especially narrow field-of-view instruments (such as the MER Mini- TES spectrometer or the 2009 MSL ChemCam spectrometer) must be selected manually based on imagery already on the ground with the operations team. OASIS will enable the rover flight software to analyze imagery onboard in order to autonomously select and sequence targeted remote-sensing observations in an opportunistic fashion. We are in the process of scheduling an onboard MER experiment to demonstrate the OASIS capability in early 2009.

  4. One-Pot Reverse Transcriptional Loop-Mediated Isothermal Amplification (RT-LAMP) for Detecting MERS-CoV

    PubMed Central

    Lee, Se Hee; Baek, Yun Hee; Kim, Yang-Hoon; Choi, Young-Ki; Song, Min-Suk; Ahn, Ji-Young

    2017-01-01

    Due to the limitation of rapid development of specific antiviral drug or vaccine for novel emerging viruses, an accurate and rapid diagnosis is a key to manage the virus spread. We developed an efficient and rapid method with high specificity for the Middle East Respiratory Syndrome coronavirus (MERS-CoV), based on one-pot reverse transcription loop-mediated isothermal amplification (one-pot RT-LAMP). A set of six LAMP primers [F3, B3, FIP, BIP, LF (Loop-F), and LB (Loop-B)] were designed using the sequence of nucleocapsid (N) gene with optimized RT-LAMP enzyme conditions: 100 U M-MLV RTase and 4 U Bst polymerase, implying that the reaction was able to detect four infectious viral genome copies of MERS-CoV within a 60 min reaction time period. Significantly, EvaGreen dye has better signal read-out properties in one-pot RT-LAMP reaction and is more compatible with DNA polymerase than SYBR green I. Isothermally amplified specific N genes were further evaluated using field-deployable microchamber devices, leading to the specific identification of as few as 0.4 infectious viral genome copies, with no cross-reaction to the other acute respiratory disease viruses, including influenza type A (H1N1 and H3N2), type B, human coronavirus 229E, and human metapneumovirus. This sensitive, specific and feasible method provides a large-scale technical support in emergencies, and is also applied as a sample-to-detection module in Point of Care Testing devices. PMID:28119682

  5. One-Pot Reverse Transcriptional Loop-Mediated Isothermal Amplification (RT-LAMP) for Detecting MERS-CoV.

    PubMed

    Lee, Se Hee; Baek, Yun Hee; Kim, Yang-Hoon; Choi, Young-Ki; Song, Min-Suk; Ahn, Ji-Young

    2016-01-01

    Due to the limitation of rapid development of specific antiviral drug or vaccine for novel emerging viruses, an accurate and rapid diagnosis is a key to manage the virus spread. We developed an efficient and rapid method with high specificity for the Middle East Respiratory Syndrome coronavirus (MERS-CoV), based on one-pot reverse transcription loop-mediated isothermal amplification (one-pot RT-LAMP). A set of six LAMP primers [F3, B3, FIP, BIP, LF (Loop-F), and LB (Loop-B)] were designed using the sequence of nucleocapsid (N) gene with optimized RT-LAMP enzyme conditions: 100 U M-MLV RTase and 4 U Bst polymerase, implying that the reaction was able to detect four infectious viral genome copies of MERS-CoV within a 60 min reaction time period. Significantly, EvaGreen dye has better signal read-out properties in one-pot RT-LAMP reaction and is more compatible with DNA polymerase than SYBR green I. Isothermally amplified specific N genes were further evaluated using field-deployable microchamber devices, leading to the specific identification of as few as 0.4 infectious viral genome copies, with no cross-reaction to the other acute respiratory disease viruses, including influenza type A (H1N1 and H3N2), type B, human coronavirus 229E, and human metapneumovirus. This sensitive, specific and feasible method provides a large-scale technical support in emergencies, and is also applied as a sample-to-detection module in Point of Care Testing devices.

  6. Synthesizing data and models for the spread of MERS-CoV, 2013: key role of index cases and hospital transmission

    PubMed Central

    Chowell, Gerardo; Blumberg, Seth; Simonsen, Lone; Miller, Mark A.; Viboud, Cécile

    2014-01-01

    The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 209 deaths and 699 laboratory-confirmed cases in the Arabian Peninsula as of June 11, 2014. Preparedness efforts are hampered by considerable uncertainty about the nature and intensity of human-to-human transmission, with previous reproduction number estimates ranging from 0.4 to 1.5. Here we synthesize epidemiological data and transmission models for the MERS-CoV outbreak during April-October 2013 to resolve uncertainties in epidemic risk, while considering the impact of observation bias. We match the progression of MERS-CoV cases in 2013 to a dynamic transmission model that incorporates community and hospital compartments, and distinguishes transmission by zoonotic (index) cases and secondary cases. When observation bias is assumed to account for the fact that all reported zoonotic cases are severe, but only ~57% of secondary cases are symptomatic, the average reproduction number of MERS-CoV is estimated to be 0.45 (95%CI:0.29–0.61). Alternatively, if these epidemiological observations are taken at face value, index cases are estimated to transmit substantially more effectively than secondary cases, (Ri =0.84 (0.58–1.20) vs Rs=0.36 (0.24–0.51)). In both scenarios the relative contribution of hospital-based transmission is over four times higher than that of community transmission, indicating that disease control should be focused on hospitalized patients. Adjusting previously published estimates for observation bias confirms a strong support for the average R < 1 in the first stage of the outbreak in 2013 and thus, transmissibility of secondary cases of MERS-CoV remained well below the epidemic threshold. More information on the observation process is needed to clarify whether MERS-CoV is intrinsically weakly transmissible between people or whether existing control measures have contributed meaningfully to reducing the transmissibility of secondary cases. Our results could

  7. Computer aided prediction and identification of potential epitopes in the receptor binding domain (RBD) of spike (S) glycoprotein of MERS-CoV.

    PubMed

    Ali, Mohammad Tuhin; Morshed, Mohammed Monzur; Gazi, Md Amran; Musa, Md Abu; Kibria, Md Golam; Uddin, Md Jashim; Khan, Md Anik Ashfaq; Hasan, Shihab

    2014-01-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) belongs to the coronaviridae family. In spite of several outbreaks in the very recent years, no vaccine against this deadly virus is developed yet. In this study, the receptor binding domain (RBD) of Spike (S) glycoprotein of MERS-CoV was analyzed through Computational Immunology approach to identify the antigenic determinants (epitopes). In order to do so, the sequences of S glycoprotein that belong to different geographical regions were aligned to observe the conservancy of MERS-CoV RBD. The immune parameters of this region were determined using different in silico tools and Immune Epitope Database (IEDB). Molecular docking study was also employed to check the affinity of the potential epitope towards the binding cleft of the specific HLA allele. The N-terminus RBD (S367-S606) of S glycoprotein was found to be conserved among all the available strains of MERS-CoV. Based on the lower IC50 value, a total of eight potential T-cell epitopes and 19 major histocompatibility complex (MHC) class-I alleles were identified for this conserved region. A 9-mer epitope CYSSLILDY displayed interactions with the maximum number of MHC class-I molecules and projected the highest peak in the B-cell antigenicity plot which concludes that it could be a better choice for designing an epitope based peptide vaccine against MERSCoV considering that it must undergo further in vitro and in vivo experiments. Moreover, in molecular docking study, this epitope was found to have a significant binding affinity of -8.5 kcal/mol towards the binding cleft of the HLA-C*12:03 molecule.

  8. The Same Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) yet Different Outbreak Patterns and Public Health Impacts on the Far East Expert Opinion from the Rapid Response Team of the Republic of Korea.

    PubMed

    2015-12-01

    A Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) outbreak, the largest outbreak outside the Middle East in 2012, occurred in the Republic of Korea and resulted in a large number of cases, with 186 infected people, including 38 deaths. A Rapid Response Team (RRT) was appointed after a request from the Korean government on June 8, 2015 calling for specialists to manage and control the MERS-CoV outbreak. This report presents the opinion of the RRT who worked to manage this healthcare-associated MERS-CoV outbreak in Korea.

  9. Expansion of quiescent lung adenocarcinoma CD8+ T cells by MUC1-8-mer peptide-T2 cell-β2 microglobulin complexes

    PubMed Central

    ATZIN-MÉNDEZ, J.A.; LÓPEZ-GONZÁLEZ, J.S.; BÁEZ, R.; ARENAS-DEL ANGEL, M.C.; MONTAÑO, L.F.; SILVA-ADAYA, D.; LASCURAIN, R.; GOROCICA, P.

    2016-01-01

    Adoptive immunotherapy requires the isolation of CD8+ T cells specific for tumor-associated antigens, their expansion in vitro and their transfusion to the patient to mediate a therapeutic effect. MUC1 is an important adenocarcinoma antigen immunogenic for T cells. The MUC1-derived SAPDTRPA (MUC1-8-mer) peptide is a potent epitope recognized by CD8+ T cells in murine models. Likewise, the T2 cell line has been used as an antigen-presenting cell to activate CD8+ T cells, but so far MUC1 has not been assessed in this context. We evaluated whether the MUC1-8-mer peptide can be presented by T2 cells to expand CD25+CD8+ T cells isolated from HLA-A2+ lung adenocarcinoma patients with stage III or IV tumors. The results showed that MUC1-8-mer peptide-loaded T2 cells activated CD8+ T cells from cancer HLA-A2+ patients when anti-CD2, anti-CD28 antibodies and IL-2 were added. The percentage of CD25+CD8+ T cells was 3-fold higher than those in the non-stimulated cells (P=0.018). HLA-A2+ patient cells showed a significant difference (2.3-fold higher) in activation status than HLA-A2+ healthy control cells (P=0.04). Moreover, 77.6% of MUC1-8-mer peptide-specific CD8+ T cells proliferated following a second stimulation with MUC1-8-mer peptide-loaded T2 cells after 10 days of cell culture. There were significant differences in the percentage of basal CD25+CD8+ T cells in relation to the cancer stage; this difference disappeared after MUC1-8-mer peptide stimulation. In conclusion, expansion of CD25+CD8+ T cells by MUC1-8 peptide-loaded T2 cells plus costimulatory signals via CD2, CD28 and IL-2 can be useful in adoptive immunotherapy. PMID:26498650

  10. Discovery of Carbonate-Rich Outcrops in the Gusev Crater Columbia Hills by the MER Rover Spirit

    NASA Technical Reports Server (NTRS)

    Morris, Richard V.; Ruff, Steven W.; Gellert, Ralf; Ming, Douglas W.; Arvidson, Raymond E.; Clark, Benton C.; Golden, Dadi C.; Siebach, Kirsten L.; Klingelhoefer, Goestar; Schroeder, Christian; Fleischer, Iris; Yen, Albert S.; Squyres, Steven W.

    2010-01-01

    The chemical composition, global abundance, distribution, and formation pathways of carbonates are central to understanding aqueous processes, climate, and habitability of early Mars. The Mars Exploration Rover (MER) Spirit analyzed a series of olivine-rich outcrops while descending from the summit region of Husband Hill into the Inner Basin of the Columbia Hills of Gusev Crater to the eastern edge of the El Dorado ripple field in late 2005. Reanalysis of Spirit s mineralogical data from the Moessbauer Spectrometer (MB) and the Miniature Thermal Emission Spectrometer (Mini-TES) and chemical data from the Alpha Particle X-Ray Spectrometer (APXS) in 2010, coupled with new laboratory data for carbonate-bearing samples, lead to identification of carbonate in one of the outcrops (Comanche) [Morris, R.V., et al., Science, 329, 421-424]. The carbonate is rich in magnesium and iron (Mc62Sd25Cc11Rh2, assuming all Ca and Mn is associated with the carbonate) and is a major component of the Comanche outcrops (16 to 34 wt.%). The mineralogical, chemical, and abundance data are constrained in multiple, mutually consistent ways by the MER analyses. For example, a low-Ca carbonate is required by the MB and APXS data and is consistent with Mini-TES data. Three spectral features attributable to fundamental infrared vibrational modes of low-Ca carbonate are present in the Mini-TES spectra of Comanche outcrops. The average composition of Comanche carbonate approximates the average composition of the carbonate globules in Martian meteorite ALH 84001. Analogy with ALH 84001, terrestrial, and synthetic carbonate globules suggests that Comanche carbonate precipitated from aqueous solutions under hydrothermal conditions at near neutral pH in association with volcanic activity during the Noachian era. Comanche outcrop morphology suggests they are remnants of a larger carbonate-bearing formation that evolved in ultramafic rock and then preferentially eroded by a combination of aeolian

  11. Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model.

    PubMed

    de Wilde, Adriaan H; Falzarano, Darryl; Zevenhoven-Dobbe, Jessika C; Beugeling, Corrine; Fett, Craig; Martellaro, Cynthia; Posthuma, Clara C; Feldmann, Heinz; Perlman, Stanley; Snijder, Eric J

    2017-01-15

    Currently, there is no registered treatment for infections with emerging zoonotic coronaviruses like SARS- and MERS-coronavirus. We here report that in cultured cells low-micromolar concentrations of alisporivir, a non-immunosuppressive cyclosporin A-analog, inhibit the replication of four different coronaviruses, including MERS- and SARS-coronavirus. Ribavirin was found to further potentiate the antiviral effect of alisporivir in these cell culture-based infection models, but this combination treatment was unable to improve the outcome of SARS-CoV infection in a mouse model. Nevertheless, our data provide a basis to further explore the potential of Cyp inhibitors as host-directed, broad-spectrum inhibitors of coronavirus replication.

  12. Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection

    PubMed Central

    Pascal, Kristen E.; Coleman, Christopher M.; Mujica, Alejandro O.; Kamat, Vishal; Badithe, Ashok; Fairhurst, Jeanette; Hunt, Charleen; Strein, John; Berrebi, Alexander; Sisk, Jeanne M.; Matthews, Krystal L.; Babb, Robert; Chen, Gang; Lai, Ka-Man V.; Huang, Tammy T.; Olson, William; Yancopoulos, George D.; Stahl, Neil; Frieman, Matthew B.; Kyratsous, Christos A.

    2015-01-01

    Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside the VelociGene technology (which allows for rapid engineering of the mouse genome) to quickly develop and evaluate antibodies against an emerging viral disease. Specifically, we show the rapid generation of fully human neutralizing antibodies against the recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) and development of a humanized mouse model for MERS-CoV infection, which was used to demonstrate the therapeutic efficacy of the isolated antibodies. The VelocImmune and VelociGene technologies are powerful platforms that can be used to rapidly respond to emerging epidemics. PMID:26124093

  13. Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection.

    PubMed

    Pascal, Kristen E; Coleman, Christopher M; Mujica, Alejandro O; Kamat, Vishal; Badithe, Ashok; Fairhurst, Jeanette; Hunt, Charleen; Strein, John; Berrebi, Alexander; Sisk, Jeanne M; Matthews, Krystal L; Babb, Robert; Chen, Gang; Lai, Ka-Man V; Huang, Tammy T; Olson, William; Yancopoulos, George D; Stahl, Neil; Frieman, Matthew B; Kyratsous, Christos A

    2015-07-14

    Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside the VelociGene technology (which allows for rapid engineering of the mouse genome) to quickly develop and evaluate antibodies against an emerging viral disease. Specifically, we show the rapid generation of fully human neutralizing antibodies against the recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) and development of a humanized mouse model for MERS-CoV infection, which was used to demonstrate the therapeutic efficacy of the isolated antibodies. The VelocImmune and VelociGene technologies are powerful platforms that can be used to rapidly respond to emerging epidemics.

  14. CDC's Early Response to a Novel Viral Disease, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), September 2012–May 2014

    PubMed Central

    Dunville, Richard L.; Gerber, Susan I.; Erdman, Dean D.; Pesik, Nicki; Kuhar, David; Mason, Karen A.; Haynes, Lia; Rotz, Lisa; St. Pierre, Jeanette; Poser, Sarah; Bunga, Sudhir; Pallansch, Mark A.; Swerdlow, David L.

    2015-01-01

    The first ever case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was reported in September 2012. This report describes the approaches taken by CDC, in collaboration with the World Health Organization (WHO) and other partners, to respond to this novel virus, and outlines the agency responses prior to the first case appearing in the United States in May 2014. During this time, CDC's response integrated multiple disciplines and was divided into three distinct phases: before, during, and after the initial activation of its Emergency Operations Center. CDC's response to MERS-CoV required a large effort, deploying at least 353 staff members who worked in the areas of surveillance, laboratory capacity, infection control guidance, and travelers' health. This response built on CDC's experience with previous outbreaks of other pathogens and provided useful lessons for future emerging threats. PMID:26345122

  15. Unsupervised learning applied in MER and ECG signals through Gaussians mixtures with the Expectation-Maximization algorithm and Variational Bayesian Inference.

    PubMed

    Vargas Cardona, Hernán Darío; Orozco, Álvaro Ángel; Álvarez, Mauricio A

    2013-01-01

    Automatic identification of biosignals is one of the more studied fields in biomedical engineering. In this paper, we present an approach for the unsupervised recognition of biomedical signals: Microelectrode Recordings (MER) and Electrocardiography signals (ECG). The unsupervised learning is based in classic and bayesian estimation theory. We employ gaussian mixtures models with two estimation methods. The first is derived from the frequentist estimation theory, known as Expectation-Maximization (EM) algorithm. The second is obtained from bayesian probabilistic estimation and it is called variational inference. In this framework, both methods are used for parameters estimation of Gaussian mixtures. The mixtures models are used for unsupervised pattern classification, through the responsibility matrix. The algorithms are applied in two real databases acquired in Parkinson's disease surgeries and electrocardiograms. The results show an accuracy over 85% in MER and 90% in ECG for identification of two classes. These results are statistically equal or even better than parametric (Naive Bayes) and nonparametric classifiers (K-nearest neighbor).

  16. Bat-to-human: spike features determining 'host jump' of coronaviruses SARS-CoV, MERS-CoV, and beyond.

    PubMed

    Lu, Guangwen; Wang, Qihui; Gao, George F

    2015-08-01

    Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic pathogens that crossed the species barriers to infect humans. The mechanism of viral interspecies transmission is an important scientific question to be addressed. These coronaviruses contain a surface-located spike (S) protein that initiates infection by mediating receptor-recognition and membrane fusion and is therefore a key factor in host specificity. In addition, the S protein needs to be cleaved by host proteases before executing fusion, making these proteases a second determinant of coronavirus interspecies infection. Here, we summarize the progress made in the past decade in understanding the cross-species transmission of SARS-CoV and MERS-CoV by focusing on the features of the S protein, its receptor-binding characteristics, and the cleavage process involved in priming.

  17. Skip the alignment: degenerate, multiplex primer and probe design using K-mer matching instead of alignments.

    PubMed

    Hysom, David A; Naraghi-Arani, Pejman; Elsheikh, Maher; Carrillo, A Celena; Williams, Peter L; Gardner, Shea N

    2012-01-01

    PriMux is a new software package for selecting multiplex compatible, degenerate primers and probes to detect diverse targets such as viruses. It requires no multiple sequence alignment, instead applying k-mer algorithms, hence it scales well for large target sets and saves user effort from curating sequences into alignable groups. PriMux has the capability to predict degenerate primers as well as probes suitable for TaqMan or other primer/probe triplet assay formats, or simply probes for microarray or other single-oligo assay formats. PriMux employs suffix array methods for efficient calculations on oligos 10-~100 nt in length. TaqMan® primers and probes for each segment of Rift Valley fever virus were designed using PriMux, and lab testing comparing signatures designed using PriMux versus those designed using traditional methods demonstrated equivalent or better sensitivity for the PriMux-designed signatures compared to traditional signatures. In addition, we used PriMux to design TaqMan® primers and probes for unalignable or poorly alignable groups of targets: that is, all segments of Rift Valley fever virus analyzed as a single target set of 198 sequences, or all 2863 Dengue virus genomes for all four serotypes available at the time of our analysis. The PriMux software is available as open source from http://sourceforge.net/projects/PriMux.

  18. Skip the Alignment: Degenerate, Multiplex Primer and Probe Design Using K-mer Matching Instead of Alignments

    PubMed Central

    Hysom, David A.; Naraghi-Arani, Pejman; Elsheikh, Maher; Carrillo, A. Celena; Williams, Peter L.; Gardner, Shea N.

    2012-01-01

    PriMux is a new software package for selecting multiplex compatible, degenerate primers and probes to detect diverse targets such as viruses. It requires no multiple sequence alignment, instead applying k-mer algorithms, hence it scales well for large target sets and saves user effort from curating sequences into alignable groups. PriMux has the capability to predict degenerate primers as well as probes suitable for TaqMan or other primer/probe triplet assay formats, or simply probes for microarray or other single-oligo assay formats. PriMux employs suffix array methods for efficient calculations on oligos 10-∼100 nt in length. TaqMan® primers and probes for each segment of Rift Valley fever virus were designed using PriMux, and lab testing comparing signatures designed using PriMux versus those designed using traditional methods demonstrated equivalent or better sensitivity for the PriMux-designed signatures compared to traditional signatures. In addition, we used PriMux to design TaqMan® primers and probes for unalignable or poorly alignable groups of targets: that is, all segments of Rift Valley fever virus analyzed as a single target set of 198 sequences, or all 2863 Dengue virus genomes for all four serotypes available at the time of our analysis. The PriMux software is available as open source from http://sourceforge.net/projects/PriMux. PMID:22485178

  19. A First Look at the Mineralogy and Geochemistry of the MER-B Landing Site in Meridiani Planum

    NASA Technical Reports Server (NTRS)

    Morris, Richard V.; Squyres, S.; Arvidson, R. E.; Bell, J. F., III; Christensen, P. C.; Gorevan, S.; Herkenhoff, K.; Klingelhoefer, G.; Rieder, R.; Farrand, W.

    2004-01-01

    The second MER rover (Opportunity) landed on Meridiani Planum on January 24, 2004 inside a shallow crater. The science rational for the selection of the landing site centered on detection of the mineral hematite from martian orbit by the Mars Global Surveyor Thermal Emission Spectrometer (MGS-TES) [1,2]. Other smaller occurrences of hematite are in Aram Chaos and several isolated spots in Valles Marineris. Proposed formation pathways for martian hematite include both aqueous (e.g., low temperature precipitation of Fe oxides/oxyhydroxides in a lacustrine environment, laterite-style weathering, and precipitation from fluids having a hydrothermal origin) and dry (e.g., oxidation of magnetite rich ash) processes [e.g., 1,2,3]. The crystallographic c-face of martian hematite must be exaggerated to account for the thermal emissions spectra and it must be gray in color so as to account for the absence of the characteristic spectral signature of red hematite at visible wavelengths

  20. Structure of HIV-1 reverse transcriptase bound to a novel 38-mer hairpin template-primer DNA aptamer.

    PubMed

    Miller, Matthew T; Tuske, Steve; Das, Kalyan; DeStefano, Jeffrey J; Arnold, Eddy

    2016-01-01

    The development of a modified DNA aptamer that binds HIV-1 reverse transcriptase (RT) with ultra-high affinity has enabled the X-ray structure determination of an HIV-1 RT-DNA complex to 2.3 Å resolution without the need for an antibody Fab fragment or RT-DNA cross-linking. The 38-mer hairpin-DNA aptamer has a 15 base-pair duplex, a three-deoxythymidine hairpin loop, and a five-nucleotide 5'-overhang. The aptamer binds RT in a template-primer configuration with the 3'-end positioned at the polymerase active site and has 2'-O-methyl modifications at the second and fourth duplex template nucleotides that interact with the p66 fingers and palm subdomains. This structure represents the highest resolution RT-nucleic acid structure to date. The RT-aptamer complex is catalytically active and can serve as a platform for studying fundamental RT mechanisms and for development of anti-HIV inhibitors through fragment screening and other approaches. Additionally, the structure allows for a detailed look at a unique aptamer design and provides the molecular basis for its remarkably high affinity for RT.

  1. Estimation of the Whitefly Bemisia tabaci Genome Size Based on k-mer and Flow Cytometric Analyses.

    PubMed

    Chen, Wenbo; Hasegawa, Daniel K; Arumuganathan, Kathiravetpillai; Simmons, Alvin M; Wintermantel, William M; Fei, Zhangjun; Ling, Kai-Shu

    2015-07-28

    Whiteflies of the Bemisia tabaci (Hemiptera: Aleyrodidae) cryptic species complex are among the most important agricultural insect pests in the world. These phloem-feeding insects can colonize over 1000 species of plants worldwide and inflict severe economic losses to crops, mainly through the transmission of pathogenic viruses. Surprisingly, there is very little genomic information about whiteflies. As a starting point to genome sequencing, we report a new estimation of the genome size of the B. tabaci B biotype or Middle East-Asia Minor 1 (MEAM1) population. Using an isogenic whitefly colony with over 6500 haploid male individuals for genomic DNA, three paired-end genomic libraries with insert sizes of ~300 bp, 500 bp and 1 Kb were constructed and sequenced on an Illumina HiSeq 2500 system. A total of ~50 billion base pairs of sequences were obtained from each library. K-mer analysis using these sequences revealed that the genome size of the whitefly was ~682.3 Mb. In addition, the flow cytometric analysis estimated the haploid genome size of the whitefly to be ~690 Mb. Considering the congruency between both estimation methods, we predict the haploid genome size of B. tabaci MEAM1 to be ~680-690 Mb. Our data provide a baseline for ongoing efforts to assemble and annotate the B. tabaci genome.

  2. Subunit sequences of the 4 x 6-mer hemocyanin from the golden orb-web spider, Nephila inaurata.

    PubMed

    Averdam, Anne; Markl, Jürgen; Burmester, Thorsten

    2003-08-01

    The transport of oxygen in the hemolymph of many arthropod and mollusc species is mediated by large copper-proteins that are referred to as hemocyanins. Arthropod hemocyanins are composed of hexamers and oligomers of hexamers. Arachnid hemocyanins usually form 4 x 6-mers consisting of seven distinct subunit types (termed a-g), although in some spider taxa deviations from this standard scheme have been observed. Applying immunological and electrophoretic methods, six distinct hemocyanin subunits were identified in the red-legged golden orb-web spider Nephila inaurata madagascariensis (Araneae: Tetragnathidae). The complete cDNA sequences of six subunits were obtained that corresponded to a-, b-, d-, e-, f- and g-type subunits. No evidence for a c-type subunit was found in this species. The inclusion of the N. inaurata hemocyanins in a multiple alignment of the arthropod hemocyanins and the application of the Bayesian method of phylogenetic inference allow, for the first time, a solid reconstruction of the intramolecular evolution of the chelicerate hemocyanin subunits. The branch leading to subunit a diverged first, followed by the common branch of the dimer-forming b and c subunits, while subunits d and f, as well as subunits e and g form common branches. Assuming a clock-like evolution of the chelicerate hemocyanins, a timescale for the evolution of the Chelicerata was obtained that agrees with the fossil record.

  3. Conformational state of a 25-mer peptide from the cyclophilin-binding loop of the HIV type 1 capsid protein.

    PubMed Central

    Reimer, U; Drewello, M; Jakob, M; Fischer, G; Schutkowski, M

    1997-01-01

    Recently a 25-residue part of Gag polyprotein from HIV type 1 (HIV-1) was reported to bind to the cytosolic 18 kDa cyclophilin (Cyp18) with an IC50 value of 180 microM. This peptide corresponds to the Cyp18-binding domain of HIV-1 Gag. A replacement of Gly with Ala in the cyclophilin-binding loop of HIV-1 Gag polyprotein results in the prevention of the packaging of Cyp18 into virions. We found only two conformers of this peptide among 16 possible expected conformers, owing to cis/trans isomerization of four peptidyl-prolyl bonds. Although this finding implicates the existence of a stabilizing structure, we were not able to detect secondary structure formation by 1H-NMR and CD spectroscopy. We characterized the peptide as a substrate for Cyp18 by two-dimensional exchange 1H-NMR spectroscopy. Surprisingly, we found similar binding characteristics for a peptide corresponding to 25-mer peptide containing the above-mentioned Gly to Ala substitution. PMID:9337866

  4. A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis

    PubMed Central

    Lund, Maria E.; Greer, Judith; Dixit, Aakanksha; Alvarado, Raquel; McCauley-Winter, Padraig; To, Joyce; Tanaka, Akane; Hutchinson, Andrew T.; Robinson, Mark W.; Simpson, Ann M.; O’Brien, Bronwyn A.; Dalton, John P.; Donnelly, Sheila

    2016-01-01

    Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases. PMID:27883079

  5. Development and evaluation of 50-mer oligonucleotide arrays for detecting microbial populations in Acid Mine Drainages and bioleaching systems.

