WorldWideScience

Sample records for mg l-1 h-1

  1. The low noise L1 trigger of the H1 lead/scintillating-fibre electromagnetic calorimeter

    International Nuclear Information System (INIS)

    Moreau, F.

    1998-01-01

    The first level trigger performance of the H1 Spacal electromagnetic calorimeter is presented for the 1996 data taking. A newly developed wideband f ≤ 200 MHz preamplification is performed with a negligible noise contribution of 0.4 MeV. A nanosecond resolution calorimetric time-of flight rejects background events by a factor of ∝10 4 . Electron trigger efficiency greater than 99.9% at a threshold energy value of ∝500 MeV is currently achieved. (orig.)

  2. PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1 Virus Impairs the Human T Cell Response

    Directory of Open Access Journals (Sweden)

    Nuriban Valero-Pacheco

    2013-01-01

    Full Text Available PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1pdm09, and its effects on the T cell response have not been widely explored. We found that A(H1N1pdm09 virus induced PD-L1 expression on human dendritic cells (DCs and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1pdm09 virus.

  3. Effect of TiON–MgO intermediate layer on microstructure and magnetic properties of L1{sub 0} FePt–C–SiO{sub 2} films

    Energy Technology Data Exchange (ETDEWEB)

    Deng, J.Y. [Department of Materials Science and Engineering, National University of Singapore, Singapore 117576 (Singapore); Dong, K.F. [School of Automation, China University of Geosciences, Wuhan 430074 (China); Peng, Y.G.; Ju, G.P. [Seagate Technology, Fremont, CA 94538 (United States); Hu, J.F. [Data Storage Institute (DSI), Singapore 117608 (Singapore); Chow, G.M.; Chen, J.S. [Department of Materials Science and Engineering, National University of Singapore, Singapore 117576 (Singapore)

    2016-11-01

    The microstructure and magnetic properties of L1{sub 0} FePt–C–SiO{sub 2} films grown on TiON–MgO intermediate layer were studied. TiON–MgO layer was deposited by co-sputtering TiN and MgO–TiO{sub 2} targets at 380 °C. With increasing MgO–TiO{sub 2} doping concentration, the contact angle between FePt grains with intermediate layer gradually increased, and it was close to 90° when the volume percentage of MgO–TiO{sub 2} reached 30%. At this condition, a high out-of-plane coercivity of 19.1 kOe was obtained, while the opening-up of in-plane M-H loop was very narrow. Moreover, it was found that the out-of-plane coercivity can be further improved to 21.6 kOe, by slightly increasing the percentage of MgO–TiO{sub 2} to 35 vol%. - Highlights: • The effect of TiON–MgO intermediate layer was studied. • With increasing the MgO composition, the surface energy of intermediate layer increased, and the FePt/TiON–MgO interfacial energy decreased. The contact angle of FePt grains with intermediate layer increased with the MgO composition, and 90° contact angle could be achieved by optimizing the MgO composition. • Good perpendicular magnetic anisotropy was retained with large out-of-plane coercivity and narrow in-plane opening-up.

  4. Technology in L1

    DEFF Research Database (Denmark)

    Elf, Nikolaj Frydensbjerg; Hanghøj, Thorkild; Skaar, Håvard

    2015-01-01

    In recent decades, several Scandinavian research projects have had an explicit focus on how technology intervenes in L1 (or so-called Mother Tongue Education) practices in Swedish, Norwegian and Danish educational contexts, and how this may impact on understanding of the subject. There is currently......-of-school literacy practices. A final finding is the emphasis on teacher uncertainty regarding how and why to integrate technology within existing paradigms of the subject. This calls for further research on how technology may be justified in L1 practice, including various forms of teacher education....... no systematic overview of the documented possibilities and challenges related to the use of technology in L1. At the same time, there is terminological confusion in use of ‘technology’ and related concepts in L1. Finally, there is a general lack of critical reflection on the relation between technological...

  5. ATG16L1

    DEFF Research Database (Denmark)

    Salem, Mohammad; Ammitzboell, Mette; Nys, Kris

    2015-01-01

    Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1...... (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong...... association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus...

  6. The H1 detector

    International Nuclear Information System (INIS)

    Cozzika, G.

    1992-11-01

    The H1 detector presently operating at the HERA e-p collider is described. A general overview of the detector is given with particular emphasis on the calorimeters, the main element of which is a liquid Argon calorimeter enclosed within a large radius solenoid. Calorimetry in the proton direction, close to the beam-pipe is provided by a copper-silicon pad hadronic calorimeter. In the electron direction a lead-scintillator electromagnetic calorimeter closes the solid angle between the rear part of the liquid Argon calorimeter and the beam-pipe. An iron limited streamer tube tail catcher using the return yoke of the solenoid as absorber completes the calorimetry of the detector. The hardware triggers derived from the calorimeters are also described and some performance details of the calorimeters are given

  7. H1 at HERA Exhibition

    CERN Multimedia

    2000-01-01

    H1 is one of the two large detectors installed at HERA, the first electron-proton accelerator, located at DESY in Hamburg. The H1 collaboration regroups physicists from 32institutes of 11countries all over the world.

  8. H1 in RSA galaxies

    Science.gov (United States)

    Richter, OTTO-G.

    1993-01-01

    The original Revised Shapley-Ames (RSA) galaxy sample of almost 1300 galaxies has been augmented with further bright galaxies from the RSA appendix as well as newer galaxy catalogs. A complete and homogeneous, strictly magnitude-limited all-sky sample of 2345 galaxies brighter than 13.4 in apparent blue magnitude was formed. New 21 cm H1 line observations for more than 600 RSA galaxies have been combined with all previously available H1 data from the literature. This new extentise data act allows detailed tests of widely accepted 'standard' reduction and analysis techniques.

  9. H1 antihistamines and driving

    OpenAIRE

    Florin-Dan, Popescu

    2008-01-01

    Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion, Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and...

  10. H1 antihistamines and driving.

    Science.gov (United States)

    Popescu, Florin Dan

    2008-01-01

    Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion. Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and visual evoked potentials), experimental simulated driving (driving simulators) and real driving studies (the Highway Driving Test, with the evaluation of the Standard Deviation Lateral Position, and the Car Following Test, with the measurement of the Brake Reaction Time) must be discussed in order to classify a H1 antihistamine as a true non-sedating one.

  11. Extrap L-1 experimental stability

    International Nuclear Information System (INIS)

    Brunsell, P.; Hellblom, G.; Karlsson, P.; Mazur, S.; Nordlund, P.; Scheffel, J.

    1990-01-01

    In the Extrap scheme a Z-pinch is stabilized by imposing a strongly inhomogeneous octupole magnetic field. This field is generated by four conductor rods, each carrying equal currents I v antiparallel to the plasma current I p itself. Theoretically, interchange stability is improved by the magnetic field, as well as long-wavelength kinks due to induced currents in the plasma and in the rods. Short wavelength kinks are, as in the 1-D pinch, stabilized by FLR and viscous-resistive effects. We have performed a set of experiments in the linear Extrap L-1 device (length 40 cm, plasma radius a 2 cm, rod distance 3 cm) in order to determine optimal performance in terms of confined current (5-20 kA) and stability during the discharge length (80 μs; of the order 100 Alfven times). In this paper we summarize our results from two types of experiments; with and without external axial magnetic field. The results are compared with theory in the final paragraph. (author) 5 figs

  12. H1N1 influenza (Swine flu)

    Science.gov (United States)

    Swine flu; H1N1 type A influenza ... The H1N1 virus is now considered a regular flu virus. It is one of the three viruses included in the regular (seasonal) flu vaccine . You cannot get H1N1 flu virus from ...

  13. PD-L1-specific T cells

    DEFF Research Database (Denmark)

    Ahmad, Shamaila Munir; Borch, Troels Holz; Hansen, Morten

    2016-01-01

    -specific T cells that recognize both PD-L1-expressing immune cells and malignant cells. Thus, PD-L1-specific T cells have the ability to modulate adaptive immune reactions by reacting to regulatory cells. Thus, utilization of PD-L1-derived T cell epitopes may represent an attractive vaccination strategy...... for targeting the tumor microenvironment and for boosting the clinical effects of additional anticancer immunotherapy. This review summarizes present information about PD-L1 as a T cell antigen, depicts the initial findings about the function of PD-L1-specific T cells in the adjustment of immune responses...

  14. Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

    2018-04-01

    Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L 1 Mab-13 (IgG 1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses. L 1 Mab-13 specifically reacted hPD-L1 of hPD-L1-overexpressed Chinese hamster ovary (CHO)-K1 cells and endogenous hPD-L1 of KMST-6 (human fibroblast) in flow cytometry and Western blot. Furthermore, L 1 Mab-13 reacted with lung cancer cell lines (EBC-1, Lu65, and Lu99) in flow cytometry and stained lung cancer tissues in a membrane-staining pattern in immunohistochemical analysis. These results indicate that a novel anti-hPD-L1 mAb, L 1 Mab-13, is very useful for detecting hPD-L1 of lung cancers in flow cytometry, Western blot, and immunohistochemical analyses.

  15. The symbiotic star H1-36

    International Nuclear Information System (INIS)

    Allen, D.A.

    1983-01-01

    Optical and infrared spectrophotometry is presented of the high-excitation emission-line star H1-36. The presence of a variable M giant is established: H1-36 may therefore be classified as a symbiotic star. The observations are interpreted in terms of the usual binary model for symbiotic stars, namely that an unseen star is heated by accretion of gas from its companion M giant. (author)

  16. Homologous histamine H1 receptor desensitization results in reduction of H1 receptor agonist efficacy

    NARCIS (Netherlands)

    Leurs, R; Smit, M J; Bast, A; Timmerman, H

    1991-01-01

    Prolonged exposure of the guinea-pig intestinal longitudinal smooth muscle to histamine caused homologous desensitization of the H1 receptor, which led to reduced H1 receptor-mediated production of [3H]inositol phosphates as well as to reduced H1 agonist-induced contractions. [3H]Mepyramine binding

  17. PODAAC-CYGNS-L1X20

    Data.gov (United States)

    National Aeronautics and Space Administration — This Level 1 (L1) dataset contains the Version 2.0 geo-located Delay Doppler Maps (DDMs) calibrated into Power Received (Watts) and Bistatic Radar Cross Section...

  18. Phobos L1 Operational Tether Experiment (PHLOTE)

    Data.gov (United States)

    National Aeronautics and Space Administration — A sensor package that “floats” just above the surface of Phobos, suspended by a tether from a small spacecraft operating at the Mars/Phobos Lagrange 1 (L1) Point...

  19. [Isolation and identification of Mn oxidizing bacterium Aminobacter sp. H1 and its oxidation mechanism].