    PubMed

    Yin, Huaqun; Cao, Linhui; Qiu, Guanzhou; Wang, Dianzuo; Kellogg, Laurie; Zhou, Jizhong; Dai, Zhimin; Liu, Xueduan

    2007-07-01

    To effectively monitor microbial populations in acidic environments and bioleaching systems, a comprehensive 50-mer-based oligonucleotide microarray was developed based on most of the known genes associated with the acidophiles. This array contained 1,072 probes in which there were 571 related to 16S rRNA and 501 related to functional genes. The functional genes in the microarray were involved in carbon metabolism (158), nitrogen metabolism (72), sulfur metabolism (39), iron metabolism (68), DNA replication and repair (97), metal-resistance (27), membrane-relate gene (16), transposon (13) and IST sequence (11). Based on the results of microarray hybridizations, specificity tests with representative pure cultures indicated that the designed probes on the arrays appeared to be specific to their corresponding target genes. The detection limit was 5 ng of genomic DNA in the absence of background DNA. Strong linear relationships between the signal intensity and the target DNA were observed (r(2) approximately 0.98). Application of this type of the microarray to analyze the acidic environments and bioleaching systems demonstrated that the developed microarray appeared to be useful for profiling differences in microbial community structures of acidic environments and bioleaching systems. Our results indicate that this technology has potential as a specific, sensitive, and quantitative tool in revealing a comprehensive picture of the compositions of genes related with acidophilic microorganism and the microbial community in acidic environments and bioleaching systems, although more work is needed to improve.

  6. Complete Taiwanese Macaque (Macaca cyclopis) Mitochondrial Genome: Reference-Assisted de novo Assembly with Multiple k-mer Strategy.

    PubMed

    Huang, Yu-Feng; Midha, Mohit; Chen, Tzu-Han; Wang, Yu-Tai; Smith, David Glenn; Pei, Kurtis Jai-Chyi; Chiu, Kuo Ping

    2015-01-01

    The Taiwanese (Formosan) macaque (Macaca cyclopis) is the only nonhuman primate endemic to Taiwan. This primate species is valuable for evolutionary studies and as subjects in medical research. However, only partial fragments of the mitochondrial genome (mitogenome) of this primate species have been sequenced, not mentioning its nuclear genome. We employed next-generation sequencing to generate 2 x 90 bp paired-end reads, followed by reference-assisted de novo assembly with multiple k-mer strategy to characterize the M. cyclopis mitogenome. We compared the assembled mitogenome with that of other macaque species for phylogenetic analysis. Our results show that, the M. cyclopis mitogenome consists of 16,563 nucleotides encoding for 13 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs. Phylogenetic analysis indicates that M. cyclopis is most closely related to M. mulatta lasiota (Chinese rhesus macaque), supporting the notion of Asia-continental origin of M. cyclopis proposed in previous studies based on partial mitochondrial sequences. Our work presents a novel approach for assembling a mitogenome that utilizes the capabilities of de novo genome assembly with assistance of a reference genome. The availability of the complete Taiwanese macaque mitogenome will facilitate the study of primate evolution and the characterization of genetic variations for the potential usage of this species as a non-human primate model for medical research.

  7. Expression of merA, trxA, amoA, and hao in continuously cultured Nitrosomonas europaea cells exposed to cadmium sulfate additions.

    PubMed

    Radniecki, Tyler S; Semprini, Lewis; Dolan, Mark E

    2009-12-01

    The effects of CdSO(4) additions on the gene expressions of a mercury reductase, merA, an oxidative stress protein, trxA, the ammonia-monooxygenase enzyme (AMO), amoA, and the hydroxylamine oxidoreductase enzyme (HAO), hao, were examined in continuously cultured N. europaea cells. The reactor was fed 50 mM NH(4)+ and was operated for 78 days with a 6.9 days hydraulic retention time. Over this period, six successive batch additions of CdSO(4) were made with increasing maximum concentrations ranging from 1 to 60 microM Cd(2+). The expression of merA was highly correlated with the level of Cd(2+) within the reactor (Rs = 0.90) with significant up-regulation measured at non-inhibitory Cd(2+) concentrations. Cd(2+) appears to target AMO specifically at lower concentrations and caused oxidative stress at higher concentrations, as indicated by the SOURs (specific oxygen uptake rates) and the up-regulation of trxA. Since Cd(2+) inhibition is irreversible and amoA was up-regulated in response to Cd(2+) inhibition, it is hypothesized that de novo synthesis of the AMO enzyme occurred and was responsible for the observed recovery in activity. Continuously cultured N. europaea cells were more resistant to Cd(2+) inhibition than previously examined batch cultured cells due to the presence of Mg(2+) and Ca(2+) in the growth media, suggesting that Cd(2+) enters the cell through Mg(2+) and Ca(2+) import channels. The up-regulation of merA during exposure to non-inhibitory Cd(2+) levels indicates that merA is an excellent early warning signal for Cd(2+) inhibition.

  8. Expression of merA, amoA and hao in continuously cultured Nitrosomonas europaea cells exposed to zinc chloride additions.

    PubMed

    Radniecki, Tyler S; Semprini, Lewis; Dolan, Mark E

    2009-02-01

    The effects of ZnCl2 additions on a mercuric reductase, merA, ammonia monooxygenase, amoA, and hydroxylamine (NH2OH) oxidoreductase, hao, gene expression were examined in continuously cultured Nitrosomonas europaea cells. The reactor was operated for 85 days with a 6.9 d hydraulic retention time and with four successive additions of ZnCl2 achieving maximum concentrations from 3 to 90 microM Zn2+. Continuously cultured N. europaea cells were more resistant to Zn2+ inhibition than previously examined batch cultured cells due to the presence of Mg2+ in the growth media, suggesting that Zn2+ enters the cell through Mg2+ import channels. The maximum merA up-regulation was 45-fold and expression increased with increases in Zn2+ concentration and decreased as Zn2+ concentrations decreased. Although Zn2+ irreversibly inactivated ammonia oxidation in N. europaea, the addition of either 600 microM CuSO4 or 2250 microM MgSO4 protected N. europaea from ZnCl2 inhibition, indicating a competition between Zn2+ and Cu2+/Mg2+ for uptake and/or AMO active sites. Since ZnCl2 inhibition is irreversible and amoA was up-regulated at 30 and 90 microM additions, it is hypothesized that de novo synthesis of the AMO enzyme is needed to overcome inhibition. The up-regulation of merA during exposure to non-inhibitory Zn2+ levels indicates that merA is an excellent early warning signal for Zn2+ inhibition.

  9. Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia

    PubMed Central

    Alshrari, Ahmed S.; Badroon, Nassrin A.; Hassan, Ahmed M.; Alsubhi, Tagreed L.; Ejeeli, Saleh

    2017-01-01

    We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time). Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2%) of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV) was the most detected pathogen (40.9%) followed by non-MERS-CoV human coronaviruses (19.3%), influenza (Flu) viruses (15.9%), and human respiratory syncytial virus (hRSV) (13.6%). Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control. PMID:28348590

  10. Diversification of the celiac disease α-gliadin complex in wheat: a 33-mer peptide with six overlapping epitopes, evolved following polyploidization.

    PubMed

    Ozuna, Carmen V; Iehisa, Julio C M; Giménez, María J; Alvarez, Juan B; Sousa, Carolina; Barro, Francisco

    2015-06-01

    The gluten proteins from wheat, barley and rye are responsible both for celiac disease (CD) and for non-celiac gluten sensitivity, two pathologies affecting up to 6-8% of the human population worldwide. The wheat α-gliadin proteins contain three major CD immunogenic peptides: p31-43, which induces the innate immune response; the 33-mer, formed by six overlapping copies of three highly stimulatory epitopes; and an additional DQ2.5-glia-α3 epitope which partially overlaps with the 33-mer. Next-generation sequencing (NGS) and Sanger sequencing of α-gliadin genes from diploid and polyploid wheat provided six types of α-gliadins (named 1-6) with strong differences in their frequencies in diploid and polyploid wheat, and in the presence and abundance of these CD immunogenic peptides. Immunogenic variants of the p31-43 peptide were found in most of the α-gliadins. Variants of the DQ2.5-glia-α3 epitope were associated with specific types of α-gliadins. Remarkably, only type 1 α-gliadins contained 33-mer epitopes. Moreover, the full immunodominant 33-mer fragment was only present in hexaploid wheat at low abundance, probably as the result of allohexaploidization events from subtype 1.2 α-gliadins found only in Aegilops tauschii, the D-genome donor of hexaploid wheat. Type 3 α-gliadins seem to be the ancestral type as they are found in most of the α-gliadin-expressing Triticeae species. These findings are important for reducing the incidence of CD by the breeding/selection of wheat varieties with low stimulatory capacity of T cells. Moreover, advanced genome-editing techniques (TALENs, CRISPR) will be easier to implement on the small group of α-gliadins containing only immunogenic peptides.

  11. Polyphyletic origin of MERS coronaviruses and isolation of a novel clade A strain from dromedary camels in the United Arab Emirates

    PubMed Central

    Lau, Susanna K P; Wernery, Renate; Wong, Emily Y M; Joseph, Sunitha; Tsang, Alan K L; Patteril, Nissy Annie Georgy; Elizabeth, Shyna K; Chan, Kwok-Hung; Muhammed, Rubeena; Kinne, Jöerg; Yuen, Kwok-Yung; Wernery, Ulrich; Woo, Patrick C Y

    2016-01-01

    Little is known regarding the molecular epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) circulating in dromedaries outside Saudi Arabia. To address this knowledge gap, we sequenced 10 complete genomes of MERS-CoVs isolated from 2 live and 8 dead dromedaries from different regions in the United Arab Emirates (UAE). Phylogenetic analysis revealed one novel clade A strain, the first detected in the UAE, and nine clade B strains. Strain D998/15 had a distinct phylogenetic position within clade A, being more closely related to the dromedary isolate NRCE-HKU205 from Egypt than to the human isolates EMC/2012 and Jordan-N3/2012. A comparison of predicted protein sequences also demonstrated the existence of two clade A lineages with unique amino acid substitutions, A1 (EMC/2012 and Jordan-N3/2012) and A2 (D998/15 and NRCE-HKU205), circulating in humans and camels, respectively. The nine clade B isolates belong to three distinct lineages: B1, B3 and B5. Two B3 strains, D1271/15 and D1189.1/15, showed evidence of recombination between lineages B4 and B5 in ORF1ab. Molecular clock analysis dated the time of the most recent common ancestor (tMRCA) of clade A to March 2011 and that of clade B to November 2011. Our data support a polyphyletic origin of MERS-CoV in dromedaries and the co-circulation of diverse MERS-CoVs including recombinant strains in the UAE. PMID:27999424

  12. Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

    DOE PAGES

    Ying, Tianlei; Prabakaran, Ponraj; Du, Lanying; ...

    2015-09-15

    The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (~36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of bindingmore » at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.« less

  13. Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

    SciTech Connect

    Ying, Tianlei; Prabakaran, Ponraj; Du, Lanying; Shi, Wei; Feng, Yang; Wang, Yanping; Wang, Lingshu; Li, Wei; Jiang, Shibo; Dimitrov, Dimiter S.; Zhou, Tongqing

    2015-09-15

    The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (~36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.

  14. Comparative analysis using K-mer and K-flank patterns provides evidence for CpG island sequence evolution in mammalian genomes.

    PubMed

    Chae, Heejoon; Park, Jinwoo; Lee, Seong-Whan; Nephew, Kenneth P; Kim, Sun

    2013-05-01

    CpG islands are GC-rich regions often located in the 5' end of genes and normally protected from cytosine methylation in mammals. The important role of CpG islands in gene transcription strongly suggests evolutionary conservation in the mammalian genome. However, as CpG dinucleotides are over-represented in CpG islands, comparative CpG island analysis using conventional sequence analysis techniques remains a major challenge in the epigenetics field. In this study, we conducted a comparative analysis of all CpG island sequences in 10 mammalian genomes. As sequence similarity methods and character composition techniques such as information theory are particularly difficult to conduct, we used exact patterns in CpG island sequences and single character discrepancies to identify differences in CpG island sequences. First, by calculating genome distance based on rank correlation tests, we show that k-mer and k-flank patterns around CpG sites can be used to correctly reconstruct the phylogeny of 10 mammalian genomes. Further, we used various machine learning algorithms to demonstrate that CpG islands sequences can be characterized using k-mers. In addition, by testing a human model on the nine different mammalian genomes, we provide the first evidence that k-mer signatures are consistent with evolutionary history.

  15. Screening sourdough samples for gliadin-degrading activity revealed Lactobacillus casei strains able to individually metabolize the coeliac-disease-related 33-mer peptide.

    PubMed

    Alvarez-Sieiro, Patricia; Redruello, Begoña; Ladero, Victor; Martín, Maria Cruz; Fernández, María; Alvarez, Miguel A

    2016-05-01

    A selective culture medium containing acid-hydrolyzed gliadins as the sole nitrogen source was used in the search for sourdough-indigenous lactic acid bacteria (LAB) with gliadin-metabolizing activity. Twenty gliadin-degrading LAB strains were isolated from 10 sourdoughs made in different ways and from different geographical regions. Fifteen of the 20 isolated strains were identified as Lactobacillus casei, a species usually reported as subdominant in sourdough populations. The other 5 gliadin-degrading strains belonged to the more commonly encountered sourdough species Leuconostoc mesenteroides and Lactobacillus plantarum. All these strains were shown to be safe in terms of their resistance to antimicrobial agents. When individually incubated with the α2-gliadin-derived immunotoxic 33-mer peptide (97.5 ppm), half of the L. casei strains metabolized at least 50% of it within 24 h. One strain metabolized 82% of the 33-mer peptide within 8 h and made it fully disappear within 12 h. These results reveal for the first time the presence in sourdough of proteolytic L. casei strains with the capacity to individually metabolize the coeliac-disease-related 33-mer peptide.

  16. Transposon Tagging of a Male-Sterility, Female-Sterility Gene, St8, Revealed that the Meiotic MER3 DNA Helicase Activity Is Essential for Fertility in Soybean

    PubMed Central

    Baumbach, Jordan; Pudake, Ramesh N.; Johnson, Callie; Kleinhans, Kaylin; Ollhoff, Alexandrea; Palmer, Reid G.; Bhattacharyya, Madan K.; Sandhu, Devinder

    2016-01-01

    The W4 locus in soybean encodes a dihydroflavonol-4-reductase (DFR2) that regulates pigmentation patterns in flowers and hypocotyl. The mutable w4-m allele that governs variegated flowers has arisen through insertion of a CACTA-type transposable element, Tgm9, in DFR2. In the w4-m line, reversion from variegated to purple flower indicates excision of Tgm9, and its insertion at a new locus. Previously, we have identified a male-sterile, female-sterile mutant among the selfed progenies of a revertant plant carrying only purple flowers. Co-segregation between Tgm9 and the sterility phenotype suggested that the mutant was generated by insertion of Tgm9 at the St8 locus. The transposon was localized to exon 10 of Glyma.16G072300 that shows high identity to the MER3 DNA helicase involved in crossing over. Molecular analysis of fertile branches from two independent revertant plants confirmed precise excision of Tgm9 from the st8 allele, which restored fertility. In soybean, the gene is expressed in flower-buds, trifoliate leaves and stem. Phylogenetic analysis placed St8 in a clade with the Arabidopsis and rice MER3 suggesting that St8 is most likely the orthologous MER3 soybean gene. This study established the utility of Tgm9 in gene identification as well as in forward and reverse genetics studies. PMID:26930200

  17. PEDF and PEDF-derived peptide 44mer inhibit oxygen-glucose deprivation-induced oxidative stress through upregulating PPARγ via PEDF-R in H9c2 cells.

    PubMed

    Zhuang, Wei; Zhang, Hao; Pan, Jiajun; Li, Zhimin; Wei, Tengteng; Cui, Huazhu; Liu, Zhiwei; Guan, Qiuhua; Dong, Hongyan; Zhang, Zhongming

    2016-04-08

    Pigment epithelial-derived factor (PEDF) is a glycoprotein with broad biological activities including inhibiting oxygen-glucose deprivation(OGD)-induced cardiomyocytes apoptosis through its anti-oxidative properties. PEDF derived peptide-44mer shows similar cytoprotective effect to PEDF. However, the molecular mechanisms mediating cardiomyocytes apoptosis have not been fully established. Here we found that PEDF and 44mer decreased the content of ROS. This content was abolished by either PEDF-R small interfering RNA (siRNA) or PPARγ antagonist. The level of Lysophosphatidic acid (LPA) and phospholipase A2 (PLA2) was observed as drawn from the ELISA assays. PEDF and 44mer sequentially induced PPARγ expression was observed both in qPCR and Western blot assays. The level of LPA and PLA2 and PPARγ expression increased by PEDF and 44mer was significantly attenuated by PEDF-R siRNA. However, PEDF and 44mer inhibited the H9c2 cells and cultured neonatal rat myocardial cells apoptosis rate. On the other hand, TUNEL assay and cleavage of procaspase-3 showed that PEDF-R siRNA or PPARγ antagonist increased the apoptosis again. We conclude that under OGD condition, PEDF and 44mer reduce H9c2 cells apoptosis and inhibit OGD-induced oxidative stress via its receptor PEDF-R and the PPARγ signaling pathway.

  18. Estimation of MERS-Coronavirus Reproductive Number and Case Fatality Rate for the Spring 2014 Saudi Arabia Outbreak: Insights from Publicly Available Data

    PubMed Central

    Majumder, Maimuna S.; Rivers, Caitlin; Lofgren, Eric; Fisman, David

    2014-01-01

    Background: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was initially recognized as a source of severe respiratory illness and renal failure in 2012. Prior to 2014, MERS-CoV was mostly associated with sporadic cases of human illness, of presumed zoonotic origin, though chains of person-to-person transmission in the healthcare setting were reported. In spring 2014, large healthcare-associated outbreaks of MERS-CoV infection occurred in Jeddah and Riyadh, Kingdom of Saudi Arabia. To date the epidemiological information published by public health investigators in affected jurisdictions has been relatively limited. However, it is important that the global public health community have access to information on the basic epidemiological features of the outbreak to date, including the basic reproduction number (R0) and best estimates of case-fatality rates (CFR). We sought to address these gaps using a publicly available line listing of MERS-CoV cases. Methods: R0 was estimated using the incidence decay with exponential adjustment (“IDEA”) method, while period-specific case fatality rates that incorporated non-attributed death data were estimated using Monte Carlo simulation. Results: 707 cases were available for evaluation. 52% of cases were identified as primary, with the rest being secondary. IDEA model fits suggested a higher R0 in Jeddah (3.5-6.7) than in Riyadh (2.0-2.8); control parameters suggested more rapid reduction in transmission in the former city than the latter. The model accurately projected final size and end date of the Riyadh outbreak based on information available prior to the outbreak peak; for Jeddah, these projections were possible once the outbreak peaked. Overall case-fatality was 40%; depending on the timing of 171 deaths unlinked to case data, outbreak CFR could be higher, lower, or equivalent to pre-outbreak CFR. Conclusions: Notwithstanding imperfect data, inferences about MERS-CoV epidemiology important for public health

  19. Mapping Hydration with the Mars Exploration Rover (MER) Pancam Instruments: Recent Results from Opportunity at Endeavour Crater

    NASA Astrophysics Data System (ADS)

    Rice, Melissa S.; Bell, James F., III; Arvidson, Raymond E.; Farrand, William H.; Johnson, Jeffrey R.; Rice, James W.; Ruff, Steven W.; Squyres, Steven W.; Wang, Alian

    2013-04-01

    Using the Mars Exploration Rover (MER) Panoramic Camera (Pancam) instruments, we have developed a "hydration signature" for mapping H2O- and/or OH-bearing materials at Mars landing sites with multispectral visible to near-infrared (Vis-NIR) images. Pancam's 13 narrowband geology filters cover 11 unique wavelengths in the visible and near infrared (434 to 1009 nm) [1-2]. The hydration signature is based on a negative slope from 934 to 1009 nm [3] that characterizes the spectra of hydrated silica-rich rocks and soils observed by MER Spirit; this feature is likely due to the 2ν1 + ν3 H2O combination band and/or the 3νOH overtone centered near ~1000 nm, whose positions vary slightly depending on bonding to nearest-neighbor atoms [4]. The hydration signature is sensitive to many - but not all - hydrated minerals, including silica, gypsum and water ice. At Gusev Crater, the hydration signature is widespread along Spirit's traverse in the Columbia Hills, which adds to the growing body of evidence that aqueous alteration has played a significant role in the complex geologic history of this site [4]. At Meridiani Planum, the hydration signature is associated with a specific stratigraphic layer ("Smith") exposed within the walls of Victoria Crater [5], in addition to light-toned veins composed of calcium sulfate at Cape York on the rim of Endeavour Crater [6]. Recently, Opportunity has completed a traverse loop at Matijevic Hill at the southern end of Cape York and has encountered numerous small, light-toned, fracture-filling veins that may be indicative of fluid flow. Spectra of these veins are also consistent with hydrated materials, as are spectra of "Whitewater Lake" outcrops at Matijevic Hill, which may contain phyllosilicate minerals [7-8]. Here we also discuss limitations to the use of the hydration signature, which can give false detections under specific viewing geometries. For example, the Pancam calibration model assumes that the calibration target behaves as a

  20. Plasmid replication initiator interactions with origin 13-mers and polymerase subunits contribute to strand-specific replisome assembly

    PubMed Central

    Wawrzycka, Aleksandra; Gross, Marta; Wasaznik, Anna; Konieczny, Igor

    2015-01-01

    Although the molecular basis for replisome activity has been extensively investigated, it is not clear what the exact mechanism for de novo assembly of the replication complex at the replication origin is, or how the directionality of replication is determined. Here, using the plasmid RK2 replicon, we analyze the protein interactions required for Escherichia coli polymerase III (Pol III) holoenzyme association at the replication origin. Our investigations revealed that in E. coli, replisome formation at the plasmid origin involves interactions of the RK2 plasmid replication initiation protein (TrfA) with both the polymerase β- and α-subunits. In the presence of other replication proteins, including DnaA, helicase, primase and the clamp loader, TrfA interaction with the β-clamp contributes to the formation of the β-clamp nucleoprotein complex on origin DNA. By reconstituting in vitro the replication reaction on ssDNA templates, we demonstrate that TrfA interaction with the β-clamp and sequence-specific TrfA interaction with one strand of the plasmid origin DNA unwinding element (DUE) contribute to strand-specific replisome assembly. Wild-type TrfA, but not the TrfA QLSLF mutant (which does not interact with the β-clamp), in the presence of primase, helicase, Pol III core, clamp loader, and β-clamp initiates DNA synthesis on ssDNA template containing 13-mers of the bottom strand, but not the top strand, of DUE. Results presented in this work uncovered requirements for anchoring polymerase at the plasmid replication origin and bring insights of how the directionality of DNA replication is determined. PMID:26195759

  1. Synthesis, structure, catalytic and calculated non-linear optical properties of cis- and trans-, mer-chlorobis(triphenyl phosphine/triphenyl arsine)-dipicolinato ruthenium III complexes

    NASA Astrophysics Data System (ADS)

    Trivedi, Manoj; Nagarajan, R.; Kumar, Abhinav; Singh, Narendra K.; Rath, Nigam P.

    2011-05-01

    The new mononuclear Ru III complexes cis-, mer-[Ru( k3-dipic)(EPh 3) 2Cl]·2H 2O (E = P ( 1), As ( 2)), (L = 2,6-pyridyldicarboxylate; dipic) have been synthesized and characterized. The X-ray crystal structure of 1 reveals that the coordination geometry around the Ru III center is distorted octahedral in which three sites are occupied by tridentate dipic ligand and remaining three sites are occupied by two mutually cis triphenyl phosphine ligands and one chloride ions. In chloroform solvent, cis-, mer-[Ru( k3-dipic)(EPh 3) 2Cl]·2H 2O (E = P ( 1), As ( 2)) complexes undergoes thermal rearrangement to more stable trans-, mer-[Ru( k3-dipic)(EPh 3) 2Cl] (E = P( 3), As( 4)) complexes. Complexes 1 and 2 show rhombic EPR spectral features, while complex 3 and 4 show tetragonal distortion. The new Ru III complexes 1 and 2 display both Ru III-Ru II reduction and Ru III-Ru IV oxidation processes. These geometric isomers exhibit textbook differences both in spectroscopic as well as structural properties in the solid state. The new complexes 1 and 2 were found to catalyze the oxidation of alcohols to carbonyl derivatives using N-methyl morpholine- N-oxide as co-oxidant. The first static hyperpolarizability ( β) for all of the complexes have been investigated by density functional theory (DFT) which suggests β value increases from trans to cis form. Also, the solvent-induced effects on the non-linear optical properties (NLO) were studied by using self-consistent reaction field (SCRF) method. As the solvent polarity increases, the β value increases monotonically. The electronic absorption bands of 1 have been assigned by time dependent density functional theory (TD-DFT).

  2. Molecular basis of a dominant T cell response to an HIV reverse transcriptase 8-mer epitope presented by the protective allele HLA-B*51:01.

    PubMed

    Motozono, Chihiro; Kuse, Nozomi; Sun, Xiaoming; Rizkallah, Pierre J; Fuller, Anna; Oka, Shinichi; Cole, David K; Sewell, Andrew K; Takiguchi, Masafumi

    2014-04-01

    CD8(+) CTL responses directed toward the HLA-B*51:01-restricted HIV-RT128-135 epitope TAFTIPSI (TI8) are associated with long-term nonprogression to AIDS. Clonotypic analysis of responses to B51-TI8 revealed a public clonotype using TRAV17/TRBV7-3 TCR genes in six out of seven HLA-B*51:01(+) patients. Structural analysis of a TRAV17/TRBV7-3 TCR in complex with HLA-B51-TI8, to our knowledge the first human TCR complexed with an 8-mer peptide, explained this bias, as the unique combination of residues encoded by these genes was central to the interaction. The relatively featureless peptide-MHC (pMHC) was mainly recognized by the TCR CDR1 and CDR2 loops in an MHC-centric manner. A highly conserved residue Arg(97) in the CDR3α loop played a major role in recognition of peptide and MHC to form a stabilizing ball-and-socket interaction with the MHC and peptide, contributing to the selection of the public TCR clonotype. Surface plasmon resonance equilibrium binding analysis showed the low affinity of this public TCR is in accordance with the only other 8-mer interaction studied to date (murine 2C TCR-H-2K(b)-dEV8). Like pMHC class II complexes, 8-mer peptides do not protrude out the MHC class I binding groove like those of longer peptides. The accumulated evidence suggests that weak affinity might be a common characteristic of TCR binding to featureless pMHC landscapes.

  3. Molecular Basis of a Dominant T Cell Response to an HIV Reverse Transcriptase 8-mer Epitope Presented by the Protective Allele HLA-B*51:01

    PubMed Central

    Motozono, Chihiro; Kuse, Nozomi; Sun, Xiaoming; Rizkallah, Pierre J.; Fuller, Anna; Oka, Shinichi; Cole, David K.; Sewell, Andrew K.

    2014-01-01

    CD8+ CTL responses directed toward the HLA-B*51:01–restricted HIV-RT128–135 epitope TAFTIPSI (TI8) are associated with long-term nonprogression to AIDS. Clonotypic analysis of responses to B51-TI8 revealed a public clonotype using TRAV17/TRBV7-3 TCR genes in six out of seven HLA-B*51:01+ patients. Structural analysis of a TRAV17/TRBV7-3 TCR in complex with HLA–B51-TI8, to our knowledge the first human TCR complexed with an 8-mer peptide, explained this bias, as the unique combination of residues encoded by these genes was central to the interaction. The relatively featureless peptide-MHC (pMHC) was mainly recognized by the TCR CDR1 and CDR2 loops in an MHC-centric manner. A highly conserved residue Arg97 in the CDR3α loop played a major role in recognition of peptide and MHC to form a stabilizing ball-and-socket interaction with the MHC and peptide, contributing to the selection of the public TCR clonotype. Surface plasmon resonance equilibrium binding analysis showed the low affinity of this public TCR is in accordance with the only other 8-mer interaction studied to date (murine 2C TCR–H-2Kb-dEV8). Like pMHC class II complexes, 8-mer peptides do not protrude out the MHC class I binding groove like those of longer peptides. The accumulated evidence suggests that weak affinity might be a common characteristic of TCR binding to featureless pMHC landscapes. PMID:24600035

  4. PM2, a group 3 LEA protein from soybean, and its 22-mer repeating region confer salt tolerance in Escherichia coli

    SciTech Connect

    Yun Liu; Zheng Yizhi . E-mail: yzzheng@szu.edu.cn

    2005-05-27

    To have knowledge of the effect of soybean PM2 protein in protecting dehydrated cells and its functional region, PM2 cDNA was isolated from soybean immature seeds. The recombinants expressing full-length PM2, truncated polypeptides of PM2A (aa 1-262) or PM2B (aa 129-262, 22-mer repeating region), or artificial polypeptide PM2C (duplication of 22-mer repeating region) were constructed. By using SDS-PAGE and mass spectrometry approaches, these fusion polypeptides were identified and proved to be hydrophilic and heat-stable. Spot assays of BL/PM2 and BL/pET28 (as control) showed that protein PM2 increased salt tolerance (500 mM NaCl or 500 mM KCl) of Escherichia coli, rather than osmotic tolerance (1100 mM sorbitol). In addition, comparing the survival ratios of the transformants under 500 mM NaCl or 500 mM KCl stresses, the results showed that: (1) the survival ratios of BL/PM2 and BL/PM2B were quite similar, both showing much higher values than those of BL/pET28. (2) The survival ratios of BL/PM2C were much higher than those of BL/PM2, BL/PM2A, and BL/PM2B. This provides the first experimental evidence that PM2 polypeptide enhances salt tolerance of E. coli cells, and the 22-mer repeat region is an important functional region.

  5. ÉmerGéantes: a new Global Climate Model to study the dynamics of Saturn's stratosphere - and beyond

    NASA Astrophysics Data System (ADS)

    Spiga, Aymeric; Guerlet, Sandrine; Sylvestre, Melody; Fouchet, Thierry

    2013-04-01

    Recent observational programs, both spatial and ground-based, have revealed the complexity of the middle atmospheres of giant planets. In particular, maps of the temperature and of the distribution of trace species in the Saturn stratosphere have been obtained by the Cassini spacecraft with unprecedented details. These maps exhibit puzzling anomalies, which cannot be explained by current photochemical and radiative models (none of them includes dynamics), and which have been interpreted as the signature of large-scale or seasonal dynamical motions. Yet Saturn's global circulation remains weakly characterized. Furthermore, on Saturn and Jupiter, equatorial oscillations in the zonal wind and temperature field have recently been discovered and are reminiscent of the Earth's Quasi-Biennial Oscillation, a fundamental dynamical phenomenon. These oscillations thus appear to be a common dynamical phenomenon in very different planetary atmospheres. We will present the development of "ÉmerGéantes", a new global climate model for giant planets. This new model is based on the LMDz dynamical core, which has been successfully adapted to terrestrial planets and moons: the Earth, Mars, Venus, Titan, Triton/Pluton. Details on the numerical challenges, the adaptations needed to simulate gas giants, and the optimization of the radiative transfer computations will be presented, along with preliminary results. The aim of this project is study in detail the atmospheric circulation of giant planets by resolving atmospheric circulations in their stratosphere (and, possibly, in the future, the coupling between their troposphere and stratosphere). It will serve as a new tool to address fundamental questions in geophysical fluid dynamics, explore the giant planets circulation patterns, and better interpret current and future observations. This new GCM will first be focused on reproducing Saturn's climate, following the harvest of observations obtained by the Cassini mission. We plan to

  6. Structural basis of thiol-based regulation of formaldehyde detoxification in H. influenzae by a MerR regulator with no sensor region

    PubMed Central

    Couñago, Rafael M.; Chen, Nathan H.; Chang, Chiung-Wen; Djoko, Karrera Y.; McEwan, Alastair G.; Kobe, Bostjan

    2016-01-01

    Pathogenic bacteria such as Haemophilus influenzae, a major cause of lower respiratory tract diseases, must cope with a range of electrophiles generated in the host or by endogenous metabolism. Formaldehyde is one such compound that can irreversibly damage proteins and DNA through alkylation and cross-linking and interfere with redox homeostasis. Its detoxification operates under the control of HiNmlR, a protein from the MerR family that lacks a specific sensor region and does not bind metal ions. We demonstrate that HiNmlR is a thiol-dependent transcription factor that modulates H. influenzae response to formaldehyde, with two cysteine residues (Cys54 and Cys71) identified to be important for its response against a formaldehyde challenge. We obtained crystal structures of HiNmlR in both the DNA-free and two DNA-bound forms, which suggest that HiNmlR enhances target gene transcription by twisting of operator DNA sequences in a two-gene operon containing overlapping promoters. Our work provides the first structural insights into the mechanism of action of MerR regulators that lack sensor regions. PMID:27307602

  7. Estimation of the genome sizes of the chigger mites Leptotrombidium pallidum and Leptotrombidium scutellare based on quantitative PCR and k-mer analysis

    PubMed Central

    2014-01-01

    Background Leptotrombidium pallidum and Leptotrombidium scutellare are the major vector mites for Orientia tsutsugamushi, the causative agent of scrub typhus. Before these organisms can be subjected to whole-genome sequencing, it is necessary to estimate their genome sizes to obtain basic information for establishing the strategies that should be used for genome sequencing and assembly. Method The genome sizes of L. pallidum and L. scutellare were estimated by a method based on quantitative real-time PCR. In addition, a k-mer analysis of the whole-genome sequences obtained through Illumina sequencing was conducted to verify the mutual compatibility and reliability of the results. Results The genome sizes estimated using qPCR were 191 ± 7 Mb for L. pallidum and 262 ± 13 Mb for L. scutellare. The k-mer analysis-based genome lengths were estimated to be 175 Mb for L. pallidum and 286 Mb for L. scutellare. The estimates from these two independent methods were mutually complementary and within a similar range to those of other Acariform mites. Conclusions The estimation method based on qPCR appears to be a useful alternative when the standard methods, such as flow cytometry, are impractical. The relatively small estimated genome sizes should facilitate whole-genome analysis, which could contribute to our understanding of Arachnida genome evolution and provide key information for scrub typhus prevention and mite vector competence. PMID:24947244

  8. Effects of operational decisions on the diffusion of epidemic disease: A system dynamics modeling of the MERS-CoV outbreak in South Korea.

    PubMed

    Shin, Nina; Kwag, Taewoo; Park, Sangwook; Kim, Yon Hui

    2017-03-27

    We evaluated the nosocomial outbreak of Middle East Respiratory Syndrome (MERS) Coronavirus (CoV) in the Republic of Korea, 2015, from a healthcare operations management perspective. Establishment of healthcare policy in South Korea provides patients' freedom to select and visit multiple hospitals. Current policy enforces hospitals preference for multi-patient rooms to single-patient rooms, to lower financial burden. Existing healthcare systems tragically contributed to 186 MERS outbreak cases, starting from single "index patient" into three generations of secondary infections. By developing a macro-level health system dynamics model, we provide empirical knowledge to examining the case from both operational and financial perspectives. In our simulation, under base infectivity scenario, high emergency room occupancy circumstance contributed to an estimated average of 101 (917%) more infected patients, compared to when in low occupancy circumstance. Economic patient room design showed an estimated 702% increase in the number of infected patients, despite the overall 98% savings in total expected costs compared to optimal room design. This study provides first time, system dynamics model, performance measurements from an operational perspective. Importantly, the intent of this study was to provide evidence to motivate public, private, and government healthcare administrators' recognition of current shortcomings, to optimize performance as a whole system, rather than mere individual aspects.

  9. Identification of Position-Specific Correlations between DNA-Binding Domains and Their Binding Sites. Application to the MerR Family of Transcription Factors

    PubMed Central

    Mironov, Andrey A.; Rakhmaininova, Alexandra B.; Gelfand, Mikhail S.

    2016-01-01

    The large and increasing volume of genomic data analyzed by comparative methods provides information about transcription factors and their binding sites that, in turn, enables statistical analysis of correlations between factors and sites, uncovering mechanisms and evolution of specific protein-DNA recognition. Here we present an online tool, Prot-DNA-Korr, designed to identify and analyze crucial protein-DNA pairs of positions in a family of transcription factors. Correlations are identified by analysis of mutual information between columns of protein and DNA alignments. The algorithm reduces the effects of common phylogenetic history and of abundance of closely related proteins and binding sites. We apply it to five closely related subfamilies of the MerR family of bacterial transcription factors that regulate heavy metal resistance systems. We validate the approach using known 3D structures of MerR-family proteins in complexes with their cognate DNA binding sites and demonstrate that a significant fraction of correlated positions indeed form specific side-chain-to-base contacts. The joint distribution of amino acids and nucleotides hence may be used to predict changes of specificity for point mutations in transcription factors. PMID:27690309

  10. MerR and ChrR mediate blue light induced photo-oxidative stress response at the transcriptional level in Vibrio cholerae

    PubMed Central

    Tardu, Mehmet; Bulut, Selma; Kavakli, Ibrahim Halil

    2017-01-01

    Blue light (BL) is a major environmental factor that affects the physiology, behavior, and infectivity of bacteria as it contributes to the generation of reactive oxygen species (ROS) while increasing photo-oxidative stress in cells. However, precise photo-oxidative response mechanism in non-phototrophic bacteria is yet to be elucidated. In this study, we investigated the effect of BL in Vibrio cholerae by using genetics and transcriptome profiling. Genome-wide analysis revealed that transcription of 6.3% of V. cholerae genes were regulated by BL. We further showed that BL enhances ROS production, which is generated through the oxidative phosphorylation. To understand signaling mechanisms, we generated several knockouts and analyzed their transcriptome under BL exposure. Studies with a double-knockout confirm an anti-sigma factor (ChrR) and putative metalloregulatory-like protein (MerR) are responsible for the genome-wide regulation to BL response in V. cholerae. Collectively, these results demonstrate that MerR-like proteins, in addition to ChrR, are required for V. cholerae to mount an appropriate response against photo-oxidative stress induced by BL. Outside its natural host, V. cholerae can survive for extended periods in natural aquatic environments. Therefore, the regulation of light response for V. cholerae may be a critical cellular process for its survival in these environments. PMID:28098242

  11. Mapping the Rust Resistant Loci MXC3 and MER in P. trichocarpa and Assessing the Intermarker Linkage Disequilibrium in MXC3 Region

    SciTech Connect

    Yin, Tongming; Difazio, Stephen P.; Gunter, Lee E; Tuskan, Gerald A

    2004-01-01

    In an attempt to elucidate the molecular mechanisms of Melampsora rust resistance in Populus trichocarpa, we have mapped two resistance loci, MXC3 and MER, and intensively characterized the flanking genomic sequence for the MXC3 locus and the level of linkage disequilibrium (LD) in natural populations. We used an interspecific backcross pedigree and a genetic map that was highly saturated with AFLP and SSR markers, and assembled shotgun-sequence data in the region containing markers linked to MXC3. The two loci were mapped to different linkage groups. Linkage disequilibrium for MXC3 was confined to two closely linked regions spanning 34 and 16 kb, respectively. The MXC3 region also contained six disease-resistance candidate genes. The MER and MXC3 loci are clearly distinct, and may have different mechanisms of resistance, as different classes of putative resistance genes were present near each locus. The suppressed recombination previously observed in the MXC3 region was possibly caused by extensive hemizygous rearrangements confined to the original parent tree. The relatively low observed LD may facilitate association studies using candidate genes for rust resistance, but will probably inhibit marker-aided selection.

  12. Development of Dual TaqMan Based One-Step rRT-PCR Assay Panel for Rapid and Accurate Diagnostic Test of MERS-CoV: A Novel Human Coronavirus, Ahead of Hajj Pilgrimage

    PubMed Central

    Hashemzadeh, Mohammad Sadegh; Rasouli, Rahimeh; Zahraei, Bentolhoda; Izadi, Morteza; Tat, Mahdi; Saadat, Seyed Hassan; Najarasl, Mohammad; Khansari Nejad, Behzad; Dorostkar, Ruhollah

    2016-01-01

    Background Coronaviruses (CoVs) are large ribonucleic acid (RNA) viruses causing primarily respiratory disease in humans. A novel human coronavirus, subsequently named middle east respiratory syndrome coronavirus (MERS-CoV), was first reported in Saudi Arabia in September of 2012. With increasing numbers of infections and deaths from MERS-CoV, development of a rapid and reliable kit was crucial to prevent further spread of MERS-CoV. Objectives In this study, we present two real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays for in-house rapid and sensitive diagnostic testing of MERS-CoV, detecting the regions upstream of the envelope gene (upE) and open reading frame (ORF) 1b, respectively, for initial screening and final confirmation of MERS-CoV infection, as recommended by the world health organization (WHO). Materials and Methods In this experimental study, acquiring patient samples was difficult; thus, according to WHO recommendations and standard protocols, we synthesized RNA sequences of upE and ORF1b genes as the template signatures and TaqMan based-diagnostic rRT-PCR assays were carried out using these synthetic genes for detection of MERS-CoV. In this research, we also inaugurated a cell-free system to transcribe these RNA sequences using the DNA templates synthesized. Results The upE and ORF1b based one-step rRT-PCR assays were optimized by testing several times via different synthetic RNAs, and validation results were highly successful. The sensitivity obtained for upE was fewer than ten copies of RNA template per reaction and for ORF1b was 50 or fewer copies per reaction. Conclusions This study showed that the developed rRT-PCR assays are rapid, reliable, reproducible, specific, sensitive, and simple tools for detection of MERS-CoV. Finally, a kit consisting of two assay signatures and controls was assembled, which can be distributed to public health laboratories in Iran to support international MERS-CoV surveillance and public

  13. The daily computed weighted averaging basic reproduction number R>0,k,ωn for MERS-CoV in South Korea

    NASA Astrophysics Data System (ADS)

    Jeong, Darae; Lee, Chang Hyeong; Choi, Yongho; Kim, Junseok

    2016-06-01

    In this paper, we propose the daily computed weighted averaging basic reproduction number R0,k,ωn for Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, May to July 2015. We use an SIR model with piecewise constant parameters β (contact rate) and γ (removed rate). We use the explicit Euler's method for the solution of the SIR model and a nonlinear least-square fitting procedure for finding the best parameters. In R0,k,ωn, the parameters n, k, and w denote days from a reference date, the number of days in averaging, and a weighting factor, respectively. We perform a series of numerical experiments and compare the results with the real-world data. In particular, using the predicted reproduction number based on the previous two consecutive reproduction numbers, we can predict the future behavior of the reproduction number.

  14. k-merSNP discovery: Software for alignment-and reference-free scalable SNP discovery, phylogenetics, and annotation for hundreds of microbial genomes

    SciTech Connect

    2014-11-18

    With the flood of whole genome finished and draft microbial sequences, we need faster, more scalable bioinformatics tools for sequence comparison. An algorithm is described to find single nucleotide polymorphisms (SNPs) in whole genome data. It scales to hundreds of bacterial or viral genomes, and can be used for finished and/or draft genomes available as unassembled contigs or raw, unassembled reads. The method is fast to compute, finding SNPs and building a SNP phylogeny in minutes to hours, depending on the size and diversity of the input sequences. The SNP-based trees that result are consistent with known taxonomy and trees determined in other studies. The approach we describe can handle many gigabases of sequence in a single run. The algorithm is based on k-mer analysis.

  15. Predicting protein structural class by incorporating patterns of over-represented k-mers into the general form of Chou's PseAAC.

    PubMed

    Qin, Yu-Fang; Wang, Chun-Hua; Yu, Xiao-Qing; Zhu, Jie; Liu, Tai-Gang; Zheng, Xiao-Qi

    2012-04-01

    Computational prediction of protein structural class based on sequence data remains a challenging problem in current protein science. In this paper, a new feature extraction approach based on relative polypeptide composition is introduced. This approach could take into account the background distribution of a given k-mer under a Markov model of order k-2, and avoid the curse of dimensionality with the increase of k by using a T-statistic feature selection strategy. The selected features are then fed to a support vector machine to perform the prediction. To verify the performance of our method, jackknife cross-validation tests are performed on four widely used benchmark datasets. Comparison of our results with existing methods shows that our method provides satisfactory performance for structural class prediction.

  16. Two new hemoglobin variants: Hb Brem-sur-Mer [beta9(A6)Ser-->Tyr] and Hb Passy [alpha81(F2)Ser-->Pro (alpha2)].

    PubMed

    Lacan, Philippe; Moreau, Mathieu; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Louis, Jean-Jacques; Couprie, Nicole; Francina, Alain

    2005-01-01

    Two new hemoglobin (Hb) variants: Hb Brem-sur-Mer [codon 9 (TCT-->TAT); beta9(A6)Ser-->Tyr] on the first exon of the beta-globin gene and Hb Passy [codon 81 (TCC-->CCC); alpha81(F2)Ser-->Pro (alpha2)] on the second exon of the alpha2-globin gene, are described. The two variants were characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities: microcytosis and hypochromia were found only in the carrier of Hb Passy. In the absence of an association with an alpha-thalassemic deletion or mutation, the mutation 81(F2)Pro could induce a possible alpha-thalassemia (thal).

  17. “Don’t forget the migrants”: exploring preparedness and response strategies to combat the potential spread of MERS-CoV virus through migrant workers in Sri Lanka

    PubMed Central

    Agampodi, Suneth B

    2013-01-01

    From September 2012 to July 2013, 81 laboratory-confirmed cases of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), including 45 deaths (a case fatality ratio of 55%) have been reported from eight countries. Human-to-human transmission is now confirmed showing potential for another pandemic of zoonotic disease, with an extremely high mortality rate. Effective surveillance strategies are required in countries with a high influx of migrants from the Middle East to mitigate the probable importation of MERS-CoV. We discuss here the risk of MERS-CoV in major labor sending countries and list the probable strategies for control and prevention of MERS-CoV using Sri Lanka as an example. It is conservatively estimated that 10% of Sri Lanka’s population work as international labor migrants (1.8 to 2 million workers), with 93% residing in the Middle East. An average of 720 workers depart each day, with the majority of these workers (71%) departing to the Kingdom of Saudi Arabia (the country with 81.5% of total MERS-CoV cases). We also describe other inbound migration categories such as tourists and resident visa holders relevant to the context of preparedness and planning. The importance of partnerships between public health authorities at national and regional levels with labor migration networks to establish institutional and/or policy mechanisms are highlighted for ensuring effective preparedness and response planning. Strategies that can be taken by public health authorities working in both labor sending and labor receiving counties are also described.  The strategies described here may be useful for other labor sending country contexts in Asia with a high frequency and volume of migrant workers to and from the Gulf region. PMID:24555078

  18. Sulfur concentrations of the Martian surface derived from orbital Mars Odyssey GRS and in-situ MER APXS measurements: implications on the selection of future landing sites

    NASA Astrophysics Data System (ADS)

    Brueckner, J.; Karunatillake, S.; Hamara, D.; Boynton, W. V.

    2009-12-01

    Since the year 2002, the NASA Mars Odyssey spacecraft (MO) has mapped continuously the entire surface of Mars with its Gamma-Ray Spectrometer (GRS) instrument suite to obtain global concentration maps of different elements. Since January 2004, the NASA Mars Exploration Rovers (MER) Spirit and Opportunity have driven several kilometers at two different landing sites, Gusev crater and Meridiani Planum (180 degrees apart). Each rover made chemical measurements of a range of samples using its Alpha Particle X-Ray Spectrometer (APXS). Distinctive differences between the two instruments are that APXS has a penetration depth of micrometers and a field of view of centimeters vs. tens of centimeters and 500 km for the GRS, respectively. We compare the sulfur concentration determined by the APXS with its GRS counterpart at each MER site. In-situ APXS measurements of soils in Gusev and Meridiani show similar mean S mass fractions, 2.6 and 2.2 % respectively. Abraded rocks in Gusev have a mean S concentration of 1 %. Large enrichments of S were discovered in some subsurface soils in Gusev, which may be confined to smaller areas. In Meridiani, the abraded sedimentary rocks show high S concentrations (up to 12 wt-%). Chemical provinces were delineated - without a priori assumptions on their nature and extent - using GRS datasets. The GRS footprint at Gusev belongs to a chemical province defined by a striking enrichment of Cl and H. Meridiani is remarkable for Ca depletion and H enrichment. Renormalizing to a volatile-free basis, Meridiani is within a distinct province. At the MER landing sites, the large GRS footprint measures comparable S concentrations. The high S contents of the Meridiani sediments are not seen by the GRS. This may be due in part to the negligible area of crater walls relative to soil cover when projected vertically. When orbital data show regional deviation of S (or other elements) relative to the global average, in-situ inspection should reveal a

  19. Comparing Apollo and Mars Exploration Rover (MER)/phoenix operations paradigms for human exploration during NASA Desert-RATS science operations

    NASA Astrophysics Data System (ADS)

    Yingst, R. A.; Cohen, B. A.; Ming, D. W.; Eppler, D. B.

    2013-10-01

    The Desert Research and Technology Studies (D-RATS) field tested two models of human-in-the-loop remote field geology: one based on the Apollo science backroom that integrated tactical and strategic decisions, and one that separated tactical and strategic processes as utilized during the Mars Exploration Rovers (MER) and Mars Phoenix Scout missions. The 2010 D-RATS field test was the first attempt at integrating best practices from these two models, to determine how best to maximize science return from future missions. The Apollo model was utilized in 2008 and 2009 as a way to integrate science into field analog studies; the model allowed for real time communications between the crew on the surface and the scientists in the backroom. This model greatly improved efficiency of field operations and scientific return, but did not allow sufficient time for hypotheses to mature to the point where they could inform operations. The MER/Phoenix model, adapted for the 2010 D-RATS test, divided the responsibilities and processes of tactical science and strategic science. This division provided opportunities to discuss science results in greater detail so that the overall planning of science observations could be iterative rather than static. However, because of the nearly complete separation of the two science teams, there was a great deal of repeated effort as the strategic team had no prior knowledge of the tactical process and the observations that led to certain tactical decisions. Lessons learned from 2010 D-RATS science operations include: (1) well-trained geologists on the crew and a science backroom with which that crew can interact are both critical components for maximizing science return; (2) sufficient time or another mechanism that increases time available to be spent on science analysis must be built into the system to allow free rein to the scientific process; (3) data flow must be improved so that time is not wasted in repetitive review of acquired datasets

  20. Multiplex paper-based colorimetric DNA sensor using pyrrolidinyl peptide nucleic acid-induced AgNPs aggregation for detecting MERS-CoV, MTB and HPV oligonucleotides.

    PubMed

    Tee-Ngam, Prinjaporn; Siangproh, Weena; Tuantranont, Adisorn; Vilaivan, Tirayut; Chailapakul, Orawon; Henry, Charles S

    2017-04-10

    The development of simple fluorescent and colorimetric assays that enable point-of-care DNA and RNA detection has been a topic of significant research because of the utility of such assays in resource limited settings. The most common motifs utilize hybridization to a complementary detection strand coupled with a sensitive reporter molecule. Here, apaper-based colorimetric assay for DNA detection based on pyrrolidinyl peptide nucleic acid (acpcPNA)-induced nanoparticle aggregationis reported as an alternative to traditional colorimetric approaches. PNA probes are an attractive alternative to DNA and RNA probes because they are chemically and biologically stable, easily synthesized, and hybridize efficiently with the complementary DNA strands. The acpcPNA probe contains a single positive charge from the lysine at C-terminus and causes aggregation of citrate anion-stabilized silver nanoparticles (AgNPs) in the absence of complementary DNA. In the presence of target DNA, formation of the anionic DNA-acpcPNA duplex results in dispersion of the AgNPs as a result of electrostatic repulsion, giving rise to a detectable color change. Factors affecting the sensitivity and selectivity of this assay were investigated, including ionic strength, AgNP concentration, PNA concentration, and DNA strand mismatches. The method was used for screening of synthetic Middle East respiratory syndrome coronavirus (MERS-CoV), mycobacterium tuberculosis (MTB) and human papillomavirus (HPV)DNA based on a colorimetric paper-based analytical device developed using the aforementioned principle. The oligonucleotide targets were detected by measuring the color change of AgNPs, giving detection limits of 1.53 nM (MERS-CoV), 1.27 nM (MTB) and 1.03 nM (HPV).The acpcPNA probe exhibited high selectivity for the complementary oligonucleotides over single-base-mismatch, two-base-mismatch and non-complementary DNA targets. The proposed paper-based colorimetric DNA sensor has potential to be an alternative

  1. Calendar-dated glacier variations in the western European Alps during the Neoglacial: the Mer de Glace record, Mont Blanc massif

    NASA Astrophysics Data System (ADS)

    Le Roy, Melaine; Nicolussi, Kurt; Deline, Philip; Astrade, Laurent; Edouard, Jean-Louis; Miramont, Cécile; Arnaud, Fabien

    2015-01-01

    Holocene glacier records from the western European Alps are still sparse, although a number of sites are well suited to constraining pre- and early- Little Ice Age (LIA) glacier advances. The present study provides the first dendrochronologically-based and calendar-dated Neoglacial glacier chronology for the Mont Blanc massif, French Alps. It is based on the analysis of over 240 glacially buried Pinus cembra subfossil logs and wood remains found either embedded-in-till or as detrital material in the Mer de Glace right lateral moraine. Only a few of the samples were found to be 'formally in situ' but we show that some logs were 'virtually in situ' (not rooted but showing little or no evidence of reworking) and could be used to accurately reconstruct past glacier margin behavior in space and time. Uncertainties regarding the other samples may relate to original growth location and/or to outer wood decay. The resulting dates (followed by a '+') were therefore considered maximum-limiting ages for glacier advances. The main burial events - interpreted as glacier advances - occurred between ca 1655+ and 1544+ BC, between ca 1230+ and 1105+ BC, between ca 1013+ and 962+/937+ BC, at ca 802-777 BC, after 608+ BC, between 312 and 337 AD, between ca 485+ AD and 606+ AD, between 1120 and 1178 AD, between ca 1248 and 1278+/1296 AD, and after 1352+ AD. These advances predate the late LIA maxima known from historical sources. The magnitude of the advances gradually increased to culminate in three near-Neoglacial maxima during the 7th, 12th and 13th centuries AD, followed by a first LIA/Neoglacial maximum in the second half of the 14th century AD. The pattern of Neoglacial events described here is coherent with Central and Eastern Alpine glacier chronologies. This indicates marked synchronicity of late Holocene glacier variability and forcing at a regional scale, although occasional differences could be detected between 'Western' and 'Eastern' records. The Mer de Glace record also

  2. Viral Phylogenomics Using an Alignment-Free Method: A Three-Step Approach to Determine Optimal Length of k-mer

    PubMed Central

    Zhang, Qian; Jun, Se-Ran; Leuze, Michael; Ussery, David; Nookaew, Intawat

    2017-01-01

    The development of rapid, economical genome sequencing has shed new light on the classification of viruses. As of October 2016, the National Center for Biotechnology Information (NCBI) database contained >2 million viral genome sequences and a reference set of ~4000 viral genome sequences that cover a wide range of known viral families. Whole-genome sequences can be used to improve viral classification and provide insight into the viral “tree of life”. However, due to the lack of evolutionary conservation amongst diverse viruses, it is not feasible to build a viral tree of life using traditional phylogenetic methods based on conserved proteins. In this study, we used an alignment-free method that uses k-mers as genomic features for a large-scale comparison of complete viral genomes available in RefSeq. To determine the optimal feature length, k (an essential step in constructing a meaningful dendrogram), we designed a comprehensive strategy that combines three approaches: (1) cumulative relative entropy, (2) average number of common features among genomes, and (3) the Shannon diversity index. This strategy was used to determine k for all 3,905 complete viral genomes in RefSeq. The resulting dendrogram shows consistency with the viral taxonomy of the ICTV and the Baltimore classification of viruses. PMID:28102365

  3. Potential toxicity of resuspended particulate matter and sediments: Environmental samples from the Bay of Banyuls-sur-Mer and Thermaikos Gulf

    NASA Astrophysics Data System (ADS)

    Cotou, E.; Gremare, A.; Charles, F.; Hatzianestis, I.; Sklivagou, E.

    2005-12-01

    This contribution attempts to determine whether, and to what degree, environmental samples of resuspended particulate matter and sediments exert a toxicological impact. Further, an attempt is made also to screen the toxic level of potentially hazardous sites, based upon established sediment toxicity criteria. Therefore, a rapid, cost-effective and highly sensitive biotest (bioluminescence assay, based upon marine bacteria) has been applied on: biological fluid extracts; bottom sediments; and sediment trap samples. Samples were taken either from the Bay of Banyuls-sur-Mer (northwestern Mediterranean, France) or Thermaikos Gulf (northeastern Mediterranean, Greece). Biological fluid extracts and sediment trap samples corresponded to periods of resuspension events, or preceding and following such events. The results have revealed that the sampling strategy and biotest implemented in this study might be a useful tool for screening the toxicity of resuspended matter and sediments. Resuspension events appear to be able to exert an influence on the chemical forms of the micro-pollutants; thus on their bioavailability and toxicity. Nevertheless, based upon chemical analysis combined with the bioassay, the toxic level of the sediment samples could be determined, with the level at potentially hazardous sites being characterised.

  4. Flexible, ab initio potential, and dipole moment surfaces for water. I. Tests and applications for clusters up to the 22-mer.

    PubMed

    Wang, Yimin; Huang, Xinchuan; Shepler, Benjamin C; Braams, Bastiaan J; Bowman, Joel M

    2011-03-07

    We report full-dimensional, ab initio potential energy and dipole moment surfaces, denoted PES and DMS, respectively, for arbitrary numbers of water monomers. The PES is a sum of 1-, 2-, and 3-body potentials which can also be augmented by semiempirical long-range higher-body interactions. The 1-body potential is a spectroscopically accurate monomer potential, and the 2- and 3-body potentials are permutationally invariant fits to tens of thousands of CCSD(T)/aug-cc-pVTZ and MP2/aug-cc-pVTZ electronic energies, respectively. The DMS is a sum of 1- and 2-body DMS, which are covariant fits to tens of thousands MP2/aug-cc-pVTZ dipole moment data. We present the details of these new 2- and 3-body potentials and then extensive applications and tests of this PES are made to the structures, classical binding energies, and harmonic frequencies of water clusters up to the 22-mer. In addition, we report the dipole moment for these clusters at various minima and compare the results against available and new ab initio calculations.

  5. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

    PubMed

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-04-22

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection.

  6. Development and optimisation of a generic micro LC-ESI-MS method for the qualitative and quantitative determination of 30-mer toxic gliadin peptides in wheat flour for food analysis.