    Science.gov (United States)

    Yan, Ping; Jiang, Li-Ying; Chen, Jian-Meng; He, Zhi-Min; Xiao, Shao-Dan; Jiang, Yi-Feng

    2014-04-01

    A bacterium with high manganese oxidizing activity was isolated from a biological manganese removal filter and named as H1. Based on its characteristics and the analysis of 16S rDNA sequence, the strain H1 belonged to the genus Aminobacter sp. and its manganese oxidizing ability had never been reported. In this paper, the microbiologic properties of the strain H1, the manganese oxidation mechanisms and characteristics of biogenic manganese oxides were investigated. The results showed that the maximal tolerant Mn concentration of strain H1 was 50 mmol x L(-1), and Mn(II) could be completely removed by strain H1 when the concentration was lower than 10 mmol x L(-1). Strain H1 could oxidize Mn2+ by both the production of manganese oxidizing activity factor and alkaline metabolites during growth, which were synthesized in the cell and then secreted into extracellular culture medium. During the oxidation process, the intermediate of soluble Mn(III) was detected. SEM showed that the biogenic manganese oxides were amorphous and poorly-crystalline, and it closely combined with bacteria. The components of the biogenic manganese oxides produced by strain H1 were identified as MnCO3, MnOOH, Mn3O4 and MnO2 by XRD, XPS and SEM-EDX.

  20. Voice and Narrative in L1 Writing

    DEFF Research Database (Denmark)

    Krogh, Ellen; Piekut, Anke

    2015-01-01

    This paper investigates issues of voice and narrative in L1 writing. Three branches of research are initial-ly discussed: research on narratives as resources for identity work, research on writer identity and voice as an essential aspect of identity, and research on Bildung in L1 writing. Subsequ...... training of voice and narratives as a resource for academic writing, and that the Bildung potential of L1 writing may be tied to this issue.......This paper investigates issues of voice and narrative in L1 writing. Three branches of research are initial-ly discussed: research on narratives as resources for identity work, research on writer identity and voice as an essential aspect of identity, and research on Bildung in L1 writing...... in lower secondary L1, she found that her previous writing strategies were not rewarded in upper secondary school. In the second empiri-cal study, two upper-secondary exam papers are investigated, with a focus on their approaches to exam genres and their use of narrative resources to address issues...

  1. The H1 Data Preservation Project

    International Nuclear Information System (INIS)

    South, D M; Steder, M

    2012-01-01

    The H1 data preservation project was started in 2009 as part of the global data preservation initiative in high-energy physics, DPHEP. In order to retain the full potential for future improvements, the H1 Collaboration aims for level 4 of the DPHEP recommendations, which requires the full simulation and reconstruction chain as well as the data to be preserved for future analysis. A major goal of the H1 project is therefore to provide secure, long-lived and validated access to the H1 data and analysis software, which is realised in collaboration with DESY-IT using virtualisation techniques. By implementing such a system, it is hoped that the lifetime of the unique ep collision data from HERA will be extended, providing the possibility for novel analysis in the future. The preservation of the data and software is performed alongside a consolidation programme of digital and non-digital documentation, some of which dates back to the early 1980s. A new organisational model of the H1 Collaboration, reflecting the change to the long term phase, is to be adopted in July 2012.

  2. Validation of ATLAS L1 Topological Triggers

    CERN Document Server

    Praderio, Marco

    2017-01-01

    The Topological trigger (L1Topo) is a new component of the ATLAS L1 (Level-1) trigger. Its purpose is that of reducing the otherwise too high rate of data collection from the LHC by rejecting those events considered “uninteresting” (meaning that they have already been studied). This event rate reduction is achieved by applying topological requirements to the physical objects present in each event. It is very important to make sure that this trigger does not reject any “interesting” event. Therefore we need to verify its correct functioning. The goal of this summer student project is to study the response of two L1Topo algorithms (concerning ∆R and invariant mass). To do so I will compare the trigger decisions produced by the L1Topo hardware with the ones produced by the “official” L1Topo simulation. This way I will be able to identify events that could be incorrectly rejected. Simultaneously I will produce an emulation of these triggers that will help me understand the cause of disagreements bet...

  3. Antiviral Prophylaxis and H1N1

    Centers for Disease Control (CDC) Podcasts

    2011-07-14

    Dr. Richard Pebody, a consultant epidemiologist at the Health Protection Agency in London, UK, discusses the use of antiviral post-exposure prophylaxis and pandemic H1N1.  Created: 7/14/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 7/18/2011.

  4. Pandemic influenza A (H1N1)

    African Journals Online (AJOL)

    ... in Port Shepstone, South Africa. Introduction. Influenza A (H1N1) 2009 'swine flu' variant is currently a global pandemic.1 The infection associated with this virus is usually a mild, self-limiting illness. However, it may progress to severe pneumonia requiring intensive care unit (ICU) therapy in 31% of patients.2 This may.

  5. Antiallergic effects of H1-receptor antagonists.

    Science.gov (United States)

    Baroody, F M; Naclerio, R M

    2000-01-01

    The primary mechanism of antihistamine action in the treatment of allergic diseases is believed to be competitive antagonism of histamine binding to cellular receptors (specifically, the H1-receptors), which are present on nerve endings, smooth muscles, and glandular cells. This notion is supported by the fact that structurally unrelated drugs antagonize the H1-receptor and provide clinical benefit. However, H1-receptor antagonism may not be their sole mechanism of action in treating allergic rhinitis. On the basis of in vitro and animal experiments, drugs classified as H1-receptor antagonists have long been recognized to have additional pharmacological properties. Most first-generation H1-antihistamines have anticholinergic, sedative, local anaesthetic, and anti-5-HT effects, which might favourably affect the symptoms of the allergic response but also contribute to side-effects. These additional properties are not uniformly distributed among drugs classified as H1-receptor antagonists. Azatadine, for example, inhibits in vitro IgE-mediated histamine and leukotriene (LT) release from mast cells and basophils. In human challenge models, terfenadine, azatadine, and loratadine reduce IgE-mediated histamine release. Cetirizine reduces eosinophilic infiltration at the site of antigen challenge in the skin, but not the nose. In a nasal antigen challenge model, cetirizine pretreatment did not affect the levels of histamine and prostaglandin D2 recovered in postchallenge lavages, whereas the levels of albumin, N-tosyl-L-arginine methyl ester (TAME) esterase activity, and LTs were reduced. Terfenadine, cetirizine, and loratadine blocked allergen-induced hyperresponsiveness to methacholine. In view of the complexity of the pathophysiology of allergy, a number of H1 antagonists with additional properties are currently under development for allergic diseases. Mizolastine, a new H1-receptor antagonist, has been shown to have additional actions that should help reduce the

  6. Generalized L1 penalized matrix factorization

    DEFF Research Database (Denmark)

    Rasmussen, Morten Arendt

    2017-01-01

    Traditionally, chemometric models consists of parameters found by solving a least squares criterion. However, these models can suffer from overfitting, as well as being hard to interpret because of the large number of active parameters. This work proposes the use of a generalized L1 norm penalty ...

  7. Dirichlet expression for L(1, χ )

    Indian Academy of Sciences (India)

    We show that this expression with obvious modification is valid for the general primitive Dirichlet character χ. Keywords. Hurwitz zeta function; Dirichlet character; Dirichlet L-series; primitive character. 1. Introduction. In Dirichlet's famous work dealing with class number formula, the value of L(1,χ) is expressed in terms of finite ...

  8. Antifungal properties of wheat histones (H1-H4) and purified wheat histone H1

    Science.gov (United States)

    Wheat (Triticum sp.) histones H1, H2, H3, and H4 were extracted. H1 was further purified. Their activities against fungi with varying degrees of wheat pathogenicity were determined. They included Aspergillus flavus, A. fumigatus, A. niger, F. oxysporum, F. verticillioides, F. solani, F. graminearu...

  9. The H1 silicon vertex detector

    International Nuclear Information System (INIS)

    Pitzl, D.; Behnke, O.; Biddulph, M.; Boesiger, K.; Eichler, R.; Erdmann, W.; Gabathuler, K.; Gassner, J.; Haynes, W.J..; Horisberger, R.; Kausch, M.; Lindstroem, M.; Niggli, H.; Noyes, G.; Pollet, P.; Steiner, S.; Streuli, S.; Szeker, K.; Truoel, P.

    2000-01-01

    The design, construction and performance of the H1 silicon vertex detector is described. It consists of two cylindrical layers of double-sided, double-metal silicon sensors read out by a custom designed analog pipeline chip. The analog signals are transmitted by optical fibres to a custom-designed ADC board and are reduced on PowerPC processors. Details of the design and construction are given and performance figures from the first data-taking periods are presented

  10. Symbiotic star H1-36

    Energy Technology Data Exchange (ETDEWEB)

    Allen, D A

    1983-01-01

    It is suggested that H1-36 should be classified as a symbiotic star rather than a planetary nebula. Evidence of a cool giant now exists and the high-excitation emission-line spectrum resembles the spectra of many symbiotic stars. The optical spectrum, radio spectrum, high spectral index of +0.9 and computed mass-loss rate are among the features discussed.

  11. The symbiotic star H1-36

    International Nuclear Information System (INIS)

    Allen, D.A.

    1983-01-01

    It is suggested that H1-36 should be classified as a symbiotic star rather than a planetary nebula. Evidence of a cool giant now exists and the high-excitation emission-line spectrum resembles the spectra of many symbiotic stars. The optical spectrum, radio spectrum, high spectral index of +0.9 and computed mass-loss rate are among the features discussed

  12. The H1 liquid argon calorimeter system

    International Nuclear Information System (INIS)

    Andrieu, B.; Babayev, A.; Ban, J.

    1993-06-01

    The liquid argon calorimeter of the H1 detector presently taking data at the HERA ep - collider at DESY, Hamburg, is described here. The main physics requirements and the most salient design features relevant to this calorimeter are given. The aim to have smooth and hermetic calorimetric coverage over the polar angular range 4 ≤ θ ≤ 154 is achieved by a single liquid argon cryostat containing calorimeter stacks structured in wheels and octants for easy handling. The absorber materials used are lead in the electromagnetic part and stainless steel in the hadronic part. The read-out system is pipelined to reduce the dead time induced by the high trigger rate expected at the HERA collider where consecutive bunches are separated in time by 96 ns. The main elements of the calorimeter, such as the cryostat, with its associated cryogenics, the stack modules, the read-out, calibration and trigger electronics as well as the data acquisition system are described. Performance results from data taken in calibration runs with full size H1 calorimeter stacks at a CERN test beam, as well as results from data collected with the complete H1 detector using cosmic rays during the initial phase of ep operations are presented. The observed energy resolutions and linearities are well in agreement with the requirements. (orig.)