    PubMed

    Vatansever, Bilgin; Muñoz, Amalia; Klein, Christoph L; Reinert, Knut

    2017-02-01

    We sometimes see manufactured bakery products on the market which are labelled as being gluten free. Why is the content of such gluten proteins of importance for the fabrication of bakery industry and for the products? The gluten proteins represent up to 80 % of wheat proteins, and they are conventionally subdivided into gliadins and glutenins. Gliadins belong to the proline and glutamine-rich prolamin family. Its role in human gluten intolerance, as a consequence of its harmful effects, is well documented in the scientific literature. The only known therapy so far is a gluten-free diet, and hence, it is important to develop robust and reliable analytical methods to quantitatively assess the presence of the identified peptides causing the so-called coeliac disease. This work describes the development of a new, fast and robust micro ion pair-LC-MS analytical method for the qualitative and quantitative determination of 30-mer toxic gliadin peptides in wheat flour. The use of RapiGest™ SF as a denaturation reagent prior to the enzymatic digestion showed to shorten the measuring time. During the optimisation of the enzymatic digestion step, the best 30-mer toxic peptide was identified from the maximum recovery after 3 h of digestion time. The lower limit of quantification was determined to be 0.25 ng/μL. The method has shown to be linear for the selected concentration range of 0.25-3.0 ng/μL. The uncertainty related to reproducibility of measurement procedure, excluding the extraction step, has shown to be 5.0 % (N = 12). Finally, this method was successfully applied to the quantification of 30-mer toxic peptides from commercial wheat flour with an overall uncertainty under reproducibility conditions of 6.4 % including the extraction of the gliadin fraction. The results were always expressed as the average of the values from all standard concentrations. Subsequently, the final concentration of the 30-mer toxic peptide in the flour was calculated and

  7. Photochemistry in a 3D metal-organic framework (MOF): monitoring intermediates and reactivity of the fac-to-mer photoisomerization of Re(diimine)(CO)3Cl incorporated in a MOF.

    PubMed

    Easun, Timothy L; Jia, Junhua; Calladine, James A; Blackmore, Danielle L; Stapleton, Christopher S; Vuong, Khuong Q; Champness, Neil R; George, Michael W

    2014-03-03

    The mechanism and intermediates in the UV-light-initiated ligand rearrangement of fac-Re(diimine)(CO)3Cl to form the mer isomer, when incorporated into a 3D metal-organic framework (MOF), have been investigated. The structure hosting the rhenium diimine complex is a 3D network with the formula {Mn(DMF)2[LRe(CO)3Cl]}∞ (ReMn; DMF = N,N-dimethylformamide), where the diimine ligand L, 2,2'-bipyridine-5,5'-dicarboxylate, acts as a strut of the MOF. The incorporation of ReMn into a KBr disk allows spatial distribution of the mer-isomer photoproduct in the disk to be mapped and spectroscopically characterized by both Fourier transform infrared and Raman microscopy. Photoisomerization has been monitored by IR spectroscopy and proceeds via dissociation of a CO to form more than one dicarbonyl intermediate. The dicarbonyl species are stable in the solid state at 200 K. The photodissociated CO ligand appears to be trapped within the crystal lattice and, upon warming above 200 K, readily recombines with the dicarbonyl intermediates to form both the fac-Re(diimine)(CO)3Cl starting material and the mer-Re(diimine)(CO)3Cl photoproduct. Experiments over a range of temperatures (265-285 K) allow estimates of the activation enthalpy of recombination for each process of ca. 16 (±6) kJ mol(-1) (mer formation) and 23 (±4) kJ mol(-1) (fac formation) within the MOF. We have compared the photochemistry of the ReMn MOF with a related alkane-soluble Re(dnb)(CO)3Cl complex (dnb = 4,4'-dinonyl-2,2'-bipyridine). Time-resolved IR measurements clearly show that, in an alkane solution, the photoinduced dicarbonyl species again recombines with CO to both re-form the fac-isomer starting material and form the mer-isomer photoproduct. Density functional theory calculations of the possible dicarbonyl species aids the assignment of the experimental data in that the ν(CO) IR bands of the CO loss intermediate are, as expected, shifted to lower energy when the metal is bound to DMF rather than to an

  8. Assessment by regional modelling of the impact of monopile foundations on the hydrodynamics and sediment transport: case of Courseulles-sur-Mer (France) wind farm

    NASA Astrophysics Data System (ADS)

    Rivier, Aurélie; Bennis, Anne-Claire; Pinon, Grégory; Magar, Vanesa; Gross, Markus

    2015-04-01

    Offshore monopile foundations of wind turbines modify hydrodynamics and sediment transport at local scale and also at regional scale. The aim of this work is to assess these changes and to parametrize them in a regional model. These modifications were previously evaluated using the regional circulation model MARS3D (Lazure and Dumas, 2008) in tests-cases (Rivier et al., 2014) using two approaches: in the first approach, monopiles are explicitly modelled in the mesh as dry cells and in the second approach a sub-grid parametrization which considers the drag force exerted by a monopile on the flow is used. The sub-grid parametrization is improved close to the bed in this paper by adding a drag force term in the momentum equations, source terms in the turbulence model and by increasing the bed shear stress at monopile location. Changes in hydrodynamics regime, especially near-bed, affect sediment transport regime and modifications due to monopiles on sediment dynamics is also investigated using the MARS3D sediment transport module (Le Hir et al., 2011) which solves the advection-diffusion equations. Test-cases are run using hydrodynamical conditions and sediment grain sizes typical from the area located off Courseulles-sur-Mer (Normandy, France) where an offshore wind farm is planned to be built. Velocity, turbulent kinetic energy and bed thickness changes due to the monopile simulated by both approaches are compared to each other and to experimental measurements made in a flume at the University of Caen or to published data (e.g. Roulund et al., 2005; Dargahi,1989). Then the model is applied in a real configuration on an area including the future offshore wind farm of Courseulles-sur-Mer. Four monopiles are represented in the model using both approaches and modifications of the hydrodynamics and sediment transport are assessed along a tidal cycle. Currents increase at the side edge of the monopile and decrease in front of and downstream the monopile. Turbulent kinetic

  9. The MerR-like regulator BrlR confers biofilm tolerance by activating multidrug efflux pumps in Pseudomonas aeruginosa biofilms.

    PubMed

    Liao, Julie; Schurr, Michael J; Sauer, Karin

    2013-08-01

    A defining characteristic of biofilms is antibiotic tolerance that can be up to 1,000-fold greater than that of planktonic cells. In Pseudomonas aeruginosa, biofilm tolerance to antimicrobial agents requires the biofilm-specific MerR-type transcriptional regulator BrlR. However, the mechanism by which BrlR mediates biofilm tolerance has not been elucidated. Genome-wide transcriptional profiling indicated that brlR was required for maximal expression of genes associated with antibiotic resistance, in particular those encoding the multidrug efflux pumps MexAB-OprM and MexEF-OprN. Chromatin immunoprecipitation (ChIP) analysis revealed a direct regulation of these genes by BrlR, with DNA binding assays confirming BrlR binding to the promoter regions of the mexAB-oprM and mexEF-oprN operons. Quantitative reverse transcriptase PCR (qRT-PCR) analysis further indicated BrlR to be an activator of mexAB-oprM and mexEF-oprN gene expression. Moreover, immunoblot analysis confirmed increased MexA abundance in cells overexpressing brlR. Inactivation of both efflux pumps rendered biofilms significantly more susceptible to five different classes of antibiotics by affecting MIC but not the recalcitrance of biofilms to killing by bactericidal agents. Overexpression of either efflux pump in a ΔbrlR strain partly restored tolerance of ΔbrlR biofilms to antibiotics. Expression of brlR in mutant biofilms lacking both efflux pumps partly restored antimicrobial tolerance of biofilms to wild-type levels. Our results indicate that BrlR acts as an activator of multidrug efflux pumps to confer tolerance to P. aeruginosa biofilms and to resist the action of antimicrobial agents.

  10. Strongly structured DNA sequences as targets for genosensing: sensing phase design and coupling to PCR amplification for a highly specific 33-mer gliadin DNA fragment.

    PubMed

    Martín-Fernández, Begoña; Miranda-Ordieres, Arturo J; Lobo-Castañón, María Jesús; Frutos-Cabanillas, Gloria; de-los-Santos-Álvarez, Noemí; López-Ruiz, Beatriz

    2014-10-15

    Electrochemical genosensors are becoming cost-effective miniaturizable alternatives to real-time PCR (RT-PCR) methods for the detection of sequence-specific DNA fragments. We report on the rapid detection of PCR amplicons without the need of purification or strand separation. A challenging target sequence for both PCR amplification and electrochemical detection allowed us to address some difficulties associated to hybridization on electrode surfaces. The target was a highly specific oligonucleotide sequence of wheat encoding the most immunogenic peptide of gliadin that triggers the immune response of celiac disease (CD), the 33-mer. With a sandwich assay format and a rational design of the capture and tagged-signaling probes the problems posed by the strong secondary structure of the target and complementary probes were alleviated. Using a binary self-assembled monolayer and enzymatic amplification, a limit of detection of 0.3 nM was obtained. The genosensor did not respond to other gluten-containing cereals such as rye and barley. Coupling to PCR to analyze wheat flour samples required tailoring both the capture and signaling probes. This is the first time that deleterious steric hindrance from long single-stranded regions adjacent to the electrode surface is reported for relatively short amplicons (less than 200 bp). The importance of the location of the recognition site within the DNA sequence is discussed. Since the selected gene fragment contains several repetitions of short sequences, a careful optimization of the PCR conditions had to be performed to circumvent the amplification of non-specific fragments from wheat flour.

  11. Nutrient Addition Leads to a Weaker CO2 Sink and Higher CH4 Emissions through Vegetation-Microclimate Feedbacks at Mer Bleue Bog, Canada

    NASA Astrophysics Data System (ADS)

    Bubier, J. L.; Arnkil, S.; Humphreys, E.; Juutinen, S.; Larmola, T.; Moore, T. R.

    2015-12-01

    Atmospheric nitrogen (N) deposition has led to nutrient enrichment in wetlands globally, affecting plant community composition, carbon (C) cycling, and microbial dynamics. Nutrient-limited boreal bogs are long-term sinks of carbon dioxide (CO2), but sources of methane (CH4), an important greenhouse gas. We fertilized Mer Bleue Bog, a Sphagnum moss and evergreen shrub-dominated ombrotrophic bog near Ottawa, Ontario, for 10-15 years with N as NO3 and NH4 at 5, 10 and 20 times ambient N deposition (0.6-0.8 g N m-2 y-1), with and without phosphorus (P) and potassium (K). Treatments were applied to triplicate plots (3 x 3 m) from May - August 2000-2015 and control plots received distilled water. We measured net ecosystem CO2 exchange (NEE), ecosystem photosynthesis and respiration, and CH4 flux with climate-controlled chambers; leaf-level CO2 exchange and biochemistry; substrate-induced respiration, CH4 production and consumption potentials with laboratory incubations; plant species composition and abundance; and microclimate (peat temperature, moisture, light interception). After 15 years, we have found that NEE has decreased, and CH4 emissions have increased, in the highest nutrient treatments owing to changes in vegetation, microtopography, and peat characteristics. Vegetation changes include a loss of Sphagnum moss and introduction of new deciduous species. Simulated atmospheric N deposition has not benefitted the photosynthetic apparatus of the dominant evergreen shrubs, but resulted in higher foliar respiration, contributing to a weaker ecosystem CO2 sink. Loss of moss has led to wetter near-surface substrate, higher rates of decomposition and CH4 emission, and a shift in microbial communities. Thus, elevated atmospheric deposition of nutrients may endanger C storage in peatlands through a complex suite of feedbacks and interactions among vegetation, microclimate, and microbial communities.

  12. A β-hairpin structure in a 13-mer peptide that binds α-bungarotoxin with high affinity and neutralizes its toxicity

    PubMed Central

    Scherf, Tali; Kasher, Roni; Balass, Moshe; Fridkin, Mati; Fuchs, Sara; Katchalski-Katzir, Ephraim

    2001-01-01

    Snake-venom α-bungarotoxin is a member of the α-neurotoxin family that binds with very high affinity to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. The structure of the complex between α-bungarotoxin and a 13-mer peptide (WRYYESSLEPYPD) that binds the toxin with high affinity, thus inhibiting its interactions with AChR with an IC50 of 2 nM, has been solved by 1H-NMR spectroscopy. The bound peptide folds into a β-hairpin structure created by two antiparallel β-strands, which combine with the already existing triple-stranded β-sheet of the toxin to form a five-stranded intermolecular, antiparallel β-sheet. Peptide residues Y3P, E5P, and L8P have the highest intermolecular contact area, indicating their importance in the binding of α-bungarotoxin; W1P, R2P, and Y4P also contribute significantly to the binding. A large number of characteristic hydrogen bonds and electrostatic and hydrophobic interactions are observed in the complex. The high-affinity peptide exhibits inhibitory potency that is better than any known peptide derived from AChR, and is equal to that of the whole α-subunit of AChR. The high degree of sequence similarity between the peptide and various types of AChRs implies that the binding mode found within the complex might possibly mimic the receptor binding to the toxin. The design of the high-affinity peptide was based on our previous findings: (i) the detection of a lead peptide (MRYYESSLKSYPD) that binds α-bungarotoxin, using a phage-display peptide library, (ii) the information about the three-dimensional structure of α-bungarotoxin/lead-peptide complex, and (iii) the amino acid sequence analysis of different AChRs. PMID:11381118

  13. Numerical modelling of circulation and dispersion processes in Boulogne-sur-Mer harbour (Eastern English Channel): sensitivity to physical forcing and harbour design

    NASA Astrophysics Data System (ADS)

    Jouanneau, Nicolas; Sentchev, Alexei; Dumas, Franck

    2013-12-01

    The MARS-3D model in conjunction with the particle tracking module Ichthyop is used to study circulation and tracer dynamics under a variety of forcing conditions in the eastern English Channel, and in the Boulogne-sur-Mer harbour (referred to hereafter as BLH). Results of hydrodynamic modelling are validated against the tidal gauge data, VHF radar surface velocities and ADCP measurements. Lagrangian tracking experiments are performed with passive particles to study tracer dispersal along the northern French coast, with special emphasis on the BLH. Simulations revealed an anticyclonic eddy generated in the harbour at rising tide. Tracers, released during flood tide at the Liane river mouth, move northward with powerful clockwise rotating current. After the high water, the current direction changes to westward, and tracers leave the harbour through the open boundary. During ebb tide, currents convergence along the western open boundary but no eddy is formed, surface currents inside the harbour are much weaker and the tracer excursion length is small. After the current reversal at low water, particles are advected shoreward resulting in a significant increase of the residence time of tracers released during ebb tide. The effect of wind on particle dispersion was found to be particularly strong. Under strong SW wind, the residence time of particles released during flood tide increases from 1.5 to 6 days. For release during ebb tide, SW wind weakens the southward tidally induced drift and thus the residence time decreases. Similar effects are observed when the freshwater inflow to the harbour is increased from 2 to 10 m3/s during the ebb tide flow. For flood tide conditions, the effect of freshwater inflow is less significant. We also demonstrate an example of innovative coastal management targeted at the reduction of the residence time of the pathogenic material accidentally released in the harbour.

  14. The MerR-Like Regulator BrlR Confers Biofilm Tolerance by Activating Multidrug Efflux Pumps in Pseudomonas aeruginosa Biofilms

    PubMed Central

    Liao, Julie; Schurr, Michael J.

    2013-01-01

    A defining characteristic of biofilms is antibiotic tolerance that can be up to 1,000-fold greater than that of planktonic cells. In Pseudomonas aeruginosa, biofilm tolerance to antimicrobial agents requires the biofilm-specific MerR-type transcriptional regulator BrlR. However, the mechanism by which BrlR mediates biofilm tolerance has not been elucidated. Genome-wide transcriptional profiling indicated that brlR was required for maximal expression of genes associated with antibiotic resistance, in particular those encoding the multidrug efflux pumps MexAB-OprM and MexEF-OprN. Chromatin immunoprecipitation (ChIP) analysis revealed a direct regulation of these genes by BrlR, with DNA binding assays confirming BrlR binding to the promoter regions of the mexAB-oprM and mexEF-oprN operons. Quantitative reverse transcriptase PCR (qRT-PCR) analysis further indicated BrlR to be an activator of mexAB-oprM and mexEF-oprN gene expression. Moreover, immunoblot analysis confirmed increased MexA abundance in cells overexpressing brlR. Inactivation of both efflux pumps rendered biofilms significantly more susceptible to five different classes of antibiotics by affecting MIC but not the recalcitrance of biofilms to killing by bactericidal agents. Overexpression of either efflux pump in a ΔbrlR strain partly restored tolerance of ΔbrlR biofilms to antibiotics. Expression of brlR in mutant biofilms lacking both efflux pumps partly restored antimicrobial tolerance of biofilms to wild-type levels. Our results indicate that BrlR acts as an activator of multidrug efflux pumps to confer tolerance to P. aeruginosa biofilms and to resist the action of antimicrobial agents. PMID:23687276

  15. Induction of eEF2-specific antitumor CTL responses in vivo by vaccination with eEF2-derived 9mer-peptides.

    PubMed

    Nakajima, Hiroko; Murakami, Yui; Morii, Eiichi; Akao, Toshiki; Tatsumi, Naoya; Odajima, Satoko; Fukuda, Mari; Machitani, Takao; Iwai, Miki; Kawata, Sayo; Hojo, Nozomi; Oka, Yoshihiro; Sugiyama, Haruo; Oji, Yusuke

    2016-04-01

    Eukaryotic elongation factor 2 (eEF2) is an essential factor for protein synthesis. Previous studies have shown that the eEF2 gene was overexpressed and plays an oncogenic role in various types of cancers and that eEF2 gene product elicited both humoral immune responses to produce eEF2-specific IgG autoantibody in cancer-bearing individuals and cellular immune responses to induce eEF2 peptide-specific cytotoxic T lymphocytes (CTLs) in vitro. The purpose of the present study was to induce eEF2-specific, antitumor CTL responses in vivo by vaccination with MHC class I-binding eEF2-derived peptide. First, two mouse MHC class I-restricted eEF2‑derived, 9-mer peptides, EF17 (17-25 aa, ANIRNMSVI) and EF180 (180-188 aa, RIVENVNVI) were identified as eEF2-specific CTL peptides, and mice were vaccinated intradermally eight times with either EF17 or EF180 peptide emulsified with Montanide ISA51 adjuvant. Cytotoxicity assay showed that eEF2-specific CTLs were induced in both EF17‑and EF180‑vaccinated mice, and histological study showed no detectable damage in the organs of these mice. Next, to examine in vivo antitumor effects of eEF2 peptide vaccination in a therapeutic model, mice were vaccinated four times with one each of the two eEF2 peptides at weekly intervals after implantation of eEF2-expressing leukemia cells. The vaccination with eEF2 peptides induced eEF2-specific CTLs and suppressed tumor growth, and disease-free survival was significantly longer in EF180-vaccinated mice compared to control mice. The survival was associated with the robustness of eEF2-specific CTL induction. These results indicate that vaccination with MHC class I-binding eEF2 peptide induced eEF2-targeting, antitumor CTL responses in vivo without damage to normal organs, which provided us a rationale for eEF2 peptide-based cancer immunotherapy.

  16. Human full-length coagulation factor X and a GLA domain-derived 40-mer polypeptide bind to different regions of the adenovirus serotype 5 hexon capsomer.

    PubMed

    Sumarheni, Sudir; Hong, Saw See; Josserand, Véronique; Coll, Jean-Luc; Boulanger, Pierre; Schoehn, Guy; Fender, Pascal

    2014-04-01

    The interaction of human adenovirus (HAdV)-C5 and many other adenoviruses with blood coagulation factors (e.g., human factor X, FX) involves the binding of their GLA domain to the hexon capsomers, resulting in high levels of hepatotropism and potential hepatotoxicity. In this study, we tested the possibility of preventing these undesirable effects by using a GLA-mimicking peptide as a competitor. An FX GLA domain-derived, 40-mer polypeptide carrying 12 carboxyglutamate residues was synthesized (GLA(mim)). Surface plasmon resistance (SPR) analysis showed that GLA(mim) reacted with free and capsid-embedded hexon with a nanomolar affinity. Unexpectedly, GLA(mim) failed to compete with FX for hexon binding, and instead significantly increased the formation of FX-hexon or FX-adenovirion complexes. This observation was confirmed by in vitro cell transduction experiments using HAdV-C5-Luciferase vector (HAdV5-Luc), as preincubation of HAdV5-Luc with GLA(mim) before FX addition resulted in a higher transgene expression compared with FX alone. HAdV-C5 virions complexed with GLA(mim) were analyzed by cryoelectron microscopy. Image reconstruction demonstrated the bona fide hexon-GLA(mim) interaction, as for the full-length FX, although with considerable differences in stoichiometry and relative location on the hexon capsomer. Three extra densities were found at the periphery of each hexon, whereas one single FX molecule occupied the central cavity of the hexon trimeric capsomer. A refined analysis indicated that each extra density is found at the expected location of one highly variable loop 1 of the hexon, involved in scavenger receptor recognition. HAdV5-Luc complexed with a bifunctional GLA(mim)RGD peptide showed a lesser hepatotropism, compared with control HAdV5-Luc alone, and efficiently targeted αβ-integrin-overexpressing tumor cells in an in vivo mouse tumor model. Collectively, our findings open new perspectives in the design of adenoviral vectors for biotherapy.

  17. Statistical properties and time-frequency analysis of temperature, salinity and turbidity measured by the MAREL Carnot station in the coastal waters of Boulogne-sur-Mer (France)

    NASA Astrophysics Data System (ADS)

    Kbaier Ben Ismail, Dhouha; Lazure, Pascal; Puillat, Ingrid

    2016-10-01

    In marine sciences, many fields display high variability over a large range of spatial and temporal scales, from seconds to thousands of years. The longer recorded time series, with an increasing sampling frequency, in this field are often nonlinear, nonstationary, multiscale and noisy. Their analysis faces new challenges and thus requires the implementation of adequate and specific methods. The objective of this paper is to highlight time series analysis methods already applied in econometrics, signal processing, health, etc. to the environmental marine domain, assess advantages and inconvenients and compare classical techniques with more recent ones. Temperature, turbidity and salinity are important quantities for ecosystem studies. The authors here consider the fluctuations of sea level, salinity, turbidity and temperature recorded from the MAREL Carnot system of Boulogne-sur-Mer (France), which is a moored buoy equipped with physico-chemical measuring devices, working in continuous and autonomous conditions. In order to perform adequate statistical and spectral analyses, it is necessary to know the nature of the considered time series. For this purpose, the stationarity of the series and the occurrence of unit-root are addressed with the Augmented-Dickey Fuller tests. As an example, the harmonic analysis is not relevant for temperature, turbidity and salinity due to the nonstationary condition, except for the nearly stationary sea level datasets. In order to consider the dominant frequencies associated to the dynamics, the large number of data provided by the sensors should enable the estimation of Fourier spectral analysis. Different power spectra show a complex variability and reveal an influence of environmental factors such as tides. However, the previous classical spectral analysis, namely the Blackman-Tukey method, requires not only linear and stationary data but also evenly-spaced data. Interpolating the time series introduces numerous artifacts to the

  18. Real-Time Pathogen Detection in the Era of Whole-Genome Sequencing and Big Data: Comparison of k-mer and Site-Based Methods for Inferring the Genetic Distances among Tens of Thousands of Salmonella Samples

    PubMed Central

    Pettengill, James B.; Pightling, Arthur W.; Baugher, Joseph D.; Rand, Hugh; Strain, Errol

    2016-01-01

    The adoption of whole-genome sequencing within the public health realm for molecular characterization of bacterial pathogens has been followed by an increased emphasis on real-time detection of emerging outbreaks (e.g., food-borne Salmonellosis). In turn, large databases of whole-genome sequence data are being populated. These databases currently contain tens of thousands of samples and are expected to grow to hundreds of thousands within a few years. For these databases to be of optimal use one must be able to quickly interrogate them to accurately determine the genetic distances among a set of samples. Being able to do so is challenging due to both biological (evolutionary diverse samples) and computational (petabytes of sequence data) issues. We evaluated seven measures of genetic distance, which were estimated from either k-mer profiles (Jaccard, Euclidean, Manhattan, Mash Jaccard, and Mash distances) or nucleotide sites (NUCmer and an extended multi-locus sequence typing (MLST) scheme). When analyzing empirical data (whole-genome sequence data from 18,997 Salmonella isolates) there are features (e.g., genomic, assembly, and contamination) that cause distances inferred from k-mer profiles, which treat absent data as informative, to fail to accurately capture the distance between samples when compared to distances inferred from differences in nucleotide sites. Thus, site-based distances, like NUCmer and extended MLST, are superior in performance, but accessing the computing resources necessary to perform them may be challenging when analyzing large databases. PMID:27832109

  19. Real-Time Pathogen Detection in the Era of Whole-Genome Sequencing and Big Data: Comparison of k-mer and Site-Based Methods for Inferring the Genetic Distances among Tens of Thousands of Salmonella Samples.

    PubMed

    Pettengill, James B; Pightling, Arthur W; Baugher, Joseph D; Rand, Hugh; Strain, Errol

    2016-01-01

    The adoption of whole-genome sequencing within the public health realm for molecular characterization of bacterial pathogens has been followed by an increased emphasis on real-time detection of emerging outbreaks (e.g., food-borne Salmonellosis). In turn, large databases of whole-genome sequence data are being populated. These databases currently contain tens of thousands of samples and are expected to grow to hundreds of thousands within a few years. For these databases to be of optimal use one must be able to quickly interrogate them to accurately determine the genetic distances among a set of samples. Being able to do so is challenging due to both biological (evolutionary diverse samples) and computational (petabytes of sequence data) issues. We evaluated seven measures of genetic distance, which were estimated from either k-mer profiles (Jaccard, Euclidean, Manhattan, Mash Jaccard, and Mash distances) or nucleotide sites (NUCmer and an extended multi-locus sequence typing (MLST) scheme). When analyzing empirical data (whole-genome sequence data from 18,997 Salmonella isolates) there are features (e.g., genomic, assembly, and contamination) that cause distances inferred from k-mer profiles, which treat absent data as informative, to fail to accurately capture the distance between samples when compared to distances inferred from differences in nucleotide sites. Thus, site-based distances, like NUCmer and extended MLST, are superior in performance, but accessing the computing resources necessary to perform them may be challenging when analyzing large databases.

  20. Effect of the six-mer synthetic peptide (AT1002) fragment of zonula occludens toxin on the intestinal absorption of cyclosporin A.

    PubMed

    Song, Keon-Hyoung; Fasano, Alessio; Eddington, Natalie D

    2008-03-03

    Zonula occludens toxin (Zot) and its biologically active fragment, delta G, have been shown to reversibly open tight junctions (TJ) in endothelial and epithelial cells. Recently, a six-mer synthetic peptide H-FCIGRL-OH (AT1002) was identified and synthesized that retains the Zot permeating effect on intercellular TJ. The objective of this study was to evaluate the biological activity of AT1002 on enhancing the oral administration of cyclosporin A (CsA). The intestinal permeability enhancing effect of AT1002 on the transport of CsA across Caco-2 cell monolayers was examined after the following treatments, i.e., CsA, CsA/protease inhibitors (PI), CsA/PI/benzalkonium chloride (BC), CsA/AT1002, CsA/PI/AT1002, and CsA/PI/BC/AT1002 (CsA 0.5 microCi/ml, PI (bestatin 15 mM and E-64 5mM), BC 0.005 w/v%, and AT1002 5mM, respectively). Apparent permeability coefficients (P app) were calculated for each treatment. In addition, four treatments, i.e., CsA, CsA/PI/BC, CsA/AT1002, and CsA/PI/BC/AT1002 (CsA 120 microCi/kg, PI (bestatin 30 mg/kg and E-64 10mg/kg), BC 0.1 w/v%, and AT1002 doses of 5, 10 or 40 mg/kg, respectively) were prepared and administered intraduodenally to male Sprague-Dawley rats (230-280 g, n=4-5). Blood samples were collected at 0, 20, 60, and 120 min post-dosing and CsA plasma concentrations were determined subsequently using a Beckman Liquid Scintillation Counter. No significant increases in CsA transport were observed in the Caco-2 cell culture experiments following pre-treatment with AT1002 (5mM). Even though, AT1002 appeared to increase the P app of CsA in each treatment (CsA/AT1002, 1.54+/-0.13 x 10(-6)cm/s and CsA/PI/AT1002, 1.76+/-0.05 x 10(-6)cm/s) compared to each control (CsA and CsA/PI), respectively. The plasma concentration of CsA was significantly increased over a range of 1.55-2.50 at 10 and 40 mg/kg dose of AT1002. Also, AUC 0-120 min of CsA over a range of 1.64-2.14 and the Cmax of CsA over a range of 1.77-2.56 was statistically and

  1. C/EBPβ (CEBPB) protein binding to the C/EBP|CRE DNA 8-mer TTGC|GTCA is inhibited by 5hmC and enhanced by 5mC, 5fC, and 5caC in the CG dinucleotide.

    PubMed

    Sayeed, Syed Khund; Zhao, Jianfei; Sathyanarayana, Bangalore K; Golla, Jaya Prakash; Vinson, Charles

    2015-06-01

    During mammalian development, some methylated cytosines (5mC) in CG dinucleotides are iteratively oxidized by TET dioxygenases to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). The effect of these cytosine oxidative products on the sequence-specific DNA binding of transcription factors is being actively investigated. Here, we used the electrophoretic mobility shift assay (EMSA) to examine C/EBPα and C/EBPβ homodimers binding to all 25 chemical forms of a CG dinucleotide for two DNA sequences: the canonical C/EBP 8-mer TTGC|GCAA and the chimeric C/EBP|CRE 8-mer TTGC|GTCA. 5hmC in the CG dinucleotide in the C/EBP|CRE motif 8-mer TGAC|GCAA inhibits binding of C/EBPβ but not C/EBPα. Binding was increased by 5mC, 5fC and 5caC. Circular dichroism monitored thermal denaturations for C/EBPβ bound to the C/EBP|CRE motif confirmed the EMSA. The structural differences between C/EBPα and C/EBPβ that may account for the difference in binding 5hmC in the 8-mer TGAC|GCAA are explored.

  2. Isolation and Characterization of Dromedary Camel Coronavirus UAE-HKU23 from Dromedaries of the Middle East: Minimal Serological Cross-Reactivity between MERS Coronavirus and Dromedary Camel Coronavirus UAE-HKU23.

    PubMed

    Woo, Patrick C Y; Lau, Susanna K P; Fan, Rachel Y Y; Lau, Candy C Y; Wong, Emily Y M; Joseph, Sunitha; Tsang, Alan K L; Wernery, Renate; Yip, Cyril C Y; Tsang, Chi-Ching; Wernery, Ulrich; Yuen, Kwok-Yung

    2016-05-07

    Recently, we reported the discovery of a dromedary camel coronavirus UAE-HKU23 (DcCoV UAE-HKU23) from dromedaries in the Middle East. In this study, DcCoV UAE-HKU23 was successfully isolated in two of the 14 dromedary fecal samples using HRT-18G cells, with cytopathic effects observed five days after inoculation. Northern blot analysis revealed at least seven distinct RNA species, corresponding to predicted subgenomic mRNAs and confirming the core sequence of transcription regulatory sequence motifs as 5'-UCUAAAC-3' as we predicted previously. Antibodies against DcCoV UAE-HKU23 were detected in 58 (98.3%) and 59 (100%) of the 59 dromedary sera by immunofluorescence and neutralization antibody tests, respectively. There was significant correlation between the antibody titers determined by immunofluorescence and neutralization assays (Pearson coefficient = 0.525, p < 0.0001). Immunization of mice using recombinant N proteins of DcCoV UAE-HKU23 and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively, and heat-inactivated DcCoV UAE-HKU23 showed minimal cross-antigenicity between DcCoV UAE-HKU23 and MERS-CoV by Western blot and neutralization antibody assays. Codon usage and genetic distance analysis of RdRp, S and N genes showed that the 14 strains of DcCoV UAE-HKU23 formed a distinct cluster, separated from those of other closely related members of Betacoronavirus 1, including alpaca CoV, confirming that DcCoV UAE-HKU23 is a novel member of Betacoronavirus 1.

  3. Isolation and Characterization of Dromedary Camel Coronavirus UAE-HKU23 from Dromedaries of the Middle East: Minimal Serological Cross-Reactivity between MERS Coronavirus and Dromedary Camel Coronavirus UAE-HKU23

    PubMed Central

    Woo, Patrick C. Y.; Lau, Susanna K. P.; Fan, Rachel Y. Y.; Lau, Candy C. Y.; Wong, Emily Y. M.; Joseph, Sunitha; Tsang, Alan K. L.; Wernery, Renate; Yip, Cyril C. Y.; Tsang, Chi-Ching; Wernery, Ulrich; Yuen, Kwok-Yung

    2016-01-01

    Recently, we reported the discovery of a dromedary camel coronavirus UAE-HKU23 (DcCoV UAE-HKU23) from dromedaries in the Middle East. In this study, DcCoV UAE-HKU23 was successfully isolated in two of the 14 dromedary fecal samples using HRT-18G cells, with cytopathic effects observed five days after inoculation. Northern blot analysis revealed at least seven distinct RNA species, corresponding to predicted subgenomic mRNAs and confirming the core sequence of transcription regulatory sequence motifs as 5′-UCUAAAC-3′ as we predicted previously. Antibodies against DcCoV UAE-HKU23 were detected in 58 (98.3%) and 59 (100%) of the 59 dromedary sera by immunofluorescence and neutralization antibody tests, respectively. There was significant correlation between the antibody titers determined by immunofluorescence and neutralization assays (Pearson coefficient = 0.525, p < 0.0001). Immunization of mice using recombinant N proteins of DcCoV UAE-HKU23 and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively, and heat-inactivated DcCoV UAE-HKU23 showed minimal cross-antigenicity between DcCoV UAE-HKU23 and MERS-CoV by Western blot and neutralization antibody assays. Codon usage and genetic distance analysis of RdRp, S and N genes showed that the 14 strains of DcCoV UAE-HKU23 formed a distinct cluster, separated from those of other closely related members of Betacoronavirus 1, including alpaca CoV, confirming that DcCoV UAE-HKU23 is a novel member of Betacoronavirus 1. PMID:27164099

  4. Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide.

    PubMed

    Eikawa, Shingo; Kakimi, Kazuhiro; Isobe, Midori; Kuzushima, Kiyotaka; Luescher, Immanuel; Ohue, Yoshihiro; Ikeuchi, Kazuhiro; Uenaka, Akiko; Nishikawa, Hiroyoshi; Udono, Heiichiro; Oka, Mikio; Nakayama, Eiichi

    2013-01-15

    Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response.

  5. X-ray Structure of a Hg2+ Complex of Mercuric Reductase (MerA) and Quantum Mechanical/Molecular Mechanical Study of Hg2+ Transfer between the C-Terminal and Buried Catalytic Site Cysteine Pairs

    PubMed Central

    2015-01-01

    Mercuric reductase, MerA, is a key enzyme in bacterial mercury resistance. This homodimeric enzyme captures and reduces toxic Hg2+ to Hg0, which is relatively unreactive and can exit the cell passively. Prior to reduction, the Hg2+ is transferred from a pair of cysteines (C558′ and C559′ using Tn501 numbering) at the C-terminus of one monomer to another pair of cysteines (C136 and C141) in the catalytic site of the other monomer. Here, we present the X-ray structure of the C-terminal Hg2+ complex of the C136A/C141A double mutant of the Tn501 MerA catalytic core and explore the molecular mechanism of this Hg transfer with quantum mechanical/molecular mechanical (QM/MM) calculations. The transfer is found to be nearly thermoneutral and to pass through a stable tricoordinated intermediate that is marginally less stable than the two end states. For the overall process, Hg2+ is always paired with at least two thiolates and thus is present at both the C-terminal and catalytic binding sites as a neutral complex. Prior to Hg2+ transfer, C141 is negatively charged. As Hg2+ is transferred into the catalytic site, a proton is transferred from C136 to C559′ while C558′ becomes negatively charged, resulting in the net transfer of a negative charge over a distance of ∼7.5 Å. Thus, the transport of this soft divalent cation is made energetically feasible by pairing a competition between multiple Cys thiols and/or thiolates for Hg2+ with a competition between the Hg2+ and protons for the thiolates. PMID:25343681

  6. Carbonyl derivatives of chloride-dimethyl sulfoxide-ruthenium(III) complexes: Synthesis, crystal structure, and reactivity of [(DMSO){sub 2}H][trans-RuCl{sub 4}(DMSO)(CO)] and mer,cis-RuCl{sub 3}(DMSO){sub 2}(CO)

    SciTech Connect

    Alessio, E.; Bolle, M.; Milani, B.

    1995-09-13

    [(DMSO){sub 2}{sub 2}H][trans-RuCl{sub 4}(DMSO){sub 2}] (1) and mer,trans-RuCl{sub 3}(DMSO){sub 2}(DMSO) (2) (DMSO = S-bonded dimethyl sulfoxide; DMSO = O-bonded dimethyl sulfoxide; DMSO = O bonded dimethyl sulfoxide) react with carbon monoxide at room temperature and atmospheric pressure to give [(DMSO){sub 2}H][trans-RuCl{sub 4}(DMSO)(CO)] (3) and mer,cis-RuCl{sub 3}(DMSO){sub 2-} (CO) (4), respectively. Coordination of carbon monoxide induces the S to O linkage iosmerization of the DMSO ligand trans to it. Compounds 3 and 4 represent the first example of Ru-(III) chloride-DMSO-carbonyl complexes. In both 3 and 4 the DMSO ligand trans to CO is weakly bonded and easily replaced by a nitrogen donor ligand.

  7. N-terminal 5-mer peptide analog P165 of amyloid precursor protein inhibits UVA-induced MMP-1 expression by suppressing the MAPK pathway in human dermal fibroblasts.

    PubMed

    Wang, Ying; Chen, Hui; Wang, Wen; Wang, Rong; Liu, Zi-Lian; Zhu, Wei; Lian, Shi

    2014-07-05

    Exposure to ultraviolet (UV) radiation leads to a progressive increase in dermal damage through the degradation of collagen, which is mediated by matrix metalloproteinases (MMPs). UV radiation alters the intracellular signaling events that regulate the elaboration of MMPs. Our previous study showed that P165, the N-terminal 5-mer peptide analog of amyloid precursor protein, exerts a protective effect on ultraviolet A (UVA)-induced loss of collagen type I in human dermal fibroblasts (HDFs) by inhibiting the generation of intracellular reactive oxygen species and MMP-1. In this study, we focused on specific signal transduction pathways to elucidate the possible photoprotective mechanisms of P165 in controlling MMP-1 inhibition. Results from western blot analyses indicated that pretreatment with P165 dose-dependently inhibited UVA-induced phosphorylation of extracellular regulated protein kinases (ERK), c-Jun N-terminal kniase (JNK), p38 mitogen-activated protein kinases (MAPKs), and the phosphorylation of their downstream targets c-Jun and c-Fos. The photoprotective effects of P165 were further demonstrated in collagen type I secretion and cellular senescence induced by UVA irradiation. These findings suggest that P165 exerts photoprotective activity in UVA-treated HDFs by regulating MMP-1 generation. This activity may be mediated by inhibiting the MAPK signaling pathways. Thus, P165 is a potential agent for the prevention of skin photoaging.

  8. RP-HPLC-ESI-MS evidenced that salivary cystatin B is detectable in adult human whole saliva mostly as S-modified derivatives: S-Glutathionyl, S-cysteinyl and S-S 2-mer.

    PubMed

    Cabras, Tiziana; Manconi, Barbara; Iavarone, Federica; Fanali, Chiara; Nemolato, Sonia; Fiorita, Antonella; Scarano, Emanuele; Passali, Giulio Cesare; Manni, Armando; Cordaro, Massimo; Paludetti, Gaetano; Faa, Gavino; Messana, Irene; Castagnola, Massimo

    2012-01-04

    An HPLC-ESI-MS analysis of adult human whole saliva evidenced three protein masses (M average 11,487±2, 11,301±2 and 22,362±3Da) eluting in the 32.5-35.0min range. Treatment in reducing conditions allowed establishing that they are S-derivatives of N-terminal acetylated cystatin B, namely its S-glutathionyl, S-cysteinyl and S-S dimer. The identification was confirmed by high resolution HPLC-ESI-MS-MS experiments on the intact naturally occurring proteins and their tryptic digests. S-unmodified cystatin B is rarely detectable in whole saliva of healthy adults (5 subjects out of 65) and its percentage does not overcome approximately 20% of total cystatin B (11±9%). In the majority of subjects (60 out of 65) the mean percentages of the S-modified derivatives were S-glutathionyl 53±13%, S-cysteinyl 15±5%, S-S 2-mer 32±13%. Variations of the percentages of these S-modified derivatives of cystatin B could be indicative of oral oxidative stress. As we are aware, this is the first time that S-glutathionylation and S-cysteinylation were described as extensive PTM of a salivary protein and the first time that these PTMs were detected in naturally occurring cystatin B.

  9. Genome-wide responses to carbonyl electrophiles in Bacillus subtilis: control of the thiol-dependent formaldehyde dehydrogenase AdhA and cysteine proteinase YraA by the MerR-family regulator YraB (AdhR).

    PubMed

    Nguyen, Thi Thu Huyen; Eiamphungporn, Warawan; Mäder, Ulrike; Liebeke, Manuel; Lalk, Michael; Hecker, Michael; Helmann, John D; Antelmann, Haike

    2009-02-01

    Quinones and alpha,beta-unsaturated carbonyls are naturally occurring electrophiles that target cysteine residues via thiol-(S)-alkylation. We analysed the global expression profile of Bacillus subtilis to the toxic carbonyls methylglyoxal (MG) and formaldehyde (FA). Both carbonyl compounds cause a stress response characteristic for thiol-reactive electrophiles as revealed by the induction of the Spx, CtsR, CymR, PerR, ArsR, CzrA, CsoR and SigmaD regulons. MG and FA triggered also a SOS response which indicates DNA damage. Protection against FA is mediated by both the hxlAB operon, encoding the ribulose monophosphate pathway for FA fixation, and a thiol-dependent formaldehyde dehydrogenase (AdhA) and DJ-1/PfpI-family cysteine proteinase (YraA). The adhA-yraA operon and the yraC gene, encoding a gamma-carboxymuconolactone decarboxylase, are positively regulated by the MerR-family regulator, YraB(AdhR). AdhR binds specifically to its target promoters which contain a 7-4-7 inverted repeat (CTTAAAG-N4-CTTTAAG) between the -35 and -10 elements. Activation of adhA-yraA transcription by AdhR requires the conserved Cys52 residue in vivo. We speculate that AdhR is redox-regulated via thiol-(S)-alkylation by aldehydes and that AdhA and YraA are specifically involved in reduction of aldehydes and degradation or repair of damaged thiol-containing proteins respectively.

  10. Specific anti-integrase abzymes from HIV-infected patients: a comparison of the cleavage sites of intact globular HIV integrase and two 20-mer oligopeptides corresponding to its antigenic determinants.

    PubMed

    Odintsova, Elena S; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A

    2013-03-01

    HIV-infected patients possess anti-integrase (IN) IgGs and IgMs that, after isolation by chromatography on IN-Sepharose, unlike canonical proteases, specifically hydrolyze only IN but not many other tested proteins. Hydrolysis of intact globular IN first leads to formation of many long fragments of protein, while its long incubation with anti-IN antibodies, especially in the case of abzymes (Abzs) with a high proteolytic activity, results in the formation of short and very short oligopeptides (OPs). To identify all sites of IgG-mediated proteolysis corresponding to known AGDs of integrase, we have used a combination of reverse-phase chromatography, matrix-assisted laser desorption/ionization spectrometry, and thin-layer chromatography to analyze the cleavage products of two 20-mer OPs corresponding to these AGDs. Both OPs contained 9-10 mainly clustered major, medium, and minor sites of cleavage. The main superficial cleavage sites of the AGDs in the intact IN and sites of partial or deep hydrolysis of the peptides analyzed do not coincide. The active sites of anti-IN Abzs are localized on their light chains, whereas the heavy chains are responsible for the affinity of protein substrates. Interactions of intact globular proteins with both light and heavy chains of Abzs provide high specificity of IN hydrolysis. The affinity of anti-IN Abzs for intact integrase was ~1000-fold higher than for the OPs. The data suggest that both OPs interact mainly with the light chains of different monoclonal Abzs of the total pool of IgGs, which possesses lower affinity for substrates; and therefore, depending on the oligopeptide sequences, their hydrolysis may be less specific and remarkably different in comparison with the cleavage of intact globular IN.

  11. The bldC Developmental Locus of Streptomyces coelicolor Encodes a Member of a Family of Small DNA-Binding Proteins Related to the DNA-Binding Domains of the MerR Family

    PubMed Central

    Hunt, Alison C.; Servín-González, Luis; Kelemen, Gabriella H.; Buttner, Mark J.

    2005-01-01

    The bldC locus, required for formation of aerial hyphae in Streptomyces coelicolor, was localized by map-based cloning to the overlap between cosmids D17 and D25 of a minimal ordered library. Subcloning and sequencing showed that bldC encodes a member of a previously unrecognized family of small (58- to 78-residue) DNA-binding proteins, related to the DNA-binding domains of the MerR family of transcriptional activators. BldC family members are found in a wide range of gram-positive and gram-negative bacteria. Constructed ΔbldC mutants were defective in differentiation and antibiotic production. They failed to form an aerial mycelium on minimal medium and showed severe delays in aerial mycelium formation on rich medium. In addition, they failed to produce the polyketide antibiotic actinorhodin, and bldC was shown to be required for normal and sustained transcription of the pathway-specific activator gene actII-orf4. Although ΔbldC mutants produced the tripyrrole antibiotic undecylprodigiosin, transcripts of the pathway-specific activator gene (redD) were reduced to almost undetectable levels after 48 h in the bldC mutant, in contrast to the bldC+ parent strain in which redD transcription continued during aerial mycelium formation and sporulation. This suggests that bldC may be required for maintenance of redD transcription during differentiation. bldC is expressed from a single promoter. S1 nuclease protection assays and immunoblotting showed that bldC is constitutively expressed and that transcription of bldC does not depend on any of the other known bld genes. The bldC18 mutation that originally defined the locus causes a Y49C substitution that results in instability of the protein. PMID:15629942

  12. The bldC developmental locus of Streptomyces coelicolor encodes a member of a family of small DNA-binding proteins related to the DNA-binding domains of the MerR family.

    PubMed

    Hunt, Alison C; Servín-González, Luis; Kelemen, Gabriella H; Buttner, Mark J

    2005-01-01

    The bldC locus, required for formation of aerial hyphae in Streptomyces coelicolor, was localized by map-based cloning to the overlap between cosmids D17 and D25 of a minimal ordered library. Subcloning and sequencing showed that bldC encodes a member of a previously unrecognized family of small (58- to 78-residue) DNA-binding proteins, related to the DNA-binding domains of the MerR family of transcriptional activators. BldC family members are found in a wide range of gram-positive and gram-negative bacteria. Constructed DeltabldC mutants were defective in differentiation and antibiotic production. They failed to form an aerial mycelium on minimal medium and showed severe delays in aerial mycelium formation on rich medium. In addition, they failed to produce the polyketide antibiotic actinorhodin, and bldC was shown to be required for normal and sustained transcription of the pathway-specific activator gene actII-orf4. Although DeltabldC mutants produced the tripyrrole antibiotic undecylprodigiosin, transcripts of the pathway-specific activator gene (redD) were reduced to almost undetectable levels after 48 h in the bldC mutant, in contrast to the bldC+ parent strain in which redD transcription continued during aerial mycelium formation and sporulation. This suggests that bldC may be required for maintenance of redD transcription during differentiation. bldC is expressed from a single promoter. S1 nuclease protection assays and immunoblotting showed that bldC is constitutively expressed and that transcription of bldC does not depend on any of the other known bld genes. The bldC18 mutation that originally defined the locus causes a Y49C substitution that results in instability of the protein.

  13. MERS in the U.S.

    MedlinePlus

    ... U.S. (Indiana) from Saudi Arabia, via London and Chicago. The traveler was a U.S. citizen who lived ... traveled by plane to London, England, then to Chicago, Illinois. The traveler then took a bus from ...

  14. Travelers' Health: MERS in the Arabian Peninsula

    MedlinePlus

    ... Share Compartir Warning - Level 3, Avoid Nonessential Travel Alert - Level 2, Practice Enhanced Precautions Watch - Level 1, ... overseas. Clinician Information: Health care providers should be alert to patients who develop fever and symptoms of ...

  15. Water 16-mers and hexamers: assessment of the three-body and electrostatically embedded many-body approximations of the correlation energy or the nonlocal energy as ways to include cooperative effects.

    PubMed

    Qi, Helena W; Leverentz, Hannah R; Truhlar, Donald G

    2013-05-30

    This work presents a new fragment method, the electrostatically embedded many-body expansion of the nonlocal energy (EE-MB-NE), and shows that it, along with the previously proposed electrostatically embedded many-body expansion of the correlation energy (EE-MB-CE), produces accurate results for large systems at the level of CCSD(T) coupled cluster theory. We primarily study water 16-mers, but we also test the EE-MB-CE method on water hexamers. We analyze the distributions of two-body and three-body terms to show why the many-body expansion of the electrostatically embedded correlation energy converges faster than the many-body expansion of the entire electrostatically embedded interaction potential. The average magnitude of the dimer contributions to the pairwise additive (PA) term of the correlation energy (which neglects cooperative effects) is only one-half of that of the average dimer contribution to the PA term of the expansion of the total energy; this explains why the mean unsigned error (MUE) of the EE-PA-CE approximation is only one-half of that of the EE-PA approximation. Similarly, the average magnitude of the trimer contributions to the three-body (3B) term of the EE-3B-CE approximation is only one-fourth of that of the EE-3B approximation, and the MUE of the EE-3B-CE approximation is one-fourth that of the EE-3B approximation. Finally, we test the efficacy of two- and three-body density functional corrections. One such density functional correction method, the new EE-PA-NE method, with the OLYP or the OHLYP density functional (where the OHLYP functional is the OptX exchange functional combined with the LYP correlation functional multiplied by 0.5), has the best performance-to-price ratio of any method whose computational cost scales as the third power of the number of monomers and is competitive in accuracy in the tests presented here with even the electrostatically embedded three-body approximation.

  16. Reinvestigation of the Reaction of (NH4)2[Ce(N03)6] with Triphenylphosphine Oxide; the Crystal Structure and Magnetic Properties of mer-Ce(NO3)3(OPPh3)3 • 2 (CH3)2CO

    NASA Astrophysics Data System (ADS)

    Lin, Jianhua; Hey-Hawkins, Evamarie; von Schnering, Hans Georg

    1990-12-01

    The reaction of (NH4)2[Ce(NO3)6 ] with two equivalents of OPPh3(Ph = C6H5 ) in acetonitrile yields Ce(NO3 ) 4(OPPh3 )2 (1) in high yield, whereas using acetone as solvent affords mer- Ce(NO3 )3(OPPh3)3 • 2(CH3)2CO (2), the yield of which is dependent on the reaction time. A crystal structure determination of 2 shows that the Ce atom is coordinated with three bidentate nitrato groups and three OPPh3 ligands, thus achieving a coordination number of nine. Eight non-coordinating acetone molecules are present in the unit cell. Crystal data (292 K): space group P21/n (no. 14), 0=12.438(2), b = 25.532(4), c = 20.379 (4) Å, β = 96.33(2)°, V = 6432(1) , Z = 4, dcalc = 1.318 g em 3. Due to poor crystal quality the refinement converges at R = 0.11, Rw = 0.09. 2 is paramagnetic, but it does not follow the Curie-Weiss law at low temperature. Therefore crystal field theory was used in order to explain these findings.

  17. Strategic analysis for the MER Cape Verde approach

    USGS Publications Warehouse

    Gaines, D.; Belluta, P.; Herman, J.; Hwang, P.; Mukai, R.; Porter, D.; Jones, B.; Wood, E.; Grotzinger, J.; Edgar, L.; Hayes, A.; Hare, T.; Squyres, S.

    2009-01-01

    The Mars Exploration Rover Opportunity has recently completed a two year campaign studying Victoria Crater. The campaign culminated in a close approach of Cape Verde in order to acquire high resolution imagery of the exposed stratigraphy in the cliff face. The close approach to Cape Verde provided significant challenges for every subsystem of the rover as the rover needed to traverse difficult, uncharacterised terrain and approach a cliff face with the potential of blocking out solar energy and communications with Earth. In this paper we describe the strategic analyses performed by the science and engineering teams so that we could successfully achieve the science objectives while keeping the rover safe. ??2009 IEEE.

  18. Discovery of 12-mer peptides that bind to wood lignin.

    PubMed

    Yamaguchi, Asako; Isozaki, Katsuhiro; Nakamura, Masaharu; Takaya, Hikaru; Watanabe, Takashi

    2016-02-23

    Lignin, an abundant terrestrial polymer, is the only large-volume renewable feedstock composed of an aromatic skeleton. Lignin has been used mostly as an energy source during paper production; however, recent interest in replacing fossil fuels with renewable resources has highlighted its potential value in providing aromatic chemicals. Highly selective degradation of lignin is pivotal for industrial production of paper, biofuels, chemicals, and materials. However, few studies have examined natural and synthetic molecular components recognizing the heterogeneous aromatic polymer. Here, we report the first identification of lignin-binding peptides possessing characteristic sequences using a phage display technique. The consensus sequence HFPSP was found in several lignin-binding peptides, and the outer amino acid sequence affected the binding affinity of the peptides. Substitution of phenylalanine7 with Ile in the lignin-binding peptide C416 (HFPSPIFQRHSH) decreased the affinity of the peptide for softwood lignin without changing its affinity for hardwood lignin, indicating that C416 recognised structural differences between the lignins. Circular dichroism spectroscopy demonstrated that this peptide adopted a highly flexible random coil structure, allowing key residues to be appropriately arranged in relation to the binding site in lignin. These results provide a useful platform for designing synthetic and biological catalysts selectively bind to lignin.

  19. MER vistas: ground-truth for Earth-based radar

    NASA Technical Reports Server (NTRS)

    Haldemann, Albert F.; Larsen, Kristopher W.; Jurgens, Raymond F.; Golombek, Matthew P.; Slade, Martin A.

    2004-01-01

    Earth-based delay-Doppler radar observations of Mars with four receiving stations were carried out during the Mars oppositions of 2001 and 2003 in support of Mars Exploration Rover landing site selection. This interferometric planetary radar technique has demonstrated radar mapping of Mars with a 5 km spatial resolution.

  20. Undercut Rocks at the MER Gusev Landing Site

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A.

    2004-01-01

    On January 3 2004, the NASA Spirit rover landed on the plains inside the Gusev Crater in the southern hemisphere of Mars, and has made observations of the landing site and nearby region in visual and infrared wavelengths, as well as making in-situ measurements of rocks and soil. A number of rocks at the Gusev site are perched, with a significant undercut above the surface; additional rocks show a feature of being eroded or etched at a height of one to three centimeters immediately above the soil line. Some rocks also show terracing, and others show a two-tone pattern of albedo, with a distinct dividing line between a lighter area near the surface and a darker color above the surface. In a small number of cases, the dividing line is correlated with a visible horizontal groove in the rock, most likely indicating an earlier location of burial of the rock. A number of explanations for this undercutting are possible. Perched rocks can be placed on the surface by deflation of the soil from underneath the rock. The surface etching may be abrasion due to reptation. Reptation, or surface creep, occurs as sand moves without leaving the surface, as small (100-200 micron particles) moved by saltation set larger particles in motion. These large particles are effective at abrading the rocks at the surface level. The structure of "ripple" features at the site is evidence to support reptation at the Gusev site. An alternate explanation is etching at the surface by chemically active grit.

  1. Antibody Response and Disease Severity in Healthcare Worker MERS Survivors

    PubMed Central

    Khalid, Imran; Ahmed, Waleed A.; Dada, Ashraf M.; Bayumi, Daniyah T.; Malic, Laut S.; Althawadi, Sahar; Ignacio, Kim; Alsalmi, Hanadi S.; Al-Abdely, Hail M.; Wali, Ghassan Y.; Qushmaq, Ismael A.; Alraddadi, Basem M.; Perlman, Stanley

    2016-01-01

    We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for >18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease. PMID:27192543

  2. Discovery of 12-mer peptides that bind to wood lignin

    PubMed Central

    Yamaguchi, Asako; Isozaki, Katsuhiro; Nakamura, Masaharu; Takaya, Hikaru; Watanabe, Takashi

    2016-01-01

    Lignin, an abundant terrestrial polymer, is the only large-volume renewable feedstock composed of an aromatic skeleton. Lignin has been used mostly as an energy source during paper production; however, recent interest in replacing fossil fuels with renewable resources has highlighted its potential value in providing aromatic chemicals. Highly selective degradation of lignin is pivotal for industrial production of paper, biofuels, chemicals, and materials. However, few studies have examined natural and synthetic molecular components recognizing the heterogeneous aromatic polymer. Here, we report the first identification of lignin-binding peptides possessing characteristic sequences using a phage display technique. The consensus sequence HFPSP was found in several lignin-binding peptides, and the outer amino acid sequence affected the binding affinity of the peptides. Substitution of phenylalanine7 with Ile in the lignin-binding peptide C416 (HFPSPIFQRHSH) decreased the affinity of the peptide for softwood lignin without changing its affinity for hardwood lignin, indicating that C416 recognised structural differences between the lignins. Circular dichroism spectroscopy demonstrated that this peptide adopted a highly flexible random coil structure, allowing key residues to be appropriately arranged in relation to the binding site in lignin. These results provide a useful platform for designing synthetic and biological catalysts selectively bind to lignin. PMID:26903196

  3. Characterization of Martian Rock Shape for MER Airbag Drop Tests

    NASA Technical Reports Server (NTRS)

    DiMaggio, E. N.; Schroeder, R. D.; Golombek, M. P.; Haldemann, A.; Castle, N.