  13. Small Molecule Agonists of Cell Adhesion Molecule L1 Mimic L1 Functions In Vivo.

    Science.gov (United States)

    Kataria, Hardeep; Lutz, David; Chaudhary, Harshita; Schachner, Melitta; Loers, Gabriele

    2016-09-01

    Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery after injury, leading to severe disabilities in motor functions and pain. Peripheral nerve injury impairs motor, sensory, and autonomic functions, particularly in cases where nerve gaps are large and chronic nerve injury ensues. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration after acute injury. We screened libraries of known drugs for small molecule agonists of L1 and evaluated the effect of hit compounds in cell-based assays in vitro and in mice after femoral nerve and spinal cord injuries in vivo. We identified eight small molecule L1 agonists and showed in cell-based assays that they stimulate neuronal survival, neuronal migration, and neurite outgrowth and enhance Schwann cell proliferation and migration and myelination of neurons in an L1-dependent manner. In a femoral nerve injury mouse model, enhanced functional regeneration and remyelination after application of the L1 agonists were observed. In a spinal cord injury mouse model, L1 agonists improved recovery of motor functions, being paralleled by enhanced remyelination, neuronal survival, and monoaminergic innervation, reduced astrogliosis, and activation of microglia. Together, these findings suggest that application of small organic compounds that bind to L1 and stimulate the beneficial homophilic L1 functions may prove to be a valuable addition to treatments of nervous system injuries.

  14. L-1 constraint in Liouville gravity

    International Nuclear Information System (INIS)

    Kitazawa, Y.

    1992-01-01

    In this paper, the authors study recursion relations among the amplitudes which involve discrete states in c = 1 Liouville gravity on the sphere. The authors find that the spin J = 1/2 discrete state gives rise to the L -1 type recursion relation. Multiple point correlation functions are determined recursively from fewer point functions by this recursion relation. The authors further point out that the analogs of J = 1/2 state exist in c -1 type recursion relation

  15. The H1 forward muon spectrometer

    International Nuclear Information System (INIS)

    Kenyon, I.R.; Phillips, H.; Cronstroem, H.I.; Hedberg, V.; Jacobsson, C.; Joensson, L.; Lohmander, H.; Nyberg, M.; Biddulph, P.; Finnegan, P.; Foster, J.; Gilbert, S.; Hilton, C.; Ibbotson, M.; Mehta, A.; Sutton, P.; Stephens, K.; Thompson, R.

    1993-02-01

    The H1 detector started taking data at the electron- proton collider HERA in the beginning of 1992. In HERA 30 GeV electrons collide with 820 GeV protons giving a strong boost of the centre-of-mass system in the direction of the proton, also called the forward region. For the detection of high momentum muons in this region a muon spectrometer has been constructed, consisting of six drift chamber planes, three either side of a toroidal magnet. A first brief description of the system and its main parameters as well as the principles for track reconstruction and Τ 0 determination is given. (orig.)

  16. Photoperiod-H1 (Ppd-H1) Controls Leaf Size1[OPEN

    Science.gov (United States)

    Digel, Benedikt; Tavakol, Elahe; Verderio, Gabriele; Xu, Xin

    2016-01-01

    Leaf size is a major determinant of plant photosynthetic activity and biomass; however, it is poorly understood how leaf size is genetically controlled in cereal crop plants like barley (Hordeum vulgare). We conducted a genome-wide association scan for flowering time, leaf width, and leaf length in a diverse panel of European winter cultivars grown in the field and genotyped with a single-nucleotide polymorphism array. The genome-wide association scan identified PHOTOPERIOD-H1 (Ppd-H1) as a candidate gene underlying the major quantitative trait loci for flowering time and leaf size in the barley population. Microscopic phenotyping of three independent introgression lines confirmed the effect of Ppd-H1 on leaf size. Differences in the duration of leaf growth and consequent variation in leaf cell number were responsible for the leaf size differences between the Ppd-H1 variants. The Ppd-H1-dependent induction of the BARLEY MADS BOX genes BM3 and BM8 in the leaf correlated with reductions in leaf size and leaf number. Our results indicate that leaf size is controlled by the Ppd-H1- and photoperiod-dependent progression of plant development. The coordination of leaf growth with flowering may be part of a reproductive strategy to optimize resource allocation to the developing inflorescences and seeds. PMID:27457126

  17. Photoperiod-H1 (Ppd-H1) Controls Leaf Size.

    Science.gov (United States)

    Digel, Benedikt; Tavakol, Elahe; Verderio, Gabriele; Tondelli, Alessandro; Xu, Xin; Cattivelli, Luigi; Rossini, Laura; von Korff, Maria

    2016-09-01

    Leaf size is a major determinant of plant photosynthetic activity and biomass; however, it is poorly understood how leaf size is genetically controlled in cereal crop plants like barley (Hordeum vulgare). We conducted a genome-wide association scan for flowering time, leaf width, and leaf length in a diverse panel of European winter cultivars grown in the field and genotyped with a single-nucleotide polymorphism array. The genome-wide association scan identified PHOTOPERIOD-H1 (Ppd-H1) as a candidate gene underlying the major quantitative trait loci for flowering time and leaf size in the barley population. Microscopic phenotyping of three independent introgression lines confirmed the effect of Ppd-H1 on leaf size. Differences in the duration of leaf growth and consequent variation in leaf cell number were responsible for the leaf size differences between the Ppd-H1 variants. The Ppd-H1-dependent induction of the BARLEY MADS BOX genes BM3 and BM8 in the leaf correlated with reductions in leaf size and leaf number. Our results indicate that leaf size is controlled by the Ppd-H1- and photoperiod-dependent progression of plant development. The coordination of leaf growth with flowering may be part of a reproductive strategy to optimize resource allocation to the developing inflorescences and seeds. © 2016 American Society of Plant Biologists. All rights reserved.

  18. Characterization of a Novel Alginate Lyase from Marine Bacterium Vibrio furnissii H1

    Directory of Open Access Journals (Sweden)

    Xiaoyan Zhu

    2018-01-01

    Full Text Available Alginate lyases show great potential for industrial and medicinal applications, especially as an attractive biocatalyst for the production of oligosaccharides with special bioactivities. A novel alginate lyase, AlyH1, from the marine bacterium Vibrio furnissii H1, which has been newly isolated from rotten seaweed, was purified and characterized. The purified enzyme showed the specific activity of 2.40 U/mg. Its molecular mass was 35.8 kDa. The optimal temperature and pH were 40 °C and pH 7.5, respectively. AlyH1 maintained stability at neutral pH (7.0–8.0 and temperatures below 30 °C. Metal ions Na+, Mg2+, and K+ increased the activity of the enzyme. With sodium alginate as the substrate, the Km and Vmax values of AlyH1 were 2.28 mg/mL and 2.81 U/mg, respectively. AlyH1 exhibited activities towards both polyguluronate and polymannuronate, and preferentially degraded polyguluronate. Products prepared from sodium alginate by AlyH1 were displayed to be di-, tri-, and tetra-alginate oligosaccharides. A partial amino acid sequence (190 aa of AlyH1 analysis suggested that AlyH1 was an alginate lyase of polysaccharide lyase family 7. The sequence showed less than 77% identity to the reported alginate lyases. These data demonstrated that AlyH1 could be as a novel and potential candidate in application of alginate oligosaccharides production with low polymerization degrees.

  19. Helical magnetic axis configuration combined with l = 1 and weak l = -1 torsatron fields

    International Nuclear Information System (INIS)

    Kikuchi, Hitoshi; Saito, Katsunori; Gesso, Hirokazu; Shiina, Shoichi

    1989-01-01

    The superposition of a relatively weak l = -1 torsatron field on a main l = 1 torsatron field leads to the improvement of the confinement properties due to the formation of a local magnetic well, which results from the local curvature of the helical magnetic axis with a larger excursion in the major radius direction. This l±1 helical magnetic axis system has a comparatively simple, compact coil structure. Here the vacuum configuration properties of l = ±1 system are described. (author)

  20. Three cases with L1 syndrome and two novel mutations in the L1CAM gene.

    Science.gov (United States)

    Marín, Rosario; Ley-Martos, Miriam; Gutiérrez, Gema; Rodríguez-Sánchez, Felicidad; Arroyo, Diego; Mora-López, Francisco

    2015-11-01

    Mutations in the L1CAM gene have been identified in the following various X-linked neurological disorders: congenital hydrocephalus; mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome; spastic paraplegia; and agenesis of the corpus callosum. These conditions are currently considered different phenotypes of a single entity known as L1 syndrome. We present three families with L1 syndrome. Sequencing of the L1CAM gene allowed the identification of the following mutations involved: a known splicing mutation (c.3531-12G>A) and two novel ones: a missense mutation (c.1754A>C; p.Asp585Ala) and a nonsense mutation (c.3478C>T; p.Gln1160Stop). The number of affected males and carrier females identified in a relatively small population suggests that L1 syndrome may be under-diagnosed. L1 syndrome should be considered in the differential diagnosis of intellectual disability or mental retardation in children, especially when other signs such as hydrocephalus or adducted thumbs are present.

  1. Preparation of a Ni-MgO-Al2O3 catalyst with high activity and resistance to potassium poisoning during direct internal reforming of methane in molten carbonate fuel cells

    Science.gov (United States)

    Jang, Won-Jun; Jung, You-Shick; Shim, Jae-Oh; Roh, Hyun-Seog; Yoon, Wang Lai

    2018-02-01

    Steam reforming of methane (SRM) is conducted using a series of Ni-MgO-Al2O3 catalysts for direct internal reforming (DIR) in molten carbonate fuel cells (MCFCs). Ni-MgO-Al2O3 catalysts are prepared by the homogeneous precipitation method with a variety of MgO loading amounts ranging from 3 to 15 wt%. In addition, each precursor concentrations are systemically changed (Ni: 1.2-4.8 mol L-1; Mg: 0.3-1.2 mol L-1; Al: 0.4-1.6 mol L-1) at the optimized composition (10 wt% MgO). The effects of MgO loading and precursor concentration on the catalytic performance and resistance against poisoning of the catalyst by potassium (K) are investigated. The Ni-MgO-Al2O3 catalyst with 10 wt% MgO and the original precursor concentration (Ni: 1.2 mol L-1; Mg: 0.3 mol L-1; Al: 0.4 mol L-1) exhibits the highest CH4 conversion and resistance against K poisoning even at the extremely high gas space velocity (GHSV) of 1,512,000 h-1. Excellent SRM performance of the Ni-MgO-Al2O3 catalyst is attributed to strong metal (Ni) to alumina support interaction (SMSI) when magnesium oxide (MgO) is co-precipitated with the Ni-Al2O3. The enhanced interaction of the Ni with MgO-Al2O3 support is found to protect the active Ni species against K poisoning.

  2. H1-antihistamines in pregnancy and lactation.

    Science.gov (United States)

    Schatz, Michael

    2002-01-01

    Antihistamines may be used for the treatment of allergic rhinitis, upper respiratory infections, urticaria/angioedema, atopic dermatitis, and, rarely, as adjunctive treatment for anaphylaxis, during pregnancy. Because these illnesses may affect maternal comfort and safety as well as threaten the fetus directly (anaphylaxis) or indirectly, they often require therapy during pregnancy. Based on the information available to date, in this chapter we have attempted to provide rational guidelines for the gestational use of H1-receptor antagonists in a manner that will lead to the optimal well-being of both the mother and her infant. As more information becomes available, the recommendations herein may require modification. Although this chapter has dealt specifically with gestational management, a case can be made for considering this information when making therapeutic decisions in all women of childbearing potential. First, most pregnancies are unplanned, and the peak period of fetal vulnerability to drug-induced teratogenesis begins the day a woman's period is due. Second, during gestation, substantial alterations in a previously successful but not optimal-for-pregnancy chronic therapeutic regimen may be psychologically threatening to the patient and may lead to either uncontrolled disease or unanticipated side effects. Thus, pregnancy-appropriate regimens should ideally be discussed with all women of childbearing age as part of the informed therapeutic decision-making process.

  3. Contribution of L1 in EFL Teaching

    Directory of Open Access Journals (Sweden)

    Wahjuningsih Usadiati

    2009-01-01

    Full Text Available This study is conducted in a classroom action research to improve the students’ achievement in writing English sentences in Present Perfect Tense in Structure 1 lessons. The subject consisted of 20 Semester II students who took Structure I lessons in English Education Department of Palangka Raya University, Central Kalimantan, Indonesia. The data were taken from the results of pre test and post test after the action was done. The results show that in cycle 1, in which the explanations were fully in English, only 40% of the students got a good achievement; 5-7 out of 20 test items were correct. After cycle 2 was done using L1 interchangeably with English in the explanations, the students’ achievement of writing English sentences in Present Perfect Tense increased to 75%, in which 15-18 out 20 test items were correct.

  4. Functional Expression of Programmed Death-Ligand 1 (B7-H1 by Immune Cells and Tumor Cells

    Directory of Open Access Journals (Sweden)

    Rachel M. Gibbons Johnson

    2017-08-01

    Full Text Available The programmed death-1 (PD-1 and its ligand PD-L1 (B7-H1 signaling pathway has been the focus of much enthusiasm in the fields of tumor immunology and oncology with recent FDA approval of the anti-PD-1 antibodies pembrolizumab and nivolumab and the anti-PD-L1 antibodies durvalumab, atezolimuab, and avelumab. These therapies, referred to here as PD-L1/PD-1 checkpoint blockade therapies, are designed to block the interaction between PD-L1, expressed by tumor cells, and PD-1, expressed by tumor-infiltrating CD8+ T cells, leading to enhanced antitumor CD8+ T cell responses and tumor regression. The influence of PD-L1 expressed by tumor cells on antitumor CD8+ T cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well defined for antitumor CD8+ T cell responses. Although PD-L1 expression by tumor cells has been used as a biomarker in selection of patients for PD-L1/PD-1 checkpoint blockade therapies, patients whose tumor cells lack PD-L1 expression often respond positively to PD-L1/PD-1 checkpoint blockade therapies. This suggests that PD-L1 expressed by non-malignant cells may also contribute to antitumor immunity. Here, we review the functions of PD-L1 expressed by immune cells in the context of CD8+ T cell priming, contraction, and differentiation into memory populations, as well as the role of PD-L1 expressed by tumor cells in regulating antitumor CD8+ T cell responses.

  5. Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

    Science.gov (United States)

    Soman, A; Honeybourne, D; Andrews, J; Jevons, G; Wise, R

    1999-12-01

    The concentrations of moxifloxacin achieved after a single 400 mg dose were measured in serum, epithelial lining fluid (ELF), alveolar macrophages (AM) and bronchial mucosa (BM). Concentrations were determined using a microbiological assay. Nineteen patients undergoing fibre-optic bronchoscopy were studied. Mean serum, ELF, AM and BM concentrations at 2.2, 12 and 24 h were as follows: 2.2 h: 3.2 mg/L, 20.7 mg/L, 56.7 mg/L, 5.4 mg/kg; 12 h: 1.1 mg/L, 5.9 mg/L, 54.1 mg/L, 2.0 mg/kg; 24 h: 0.5 mg/L, 3.6 mg/L, 35.9 mg/L, 1.1 mg/kg, respectively. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.25 mg/L), Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.12 mg/L), Chlamydia pneumoniae (0.12 mg/L) and Mycoplasma pneumoniae (0. 12 mg/L) and indicate that moxifloxacin should be effective in the treatment of community-acquired, lower respiratory tract infections.

  6. Labelling of MoAb with 153SmH1ETA: Preliminary results

    International Nuclear Information System (INIS)

    Ferro-Flores, G.; De, F.; Ramirez, M.; Pedraza-Lopez, M.; Tendilla, J.I.; Melendez-Alafort, L.; Murphy, C.A.

    2001-01-01

    A method to label MoAb with Sm-153 using 1,5,9,13-tetraazacyclohexadecane N,N',N'',N''' tetraacetic acid (H 4 ETA) as a bifunctional chelator was developed. H 4 ETA and SmH 1 ETA were synthesized in our laboratory and characterized by IR spectroscopy, TGA (thermogravimetric analysis), SEM (Scattering Electronic Microscopy), EDAX (Elemental Dispersion Analysis by X-rays) and EPR (Electron Paramagnetic Resonance) at 6 K. The 153 SmH 1 ETAMoAb was prepared by a simple incubation of the MoAb ior cea1, and the 153 SmH 1 ETA complex at neutral pH and at room temperature for 24 h. The specific activity of the labelled antibody was 111 MBq/mg (3 mCi/mg). Sm-153(III) is commercially available with specific activities up to 318.2 GBq/mg. Therefore, under the conditions described above 153 SmH 1 ETA labelled MoAb could be obtained with specific activity up to 1.14 GBq/mg (30.7 mCi/mg). (author)

  7. Rendezvous missions with minimoons from L1

    Science.gov (United States)

    Chyba, M.; Haberkorn, T.; Patterson, G.

    2014-07-01

    We propose to present asteroid capture missions with the so-called minimoons. Minimoons are small asteroids that are temporarily captured objects on orbits in the Earth-Moon system. It has been suggested that, despite their small capture probability, at any time there are one or two meter diameter minimoons, and progressively greater numbers at smaller diameters. The minimoons orbits differ significantly from elliptical orbits which renders a rendezvous mission more challenging, however they offer many advantages for such missions that overcome this fact. First, they are already on geocentric orbits which results in short duration missions with low Delta-v, this translates in cost efficiency and low-risk targets. Second, beside their close proximity to Earth, an advantage is their small size since it provides us with the luxury to retrieve the entire asteroid and not only a sample of material. Accessing the interior structure of a near-Earth satellite in its morphological context is crucial to an in-depth analysis of the structure of the asteroid. Historically, 2006 RH120 is the only minimoon that has been detected but work is ongoing to determine which modifications to current observation facilities is necessary to provide detection algorithm capabilities. In the event that detection is successful, an efficient algorithm to produce a space mission to rendezvous with the detected minimoon is highly desirable to take advantage of this opportunity. This is the main focus of our work. For the design of the mission we propose the following. The spacecraft is first placed in hibernation on a Lissajoux orbit around the liberation point L1 of the Earth-Moon system. We focus on eight-shaped Lissajoux orbits to take advantage of the stability properties of their invariant manifolds for our transfers since the cost to minimize is the spacecraft fuel consumption. Once a minimoon has been detected we must choose a point on its orbit to rendezvous (in position and velocities

  8. Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice.

    Science.gov (United States)

    Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan

    2016-07-19

    Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Suv39h1 Protects from Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Bo Yang

    2014-04-01

    Full Text Available Background: Patients with diabetes are at increased risk of ischemic events. Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9, which is associated with the suppression of inflammatory genes in diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R injury under diabetic condition has not been evaluated. Methods: To generate diabetic model, male SD rats were fed with 60% fat diet followed by intraperitoneal injection with 40mg/kg streptozotocin. Adenovirus encoding Suv39h1 gene was used for Suv39h1 overexpression. Each rat received injections of adenovirus at five myocardial sites. Three days after gene transfection, each rat was subjected to left main coronary artery occlusion and reperfusion. After 30 min ischemia and reperfusion for 4 h, the rats were euthanized for real-time PCR, Western blot, immunohistochemical staining, and morphometric analysis. Results: Delivery of Ad-Suv39h1 into the hearts of diabetic rats could markedly increase Suv39h1 expression. Up-regulation of Suv39h1 significantly reduced infarct size and tissue damage after I/R injury, which was associated with protection from apoptosis of cardiac myocytes and reduction of inflammatory response. In addition, compared with injury group, Ad-Suv39h1 led to a decreased activity of mitogen-activated protein kinase family and its down-steam transcriptional factor NF-κB. Conclusion: Overexpression of Suv39h1 results in the de-activation of proinflammatory pathways and reduced apoptosis and myocardial injury. Therefore, Suv39h1 might represent a novel therapeutic strategy to reduce I/R injury under diabetic condition.

  10. 2009 H1N1 Flu Vaccine Facts

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Flu 2009 H1N1 Flu Vaccine Facts Past Issues / Fall 2009 Table of ... the H1N1 flu vaccine. 1 The 2009 H1N1 flu vaccine is safe and well tested. Clinical trials ...

  11. Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab.

    Science.gov (United States)

    Lee, Hyun Tae; Lee, Ju Yeon; Lim, Heejin; Lee, Sang Hyung; Moon, Yu Jeong; Pyo, Hyo Jeong; Ryu, Seong Eon; Shin, Woori; Heo, Yong-Seok

    2017-07-17

    In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents. Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 antibodies provides a better understanding of the mechanism of PD-L1 blockade as well as new insights into the rational design of improved anti-PD-L1 therapeutics.