    2003-01-01

    Using the Viking and Mars Pathfinder landing sites as a guide, this study assessed rock shapes, sizes and burial so they could be compared with rocks on the test platforms. This work allowed comparison of the severity of the rock distributions on the test platforms with the 3 landing sites and helped guide the rocks used on the test platforms during the final airbag qualification tests.

  4. MER Analyses of the Soils at the Meridiani Landing Site

    NASA Astrophysics Data System (ADS)

    Weitz, C.; Athena Team

    We have used the different science instruments on the Opportunity rover at Meridiani Planum to understand the soil characteristics within the 20 m diameter crater where the rover landed. The majority of the soils consist of a well sorted lag deposit composed of millimeter-size grains of multiple sources superimposed on a finer soil matrix. The millimeter-size grains vary in size and morphology across the crater floor, with the largest (2-10 mm diameter) and most spherical grains adjacent to the layered outcrop, and smaller, more irregular sizes moving away from the outcrop towards the center of the crater. The soil right next to the lander is mostly composed of very fine grains (avg. 150 microns) with larger grains between 1 and 2 mm in diameter. Adjacent to the outcrop, the soils are dominated by spherules that have weathered out intact from the layered outcrop. It's likely that some of the non-spherule millimeter grains represent outcrop material that has been weathered to finer particle sizes and subsequently mixed into the soil. Underlying the spherules is a darker, finer soil that is spectrally similar to the soils near the lander. Undisturbed hematite-poor and hematite-rich soils, as determined by the Mini-TES instrument, show no significant differences in grain shapes or sizes. Rover wheel tracks show that the spherules and millimeter-size grains have been pushed down into the finer soil by the movement of the rover, but they have not been crushed. A similar effect was seen both from the Mossbauer contact plate after it was pushed into the soil, and also in the airbag bounce marks where the larger spherules have disappeared within the bounce marks, most likely due to burial, and there is a corresponding lower hematite signature. A 10 cm deep trench dug by a rover wheel reveals a brighter substrate on the trench floor, and a bumpy texture of soil with embedded shiny spherules in the upper wall. The brighter trench floor may be a photometric effect from the compaction rather than a distinct soil type. Linear ripples spaced 5-8 cm apart are concentrated adjacent to the lander and near the center of the crater. The ripples lack the millimeter-size grains visible throughout the crater floor. Intra-ripple soil within the larger ripples contains patches of brighter material that is spectrally distinct from all other soils and rocks thus far analyzed by Pancam, including the layered outcrop. Based upon orbital images of the landing site, the crater floor has a lower albedo than the terrain outside the crater. Consequently, the soils we have analyzed thus far inside the crater may either contain a higher percentage of darker grains or they may not be representative of the soils covering the plains of Meridiani Planum.

  5. Strategic Analysis for the MER Cape Verde Approach

    NASA Technical Reports Server (NTRS)

    Gaines, Daniel; Belluta, Paolo; Herman, Jennifer; Hwang, Pauline; Mukai, Ryan; Porter, Dan; Jones, Byron; Wood, Eric; Grotzinger, John; Edgar, Lauren; Hayes, Alex; Hare, Trent; Squyres, Steve

    2009-01-01

    The Mars Exploration Rover Opportunity has recently completed a two year campaign studying Victoria Crater. The campaign culminated in a close approach of Cape Verde in order to acquire high resolution imagery of the exposed stratigraphy in the cliff face. The close approach to Cape Verde provided significant challenges for every subsystem of the rover as the rover needed to traverse difficult, uncharacterised terrain and approach a cliff face with the potential of blocking out solar energy and communications with Earth. In this paper we describe the strategic analyses performed by the science and engineering teams so that we could successfully achieve the science objectives while keeping the rover safe.

  6. Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp 70 Derived 14-Mer Peptide (TKD) on the Expression of NK Cell Activatory and Inhibitory Receptors on Peripheral Blood T Cells, B Cells and NKT Cells.

    PubMed

    Hromadnikova, Ilona; Li, Shuang; Kotlabova, Katerina; Dickinson, Anne M

    2016-01-01

    Previous studies from Multhoff and colleagues reported that plasma membrane Hsp70 acts as a tumour-specific recognition structure for activated NK cells, and that the incubation of NK cells with Hsp70 and/or a 14-mer peptide derived from the N-terminal sequence of Hsp70 (TKDNNLLGRFELSG, TKD, aa 450-463) plus a low dose of IL-2 triggers NK cell proliferation and migration, and their capacity to kill cancer cells expressing membrane Hsp70. Herein, we have used flow cytometry to determine the influence of in vitro stimulation of peripheral blood mononuclear cells from healthy individuals with IL-2 or IL-15, either alone or in combination with TKD peptide on the cell surface expression of CD94, NK cell activatory receptors (CD16, NK2D, NKG2C, NKp30, NKp44, NKp46, NKp80, KIR2DL4, DNAM-1 and LAMP1) and NK cell inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2 and NKR-P1A) by CD3+CD56+ (NKT), CD3+CD4+, CD3+CD8+ and CD19+ populations. NKG2D, DNAM-1, LAMP1 and NKR-P1A expression was upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD in NKT, CD8+ T cells and B cells. CD94 was upregulated in NKT and CD8+ T cells. Concurrently, an increase in a number of CD8+ T cells expressing LIR1/ILT-2 and CD4+ T cells positive for NKR-P1A was observed. The proportion of CD8+ T cells that expressed NKG2D was higher after IL-2/TKD treatment, when compared with IL-2 treatment alone. In comparison with IL-15 alone, IL-15/TKD treatment increased the proportion of NKT cells that were positive for CD94, LAMP1 and NKRP-1A. The more potent effect of IL-15/TKD on cell surface expression of NKG2D, LIR1/ILT-2 and NKRP-1A was observed in B cells compared with IL-15 alone. However, this increase was not of statistical significance. IL-2/TKD induced significant upregulation of LAMP1 in CD8+ T cells compared with IL-2 alone. Besides NK cells, other immunocompetent cells present within the fraction of peripheral blood mononuclear cells were influenced by the treatment

  7. Diagnosing Vincent van Gogh, an expedition from the sources to the present "mer à boire".

    PubMed

    Voskuil, Piet

    2013-08-01

    The paintings and writings of Vincent van Gogh are widely admired for their great artistic value. This makes it interesting for doctors and patient groups to mold van Gogh's disease into a figurehead of their own specialty or illness. The recent article of ter Borg and Kasteleijn (2012) [1] in this Journal had a welcome approach by placing the diagnoses given in his lifetime in a historical and cultural context. In this article, the author will explore the diagnosis of epilepsy, adding more details without jumping quickly to conclusions. Apart from the information of eyewitnesses, special efforts are made to look critically at the medical sources as well as to investigate the original family chronicles. There is no easy access to that information. The Dutch vocabulary in the family notes made it tempting, for earlier scholars in this field, to easily link all kinds of attacks in family members to the original diagnosis of epilepsy. A part of the archives of the Willem Arntszhuis Utrecht describing the last days of Vincent's brother Theo, so far published only in Dutch (Voskuil, 2009 [16]), is included here. To integrate all this information, interdisciplinary research in a nonmutually excluding, but complementary, synthesis of today's knowledge is the most fruitful way to understand Vincent's behavior and its disturbances while continuing to admire his beautiful art.

  8. Acute Respiratory Infections in Travelers Returning from MERS-CoV-Affected Areas.

    PubMed

    German, Matthew; Olsha, Romy; Kristjanson, Erik; Marchand-Austin, Alex; Peci, Adriana; Winter, Anne-Luise; Gubbay, Jonathan B

    2015-09-01

    We examined which respiratory pathogens were identified during screening for Middle East respiratory syndrome coronavirus in 177 symptomatic travelers returning to Ontario, Canada, from regions affected by the virus. Influenza A and B viruses (23.1%) and rhinovirus (19.8%) were the most common pathogens identified among these travelers.

  9. Characterization of Rock Types at Meridiani Planum, Mars using MER 13-Filter Pancam Spectra

    NASA Technical Reports Server (NTRS)

    Nuding, D. L.; Cohen, B. A.

    2009-01-01

    The Mars Exploration Rover Opportunity has traversed more than 13 km across Meridiani Planum, finding evidence of ancient aqueous environments that, in the past, may have been suitable for life. Meridiani bedrock along the rover traverse is a mixture in composition and bulk mineralogy between a sulfate-rich sedimentary rock and hematite spherules ("blueberries"). On top of the bedrock, numerous loose rocks exist. These rocks consist of both local bedrock and "cobbles" of foreign origin. The cobbles provide a window into lithologic diversity and a chance to understand other types of martian rocks and meteorites. This study was also an attempt to establish a method to expand upon those of Mini-TES to remotely identify rocks of interest to make efficient use of the rover s current resources.

  10. Two Martian Winters at Gusev Crater and Meridiani Planum: New Results From the MER Mossbauer Spectrometers

    NASA Technical Reports Server (NTRS)

    Klingelhoefer, Goestar; Morris, Richard V.; Schroeder, Christian; Rodionov, Daniel S.; Yen, Albert S.; Ming, Douglas W.; Cohen, Barbara A.; Fleischer, Iris; Mittlefehldt, David W.; McCoy, Tim; de Souza, Paulo Jr.

    2006-01-01

    After sol 511 of its mission in Gusev Crater, Spirit traversed from the top of Husband Hill to its current Winter Haven on Low Ridge. M ssbauer analyses of several rock and soil targets along the traverse yielded further evidence for the wide-spread occurrence of aqueous processes in the Columbia Hills. The rock Independence was found on the flank of Husband Hill. It has low total Fe with about 24-30 % of its iron in ilmenite. This assemblage implies alteration under aqueous conditions; some phases were altered and elements such as Fe were leached out, while less soluble Fe-bearing phases such as ilmenite remain. The soil target Dead_Sea_Samra was found in subsurface soil revealed when the wheels dug into soil during the traverse from Husband Hill to Home Plate. Its M ssbauer spectrum shows a high abundance of ferric sulfate, similar to the Paso Robles soil targets found on Husband Hill. At its current location at Winter Haven Spirit investigated the target Halley which appears to be part of a wider-spread indurated layer underlying basaltic soil. This target shows the highest abundance of hematite in all Gusev soil and rock targets investigated to date. Opportunity at Meridiani Planum traversed from the 300 m diameter buried Erebus Crater towards 800 m Victoria Crater. The main components of Meridiani Planum jarosite-bearing outcrop rocks, basaltic soil, and a hematite lag remain remarkably constant in M ssbauer spectra throughout the traverse. Cobbles (rock fragments greater than 1 cm) show variability however. A meteorite (Barberton) has been identified based on kamacite peaks in the M ssbauer spectrum. Other cobbles show Mossbauer spectra similar to jarosite-bearing outcrops, or to basaltic rock, or mixtures thereof, suggesting an origin as impact breccias. Some cobbles were investigated at the edge of the annulus of Victoria Crater from which they may have been excavated. Mossbauer spectra reveal a basaltic signature, dominated by olivine and pyroxene. In general for both rovers the radioactive Mossbauer source became naturally weaker, but both instruments are still able to perform good quality measurements.

  11. An Extended Kalman filter (EKF) for Mars Exploration Rover (MER) entry, descent, and landing reconstruction

    NASA Technical Reports Server (NTRS)

    Lisano, M. E.

    2003-01-01

    This paper describes the design and initial test results of an extended Kalman filter that has been developed at Jet Propulsion Laboratory (JPL) for post-flight reconstruction of the trajectory and attitude history of a spacecraft entering a planetary atmosphere and descending upon a parachute.

  12. Moessbauer Spectroscopy on the Martian Surface: Constraints on Interpretation of MER Data

    NASA Technical Reports Server (NTRS)

    Dyar, M. D.; Schaefer, M. W.

    2003-01-01

    Moessbauer spectrometers will be used on martian landers and rovers to identify and quantify relative amounts of Fe-bearing minerals, as well as to determine their Fe(3+)/Fe(2+) ratios, allowing more realistic modeling of martian mineralogy and evolution. However, derivation of mineral modes, Fe(3+)/Fe(2+) ratios, and phase identification via Moessbauer spectroscopy (MS) does have limitations. We discuss here the exciting potential of MS for remote planetary exploration, as well as constraints on interpretation of remote Moessbauer data.

  13. La conquête des mers siluriennes par les Spiriferida (Brachiopoda)

    NASA Astrophysics Data System (ADS)

    Gourvennec, Rémy

    1999-11-01

    The spiriferid brachiopods appeared in the Late Ordovician (Middle Ashgill) in southeastern Asia and then spread throughout the world during the Silurian. The strategies of expansion of the group and the changes in its diversity during this period are discussed here.

  14. Distinct Igneous APXS Rock Compositions on Mars from Pathfinder, MER and MSL

    NASA Technical Reports Server (NTRS)

    Gellert, Ralf; Arvidson, Raymond; Clark, Benton, III; Ming, Douglas W.; Morris, Richard V.; Squyres, Steven W.; Yen, Albert S.

    2015-01-01

    The alpha particle x-ray spectrometer (APXS) on all four Mars Rovers returned geochemical data from about 1000 rocks and soils along the combined traverses of over 50 kilometers. Here we discuss rocks likely of igneous origin, which might represent source materials for the soils and sediments identified along the traverses. Adirondack-type basalts, abundant in the plains of Gusev Crater, are primitive, olivine bearing basalts. They resemble in composition the basaltic soils encountered at all landing sites, except the ubiquitous elevated S, Cl and Zn in soils. They have been postulated to represent closely the average Martian crust composition. The recently identified new Martian meteorite Black Beauty has similar overall geochemical composition, very distinct from the earlier established SNC meteorites. The rim of the Noachian crater Endeavour, predating the sulfate-bearing Burns formation at Meridiani Planum, also resembles closely the composition of Adirondack basalts. At Gale Crater, the MSL Curiosity rover identified a felsic rock type exemplified by the mugearitic float rock JakeM, which is widespread along the traverse at Gale. While a surprise at that time, possibly related more evolved, alkaline rocks had been previously identified on Mars. Spirit encountered the Wishstone rocks in the Columbia Hills with approx. 6% Na2O+K2O, 15 % Al2O3 and low 12% FeO. Pathfinder rocks with elevated K and Na and >50% SiO2 were postulated to be andesitic. Recently Opportunity encountered the rock JeanBaptisteCharbonneau with >15% Al2O3, >50% SiO2 and approx. 10% FeO. A common characteristic all these rocks is the very low abundance of Cr, Ni and Zn, and an Fe/Mn ratio of about 50, indicating an unaltered Fe mineralogy. Beside these likely igneous rock types, which occurred always in several rocks, a few unique rocks were encountered, e.g. Bounce Rock, a pyroxene-bearing ejecta rock fragment resembling the Shergottite EETA 79001B meteorite. The APXS data can be used to relate the findings of all 4 landing sites, constrain the water to rock ratio of sediments or imply source rock provenance. Beyond that the capability to quantify important volatile elements like P, S, Cl, and Br have provided new insights into the chemistry and the environment present during the formation of the sediments.

  15. Hematite at Meridiani Planum, Mars, Investigated by Simultaneous Fitting of MER Mossbauer Spectra

    NASA Technical Reports Server (NTRS)

    Fleischer, I.; Agresti, D. G.; Klingelhoefer, G.; Morris, Richard V.

    2010-01-01

    The Mars Exploration Rover Opportunity encountered sedimentary outcrop rocks at its landing site. Spherules with diameters in the millimeter range were found to weather from the outcrop rocks. With Opportunity s miniaturised M ssbauer spectrometer MIMOS II, hematite was detected in spherules and in the outcrop matrix [1,2]. Figure 1 shows the target Berry Bowl, where brushed outcrop and an accumulation of spherules could be investigated on sols 46 and 48 of Opportunity s mission. Hematite undergoes a transition from a weakly ferromagnetic above to an antiferromagnetic state below the Morin temperature (T(sub M) approx.265 K for chemically pure, crystalline hematite). The magnetic hyperfine splitting (B(sub hf)) shows a general decrease with increasing temperature and a drop of approx.0.8 T at T(sub M). The quadrupole splitting ((Delta)EQ) changes its sign at T(sub M), with negative values above and positive values below the transition. Crystallinity and particle size influence the magnitude and temperature dependence of the magnetic splitting and the quadrupole splitting [3].

  16. Variations in Spike Glycoprotein Gene of MERS-CoV, South Korea, 2015.

    PubMed

    Kim, Dae-Won; Kim, You-Jin; Park, Sung Han; Yun, Mi-Ran; Yang, Jeong-Sun; Kang, Hae Ji; Han, Young Woo; Lee, Han Saem; Kim, Heui Man; Kim, Hak; Kim, A-Reum; Heo, Deok Rim; Kim, Su Jin; Jeon, Jun Ho; Park, Deokbum; Kim, Joo Ae; Cheong, Hyang-Min; Nam, Jeong-Gu; Kim, Kisoon; Kim, Sung Soon

    2016-01-01

    An outbreak of nosocomial infections with Middle East respiratory syndrome coronavirus occurred in South Korea in May 2015. Spike glycoprotein genes of virus strains from South Korea were closely related to those of strains from Riyadh, Saudi Arabia. However, virus strains from South Korea showed strain-specific variations.

  17. Clues to Martian brines based on halogens in salts from nakhlites and MER samples

    NASA Astrophysics Data System (ADS)

    Rao, M. N.; Sutton, S. R.; McKay, D. S.; Dreibus, G.

    2005-12-01

    Chlorine and Br abundances in fracture-filling secondary salts in Nakhla veins determined in this study by Synchrotron X-ray Microprobe (Br) and Electron Microprobe (Cl) techniques compare well to the halogens determined recently by APXS instruments in soils and rock rinds at the Gusev and Meridiani sites. The salts in these Mars rocks arise from Martian brines that have undergone evaporative or freezing concentration. The halogen abundances in these salts are corrected for ``dilution effect'' (because of mixing with halogen-poor phases) to obtain their ``true'' abundances, which seem to be close to the halogen abundances in terrestrial sea brines. Consistent with the petrographic evidence for evaporative salt deposition sequence of carbonate-sulfate-halite in nakhlite meteorites, Nakhla veins yield high Br (~250 ppm) and low Cl/Br ratios (~10-50), suggesting possible salt deposition from concentrated brines, whereas Lafayette iddingsite, with low Br (11 ppm) and high Cl/Br ratios (~250-300), indicates salt deposition from dilute brines on Mars. The low Cl/Br ratios (~20 to 80) in salts from Gusev and Meridiani rock rinds indicate that they presumably originate from concentrated subsurface Martian brines. The high Cl/Br ratio (~270) in salts deposited by dilute solutions in Lafayette and Adirondack is similar to the chondritic Cl/Br ratio, which seems to characterize the dilute brines on Mars (prior to halite precipitation) including ``Early Mars Waters'' (Noachian or earlier). Our results seem to be consistent with the Burt-Knauth model involving density stratification during evaporation/freezing of brine solutions in Martian regolith.

  18. Etude paleomagnetique des sediments holocenes de la Fosse du Mackenzie, mer de Beaufort

    NASA Astrophysics Data System (ADS)

    Barris, Elissa

    Les etudes paleomagnetiques a haute resolution sont d'importance en magnetostratigraphie et geomagnetisme, particulierement dans l'Arctique en raison de l'inaccessibilite et des faibles vitesses de sedimentation dans plusieurs secteurs. Deux carottes sedimentaires representant l'Holocene recent ont ete recoltees dans la Fosse du Mackenzie, une region avec des vitesses de sedimentation relativement elevees. Une carotte boite et un Calypso square core ont ete preleves a deux sites (690 et 680). Les proprietes physiques et magnetiques et la granulometrie ont ete mesurees, ainsi que les aimantations remanentes naturelle, anhysteretique, isothermale et isothermale saturee (NRM, ARM, IRM et SIRM). L'hysteresis magnetique indique une forte concentration de magnetite de type pseudo-single domain, un porteur ideal de remanence, alors que les mesures de la susceptibilite magnetique suggerent une concentration uniforme. Les valeurs de deviation angulaire maximale (MAD) et du champ median destructif (MDF) indiquent des donnees de direction d'excellente qualite et une coercivite typique de la magnetite, respectivement. Finalement, dans la carotte 690 et la partie intermediaire de la 680, l'inclinaison vane autour des valeurs d'un dipole axial geocentrique (GAD) pour la latitude des sites, renforcant la fiabilite du signal paleomagnetique. Finalement, des proxies de la paleointensite relative ont ete construits pour les carottes 690 et 680 en normalisant la NRM par l'IRM et l'ARM, respectivement. Vingt-et-une coquilles de pelecypodes reparties dans les deux carottes ont ete recoltees pour construire un modele d'âge au radiocarbone a chaque si te, une tâche necessaire pour la mise en contexte d'un enregistrement paleomagnetique, mais souvent difficile dans l'Arctique. En utilisant ces modeles d'âge, les enregistrements paleomagnetiques ont ete compares avec d'autres provenant du bas-Arctique et des moyennes latitudes, soulignant leur potentiel pour des etudes magnetostratigraphiques regionales et soutenant l' hypothese que le cylindre tangentiel n'influence que le comportement du champ geomagnetique dans le Haut Arctique. De plus, des cycles quasiperiodiques ont ete retrouves dans les enregistrements de la susceptibilite magnetique et pourraient refleter l'influence du cycle solaire de Suess sur les oscillations Arctique et Pacifique decennale. Finalement, les mesures granulometriques indiquent une difference de provenance entre les deux sites, specifiquement une source addition nelle de sediments cotiers plus grossiers au site distal.

  19. Effects of Variable Temperature on Mossbauer Data Acquisition: Laboratory-based and MER A Results

    NASA Technical Reports Server (NTRS)

    Rothstein, Y.; Sklute, E. C.; Dyar, M. D.; Schaefer, M. W.

    2005-01-01

    Mossbauer spectrometers on the Spirit and Opportunity rovers have played a valuable role in identifying mineralogy at both the Gusev and Meridiani landing sites. Key to the application of Mossbauer results is the issue of how accurately the peak positions, on which the mineral identifications are based, can be determined. Remote Mossbauer spectroscopy has by necessity some unusual experimental constraints that may influence the confidence with which peak positions can be fit. We present here an analysis of the effects of variable temperature and short duration run times on spectral resolution.

  20. 21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Internal Standard Method”; “Infrared Spectrophotometric Determination of Polymer Extracted from Barex 210... °F) for the finished article is 0.04 barrer. 3 1 Use methods for determination of residual... Copolymers,” and “Analytical Method for 10% Solution Viscosity of Tyril,” which are incorproated by...

  1. 21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Styrene Monomers-Gas Chromatographic Internal Standard Method”; “Infrared Spectrophotometric Determination... methods for determination of residual acrylonitrile monomer content, maximum extractable fraction, number... Weights of Acrylonitrile/Styrene Copolymers,” and “Analytical Method for 10% Solution Viscosity of...

  2. 21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Styrene Monomers-Gas Chromatographic Internal Standard Method”; “Infrared Spectrophotometric Determination... methods for determination of residual acrylonitrile monomer content, maximum extractable fraction, number... Weights of Acrylonitrile/Styrene Copolymers,” and “Analytical Method for 10% Solution Viscosity of...

  3. 21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Styrene Monomers-Gas Chromatographic Internal Standard Method”; “Infrared Spectrophotometric Determination... methods for determination of residual acrylonitrile monomer content, maximum extractable fraction, number... Weights of Acrylonitrile/Styrene Copolymers,” and “Analytical Method for 10% Solution Viscosity of...

  4. 21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Styrene Monomers-Gas Chromatographic Internal Standard Method”; “Infrared Spectrophotometric Determination... methods for determination of residual acrylonitrile monomer content, maximum extractable fraction, number... Weights of Acrylonitrile/Styrene Copolymers,” and “Analytical Method for 10% Solution Viscosity of...

  5. Constraints of knowing or constraints of growing? : Fishing and collecting by the children of mer.

    PubMed

    Bird, Rebecca Bliege; Bird, Douglas W

    2002-06-01

    Recent theoretical models suggest that the difference between human and nonhuman primate life-history patterns may be due to a reliance on complex foraging strategies requiring extensive learning. These models predict that children should reach adult levels of efficiency faster when foraging is cognitively simple. We test this prediction with data on Meriam fishing, spearfishing, and shellfishing efficiency. For fishing and spearfishing, which are cognitively difficult, we can find no significant amount of variability in return rates because of experiential factors correlated with age. However, for shellfish collecting, which is relatively easy to learn, there are strong age-related effects on efficiency. Children reach adult efficiency more quickly in fishing as compared to shellfish collecting, probably owing to the size and strength constraints of the latter.

  6. Large deviation approach to the generalized random energy model

    NASA Astrophysics Data System (ADS)

    Dorlas, T. C.; Dukes, W. M. B.

    2002-05-01

    The generalized random energy model is a generalization of the random energy model introduced by Derrida to mimic the ultrametric structure of the Parisi solution of the Sherrington-Kirkpatrick model of a spin glass. It was solved exactly in two special cases by Derrida and Gardner. A complete solution for the thermodynamics in the general case was given by Capocaccia et al. Here we use large deviation theory to analyse the model in a very straightforward way. We also show that the variational expression for the free energy can be evaluated easily using the Cauchy-Schwarz inequality.

  7. 76 FR 2920 - Notice of Correction to Notice of Realty Action: Competitive Online Auction of Public Lands in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-18

    .... The individual patents, when issued, will contain a mineral reservation to the United States for oil, gas, sodium, potassium, and all saleable minerals. FOR FURTHER INFORMATION CONTACT: Manuela Johnson...

  8. Genome Sequence of Photobacterium halotolerans MELD1, with Mercury Reductase (merA), Isolated from Phragmites australis.

    PubMed

    Mathew, Dony Chacko; Mathew, Gincy Marina; Gicana, Ronnie Gicaraya; Huang, Chieh-Chen

    2015-06-04

    Here, we present the whole-genome sequence of Photobacterium halotolerans strain, MELD1, isolated from the roots of a terrestrial plant Phragmites australis grown in soil heavily contaminated with mercury and dioxin. The genome provides further insight into the adaptation of bacteria to the toxic environment from where it was isolated.

  9. Proglacial sediment supply and channel evolution of the Arveyron of the Mer de Glace since the early 20th c.

    NASA Astrophysics Data System (ADS)

    Berthet, Johan; Astrade, Laurent

    2015-04-01

    Glacier retreat in the Alps, from the end of the Little Ice Age (LIA) to now, has released large sediment-covered areas. Those rock debris are potential massive sediment supply which could increase proglacial stream activity and worry river managers and authorities. However, because of the ice shrinkage, proglacial hydrographic pattern in the headwater is evolving. The connexion between morainic sediments and proglacial streams is thus moving. The goal of our study is to understand the evolution of sediment sources and their level of connectivity with the proglacial streams located on the French side of the Mont-Blanc massif (Chamonix Valley). We have used the Connectivity Index (IC) wich is a geostatistic method based on lidar DEM for assessing the probability for the sediment- covered areas to be connected to a certain outlet. Then, we have kept only the IC which could be supplied by the potential glacial meltwater with the LIA and 2008 glacier extension. Unfortunately, available lidar DEM does not cover the entire study area. Nevertheless, it is sufficient to get partial or full results on different glacier types: valley glacier, cirque glacier, etc. Results are checked using the mapping of - active or not - gullies and through the analyse of the large historical picture collection available in which it is possible to identify the past active sediment sources. Results show some explicit processes such as the contraction of the sediment sources inside morainic vallums whereas the outer moraine side was active during the LIA. Generally, results suggest a disconnection trend between sediment sources and the trunk valley. These results seem to be confirmed by a general tendency of decreasing activity of proglacial streams which is observed in the Chamonix valley. Even if this method shows some bias, it represents an interesting semi-quantitative and geographic approach to assess past proglacial sediment sources thanks to glacier extensions. It is also possible to imagine other applications using this method such as isolated the IC from the lithology or the nature of sediment sources.

  10. Field Reconnaissance Geologic Mapping of the Columbia Hills, Mars: Results from MER Spirit and MRO HiRISE Observations

    USGS Publications Warehouse

    Crumpler, L.S.; Arvidson, R. E.; Squyres, S. W.; McCoy, T.; Yingst, A.; Ruff, S.; Farrand, W.; McSween, Y.; Powell, M.; Ming, D. W.; Morris, R.V.; Bell, J.F.; Grant, J.; Greeley, R.; DesMarais, D.; Schmidt, M.; Cabrol, N.A.; Haldemann, A.; Lewis, Kevin W.; Wang, A.E.; Schroder, C.; Blaney, D.; Cohen, B.; Yen, A.; Farmer, J.; Gellert, Ralf; Guinness, E.A.; Herkenhoff, K. E.; Johnson, J. R.; Klingelhofer, G.; McEwen, A.; Rice, J. W.; Rice, M.; deSouza, P.; Hurowitz, J.