  12. Luminosity measurement in H1; Mesure de la luminosite pour l'experience H1

    Energy Technology Data Exchange (ETDEWEB)

    Frisson, T

    2006-10-15

    At HERA, luminosity is determined on-line and bunch by bunch by measuring the Bremsstrahlung spectrum from e-p collisions. The Hl collaboration has built a completely new luminosity system in order to sustain the harsh running conditions after the fourfold luminosity increase. Namely, the higher synchrotron radiation doses and the increased event pile-up have governed the design of the two major components, a radiation resistant quartz-fibre electro-magnetic calorimeter, and a fast read-out electronic with on-line energy histogram loading at a rate of 500 kHz. The group was in charge of the electronic and the on-line data analysis of the new luminosity system. In this thesis, I present analysis tools and methods to improve the precision of the luminosity measurement. The energy scale and acceptance calculation methods set out in this thesis permit these values to be determined every four minutes, to an accuracy of 0.5 parts per thousand for the energy scale and 2 parts per thousand for the acceptance. From these results, the degree of accuracy obtained on the luminosity measurement is between 6.5 and 9.5 parts per thousand. These results are currently undergoing validation, with the aim of becoming the standard H1 method. I also studied quasi-elastic Compton events to cross-check the luminosity measurement using the 2003- 2004 and 2005 data. Indeed, this process has a well calculable cross section and a clear experimental signature. The leptonic final state consists of a coplanar e-gamma system, both observable in the central H1 detector. (author)

  13. Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

    2018-03-01

    Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L 1 Mab-4 (IgG 2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers. L 1 Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4) in flow cytometry and stained oral cancers in a membrane-staining pattern. L 1 Mab-4 stained 106/150 (70.7%) of oral squamous cell carcinomas, indicating the very high sensitivity of L 1 Mab-4. These results indicate that L 1 Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers.

  14. Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4

    Directory of Open Access Journals (Sweden)

    Shinji Yamada

    2018-03-01

    Full Text Available Programmed cell death-ligand 1 (PD-L1, which is a ligand of programmed cell death-1 (PD-1, is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1 expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb, L1Mab-4 (IgG2b, kappa, using cell-based immunization and screening (CBIS method and investigated hPD-L1 expression in oral cancers. L1Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 in flow cytometry and stained oral cancers in a membrane-staining pattern. L1Mab-4 stained 106/150 (70.7% of oral squamous cell carcinomas, indicating the very high sensitivity of L1Mab-4. These results indicate that L1Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers. Keywords: Programmed cell death-ligand 1, Monoclonal antibody, Oral cancer

  15. Ubiquitin C-Terminal Hydrolase L1 in Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Jennifer Hurst-Kennedy

    2012-01-01

    Full Text Available Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1, aka PGP9.5 is an abundant, neuronal deubiquitinating enzyme that has also been suggested to possess E3 ubiquitin-protein ligase activity and/or stabilize ubiquitin monomers in vivo. Recent evidence implicates dysregulation of UCH-L1 in the pathogenesis and progression of human cancers. Although typically only expressed in neurons, high levels of UCH-L1 have been found in many nonneuronal tumors, including breast, colorectal, and pancreatic carcinomas. UCH-L1 has also been implicated in the regulation of metastasis and cell growth during the progression of nonsmall cell lung carcinoma, colorectal cancer, and lymphoma. Together these studies suggest UCH-L1 has a potent oncogenic role and drives tumor development. Conversely, others have observed promoter methylation-mediated silencing of UCH-L1 in certain tumor subtypes, suggesting a potential tumor suppressor role for UCH-L1. In this paper, we provide an overview of the evidence supporting the involvement of UCH-L1 in tumor development and discuss the potential mechanisms of action of UCH-L1 in oncogenesis.

  16. Histone h1 depletion impairs embryonic stem cell differentiation.

    Science.gov (United States)

    Zhang, Yunzhe; Cooke, Marissa; Panjwani, Shiraj; Cao, Kaixiang; Krauth, Beth; Ho, Po-Yi; Medrzycki, Magdalena; Berhe, Dawit T; Pan, Chenyi; McDevitt, Todd C; Fan, Yuhong

    2012-01-01

    Pluripotent embryonic stem cells (ESCs) are known to possess a relatively open chromatin structure; yet, despite efforts to characterize the chromatin signatures of ESCs, the role of chromatin compaction in stem cell fate and function remains elusive. Linker histone H1 is important for higher-order chromatin folding and is essential for mammalian embryogenesis. To investigate the role of H1 and chromatin compaction in stem cell pluripotency and differentiation, we examine the differentiation of embryonic stem cells that are depleted of multiple H1 subtypes. H1c/H1d/H1e triple null ESCs are more resistant to spontaneous differentiation in adherent monolayer culture upon removal of leukemia inhibitory factor. Similarly, the majority of the triple-H1 null embryoid bodies (EBs) lack morphological structures representing the three germ layers and retain gene expression signatures characteristic of undifferentiated ESCs. Furthermore, upon neural differentiation of EBs, triple-H1 null cell cultures are deficient in neurite outgrowth and lack efficient activation of neural markers. Finally, we discover that triple-H1 null embryos and EBs fail to fully repress the expression of the pluripotency genes in comparison with wild-type controls and that H1 depletion impairs DNA methylation and changes of histone marks at promoter regions necessary for efficiently silencing pluripotency gene Oct4 during stem cell differentiation and embryogenesis. In summary, we demonstrate that H1 plays a critical role in pluripotent stem cell differentiation, and our results suggest that H1 and chromatin compaction may mediate pluripotent stem cell differentiation through epigenetic repression of the pluripotency genes.

  17. Learners’ L1 Use in a Task-based Classroom

    DEFF Research Database (Denmark)

    Bao, Rui; Du, Xiangyun

    2015-01-01

    , but with only a very small amount oc- curring for off-task talk across tasks. L1 use mainly occurred in learners’ efforts to mediate completion of the tasks. The findings highlight the role of L1 in foreign language learning and suggest that L1 use is associated with a number of factors, such as task types......’ extensive L1 use and off-task talk. Informed by sociocultural theory, this study explored the extent to which L1s and their func- tions were used when performing tasks. The subjects were beginner-level lower-secondary school learners of Chinese. The data shows that learners have a high amount of L1 use...

  18. 1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent

    of the H1N1 pandemic virus from 1918 induce protection in ferrets against infection with a H1N1 (A/New Caledonia/20/99(H1N1)) virus which was included in the conventional vaccine for the 2006-2007 season. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein...

  19. Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic retinopathy.

    Science.gov (United States)

    Wang, Wenjun; Wang, Qing; Wan, Danyang; Sun, Yue; Wang, Lin; Chen, Hong; Liu, Chengyu; Petersen, Robert B; Li, Jianshuang; Xue, Weili; Zheng, Ling; Huang, Kun

    2017-05-04

    Autophagy plays critical and complex roles in many human diseases, including diabetes and its complications. However, the role of autophagy in the development of diabetic retinopathy remains uncertain. Core histone modifications have been reported involved in the development of diabetic retinopathy, but little is known about the histone variants. Here, we observed increased autophagy and histone HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG proteins, then promotes autophagy in cultured retinal cell line. Histone HIST1H1C overexpression also promotes inflammation and cell toxicity in vitro. Knockdown of histone HIST1H1C reduces both the basal and stresses (including high glucose)-induced autophagy, and inhibits high glucose induced inflammation and cell toxicity. Importantly, AAV-mediated histone HIST1H1C overexpression in the retinas leads to increased autophagy, inflammation, glial activation and neuron loss, similar to the pathological changes identified in the early stage of diabetic retinopathy. Furthermore, knockdown of histone Hist1h1c by siRNA in the retinas of diabetic mice significantly attenuated the diabetes-induced autophagy, inflammation, glial activation and neuron loss. These results indicate that histone HIST1H1C may offer a novel therapeutic target for preventing diabetic retinopathy.

  20. Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X.

    Science.gov (United States)

    Okuwaki, Mitsuru; Abe, Mayumi; Hisaoka, Miharu; Nagata, Kyosuke

    2016-11-01

    Linker histones play important roles in the genomic organization of mammalian cells. Of the linker histone variants, H1.X shows the most dynamic behavior in the nucleus. Recent research has suggested that the linker histone variants H1.X and H1.0 have different chromosomal binding site preferences. However, it remains unclear how the dynamics and binding site preferences of linker histones are determined. Here, we biochemically demonstrated that the DNA/nucleosome and histone chaperone binding activities of H1.X are significantly lower than those of other linker histones. This explains why H1.X moves more rapidly than other linker histones in vivo Domain swapping between H1.0 and H1.X suggests that the globular domain (GD) and C-terminal domain (CTD) of H1.X independently contribute to the dynamic behavior of H1.X. Our results also suggest that the N-terminal domain (NTD), GD, and CTD cooperatively determine the preferential binding sites, and the contribution of each domain for this determination is different depending on the target genes. We also found that linker histones accumulate in the nucleoli when the nucleosome binding activities of the GDs are weak. Our results contribute to understanding the molecular mechanisms of dynamic behaviors, binding site selection, and localization of linker histones. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1)

    DEFF Research Database (Denmark)

    Marzec, Michal; Zhang, Qian; Goradia, Ami

    2008-01-01

    The mechanisms of malignant cell transformation caused by the oncogenic, chimeric nucleophosmin (NPM)/anaplastic lymphoma kinase (ALK) remain only partially understood, with most of the previous studies focusing mainly on the impact of NPM/ALK on cell survival and proliferation. Here we report th...

  2. Epidemiological characteristics of Pandemic Influenza A (H1N1 ...

    African Journals Online (AJOL)

    Background: A novel influenza A virus strain (H1N1-2009) spread first in Mexico and the United Stated in late April 2009, leading to the first influenza pandemic of the 21st century. The objective of this study was to determine the epidemiological and virological characteristics of the pandemic influenza A (H1N1-2009) in ...

  3. Epidemiological characteristics of Pandemic Influenza A (H1N1 ...

    African Journals Online (AJOL)

    ... novel influenza A virus strain (H1N1-2009) spread first in Mexico and the United Stated in late April 2009, leading to the first influenza pandemic of the 21st century. The objective of this study was to determine the epidemiological and virological characteristics of the pandemic influenza A (H1N1-2009) in Zhanjiang, China ...

  4. (H1N1) Influenza in Saurashtra, India

    African Journals Online (AJOL)

    Mexico in April, 2009,[1] and then in United States (US).[2,3]. This was originally ... duration of hospital stay of such patients was 2‑32 days. All admitted A (H1N1) .... Because of limited resources, only 2009 A (H1N1) influenza virus was tested ...

  5. Histone H1(0) mapping using monoclonal antibodies.

    Science.gov (United States)

    Dousson, S; Gorka, C; Gilly, C; Lawrence, J J

    1989-06-01

    Monoclonal antibodies (mAb) to ox liver histone H1 degree were produced and characterized. Two sets of mice were immunized either with pure H1(0) or with an H1(0)-yeast tRNA complex. Eleven hybridomas of various clonal origin were selected. Typing of the antibodies indicated that all but three IgM belonged to the IgG1 class and contained kappa light chains. Immunoblotting experiments using peptides derived from H1(0) or H5 treated by various proteolytic agents (trypsin, N-bromosuccinimide, cyanogen bromide, acetic acid), revealed that nine of the mAb reacted with the globular part of H1(0). More advanced characterization of the antigenic determinants allowed us to determine distinct regions within this globular part which are involved in the antigenic recognition. The peptopes could be subdivided into two groups. Three mAb bound to residues 24-27 and were specific for H1(0). Six mAb bound to residues 27-30 and were specific for H1(0) except one of them which strongly cross-reacted with H5 and GH5. Two mAb reacted with the entire histone H1(0) but failed to react with any of the peptides, suggesting that the corresponding epitope is a conformational antigenic determinant. In order to confirm the localization of the two distinct regions which are involved in the antigenic recognition, a synthetic decapeptide corresponding to the beginning of human H1(0) globular part (from residue 19 to residue 28) was synthesized. Inhibition experiments of the reaction between H1(0) and the various IgG1 mAb by increasing amounts of peptide-bovine serum albumin conjugates were then performed.

  6. Attitudes held by Setswana L1-speaking university students toward ...

    African Journals Online (AJOL)

    Respondents believed that their L1 had limitations in wider society; and that it had prestige, albeit a covert one. Generally, they held favourable attitudes toward their L1. Further comprehensive research needs to be done to explore these new variables, as well as to explore their statistical significance in language attitude ...

  7. On the Link Between L1-PCA and ICA.

    Science.gov (United States)

    Martin-Clemente, Ruben; Zarzoso, Vicente

    2017-03-01

    Principal component analysis (PCA) based on L1-norm maximization is an emerging technique that has drawn growing interest in the signal processing and machine learning research communities, especially due to its robustness to outliers. The present work proves that L1-norm PCA can perform independent component analysis (ICA) under the whitening assumption. However, when the source probability distributions fulfil certain conditions, the L1-norm criterion needs to be minimized rather than maximized, which can be accomplished by simple modifications on existing optimal algorithms for L1-PCA. If the sources have symmetric distributions, we show in addition that L1-PCA is linked to kurtosis optimization. A number of numerical experiments illustrate the theoretical results and analyze the comparative performance of different algorithms for ICA via L1-PCA. Although our analysis is asymptotic in the sample size, this equivalence opens interesting new perspectives for performing ICA using optimal algorithms for L1-PCA with guaranteed global convergence while inheriting the increased robustness to outliers of the L1-norm criterion.

  8. Metabolic rate regulates L1 longevity in C. elegans.

    Directory of Open Access Journals (Sweden)

    Inhwan Lee

    Full Text Available Animals have to cope with starvation. The molecular mechanisms by which animals survive long-term starvation, however, are not clearly understood. When they hatch without food, C. elegans arrests development at the first larval stage (L1 and survives more than two weeks. Here we show that the survival span of arrested L1s, which we call L1 longevity, is a starvation response regulated by metabolic rate during starvation. A high rate of metabolism shortens the L1 survival span, whereas a low rate of metabolism lengthens it. The longer worms are starved, the slower they grow once they are fed, suggesting that L1 arrest has metabolic costs. Furthermore, mutants of genes that regulate metabolism show altered L1 longevity. Among them, we found that AMP-dependent protein kinase (AMPK, as a key energy sensor, regulates L1 longevity by regulating this metabolic arrest. Our results suggest that L1 longevity is determined by metabolic rate and that AMPK as a master regulator of metabolism controls this arrest so that the animals survive long-term starvation.

  9. Reassortant H1N1 influenza virus vaccines protect pigs against pandemic H1N1 influenza virus and H1N2 swine influenza virus challenge.

    Science.gov (United States)

    Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan

    2011-09-28

    Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Phase 1 study of pandemic H1 DNA vaccine in healthy adults.

    Directory of Open Access Journals (Sweden)

    Michelle C Crank

    Full Text Available A novel, swine-origin influenza A (H1N1 virus was detected worldwide in April 2009, and the World Health Organization (WHO declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1 influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1 licensed monovalent inactivated vaccine (MIV.20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry.Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine.H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.Clinicaltrials.gov NCT00973895.

  11. 77 FR 3284 - Comment Request for Information Collection for the H-1B Technical Skills Training (H-1B) and the...

    Science.gov (United States)

    2012-01-23

    ... concerning the collection of data about H-1B Technical Skills Training (H-1B) [SGA/DFA PY-10-13] and H-1B... DEPARTMENT OF LABOR Comment Request for Information Collection for the H-1B Technical Skills Training (H-1B) and the H-1B Jobs and Innovation Accelerator Challenge (JIAC) Grant Programs, New...

  12. Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

    Directory of Open Access Journals (Sweden)

    Kihyuck Kwak

    Full Text Available Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV L1 and L2 DNA vaccination.Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8 or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2 vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type

  13. Influenza A (H1N1) organising pneumonia.

    Science.gov (United States)

    Torrego, Alfons; Pajares, Virginia; Mola, Anna; Lerma, Enrique; Franquet, Tomás

    2010-04-27

    In November 2009, countries around the world reported confirmed cases of pandemic influenza H1N1, including over 6000 deaths. No peak in activity has been seen. The most common causes of death are pneumonia and acute respiratory distress syndrome. We report a case of a 55-year-old woman who presented with organising pneumonia associated with influenza A (H1N1) infection confirmed by transbronchial lung biopsy. Organising pneumonia should also be considered as a possible complication of influenza A (H1N1) infection, given that these patients can benefit from early diagnosis and appropriate specific management.

  14. Novel 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives: a patent review (2008 - 2011).

    Science.gov (United States)

    Ferreira, Vitor F; da Rocha, David R; da Silva, Fernando C; Ferreira, Patrícia G; Boechat, Núbia A; Magalhães, Jorge L

    2013-03-01

    The triazoles represent a class of five-membered heterocyclic compounds of great importance for the preparation of new drugs with diverse biological activities because they may present several structural variations with the same numbers of carbon and nitrogen atoms. Due to the success of various triazoles that entered the pharmaceutical market and are still being used in medicines, many companies and research groups have shown interest in developing new methods of synthesis and biological evaluation of potential uses for these compounds. In this review, the authors explored aspects of patents for the 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole families, including prototypes being considered in clinical studies between 2008 and 2011. The triazoles have been studied for over a century as an important class of heterocyclic compounds and still attract considerable attention due to their broad range of biological activities. More recently, there has been considerable interest in the development of novel triazoles with anti-inflammatory, antiplatelet, antimicrobial, antimycobacterial, antitumoral and antiviral properties and activity against several neglected diseases. This review emphasizes recent perspective and advances in the therapeutically active 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivative patents between 2008 and 2011, covering the development of new chemical entities and new pharmaceuticals. Many studies have focused on these compounds as target structures and evaluated them in several biological targets. The preparation of 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives brings to light several issues. There is a need to find new, more efficient preparations for these triazoles that take into consideration current issues in green chemistry, energy saving and sustainability. New diseases are discovered and new viruses and bacteria continue to challenge mankind, so it is imperative to find new prototypes for these

  15. Do L1 Reading Achievement and L1 Print Exposure Contribute to the Prediction of L2 Proficiency?

    Science.gov (United States)

    Sparks, Richard L.; Patton, Jon; Ganschow, Leonore; Humbach, Nancy

    2012-01-01

    The study examined whether individual differences in high school first language (L1) reading achievement and print exposure would account for unique variance in second language (L2) written (word decoding, spelling, writing, reading comprehension) and oral (listening/speaking) proficiency after adjusting for the effects of early L1 literacy and…

  16. Production, purification, crystallization and structure determination of H-1 Parvovirus

    International Nuclear Information System (INIS)

    Halder, Sujata; Nam, Hyun-Joo; Govindasamy, Lakshmanan; Vogel, Michèle; Dinsart, Christiane; Salomé, Nathalie; McKenna, Robert; Agbandje-McKenna, Mavis

    2012-01-01

    The production, purification, crystallization and crystallographic analysis of H-1 Parvovirus, a gene-therapy vector, are reported. Crystals of H-1 Parvovirus (H-1PV), an antitumor gene-delivery vector, were obtained for DNA-containing capsids and diffracted X-rays to 2.7 Å resolution using synchrotron radiation. The crystals belonged to the monoclinic space group P2 1 , with unit-cell parameters a = 255.4, b = 350.4, c = 271.6 Å, β = 90.34°. The unit cell contained two capsids, with one capsid per crystallographic asymmetric unit. The H-1PV structure has been determined by molecular replacement and is currently being refined

  17. H-1NF: Australian national fusion plasma research facility

    International Nuclear Information System (INIS)

    Blackwell, B.D.; Borg, G.G.; Dewar, R.L.; Howard, J.; Gardner, H.J.; Rudakov, D.L.; Sharp, L.E.; Shats, M.G.; Warr, G.B.

    1997-01-01

    The H-1 heliac is a helical axis stellarator of moderate size and novel, flexible configuration. Since commissioning, H-1 has operated in quasi-continuous mode at low magnetic field. For higher fields ≤1T an ECRH heating system (28GHz, 200kW) has been installed under a collaborative agreement between ANU and NIFS. H-1 has recently been promoted to national facility status (H-1NF), which will include upgrades of the rf and ech heating systems to megawatt powers, and power supply and diagnostic and data system enhancements. This facilitates collaborative research locally (through the Australian Fusion Research Group consortium) and internationally. Results of a number of basic experiments in quasi-continuous mode are presented. (author)

  18. TV-L1 optical flow for vector valued images

    DEFF Research Database (Denmark)

    Rakêt, Lars Lau; Roholm, Lars; Nielsen, Mads

    2011-01-01

    The variational TV-L1 framework has become one of the most popular and successful approaches for calculating optical flow. One reason for the popularity is the very appealing properties of the two terms in the energy formulation of the problem, the robust L1-norm of the data fidelity term combined...... with the total variation (TV) regular- ization that smoothes the flow, but preserve strong discontinuities such as edges. Specifically the approach of Zach et al. [1] has provided a very clean and efficient algorithm for calculating TV-L1 optical flows between grayscale images. In this paper we propose...