    2011-01-01

    Chemical, mineralogic, and lithologic ground truth was acquired for the first time on Mars in terrain units mapped using orbital Mars Reconnaissance Orbiter's High Resolution Imaging Science Experiment (MRO HiRISE) image data. Examination of several dozen outcrops shows that Mars is geologically complex at meter length scales, the record of its geologic history is well exposed, stratigraphic units may be identified and correlated across significant areas on the ground, and outcrops and geologic relationships between materials may be analyzed with techniques commonly employed in terrestrial field geology. Despite their burial during the course of Martian geologic time by widespread epiclastic materials, mobile fines, and fall deposits, the selective exhumation of deep and well-preserved geologic units has exposed undisturbed outcrops, stratigraphic sections, and structural information much as they are preserved and exposed on Earth. A rich geologic record awaits skilled future field investigators on Mars. The correlation of ground observations and orbital images enables construction of a corresponding geologic reconnaissance map. Most of the outcrops visited are interpreted to be pyroclastic, impactite, and epiclastic deposits overlying an unexposed substrate, probably related to a modified Gusev crater central peak. Fluids have altered chemistry and mineralogy of these protoliths in degrees that vary substantially within the same map unit. Examination of the rocks exposed above and below the major unconformity between the plains lavas and the Columbia Hills directly confirms the general conclusion from remote sensing in previous studies over past years that the early history of Mars was a time of more intense deposition and modification of the surface. Although the availability of fluids and the chemical and mineral activity declined from this early period, significant later volcanism and fluid convection enabled additional, if localized, chemical activity.

  11. A Coverage Criterion for Spaced Seeds and Its Applications to Support Vector Machine String Kernels and k-Mer Distances

    PubMed Central

    Martin, Donald E.K.

    2014-01-01

    Abstract Spaced seeds have been recently shown to not only detect more alignments, but also to give a more accurate measure of phylogenetic distances, and to provide a lower misclassification rate when used with Support Vector Machines (SVMs). We confirm by independent experiments these two results, and propose in this article to use a coverage criterion to measure the seed efficiency in both cases in order to design better seed patterns. We show first how this coverage criterion can be directly measured by a full automaton-based approach. We then illustrate how this criterion performs when compared with two other criteria frequently used, namely the single-hit and multiple-hit criteria, through correlation coefficients with the correct classification/the true distance. At the end, for alignment-free distances, we propose an extension by adopting the coverage criterion, show how it performs, and indicate how it can be efficiently computed. PMID:25393923

  12. Estimation of the whitefly Bemisia tabaci genome size based on k-mer and flow cytometry analyses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Whiteflies, Bemisia tabaci (Hemiptera: Aleyrodidae), are one of the most important agricultural insect pests in the world. These phloem-feeding insects can colonize over 500 crop plants worldwide and inflict severe economic losses, mainly through the transmission of pathogenic viruses. Surprisingl...

  13. Comparing Apollo and Mars Exploration Rover (MER) Operations Paradigms for Human Exploration During NASA Desert-Rats Science Operations

    NASA Technical Reports Server (NTRS)

    Yingst, R. A.; Cohen, B. A.; Ming, D. W.; Eppler, D. B.

    2011-01-01

    NASA's Desert Research and Technology Studies (D-RATS) field test is one of several analog tests that NASA conducts each year to combine operations development, technology advances and science under planetary surface conditions. The D-RATS focus is testing preliminary operational concepts for extravehicular activity (EVA) systems in the field using simulated surface operations and EVA hardware and procedures. For 2010 hardware included the Space Exploration Vehicles, Habitat Demonstration Units, Tri-ATHLETE, and a suite of new geology sample collection tools, including a self-contained GeoLab glove box for conducting in-field analysis of various collected rock samples. The D-RATS activities develop technical skills and experience for the mission planners, engineers, scientists, technicians, and astronauts responsible for realizing the goals of exploring planetary surfaces.

  14. Aporphine alkaloids from the leaves of Phoebe grandis (Nees) Mer. (Lauraceae) and their cytotoxic and antibacterial activities.

    PubMed

    Omar, Hanita; Hashim, Najihah Mohd; Zajmi, Asdren; Nordin, Noraziah; Abdelwahab, Siddiq Ibrahim; Azizan, Ainnul Hamidah Syahadah; Hadi, A Hamid A; Ali, Hapipah Mohd

    2013-07-29

    The oxoaporphine alkaloid lysicamine (1), and three proaporphine alkaloids, litsericinone (2), 8,9,11,12-tetrahydromecambrine (3) and hexahydromecambrine A (4) were isolated from the leaves of Phoebe grandis (Nees) Merr. (Lauraceae). Compounds 2 and 3 were first time isolated as new naturally occurring compounds from plants. The NMR data for the compounds 2-4 have never been reported so far. Compounds 1 and 2 showed significant cytotoxic activity against a MCF7 (human estrogen receptor (ER+) positive breast cancer) cell line with IC₅₀ values of 26 and 60 µg/mL, respectively. Furthermore, in vitro cytotoxic activity against HepG2 (human liver cancer) cell line was evaluated for compounds 1-4 with IC₅₀ values of 27, 14, 81 and 20 µg/mL, respectively. Lysicamine (1) displayed strong antibacterial activity against Bacillus subtilis (B145), Staphylococcus aureus (S1434) and Staphylococus epidermidis (a clinically isolated strain) with inhibition zones of 15.50 ± 0.57, 13.33 ± 0.57 and 12.00 ± 0.00 mm, respectively. However, none of the tested pathogenic bacteria were susceptible towards compounds 2 and 3.

  15. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... chapter as Type VI-B under conditions for use E, F, or G described in table 2 of § 176.170(c) of this.... (e) Accelerated extraction end test. The modified copolymer shall yield acrylonitrile monomer not in... room temperature. A sample of the extracting solvent is then withdrawn and analyzed for...

  16. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... chapter as Type VI-B under conditions for use E, F, or G described in table 2 of § 176.170(c) of this.... (e) Accelerated extraction end test. The modified copolymer shall yield acrylonitrile monomer not in... room temperature. A sample of the extracting solvent is then withdrawn and analyzed for...

  17. Zooplankton communities fluctuations from 1995 to 2005 in the Bay of Villefranche-sur-Mer (Northern Ligurian Sea, France)

    NASA Astrophysics Data System (ADS)

    Vandromme, P.; Stemmann, L.; Berline, L.; Gasparini, S.; Mousseau, L.; Prejger, F.; Passafiume, O.; Guarini, J.-M.; Gorsky, G.

    2010-12-01

    An integrated analysis of the pelagic ecosystems of the Ligurian Sea is performed combining time series of different zooplankton groups (small and large copepods, chaetognaths, appendicularians, pteropods, thaliaceans, decapods larvae, other crustaceans, other gelatinous and other zooplankton), chlorophyll-a and nutrients, seawater salinity, temperature and density and local weather at the Point B coastal station (Northern Ligurian Sea). From January 1995 to December 2005, a shift in most variables occurred ca. 2000. From 1995 to 2000 winters were wet and mild resulting in lower winter sea surface density. These years showed lower than average nutrients and zooplankton concentrations while phytoplankton biomass was higher. After 2000, winters were colder and dryer resulting in higher sea surface density. Nutrients and zooplankton showed higher concentrations while phytoplankton was lower than average. The ca. 2000 shift was observed for most zooplankton groups with a one year delay for certain groups. The observed patterns suggest that the pelagic ecosystem trophic state is mostly set by the winter forcing on the convection that upwells nutrients to the surface sustaining the spring bloom. However, low phytoplankton concentrations in higher nitrate and zooplankton conditions during the well mixed years suggest that phytoplankton is controlled by grazers. The proposed mechanisms of convection regimes hold for most of the time series, but specific years with contradicting patterns needed to be explained by other factors. The limitation of phytoplankton growth by the light availability in spring/summer was then proposed as a secondary driving force that can moderate or even reverse the winter forcing. Finally, the eleven years of observation did not reveal a clear link with the North Atlantic Oscillation, suggesting a more complex dynamics linking large scale climate to Ligurian Sea ecosystems or that the length of the plankton monitoring is not yet sufficient to detect those links.

  18. In vivo quantifying molecular specificity of Cy5.5-labeled cyclic 9-mer peptide probe with dynamic fluorescence imaging

    PubMed Central

    Dai, Yunpeng; Yin, Jipeng; Huang, Yu; Chen, Xueli; Wang, Guodong; Liu, Yajun; Zhang, Xianghan; Nie, Yongzhan; Wu, Kaichun; Liang, Jimin

    2016-01-01

    We quantified molecular specificity of Cy5.5-GX1 in vivo with dynamic fluorescence imaging to better understand its kinetic properties. According to whether or not free GX1 was injected and when it was injected, twelve of BGC-823 xenografted mice were randomly divided into three groups and underwent a 60 minute dynamic fluorescence scanning. Combined with a principal-component analysis, the binding potential (Bp) of the probe was determined by both Logan graphical analysis with reference tissue model (GARTM) and Lammertsma simplified reference tissue model (SRTM). The sum of the pharmacokinetic rate constants (SKRC) was quantified by the Gurfinkel exponential model (GEXPM). Cy5.5-GX1 specifically targeted tumor both in vitro and in vivo. We obtained similar quantification results of Bp (GARTM Bp = 0.582 ± 0.2655, SRTM Bp = 0.618 ± 0.2923), and obtained a good linear relation between the Bp value and the SKRC value. Our results indicate that the SKRC value is more suitable for an early-stage kinetic data analysis, and the Bp value depicts kinetic characteristics under the equilibrium state. Dynamic fluorescence imaging in conjunction with various kinetic models are optimal tools to quantify molecular specificity of the Cy5.5-GX1 probe in vivo. PMID:27446643

  19. The epilepsy, the protease inhibitor and the dodecamer: progressive myoclonus epilepsy, cystatin b and a 12-mer repeat expansion.

    PubMed

    Lalioti, M D; Antonarakis, S E; Scott, H S

    2003-01-01

    Progressive myoclonus epilepsy 1 (EPM1) or Unverricht-Lundborg disease is a human autosomal recessive neurodegenerative disorder caused by mutations in cystatin B (CSTB). The CSTB gene maps to human chromosome 21 and encodes an inhibitor of lysosomal cysteine proteases. Five point mutations have been found, two of which are seen in numerous unrelated patients. However, the main CSTB mutation in EPM1, even among patients of different ethnic origins, is an expansion of a dodecamer repeat (CCCCGCCCCGCG) in the 5' flanking area of CSTB. Most normal alleles contain either two or three repeats, while rarer normal alleles that are highly unstable contain between 12 and 17 repeats. Mutant expanded alleles have been reported to contain between 30 and 80 copies and are also highly unstable, particularly via parental transmission. There is no apparent correlation between mutant repeat length and disease phenotype. While the repeat expansion is outside the CSTB transcriptional unit, it results in a marked decrease in CSTB expression, at least in certain cell types in vitro. CSTB homozygous knockout mice show some parallels to the phenotype of human EPM1 including myoclonic seizures, development of ataxia and neuropathological changes associated with cell loss via apoptosis. Loss of CSTB function due to mutations is consistent with the observed neurodegenerative pathology and phenotype, but the functional link to the epileptic phenotype of EPM1 remains largely unknown.

  20. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as... of a blend of: (1) 82-88 parts by weight of a matrix copolymer produced by polymerization of 77-82... by the method titled, “Determination of β-Dodecyl-mercaptopropionitrile in NR-16 Polymer,” which...

  1. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Determination of Polymer Extracted from Borex ® 210 Resin Pellets,” which is incorporated by reference. Copies... ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces... butadiene/styrene elastomer consists of a blend of: (1) 82-88 parts by weight of a matrix copolymer...

  2. 21 CFR 177.1050 - Acrylonitrile/styrene copoly-mer modified with butadiene/styrene elastomer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Determination of Polymer Extracted from Borex ® 210 Resin Pellets,” which is incorporated by reference. Copies... ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces... butadiene/styrene elastomer consists of a blend of: (1) 82-88 parts by weight of a matrix copolymer...

  3. The meroperon of a mercury-resistant Pseudoalteromonas haloplanktis strain isolated from Minamata Bay, Japan.

    PubMed

    Iohara, K; Iiyama, R; Nakamura, K; Silver, S; Sakai, M; Takeshita, M; Furukawa, K

    2001-09-01

    A mer operon of mercury-resistant Pseudoalteromonas haloplanktis strain M1, isolated from sea water of Minamata Bay, was cloned and analyzed. The mer genes were located in the chromosome and organized as merR-merT-merP-merC-merA-merD, the same order as that in Tn21. However, the orientation of the merR gene is the same as that of other mer genes (opposite direction to Tn21), and merR was cotranscribed with other mer genes, a pattern that has not been previously seen with mer determinants from other Gram-negative bacteria. Furthermore, the amino acid similarities of the corresponding mer gene products between those from strain M1 and Tn21 were unusually low.

  4. Thermal Design and Flight Experience of the Mars Exploration Rover Spacecraft Computer-Controlled, Propulsion Line Heaters

    NASA Technical Reports Server (NTRS)

    Novak, Keith; Kinsella, Gary; Krylo, Robert; Sunada, Eric

    2004-01-01

    The viewgraph presentation examines propulsion line heater design and problems in the Mars Rover. Topics include a Mars Exploration Rover (MER) project description and MER spacecraft configuration, mission overview, MER cruise stage hardware, thermal design drivers in the propulsion lines, propulsion line control set points prior to launch, MER A and B flight trajectories, MER A early and mid cruise flight experience, MER A and B mid cruise flight experience, MER B late cruise flight experience, and lessons learned

  5. Weathering of Basaltic Rocks from the Gusev Plains up into the Columbia Hills from the Perspective of the MER Mossbauer Spectrometer

    NASA Technical Reports Server (NTRS)

    Schroeder, C.; Klingelhoefer, G.; Morris, R. V.; Rodionov, D. S.; deSouza, P. A.; Ming, D. W.; Yen, A. S.; Gellert, R.; Bell, J. F., III

    2005-01-01

    Rocks on the ejecta blanket of Bonneville crater and along Spirit s traverse over the Gusev plains towards the Columbia Hills are angular and strewn across the surface. They have a basaltic composition [1,2], and their Mossbauer spectra are dominated by an olivine doublet [1]. The ubiquitous presence of abundant olivine in rocks and in surrounding soil suggests that physical rather than chemical weathering processes currently dominate the plains at Gusev crater [1]. However, MB spectra of rocks and outcrops in the Columbia Hills suggest more aggressive alteration processes have occurred. Ascending into the hills, Spirit encountered outcrop and rocks exhibiting layered structures. Some scattered rocks at the foot of the Columbia Hills appeared "rotten" or highly altered by physical and/or chemical processes (fig. 1). Mossbauer spectra of those rocks show a decrease in olivine accompanied by an increase in the Fe-oxides magnetite, hematite, and nanophase Fe3+ -oxides (fig. 2), suggesting that chemical weathering processes in the presence of water have altered these rocks and outcrops.

  6. Solvent–amino acid interaction energies in three-dimensional-lattice Monte Carlo simulations of a model 27-mer protein: Folding thermodynamics and kinetics

    PubMed Central

    Leonhard, Kai; Prausnitz, John M.; Radke, Clayton J.

    2004-01-01

    Amino acid residue–solvent interactions are required for lattice Monte Carlo simulations of model proteins in water. In this study, we propose an interaction-energy scale that is based on the interaction scale by Miyazawa and Jernigan. It permits systematic variation of the amino acid–solvent interactions by introducing a contrast parameter for the hydrophobicity, Cs, and a mean attraction parameter for the amino acids, ω. Changes in the interaction energies strongly affect many protein properties. We present an optimized energy parameter set for best representing realistic behavior typical for many proteins (fast folding and high cooperativity for single chains). Our optimal parameters feature a much weaker hydrophobicity contrast and mean attraction than does the original interaction scale. The proposed interaction scale is designed for calculating the behavior of proteins in bulk and at interfaces as a function of solvent characteristics, as well as protein size and sequence. PMID:14739322

  7. Structural Studies of Apo Nosl, an Accessory Protein of the Nitrous Oxide Reductase System: Insights from Structural Homology with MerB, a Mercury Resistance Protein

    SciTech Connect

    Taubner, Lara M.; McGuirl, Michele A.; Dooley, David M.; Copie, Valerie

    2006-09-19

    The formation of the unique catalytic tetranuclear copper cluster (CuZ) of nitrous oxide reductase, N2OR, requires the coexpression of a multiprotein assembly apparatus encoded by the nosDFYL operon. NosL, one of the proteins encoded by this transcript, is a 20 kDa lipoprotein of the periplasm that has been shown to bind copper(I), although its function has yet to be detemined. Cu(I) EXAFS data collected on the holo protein demonstrated that features of the copper binding site are consistent with a role for this protein as a metallochaperone, a class of metal ion transporters involved in metal resistance, homeostasis, and metallocluster biosynthesis. To test this hypothesis and to gain insight into other potential functional roles for this protein in the N2OR system, the three-dimensional solution structure of apo NosL has been solved by solution NMR methods. The structure of apo NosL consists of two relatively independent homologous domains that adopt an unusual topology.

  8. Meeting on the Physical Oceanography of Sea Straits (2nd). Held in Villefanche-sur-Mer, France on 15-19 April 2002

    DTIC Science & Technology

    2002-04-19

    shallow-water layer models such as streamtube models . How well do they reproduce the physics of hydraulically driven turbulent flows with continuous...usually turbulent . Thus, while the flow types derived from simple Flow of a homogeneous fluid along a curved models are useful in interpretating...philosophy in the numerical modeling was to .7:° use the turbulent diffusivity as an independent free M parameter - generated by an unspecified source

  9. Identification of a pivotal endocytosis motif in c-Met and selective modulation of HGF-dependent aggressiveness of cancer using the 16-mer endocytic peptide.

    PubMed

    Cho, K-W; Park, J H; Park, C-W; Lee, D; Lee, E; Kim, D J; Kim, K J; Yoon, S H; Park, Y; Kim, E; Cho, S; Jang, S; Park, B-C; Chi, S-W; Yoo, S H; Jang, M H; Kim, H N; Kim, E; Jo, K; Park, Y W

    2013-02-21

    Since c-Met has an important role in the development of cancer, it is considered as an attractive target for cancer therapy. Although molecular mechanisms for oncogenic property of c-Met have been actively investigated, regulatory elements for c-Met endocytosis and its effect on c-Met signaling remain unclear. In this study, we identified a pivotal endocytic motif in c-Met and tested it for selective modulation of HGF-induced c-Met response. Using various chimeric constructs with the cytoplasmic tail of c-Met, we were able to demonstrate that a dileucine motif located in the C-terminus of c-Met acts to regulate its endocytosis. Synthetic peptide Ant-3S, consisting of antennapedia-derived protein transduction domain (designated as Ant) and c-Met-derived 16 amino-acids (designated as 3S, spanning amino-acids 1378 to 1393), rapidly moved into cancer cells and disrupted c-Met trafficking. Importantly, an extension of c-Met retention time on the membrane by Ant-3S peptide significantly decreased phosphorylation-dependent c-Met signal transduction. Additionally, the peptide effectively inhibited HGF-induced cell growth, scattering and migration. The underlying molecular mechanism for these observations has been investigated and revealed that the dileucine motif interacts with endocytic machinery, including adaptin β and caveolin-1, for sustained and enhanced signal transduction. Finally, Ant-3S peptide specifically blocked internalization of interleukin-2 receptor α-subunit/3S chimeric protein, but not the other receptors, including Glut4, Glut8 and transferrin receptor. Such results indicate the presence of a selective endocytic assembly for c-Met. It also suggests a potential for c-Met-specific anti-cancer therapy using the identified endocytic motif in this study.

  10. K-12 Science Education Linked to Mars and the MER Mission: A New Curriculum Entitled Making Tracks on Mars Teacher Resource and Activity Guide

    NASA Astrophysics Data System (ADS)

    Aubele, J. C.; Stanley, J.; Grochowski, A.; Jones, K.; Aragon, J.

    2006-03-01

    Students' interest in Mars can be used as a "hook" to teach a wide range of topics. Mars-related science is used as the basis of a new K-12 integrated curriculum created by the New Mexico Museum of Natural History and classroom educators.

  11. A phage display selected 7-mer peptide inhibitor of the Tannerella forsythia metalloprotease-like enzyme Karilysin can be truncated to Ser-Trp-Phe-Pro.

    PubMed

    Skottrup, Peter Durand; Sørensen, Grete; Ksiazek, Miroslaw; Potempa, Jan; Riise, Erik

    2012-01-01

    Tannerella forsythia is a gram-negative bacteria, which is strongly associated with the development of periodontal disease. Karilysin is a newly identified metalloprotease-like enzyme, that is secreted from T. forsythia. Karilysin modulates the host immune response and is therefore considered a likely drug target. In this study peptides were selected towards the catalytic domain from Karilysin (Kly18) by phage display. The peptides were linear with low micromolar binding affinities. The two best binders (peptide14 and peptide15), shared the consensus sequence XWFPXXXGGG. A peptide15 fusion with Maltose Binding protein (MBP) was produced with peptide15 fused to the N-terminus of MBP. The peptide15-MBP was expressed in E. coli and the purified fusion-protein was used to verify Kly18 specific binding. Chemically synthesised peptide15 (SWFPLRSGGG) could inhibit the enzymatic activity of both Kly18 and intact Karilysin (Kly48). Furthermore, peptide15 could slow down the autoprocessing of intact Kly48 to Kly18. The WFP motif was important for inhibition and a truncation study further demonstrated that the N-terminal serine was also essential for Kly18 inhibition. The SWFP peptide had a Ki value in the low micromolar range, which was similar to the intact peptide15. In conclusion SWFP is the first reported inhibitor of Karilysin and can be used as a valuable tool in structure-function studies of Karilysin.

  12. Transposon tagging of a male-sterility, female-sterility gene, St8, revealed that the meiotic MER3 DNA helicase activity is essential for fertility in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The W4 locus in soybean encodes a dihydroflavonol-4-reductase (DFR2) that regulates pigmentation patterns in flowers and hypocotyl. The mutable w4-m allele that governs variegated flowers has arisen through insertion of a CACTA-type transposable element, Tgm9, in DFR2. In the w4-m line, reversion fr...

  13. Strategy for the In Situ Search of Evaporite and Carbonate Deposits in Gusev Crater Within the 2003 MER A Landing Ellipse

    NASA Technical Reports Server (NTRS)

    Grin, E. A.; Cabrol, N. A.; Leone, G.; Orofino, V.

    2002-01-01

    Topographic profiles and MOC images suggest that the flat floor of Gusev results from sediment deposition in the absence of strong sublacustrine currents. This setting is favorable to preserve undisturbed sedimentary sequences and identify carbonates and evaporites in the landing ellipse. Additional information is contained in the original extended abstract.

  14. Inter-annual fluctuations of zooplankton communities in the Bay of Villefranche-sur-mer from 1995 to 2005 (Northern Ligurian Sea, France)

    NASA Astrophysics Data System (ADS)

    Vandromme, P.; Stemmann, L.; Berline, L.; Gasparini, S.; Mousseau, L.; Prejger, F.; Passafiume, O.; Guarini, J.-M.; Gorsky, G.

    2011-11-01

    An integrated analysis of the pelagic ecosystems of the Ligurian Sea is performed combining time series (1995-2005) of several zooplankton groups (one group for copepods smaller than 0.724 mm3 and nine groups for individuals larger than 0.724 mm3, i.e. large copepods, decapod larvæ, other crustaceans, chaetognaths, appendicularians, pteropods, thaliaceans, gelatinous predators and other zooplankton), chlorophyll-a, nutrients, salinity, temperature, density, and local weather at Point B coastal station (Northern Ligurian Sea). From 1995 to 2000 winters were wet and mild resulting in lower winter sea surface density. These years showed lower than average nutrients and zooplankton concentrations while chlorophyll-a biomass was high. After 2000, winters were colder and dryer resulting in higher sea surface density. Nutrients and zooplankton showed higher concentrations while chlorophyll-a was lower than average. The ca. 2000 change was observed for most zooplankton groups with a one-year delay for some groups. Inter-annual variability within each period was also observed. The observed patterns suggest that the pelagic ecosystem trophic state at the studied point is mostly set by the winter forcing on the vertical mixing that upwells nutrients to the surface sustaining primary production. Surprisingly, low chlorophyll-a biomass in high nitrate and zooplankton conditions during the well mixed years suggest that phytoplankton biomass is controlled by grazers. The proposed mechanisms of stronger winter vertical mixing hold for most of the time series, but specific years with contradicting patterns suggest also the possible influence of the summer climate. A review of recent literature suggests that changes in the pelagic ecosystem are not limited to the studied site but concern also the central Ligurian Sea.

  15. Short communication: Measuring the angiotensin-converting enzyme inhibitory activity of an 8-amino acid (8mer) fragment of the C12 antihypertensive peptide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An eight amino acid fragment (PFPEVFGK) of a known milk protein-derived antihypertensive peptide was synthesized by microwave-assisted solid phase peptide synthesis and purified by reverse phase HPLC. Its ability to inhibit the angiotensin-converting enzyme was assessed and compared to that of the ...

  16. Survival at Sea for Mariners, Aviators and Search and Rescue Personnel (Survie en mer pour les marins, les aviateurs et le personnel de recherche et de sauvetage)

    DTIC Science & Technology

    2008-02-01

    afflict the ship’s complement at a given sea state and condition [135]. However, large mobile drilling platforms and super-tankers of immense...sickness varies over the menstrual cycle as a consequence of hormone al variation. Using a relatively mild provocation of a video game , only the most...susceptible part of the population would have experienced significant motion sickness. In addition, the stimulus dose of a video game is difficult

  17. Group Contribution Analysis of the Damping Behavior of Homopolymers, Statistical Copolymers, and Interpenetrating Polymer Networks Based on Acrylic, Vinyl, and Styrenic Mers,

    DTIC Science & Technology

    1987-01-01

    synthesis, mixtures of monomer(s), crosslinker, and benzoin was poured into a glass mold fitted with an EPDM rubber cord gasket and exposed to U.V...dyne/cm2 in comparison with the values of 2.3 to 3.3 * 10 dyne/cm 2 (44) by ASTM test method D638. ILI.... RESULTS All samples were cut to appropriate...homologous series versus number of methylene groups in the ester side group. The asymptotic value is assumed to be the LA of backbone. Fig. 4 Test of

  18. Learning and Skills Development in a Virtual Class of Educommunication Based on Educational Proposals and Interactions

    ERIC Educational Resources Information Center

    Bohorquez Sotelo, Maria Cristina; Rodriguez Mendoza, Brigitte Julieth; Vega, Sandra Milena; Roja Higuera, Naydu Shirley; Barbosa Gomez, Luisa Fernanda

    2016-01-01

    In the present paper we describe the analysis of qualitative and quantitative data from asynchronous learning networks, the virtual forums that take place in VirtualNet 2.0, the platform of the University Manuela Beltran (UMB), inside the course of Educommunication, from the master of Digital technologies applied to education. Here, we performed a…

  19. Home and abroad: vets' role in dealing with rabies.

    PubMed

    Herrera, Manuela

    2014-11-29

    Manuela Herrera reports on a session at the BVA Congress which discussed the contributions that vets can make to tackling rabies, and how the profession can be at the forefront of a One Health approach to saving the lives of animals and people.

  20. "Disturbing the Waters": Using Relational Knowledge to Explore Methodology

    ERIC Educational Resources Information Center

    Reyes, Cynthia C.

    2008-01-01

    In this article, the author examines her racial identity and its impact on her interpretation of the schooling experiences of a 10th grade Latina in an ethnographic case study. Prior to this study, the author had been working in a university-based family literacy program where she met Zulmy's mother, Manuela. Due to her experience as a middle…

  1. Autocorrelation and Regularization of Query-Based Information Retrieval Scores

    DTIC Science & Technology

    2008-02-01

    projected scores. This problem has similar solutions to monolingual regularization. The iterative solution is, ft+1t = (1− α)yt + αStf t t (8.7) The... multilingual corpora. In Manuela M. Veloso, editor, IJCAI 2007, Proceedings of the 20th International Joint Conference on Artificial In- telligence

  2. Guidelines for the Laboratory Diagnosis of Middle East Respiratory Syndrome Coronavirus in Korea

    PubMed Central

    Sung, Heungsup; Kim, Sinyoung; Seong, Moon-Woo; Yong, Dongeun; Kim, Jae-Seok; Lee, Mi-Kyung; Choi, Jong-Rak; Kim, Jeong-Ho

    2016-01-01

    The recent outbreak of Middle East respiratory syndrome (MERS) in Korea was unexpected that laboratory response had to be built up urgently during the outbreak. The outbreak was almost all healthcare-associated, which was aggravated by lack of availability in laboratory diagnosis of MERS-CoV on site. On behalf of the MERS joint public and private sector response committee (MERS Joint committee), the Korean Society for Laboratory Medicine (KSLM) launched a MERS response task force (MERS KSLM TF) to facilitate clinical laboratories set up MERS molecular diagnosis. MERS TF established guidelines for laboratory diagnosis of MERS-CoV and provided it to all participating laboratories as the official guidance of MERS Joint committee. This guideline was used for procedure manual of molecular diagnosis of MERS-CoV and laboratory safety manual. PMID:27104019

  3. On-line Robot Adaptation to Environmental Change

    DTIC Science & Technology

    2005-08-01

    background needed to understand the thesis . This robotic system was originally de- veloped for use in the RoboCup Sony legged league which is an...The league currently uses the ERS-7 AIBO model. This platform was used for all of the robotic testing in this thesis . In the legged league...Carnegie Mellon University Pittsburgh, PA 15213 Thesis Committee: Manuela Veloso, Chair Takeo Kanade Anthony Stentz Minoru Asada, Osaka University, Japan

  4. West Europe Report

    DTIC Science & Technology

    2007-11-02

    interest than making moral judgments about the centralism of Jose Carlos Vasconcelos or Sa Borges (not to speak of the political friend of Otelo...Executive Committee, but he is a member of the National Advisory Council along with Joao Botequilha, Manuel Caetano, Jose Rabaca, and Luis Marques...sources, 18, 22 Jun 85) 34 Ideology Seen Lacking, by Jose Miguel Judice 34 Manuela Eanes Suggested 36 Importance of President’s Wife 36 Future

  5. Pointers from the Americas.

    PubMed

    Aragon-choudhury, P

    1992-01-01

    During a sharing session which took place at a conference sponsored by the Philippine Institute for Social Studies and Action in 1991, Peruvian Victoria Villanueva and US citizen Margaret Ann Schuller discussed their work. Schuller reported on her upcoming book entitled "Freedom from Violence: Women's Strategies Around the World." In addition to proposing a definition of violence against women, the book will include 12 case studies from Malaysia, Bolivia, Mexico, India, Pakistan, Thailand, Sri Lanka, Brazil, Zimbabwe, Chile, Africa, and Alaska describing how national organizations of women are dealing with the problem. An important advance is the development of a framework to look at the connection which exists between violence and health issues. Villanueva described the work of the Movimiento Manuela Ramos, which was organized informally to deal with reproductive rights and abortion and has since expanded to parent groups of women who defend legal and medical cases as paid paralegals. Manuela Ramos uses popular media, traditional drama, and even state television to publicize its issues. Manuela Ramos has accomplished important work on rape, unsafe abortion, and maternal mortality, but most importantly, the women involved with the organization have had the opportunity to develop their self-esteem.

  6. Intra- and supra­molecular inter­actions in cis,mer-diaqua­tris­(1H-imidazole-κN 3)(terephthalato-κO)cobalt(II) monohydrate

    PubMed Central

    Benkanoun, Aouaouche; Balegroune, Fadila; Guehria-Laïdoudi, Achoura; Dahaoui, Slimane; Lecomte, Claude

    2012-01-01

    In the title compound, [Co(C8H4O4)(C3H4N2)3(H2O)2]·H2O, the cisoid angles are in the range 85.59 (5)–93.56 (5)°, while two equal transoid angles deviate significantly from the ideal linear angle, the third being almost linear. One carboxyl­ate group is almost coplanar [1.23 (13)°] with the plane of its parent aromatic ring, although it has one O-atom donor involved in one coordination and one hydrogen bond as acceptor. The other carboxyl­ate group does not coordinate and is rotated out of this plane with a torsional twist of 17.27 (20)°. The coordination neutral entity, based on aqua ligands and two cyclic co-ligands seems, at first sight, monomeric. Strongly tight, via one intra­molecular hydrogen bond between aqua and carboxyl­ate O atoms, it brings out a quasi-planar six-membered ring around the CoII atom, turning the CoN3O3 coordination octa­hedron into a new building block. The rigidity of this feature associated with several hydrogen-bonded arrays yields an extended structure. In the resulting supra­molecular packing, a binuclear hydrated CoII assembly, built up from triple strands driven by different heterosynthons, embodies the synergy of coordination, covalent and hydrogen bonds. PMID:22589841

  7. Fluid Dynamics Problems of Vehicles Operating Near or in the Air-Sea Interface (Problemes de Dynamique des Fluides des Vehicules Evoluant dans ou pres de L’interface Air-Mer).

    DTIC Science & Technology

    1999-02-01

    ecoulement ä surface libre, instationnaire, couple avec des effets thermodynamiques lies aux gaz de chasse chauds et condensables. Dans une premiere...fermeture de la bulle. Dans une seconde partie une decomposition des phenomenes thermodynamiques basee sur une modelisation et des calculs numeriques [4... thermodynamiques interviennent si les gaz de chasse sont condensables. C’est ce qui arrive lorsque ces gaz resultent d’une combustion et qu’ils sont

  8. The effects of concentrate added to pineapple (Ananas comosus Linn. Mer.) waste silage in differing ratios to form complete diets, on digestion, excretion of urinary purine derivatives and blood metabolites in growing, male, Thai swamp buffaloes.

    PubMed

    Jetana, T; Suthikrai, W; Usawang, S; Vongpipatana, C; Sophon, S; Liang, J B

    2009-04-01

    Four, male, growing Thai swamp buffaloes (197 +/- 5.3 kg and all 1 year old) were used to evaluate the effects of concentrate added to pineapple waste silage in differing ratios, to form a complete diet, studying in vivo digestion, the rate of passage, microbial protein synthesis and blood metabolites. Animals were fed ad libitum with 4 diets, using four combinations of pineapple waste silage (P) and concentrate (C), in the proportions (on a dry matter basis) of 0.8:0.2 (P80:C20), 0.6:0.4 (P60:C40), 0.4:0.6 (P40:C60) and 0.2:0.8 (P20:C80). The results showed that the intakes of dry matter (DM), organic matter (OM), nitrogen (N), the N-balance, urinary purine derivatives (PD) excretion, the ratios of allantoin to creatinine (CR), PD to CR, the plasma urea-N (PUN) and insulin increased in the animals, but the intake of neutral detergent fiber (NDF), the coefficient of whole tract, apparent digestibility of NDF, the transit time (TT) and the mean retention time (TMRT) decreased, when the proportion of concentrate in the diet increased. This study indicated that the proportion of P40:C60 in the diet produced the best efficiency of urinary PD excretion (mmol) per digestible OM intake (kg DOMI).

  9. Structure of an anti-HIV-1 hammerhead ribozyme complex with a 17-mer DNA substrate analog of HIV-1 gag RNA and a mechanism for the cleavage reaction: 750 MHz NMR and computer experiments

    NASA Technical Reports Server (NTRS)

    Ojha, R. P.; Dhingra, M. M.; Sarma, M. H.; Myer, Y. P.; Setlik, R. F.; Shibata, M.; Kazim, A. L.; Ornstein, R. L.; Rein, R.; Turner, C. J.; Sarma, R. H.

    1997-01-01

    The structure of an anti-HIV-1 ribozyme-DNA abortive substrate complex was investigated by 750 MHz NMR and computer modeling experiments. The ribozyme was a chimeric molecule with 30 residues-18 DNA nucleotides, and 12 RNA residues in the conserved core. The DNA substrate analog had 17 residues. The chimeric ribozyme and the DNA substrate formed a shortened ribozyme-abortive substrate complex of 47 nucleotides with two DNA stems (stems I and III) and a loop consisting of the conserved core residues. Circular dichroism spectra showed that the DNA stems assume A-family conformation at the NMR concentration and a temperature of 15 degrees C, contrary to the conventional wisdom that DNA duplexes in aqueous solution populate entirely in the B-form. It is proposed that the A-family RNA residues at the core expand the A-family initiated at the core into the DNA stems because of the large free energy requirement for the formation of A/B junctions. Assignments of the base H8/H6 protons and H1' of the 47 residues were made by a NOESY walk. In addition to the methyl groups of all T's, the imino resonances of stems I and III and AH2's were assigned from appropriate NOESY walks. The extracted NMR data along with available crystallographic data, were used to derive a structural model of the complex. Stems I and III of the final model displayed a remarkable similarity to the A form of DNA; in stem III, a GC base pair was found to be moving into the floor of the minor groove defined by flanking AT pairs; data suggest the formation of a buckled rhombic structure with the adjacent pair; in addition, the base pair at the interface of stem III and the loop region displayed deformed geometry. The loop with the catalytic core, and the immediate region of the stems displayed conformational multiplicity within the NMR time scale. A catalytic mechanism for ribozyme action based on the derived structure, and consistent with biochemical data in the literature, is proposed. The complex between the anti HIV-1 gag ribozyme and its abortive DNA substrate manifests in the detection of a continuous track of A.T base pairs; this suggests that the interaction between the ribozyme and its DNA substrate is stronger than the one observed in the case of the free ribozyme where the bases in stem I and stem III regions interact strongly with the ribozyme core region (Sarma, R. H., et al. FEBS Letters 375, 317-23, 1995). The complex formation provides certain guidelines in the design of suitable therapeutic ribozymes. If the residues in the ribozyme stem regions interact with the conserved core, it may either prevent or interfere with the formation of a catalytically active tertiary structure.

  10. Direct synthesis and characterization of site-specific adenosyl adducts derived from the binding of a 3,4-dihydroxy-1,2-epoxybenzo[c]phenanthrene stereoisomer to an 11-mer oligodeoxyribonucleotide

    SciTech Connect

    Laryea, A.; Liu, T.; Smirnov, S.

    1995-04-01

    Site-specifically modified oligonucleotides were obtained in milligram quantities by reacting racemic 3t,4r-dihydroxy-1,2t-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (B[c]PhDE-2, or anti-B[c]PhDE) with the single deoxyadenosine (dA) residue in the oligodeoxynucleotide d(CTCTCACTTCC). Enzyme digestion of the covalently modified oligonucleotides with the exonuclease spleen phosphodiesterase yielded covalently linked B[c]PhDE-N{sup 6}-deoxyadenosyl monophosphate (dAMP) adducts. Comparisons of the reverse phase HPLC retention times and CD spectra of these B[c]PhDE-N{sup 6}-deoxyadenosyl monophosphate (dAMP) adducts. Comparisons of the reverse phase HPLC retention times and CD spectra of these B[c]PhDE-3{prime}-dAMP mononucleotide adducts, with those of standards derived from the reaction of the enantiomers (+)- and (-)-anti-B[c]PhDE with 3{prime}-dAMP, show that two major oligonucleotide adducts (I and II) were obtained upon reacting racemic anti-B[c]PhDE with d(CTCTCACTTCC). In oligonucleotide adduct I, the lesion is a (+)-trans-anti-B[c]PhDE-N{sup 6}-dA residue, and in oligonucleotide adduct II it is a (-)-trans-anti-B[c]PhDE-N{sup 6}-dA residue. These assignments were further confirmed using a standard {sup 32}P postlabeling assay of B[c]PhDE-3{prime}-dAMP mononucleotide adducts obtained from the digestion of oligonucleotides I and II by spleen phosphodiesterase. The melting points (T{sub m}) of duplexes of modified oligonucleotides I and II and their natural complementary strands are not affected significantly by the presence of the covalently bound benzo[c]phenanthrenyl residues. Opposite stereoselective resistance to enzyme digestion by the exonucleases snake venom phosphodiesterase and spleen phosphodiesterase is exhibited by the stereoisomeric (+)-trans- and (-)-trans-anti-B[c]PhDE-modified oligonucleotide adducts I and II. 58 refs., 10 figs.

  11. Photochemistry of Iron and Ruthenium Carbonyl Complexes: Evidence for Light-Induced Loss of Carbon Monoxide and Reductive Elimination of Triethylsilane from cis-mer-HM(SiEt3)(CO)3(PPh3).

    DTIC Science & Technology

    1983-05-21

    absorptivity of CO in organic glasses is -350 ± 2010 M-1 cm-1 . These data will be reported elsewhere. 12. (a) Poliakoff , M. J. Chem. Soc., Dalton Trans...1974, 210; (b) Poliakoff , M.; Turner, J.J. J. Chem. Soc., Faraday Trans., 1974, 70, 93. 13. Boxhoorn, G.; Cerfontain, M.B.; Stufkens, D.J.; Oskam, A

  12. Functions, Evolution, and Application of the Supramolecular Machines of Hg Detoxification

    SciTech Connect

    Miller, Susan M.

    2009-11-27

    The bacterial mercury resistance (mer) operon functions in Hg biogeochemistry and bioremediation by converting reactive inorganic [Hg(II)] and organic [RHg(I)] mercurials to relatively inert monoatomic mercury vapor, Hg(0). Its genes regulate expression (MerR, MerD, MerOP), import Hg(II) (MerT, MerP, and MerC), and demethylate (MerB) and reduce (MerA) mercurials. We focus on how these components interact with each other and with the host cell to allow cells to survive and detoxify Hg compounds. Understanding how this ubiquitous detoxification system fits into the biology and ecology of its bacterial host is essential to guide interventions that support and enhance Hg remediation. At a more basic level, studies of interactions between the metal ion trafficking proteins in this pathway provide insights into general mechanisms used by proteins in pathways involved in trafficking of other metal ions in cells of all types of organisms, including pathways for essential metal ions such as Cu and Zn and other toxic metal ions such as Cd. In this project we focused on investigations of proteins from mer operons found in gamma-proteobacteria with specific objectives to use biophysical and biochemical approaches to detect and define (1) interactions between the structural components of the key detoxifying mer operon enzyme, mercuric ion reductase (MerA), (2) interactions between the components of MerA and the other mer operon enzyme, organomercurial lyase (MerB), and (3) to investigate the structure and interactions of integral membrane transport proteins, MerT and MerC, with MerA.

  13. Relationships among cell survival, O6-alkylguanine-DNA alkyltransferase activity, and reactivation of methylated adenovirus 5 and herpes simplex virus type 1 in human melanoma cell lines

    SciTech Connect

    Maynard, K.; Parsons, P.G.; Cerny, T.; Margison, G.P. )

    1989-09-01

    O6-Alkylguanine-DNA alkyltransferase (ATase) activity and host cell reactivation (HCR) of 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC)-methylated viruses were compared in human melanoma cell lines that were sensitive or resistant to killing by the antitumor DNA-methylating agent MTIC. Enhanced HCR of adenovirus 5 (defined as the Mer+ phenotype) generally showed a semiquantitative correlation with the natural or induced resistance of the host cells to the toxic effects of MTIC and to the level of ATase activity. However, one MTIC-resistant cell line was found (MM170) which had a low level of ATase and intermediate HCR of adenovirus. The HCR of herpes simplex virus type 1 (HSV-1) was enhanced in the Mer+ cells that had natural resistance to MTIC compared with Mer- cells. On the other hand, HCR of HSV-1 in Mer+ cells with induced resistance to MTIC was similar to that in Mer- cells. Neither adenovirus 5 nor HSV-1 infection induced ATase activity in Mer- cells. This indicates that resistance to the toxic effects of methylating agents is not invariably associated with high levels of ATase activity in human melanoma cells. Furthermore, while induction of the Mer+ phenotype from Mer- cells was usually accompanied by the recovery of ATase activity, induced Mer+ cells had less proficient repair than natural Mer+ cells, as judged quantitatively by slightly lower cellular resistance and qualitatively by deficient HCR response for HSV-1. These results suggest that the Mer- and induced Mer+ cells lack an ATase-independent DNA repair mechanism. No differences in MTIC-induced DNA repair synthesis or strand breaks were found between the Mer-, natural Mer+, and induced Mer+ phenotypes. However, UV-induced DNA repair synthesis was higher in the natural Mer+ than in the Mer- or induced Mer+ cells, both of which had increased cellular sensitivity to the antimetabolites methotrexate and hydroxyurea.

  14. Protective Efficacy of Recombinant Modified Vaccinia Virus Ankara Delivering Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein.

    PubMed

    Volz, Asisa; Kupke, Alexandra; Song, Fei; Jany, Sylvia; Fux, Robert; Shams-Eldin, Hosam; Schmidt, Jörg; Becker, Christin; Eickmann, Markus; Becker, Stephan; Sutter, Gerd

    2015-08-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans. We tested a recombinant modified vaccinia virus Ankara (MVA) vaccine expressing full-length MERS-CoV spike (S) glycoprotein by immunizing BALB/c mice with either intramuscular or subcutaneous regimens. In all cases, MVA-MERS-S induced MERS-CoV-specific CD8(+) T cells and virus-neutralizing antibodies. Vaccinated mice were protected against MERS-CoV challenge infection after transduction with the human dipeptidyl peptidase 4 receptor. This MERS-CoV infection model demonstrates the safety and efficacy of the candidate vaccine.

  15. Geochemical Anomalies and Rock Coatings on Mars: Significance to MSR

    NASA Astrophysics Data System (ADS)

    Clark, B. C.; Gellert, R.

    2016-08-01

    Mars rover missions [Spirit (MER-A), Opportunity (MER-B), Curiosity (MSL)] have discovered unexpected geochemical extremes from aqueous alteration. Coatings and certain trace elements show large enrichment's well beyond magmatic differentiation.

  16. Molecular mechanisms of plasmid-determined mercury and cadmium resistances in bacteria

    SciTech Connect

    Nucifora, G.

    1989-01-01

    The structural basis for induction of the broad spectrum mercurial resistance operon of pDU1358 with inorganic mercury and with phenylmercury acetate was addressed by DNA sequencing analysis (that showed that a major difference occurred in the 3{prime} 29 base pairs of the ital merR gene compared to the merR genes of Tn501 and R100) and by lac-fusion transcription experiments regulated by merR in trans. The lac-fusion results were compared with those from a narrow spectrum operon, and the pDU1358 merR deleted at the 3{prime} end. A hybrid mer operon containing the merR gene from pDU1358 and lacking the merB gene was inducible by both phenylmercury and inorganic Hg{sup 2+}, showing that organomercurial lyase is not needed for induction by organomercurials. A mutant form of pDU1358 merR missing the C-terminal 17 amino acids responded to inorganic Hg{sup 2+} but not to phenylmercury, indicating that the C-terminal region of the MerR protein of the pDU1358 mer operon is required for the recognition of phenylmercury acetate. The down regulation of the mer operon by the merD gene was also measured in trans with complementing mer operons of pDU1358 or R100 or merD{sup {minus}} mutants. In the presence of the merD gene, beta-galactosidase activity was lowered by 2 to 4 fold. The merD gene gene product was visualized by autoradiography. The Cd{sup 2+} resistance determinant cadA of S. aureus was investigated. The nucleotide sequence of the DNA fragment containing the cadA determinant revealed two open reading frames the larger one of which is essential for expression of cadmium resistance.

  17. Identification of Information Types and Sources by the Public for Promoting Awareness of Middle East Respiratory Syndrome Coronavirus in Saudi Arabia

    ERIC Educational Resources Information Center

    Hoda, Jradi

    2016-01-01

    Middle East Respiratory Syndrome (MERS) is a viral respiratory disease of serious consequences caused by MERS Coronavirus (MERS-CoV). Saudi communities still lack awareness of available protective measures to prevent the transmission of the virus. It is necessary to explore the current information-seeking strategies and preferences for…

  18. Mercury Reduction and Methyl Mercury Degradation by the Soil Bacterium Xanthobacter autotrophicus Py2

    PubMed Central

    Petrus, Amanda K.; Rutner, Colin; Liu, Songnian; Wang, Yingjiao

    2015-01-01

    Two previously uncharacterized potential broad-spectrum mercury (Hg) resistance operons (mer) are present on the chromosome of the soil Alphaproteobacteria Xanthobacter autotrophicus Py2. These operons, mer1 and mer2, contain two features which are commonly found in mer operons in the genomes of soil and marine Alphaproteobacteria, but are not present in previously characterized mer operons: a gene for the mercuric reductase (MerA) that encodes an alkylmercury lyase domain typical of those found on the MerB protein, and the presence of an additional gene, which we are calling merK, with homology to glutathione reductase. Here, we demonstrate that Py2 is resistant to 0.2 μM inorganic mercury [Hg(II)] and 0.05 μM methylmercury (MeHg). Py2 is capable of converting MeHg and Hg(II) to elemental mercury [Hg(0)], and reduction of Hg(II) is induced by incubation in sub toxic concentrations of Hg(II). Transcription of the merA genes increased with Hg(II) treatment, and in both operons merK resides on the same polycistronic mRNA as merA. We propose the use of Py2 as a model system for studying the contribution of mer to Hg mobility in soil and marine ecosystems. PMID:26341208

  19. Final Report - Molecular Mechanisms of Bacterial Mercury Transformation - UCSF

    SciTech Connect

    Miller, Susan M.

    2014-04-24

    The bacterial mercury resistance (mer) operon functions in Hg biogeochemistry and bioremediation by converting reactive inorganic Hg(II) and organic [RHg(II)]1+ mercurials to relatively inert monoatomic mercury vapor, Hg(0). Its genes regulate operon expression (MerR, MerD, MerOP), import Hg(II) (MerT, MerP, and MerC), and demethylate (MerB) and reduce (MerA) mercurials. We focus on how these components interact with each other and with the host cell to allow cells to survive and detoxify Hg compounds. Understanding how this ubiquitous detoxification system fits into the biology and ecology of its bacterial host is essential to guide interventions that support and enhance Hg remediation. In the current overall project we focused on two aspects of this system: (1) investigations of the energetics of Hg(II)-ligand binding interactions, and (2) both experimental and computational approaches to investigating the molecular mechanisms of Hg(II) acquisition by MerA and intramolecular transfer of Hg(II) prior to reduction within the MerA enzyme active site. Computational work was led by Prof. Jeremy Smith and took place at the University of Tennessee, while experimental work on MerA was led by Prof. Susan Miller and took place at the University of California San Francisco.

  20. Structural Biology of The sequestration & Transport of Heavy Metal Toxins: NMR Structure Determination of Proteins Containing the CYS-X-Y-Metal Binding Motif

    SciTech Connect

    Stanley J. Opella

    2004-03-10

    The support from the Department of Energy enabled us to initiate research on several proteins from the bacterial mercury detoxification system; in particular, we were able to determine the structures of MerP and related metal binding sequences. We have also worked on the membrane transport proteins MerF and MerT.

  1. Coding, modulation, and relays for deep space communication Mars Rovers Case Study

    NASA Technical Reports Server (NTRS)

    Statman, Joseph I.; Edwards, Charles D.

    2004-01-01

    This paper presents the communications challenges for the MER mission, the use of DSN and MER tools to maximize the science return, and the application of standards-based relays to the problem. To date, more than 90% of the data returned from MER has been returned via relays, not direct-to-Earath (DTE).

  2. CENP-B box and pJalpha sequence distribution in human alpha satellite higher-order repeats (HOR).

    PubMed

    Rosandić, Marija; Paar, Vladimir; Basar, Ivan; Gluncić, Matko; Pavin, Nenad; Pilas, Ivan

    2006-01-01

    Using our Key String Algorithm (KSA) to analyze Build 35.1 assembly we determined consensus alpha satellite higher-order repeats (HOR) and consensus distributions of CENP-B box and pJalpha motif in human chromosomes 1, 4, 5, 7, 8, 10, 11, 17, 19, and X. We determined new suprachromosomal family (SF) assignments: SF5 for 13mer (2211 bp), SF5 for 13mer (2214 bp), SF2 for 11mer (1869 bp), SF1 for 18mer (3058 bp), SF3 for 12mer (2047 bp), SF3 for 14mer (2379 bp), and SF5 for 17mer (2896 bp) in chromosomes 4, 5, 8, 10, 11, 17, and 19, respectively. In chromosome 5 we identified SF5 13mer without any CENP-B box and pJalpha motif, highly homologous (96%) to 13mer in chromosome 19. Additionally, in chromosome 19 we identified new SF5 17mer with one CENP-B box and pJalpha motif, aligned to 13mer by deleting four monomers. In chromosome 11 we identified SF3 12mer, homologous to 12mer in chromosome X. In chromosome 10 we identified new SF1 18mer with eight CENP-B boxes in every other monomer (except one). In chromosome 4 we identified new SF5 13mer with CENP-B box in three consecutive monomers. We found four exceptions to the rule that CENP-B box belongs to type B and pJalpha motif to type A monomers.

  3. Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Is an Important Surface Attachment Factor That Facilitates Entry of Middle East Respiratory Syndrome Coronavirus

    PubMed Central

    Chan, Che-Man; Chu, Hin; Wang, Yixin; Wong, Bosco Ho-Yin; Zhao, Xiaoyu; Zhou, Jie; Yang, Dong; Leung, Sze Pui; Chan, Jasper Fuk-Woo; Yeung, Man-Lung; Yan, Jinghua; Lu, Guangwen; Gao, George Fu

    2016-01-01

    ABSTRACT The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5 coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5 overexpression significantly enhanced the attachment of MERS-CoV to the BHK21 cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was overexpressed in permissive cells, which suggested that CEACAM5 could facilitate MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS-CoV entry independently. Taken together, the results of our study identified CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS-CoV infection by augmenting the attachment of the virus to the host cell surface. IMPORTANCE Infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with the highest mortality rate among all known human-pathogenic coronaviruses. Currently, there are no approved vaccines or therapeutics against MERS-CoV infection. The

  4. Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus

    PubMed Central

    Yang, Yang; Liu, Chang; Du, Lanying; Jiang, Shibo; Shi, Zhengli; Baric, Ralph S.

    2015-01-01

    To understand how Middle East respiratory syndrome coronavirus (MERS-CoV) transmitted from bats to humans, we compared the virus surface spikes of MERS-CoV and a related bat coronavirus, HKU4. Although HKU4 spike cannot mediate viral entry into human cells, two mutations enabled it to do so by allowing it to be activated by human proteases. These mutations are present in MERS-CoV spike, explaining why MERS-CoV infects human cells. These mutations therefore played critical roles in the bat-to-human transmission of MERS-CoV, either directly or through intermediate hosts. PMID:26063432

  5. Effect of polymerization on hierarchical self-assembly into nanosheets.

    PubMed

    Ikeda, Taichi

    2015-01-20

    The oligomers consisting of phenyl-capped bithiophene and tetra(ethylene glycol)s linked by azide-alkyne Huisgen cycloaddition were synthesized. The relationship between the degree of polymerization and self-assembling ability was investigated in o-dichlorobenzene and dimethyl sulfoxide. From the absorption spectrum, it was confirmed that the critical degree of polymerization (CDP) for thiophene unit aggregation was 4. The morphology of the aggregated product was observed by atomic force microscopy. The oligomers 4mer and 5mer could not self-assemble into well-defined structures due to the weak driving force for the self-assembly. In the cases of 6mer and 7mer, aggregates with nonwell-defined and nanosheet structures coexisted. In the cases of 8mer and 9mer, the nanosheet was the main product. The critical point between 7mer and 8mer could be confirmed by different aggregation behaviors in the cooling process of the solution (nonsigmoidal and sigmoidal). In the cases of 8mer and 9mer, polymer folding prior to intermolecular self-assembly, which was supported by sigmoidal aggregation behavior, leads to the nanosheet formation. On the contrary, shorter oligomers than 8mer experience intermolecular aggregation prior to intramolecular polymer folding, which was supported by the nonsigmoidal aggregation behavior. This is the first report to prove the existence of CDP for folded polymer nanosheet formation which requires hierarchical self-assembly, i.e., polymer folding followed by intermolecular self-assembly.

  6. Professional tennis players' serve: correlation between segmental angular momentums and ball velocity.

    PubMed

    Martin, Caroline; Kulpa, Richard; Delamarche, Paul; Bideau, Benoit

    2013-03-01

    The purpose of the study was to identify the relationships between segmental angular momentum and ball velocity between the following events: ball toss, maximal elbow flexion (MEF), racket lowest point (RLP), maximal shoulder external rotation (MER), and ball impact (BI). Ten tennis players performed serves recorded with a real-time motion capture. Mean angular momentums of the trunk, upper arm, forearm, and the hand-racket were calculated. The anteroposterior axis angular momentum of the trunk was significantly related with ball velocity during the MEF-RLP, RLP-MER, and MER-BI phases. The strongest relationships between the transverse-axis angular momentums and ball velocity followed a proximal-to-distal timing sequence that allows the transfer of angular momentum from the trunk (MEF-RLP and RLP-MER phases) to the upper arm (RLP-MER phase), forearm (RLP-MER and MER-BI phases), and the hand-racket (MER-BI phase). Since sequence is crucial for ball velocity, players should increase angular momentums of the trunk during MEF-MER, upper arm during RLP-MER, forearm during RLP-BI, and the hand-racket during MER-BI.

  7. Using max entropy ratio of recurrence plot to measure electrocorticogram changes in epilepsy patients

    NASA Astrophysics Data System (ADS)

    Yan, Jiaqing; Wang, Yinghua; Ouyang, Gaoxiang; Yu, Tao; Li, Xiaoli

    2016-02-01

    A maximum entropy ratio (MER) method is firstly adapted to investigate the high-dimensional Electrocorticogram (ECoG) data from epilepsy patients. MER is a symbolic analysis approach for the detection of recurrence domains of complex dynamical systems from time series. Data were chosen from eight patients undergoing pre-surgical evaluation for drug-resistant temporal lobe epilepsy. MERs for interictal and ictal data were calculated and compared. A statistical test was performed to evaluate the ability of MER to separate the interictal state from the ictal state. MER showed significant changes from the interictal state into the ictal state, where MER was low at the ictal state and is significantly different with that at the interictal state. These suggest that MER is able to separate the ictal state from the interictal state based on ECoG data. It has the potential of detecting the transition between normal brain activity and the ictal state.

  8. High correlation of Middle East respiratory syndrome spread with Google search and Twitter trends in Korea.