  19. Robotic synthesis of L-[1-11C]tyrosine

    International Nuclear Information System (INIS)

    Luurtsema, Gert; Medema, Jitze; Elsinga, P.H.; Visser, G.M.; Vaalburg, Willem

    1994-01-01

    L-[1- 11 C]tyrosine promises to become an important tracer for determination of the protein synthesis rate (PSR) in tumor tissue and brain. The commercially available Anatech RB-86 robotic system is utilized for the automation of the L-[1- 11 C]tyrosine production via the isocyanide method as reported by Bolster et al. (Eur. J. Nucl. Med. 12, 321-324, 1986). The total synthesis time, including HPLC-purification and enantiomeric separation is 60 min. With a practical yield of 20 mCi L-[1- 11 C]tyrosine at a specific activity > 1000 Ci/mmol. (author)

  20. Synthesis of 4-Triazolylamino- and 4-Benzothiazolylamino-3-nitro-2H-[1]-Benzopyran-2-ones and their Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Ramiz Hoti

    2014-10-01

    Full Text Available Novel substituted benzopyran-2-one derivatives were synthesized by catalytic condensation reactions under reflux conditions. 4-(1,2,4-Triazolyl-3-amino-3-nitro-2H-[1]-benzopyran-2-ones 4(a-b were synthesized by condensation of 4-chloro-3-nitro-2H-[1]-benzopyran-2-one (2 and corresponding 3-aminotriazoles 3(a-b. 4-(4’-methoxy-2-benzothiazolylamino-3-nitro-2H-[1]-benzopyran-2-one (4c, 4-(6’-nitro-2-benzothiazolylamino-3-nitro-2H-[1]-benzopyiran-2-one (4d and 4-(6’-fluoro-2-benzothiazolylamino-3-nitro-2H-[1]-benzopyran-2-one (4e were synthesized by condensation of 4-chloro-3-nitro-2H-[1]-benzopyran-2-one (2 and corresponding 2-aminobenzothiazole 3(c-e under reflux reaction conditions. Further, alkali hydrolysis of 4(a-e afforded the 2-hydroxy-ω-nitroacetophenone (5. Antimicrobial activity of products 4(a-e against S. aurous, E. coli and Klebsiella were investigated measuring of inhibition zones around the discs which are marked with DMF, concentration 2 mg/mL, 4 mg/mL and 6 mg/mL solutions. Compounds 4c, 4e and 4d were more active against S. aureus. Emphatic activity against E. coli exhibited compounds 4b and 4e, whereas 4c and 4d were more active against Klebsiella.

  1. Early Detection of Pandemic (H1N1) 2009, Bangladesh

    Science.gov (United States)

    Rahman, Mustafizur; Al Mamun, Abdullah; Haider, Mohammad Sabbir; Zaman, Rashid Uz; Karmakar, Polash Chandra; Nasreen, Sharifa; Muneer, Syeda Mah-E; Homaira, Nusrat; Goswami, Doli Rani; Ahmed, Be-Nazir; Husain, Mohammad Mushtuq; Jamil, Khondokar Mahbuba; Khatun, Selina; Ahmed, Mujaddeed; Chakraborty, Apurba; Fry, Alicia; Widdowson, Marc-Alain; Bresee, Joseph; Azim, Tasnim; Alamgir, A.S.M.; Brooks, Abdullah; Hossain, Mohamed Jahangir; Klimov, Alexander; Rahman, Mahmudur; Luby, Stephen P.

    2012-01-01

    To explore Bangladesh’s ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June–July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population. PMID:22257637

  2. Measurement of electric fields in the H-1NF heliac

    International Nuclear Information System (INIS)

    James, B.W.; Howard, J.

    1999-01-01

    There are a number of laser induced fluorescence techniques which can be used to measure internal plasma electric fields. It is planned to use a technique based on Stark mixing of energy levels in a supersonic beam containing metastable helium atoms to measure radial electric fields in H-1NF. Enhanced values of radial electric field are associated with improved confinement modes in H-1NF and other magnetically confined plasmas

  3. Data logging and online reconstruction in H1

    International Nuclear Information System (INIS)

    Fuhrmann, P.; Gerhards, R.; Kruener-Marquis, U.; Olsson, J.E.; Szkutnik, Z.

    1994-01-01

    In spring 1992, the H1 detector at the HERA electron proton collider at DESY came into operation. The high bunch crossing rate and, correspondingly, the large data volumes are placing demanding requirements on the data logging and event reconstruction. Both tasks are performed on an SGI Challenge series computer. This note reviews the development and the experience with the data logging and online reconstruction in H1

  4. Research on Anti-influenza A H1N1 Virus in Vitro and Antipyretic Experiments of Major Decoction of Green Dragon Granule%大青龙汤颗粒剂体外抗甲型H1N1流感病毒实验研究

    Institute of Scientific and Technical Information of China (English)

    田连起; 黄鹤归; 叶晓川; 廖鹏程; 黄婕; 周爱军; 刘焱文

    2013-01-01

    Objective:To discuss the effect of Major Decoction of Green Dragon Granule in anti-influenza A H1N1 virus in Vitro and its antipyretic influences to fever rats caused by lipopolysaccharide. Methods: MDCK infected by anti-influenza A H1N1 virus, and combined cytopathic effect ( CPE ) with MTT colorimetric assay, and the drug effect of Major Decoction of Green Dragon Granule inhibiting the biosynthesis of A H1N1 influenza virus,the absorption to influenza virus,the blocking of the accession to cells and killing influenza virus were inspected. Lipopolysaccharide duplicated fever models of rats were used,and rectal temperatures of rats of different groups in different times were measured,curves were drawn,and antipyretic effects were analyzed. Results:The half maximal inhibitory concentration (IC50) of Major Decoction of Green Dragon Granule killing influenza AH1N1 was 12.40 mg·mL-1 ,the therapeutic index (TI) was 1.8. The IC50 of Ribavirin Injection in the same administration route was 0. 45 mg·mL-1 and TI was 1.0. The temperature of the model group had already rised at 1 h after establishing models, reached peak at 5 h, and sustained for 8 h. Compared to the model group, the Major Decoction of Green Dragon Granule of high-dose group and low-dose group had significant differences at 4 - 8 hour. Compared to aspirin group, the Major Decoction of Green Dragon Granule of high-dose group and low-dose group, the range of cooling the temperature was smaller at 1 - 3 hours,and was equal at 4 - 5 hour, but was larger than that of aspirin group at 6 - 8 hour. The difference between Major Decoction of Green Dragon Granule of high-dose group and low-dose group was not significant. Conclusion: Major Decoction of Green Dragon Granule shows certain effect of anti-influenza A H1N1 virus in cell level,and the function form is direct inactivation in a dose dependent manner;but the effect of Major Decoction of Green Dragon Granule in inhibiting the biosynthesis of influenza virus

  5. Fusion plasma physics research on the H-1 national facility

    International Nuclear Information System (INIS)

    Harris, J.

    1998-01-01

    Full text: Australia has a highly leveraged fusion plasma research program centred on the H-1 National Facility device at the ANU. H-1 is a heliac, a novel helical axis stellarator that was experimentally pioneered in Australia, but has a close correlation with the worldwide research program on toroidal confinement of fusion grade plasma. Experiments are conducted on H-1 by university researchers from the Australian Fusion Research Group (comprising groups from the ANU, the Universities of Sydney, Western Sydney, Canberra, New England, and Central Queensland University) under the aegis of AINSE; the scientists also collaborate with fusion researchers from Japan and the US. Recent experiments on H-1 have focused on improved confinement modes that can be accessed at very low powers in H-1, but allow the study of fundamental physics effects seen on much larger machines at higher powers. H-1 is now being upgraded in magnetic field and heating power, and will be able to confine hotter plasmas beginning in 1999, offering greatly enhanced research opportunities for Australian plasma scientists and engineers, with substantial spillover of ideas from fusion research into other areas of applied physics and engineering

  6. Germline-specific H1 variants: the "sexy" linker histones.

    Science.gov (United States)

    Pérez-Montero, Salvador; Carbonell, Albert; Azorín, Fernando

    2016-03-01

    The eukaryotic genome is packed into chromatin, a nucleoprotein complex mainly formed by the interaction of DNA with the abundant basic histone proteins. The fundamental structural and functional subunit of chromatin is the nucleosome core particle, which is composed by 146 bp of DNA wrapped around an octameric protein complex formed by two copies of each core histone H2A, H2B, H3, and H4. In addition, although not an intrinsic component of the nucleosome core particle, linker histone H1 directly interacts with it in a monomeric form. Histone H1 binds nucleosomes near the exit/entry sites of linker DNA, determines nucleosome repeat length and stabilizes higher-order organization of nucleosomes into the ∼30 nm chromatin fiber. In comparison to core histones, histone H1 is less well conserved through evolution. Furthermore, histone H1 composition in metazoans is generally complex with most species containing multiple variants that play redundant as well as specific functions. In this regard, a characteristic feature is the presence of specific H1 variants that replace somatic H1s in the germline and during early embryogenesis. In this review, we summarize our current knowledge about their structural and functional properties.

  7. Molecular treatment of the ion-pair formation reaction in H(1s) + H(1s) collisions

    International Nuclear Information System (INIS)

    Borondo, F.; Martin, F.; Yaez, M.

    1987-01-01

    All the available theoretical calculations of the cross section for the ion-pair formation reaction H(1s)+H(1s)→H + H - (1s 2 ) have been performed using methods that are only valid at high collision energies. They get good agreement with the experiments for impact energies greater than 25 keV, but fail completely at smaller energies. In this work we report the cross section for this reaction at impact energies less than 10 keV, calculated in the framework of the impact-parameter approximation and using the molecular method with a common translation factor

  8. Simultaneous removal of carbon and nitrogen by mycelial pellets of a heterotrophic nitrifying fungus-Penicillium sp. L1.

    Science.gov (United States)

    Liu, Yuxiang; Hu, Tingting; Zhao, Jing; Lv, Yongkang; Ren, Ruipeng

    2017-02-01

    A novel heterotrophic nitrifying fungus, defined as Penicillium sp. L1, can form mycelial pellets in liquid medium in this study. The effects of inoculation method, C/N ratio, initial pH, and temperature were gradually evaluated to improve the simultaneous removal of total nitrogen (TN) and chemical oxygen demand (COD) in wastewater by Penicillium sp. L1. Results showed that compared with spore inoculation, 48 h pellet inoculum could significantly increase the pellet size (from about 1.5 mm to 3.2 mm) and improve the removal capability, particularly for COD removal (from less than 50-86.20%). The removal efficiencies of TN and COD reached 98.38% (from 136.01 mg/L to 2.20 mg/L) and 92.40% (from 10,720 mg/L to 815 mg/L) under the following conditions: C/N 36, pH 3, 30°C, and inoculation with 48 h pellets. The pellet diameter reached 4.8 mm after 4-day cultivation. In this case, Penicillium sp. L1 removed TN from 415.93 mg/L to 43.39 mg/L, as well as COD from 29,533 mg/L to 8850 mg/L. Overall, the results indicated that the pellet size was closely related to the pollutant-removal ability of Penicillium sp. L1. Furthermore, mycelial pellets (4.8 mm, dead) only adsorbed 38.08% TN (from 125.45 mg/L to 77.78 mg/L), which indicated that adsorption did not play a major role in the nitrogen-removal process. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  9. Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Li Hailan

    2011-12-01

    Full Text Available Abstract Background Phosphatidylcholine (PPC formulation is used for lipolytic injection, even though its mechanism of action is not well understood. Methods The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD, and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways. Results PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations Conclusions PPC results in apoptosis of 3T3-L1 cells.

  10. 26 CFR 1.7701(l)-1 - Conduit financing arrangements.

    Science.gov (United States)

    2010-04-01

    ... determines that such recharacterization is appropriate to prevent avoidance of any tax imposed by title 26 of...) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.7701(l)-1 Conduit financing...

  11. IceBridge Atmospheric Chemistry L1B Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge Atmospheric Chemistry L1B Data set (ICHEM1B) contains measurements acquired over Antarctica using the AVOCET differential Non-Dispersive Infrared...

  12. Gold nanoparticles functionalized with a fragment of the neural cell adhesion molecule L1 stimulate L1-mediated functions

    Science.gov (United States)

    Schulz, Florian; Lutz, David; Rusche, Norman; Bastús, Neus G.; Stieben, Martin; Höltig, Michael; Grüner, Florian; Weller, Horst; Schachner, Melitta; Vossmeyer, Tobias; Loers, Gabriele

    2013-10-01

    The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1 sequence of the third fibronectin type III domain of murine L1 was identified and conjugated to gold nanoparticles (AuNPs) to obtain constructs that interact homophilically with the extracellular domain of L1 and trigger the cognate beneficial L1-mediated functions. Covalent conjugation was achieved by reacting mixtures of two cysteine-terminated forms of this L1 peptide and thiolated poly(ethylene) glycol (PEG) ligands (~2.1 kDa) with citrate stabilized AuNPs of two different sizes (~14 and 40 nm in diameter). By varying the ratio of the L1 peptide-PEG mixtures, an optimized layer composition was achieved that resulted in the expected homophilic interaction of the AuNPs. These AuNPs were stable as tested over a time period of 30 days in artificial cerebrospinal fluid and interacted with the extracellular domain of L1 on neurons and Schwann cells, as could be shown by using cells from wild-type and L1-deficient mice. In vitro, the L1-derivatized particles promoted neurite outgrowth and survival of neurons from the central and peripheral nervous system and stimulated Schwann cell process formation and proliferation. These observations raise the hope that, in combination with other therapeutic approaches, L1 peptide-functionalized AuNPs may become a useful tool to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system.The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1

  13. The Pleiotropic Role of L1CAM in Tumor Vasculature

    Directory of Open Access Journals (Sweden)

    Francesca Angiolini

    2017-01-01

    Full Text Available Angiogenesis, the formation of new vessels, is a key step in the development, invasion, and dissemination of solid tumors and, therefore, represents a viable target in the context of antitumor therapy. Indeed, antiangiogenic approaches have given promising results in preclinical models and entered the clinical practice. However, in patients, the results obtained so far with antiangiogenic drugs have not completely fulfilled expectations, especially because their effect has been transient with tumors developing resistance and evasion mechanisms. A better understanding of the mechanisms that underlie tumor vascularization and the functional regulation of cancer vessels is a prerequisite for the development of novel and alternative antiangiogenic treatments. The L1 cell adhesion molecule (L1CAM, a cell surface glycoprotein previously implicated in the development and plasticity of the nervous system, is aberrantly expressed in the vasculature of various cancer types. L1CAM plays multiple pro-angiogenic roles in the endothelial cells of tumor-associated vessels, thus emerging as a potential therapeutic target. In addition, L1CAM prevents the maturation of cancer vasculature and its inhibition promotes vessel normalization, a process that is thought to improve the therapeutic response of tumors to cytotoxic drugs. We here provide an overview on tumor angiogenesis and antiangiogenic therapies and summarize the current knowledge on the biological role of L1CAM in cancer vasculature. Finally, we highlight the clinical implications of targeting L1CAM as a novel antiangiogenic and vessel-normalizing approach.

  14. Ion chemistry of 1H-1,2,3-triazole.

    Science.gov (United States)

    Ichino, Takatoshi; Andrews, Django H; Rathbone, G Jeffery; Misaizu, Fuminori; Calvi, Ryan M D; Wren, Scott W; Kato, Shuji; Bierbaum, Veronica M; Lineberger, W Carl

    2008-01-17

    A combination of experimental methods, photoelectron-imaging spectroscopy, flowing afterglow-photoelectron spectroscopy and the flowing afterglow-selected ion flow tube technique, and electronic structure calculations at the B3LYP/6-311++G(d,p) level of density functional theory (DFT) have been employed to study the mechanism of the reaction of the hydroxide ion (HO-) with 1H-1,2,3-triazole. Four different product ion species have been identified experimentally, and the DFT calculations suggest that deprotonation by HO- at all sites of the triazole takes place to yield these products. Deprotonation of 1H-1,2,3-triazole at the N1-H site gives the major product ion, the 1,2,3-triazolide ion. The 335 nm photoelectron-imaging spectrum of the ion has been measured. The electron affinity (EA) of the 1,2,3-triazolyl radical has been determined to be 3.447 +/- 0.004 eV. This EA and the gas-phase acidity of 2H-1,2,3-triazole are combined in a negative ion thermochemical cycle to determine the N-H bond dissociation energy of 2H-1,2,3-triazole to be 112.2 +/- 0.6 kcal mol-1. The 363.8 nm photoelectron spectroscopic measurements have identified the other three product ions. Deprotonation of 1H-1,2,3-triazole at the C5 position initiates fragmentation of the ring structure to yield a minor product, the ketenimine anion. Another minor product, the iminodiazomethyl anion, is generated by deprotonation of 1H-1,2,3-triazole at the C4 position, followed by N1-N2 bond fission. Formation of the other minor product, the 2H-1,2,3-triazol-4-ide ion, can be rationalized by initial deprotonation of 1H-1,2,3-triazole at the N1-H site and subsequent proton exchanges within the ion-molecule complex. The EA of the 2H-1,2,3-triazol-4-yl radical is 1.865 +/- 0.004 eV.

  15. H1N1, globalization and the epidemiology of inequality.

    Science.gov (United States)

    Sparke, Matthew; Anguelov, Dimitar

    2012-07-01

    This paper examines the lessons learned from the 2009 H1N1 pandemic in relation to wider work on globalization and the epidemiology of inequality. The media attention and economic resources diverted to the threats posed by H1N1 were significant inequalities themselves when contrasted with weaker responses to more lethal threats posed by other diseases associated with global inequality. However, the multiple inequalities revealed by H1N1 itself in 2009 still provide important insights into the future of global health in the context of market-led globalization. These lessons relate to at least four main forms of inequality: (1) inequalities in blame for the outbreak in the media; (2) inequalities in risk management; (3) inequalities in access to medicines; and (4) inequalities encoded in the actual emergence of new flu viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Characteristics of the mouse genomic histamine H1 receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Isao; Taniuchi, Ichiro; Kitamura, Daisuke [Kyushu Univ., Fukuoka (Japan)] [and others

    1996-08-15

    We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p. 12 refs., 3 figs.

  17. Treatment and Prevention of Pandemic H1N1 Influenza.

    Science.gov (United States)

    Rewar, Suresh; Mirdha, Dashrath; Rewar, Prahlad

    2015-01-01

    Swine influenza is a respiratory infection common to pigs worldwide caused by type A influenza viruses, principally subtypes H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3. Swine influenza viruses also can cause moderate to severe illness in humans and affect persons of all age groups. People in close contact with swine are at especially high risk. Until recently, epidemiological study of influenza was limited to resource-rich countries. The World Health Organization declared an H1N1 pandemic on June 11, 2009, after more than 70 countries reported 30,000 cases of H1N1 infection. In 2015, incidence of swine influenza increased substantially to reach a 5-year high. In India in 2015, 10,000 cases of swine influenza were reported with 774 deaths. The Centers for Disease Control and Prevention recommend real-time polymerase chain reaction as the method of choice for diagnosing H1N1. Antiviral drugs are the mainstay of clinical treatment of swine influenza and can make the illness milder and enable the patient to feel better faster. Antiviral drugs are most effective when they are started within the first 48 hours after the clinical signs begin, although they also may be used in severe or high-risk cases first seen after this time. The Centers for Disease Control and Prevention recommends use of oseltamivir (Tamiflu, Genentech) or zanamivir (Relenza, GlaxoSmithKline). Prevention of swine influenza has 3 components: prevention in swine, prevention of transmission to humans, and prevention of its spread among humans. Because of limited treatment options, high risk for secondary infection, and frequent need for intensive care of individuals with H1N1 pneumonia, environmental control, including vaccination of high-risk populations and public education are critical to control of swine influenza out breaks. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Lower and upper chromatic numbers for BSTSs(2h - 1

    Directory of Open Access Journals (Sweden)

    Marco Buratti

    2001-08-01

    Full Text Available In [Discrete Math. 174, (1997 247-259] an infinite class of STSs(2h - 1 was found with the upper chromatic number not(χ=h. We prove that in this class, for all STSs(2h - 1 with h<10, the lower chromatic number coincides with the upper chromatic number, i.e. χ=not(χ=h and moreover, there exists a infinite sub-class of STSs with χ=not(χ=h for any value of h.

  19. Narcolepsy: Association with H1N1 Infection and Vaccination

    Directory of Open Access Journals (Sweden)

    Ji Hyun Song

    2016-12-01

    Full Text Available Epidemiological studies have demonstrated an association between H1N1 influenza infection and vaccinations. This article reviews the various studies, and suggests the biological mechanisms explaining why and how H1N1 influenza infection or vaccine stimulates the autoimmune response, thereby resulting in narcolepsy. Among the vaccines, the effect of Pandemrix was scrutinized more than other vaccines, due to its higher association with an increase of narcolepsy onset. The consequences of using other vaccines which contain same or different adjuvants as Pandemrix, were also analyzed.

  20. Preclinical Testing of an Oncolytic Parvovirus: Standard Protoparvovirus H-1PV Efficiently Induces Osteosarcoma Cell Lysis In Vitro.

    Science.gov (United States)

    Geiss, Carsten; Kis, Zoltán; Leuchs, Barbara; Frank-Stöhr, Monika; Schlehofer, Jörg R; Rommelaere, Jean; Dinsart, Christiane; Lacroix, Jeannine

    2017-10-17

    Osteosarcoma is the most frequent malignant disease of the bone. On the basis of early clinical experience in the 1960s with H-1 protoparvovirus (H-1PV) in osteosarcoma patients, this effective oncolytic virus was selected for systematic preclinical testing on various osteosarcoma cell cultures. A panel of five human osteosarcoma cell lines (CAL 72, H-OS, MG-63, SaOS-2, U-2OS) was tested. Virus oncoselectivity was confirmed by infecting non-malignant human neonatal fibroblasts and osteoblasts used as culture models of non-transformed mesenchymal cells. H-1PV was found to enter osteosarcoma cells and to induce viral DNA replication, transcription of viral genes, and translation to viral proteins. After H-1PV infection, release of infectious viral particles from osteosarcoma cells into the supernatant indicated successful viral assembly and egress. Crystal violet staining revealed progressive cytomorphological changes in all osteosarcoma cell lines. Infection of osteosarcoma cell lines with the standard H-1PV caused an arrest of the cell cycle in the G2 phase, and these lines had a limited capacity for standard H-1PV virus replication. The cytotoxicity of wild-type H-1PV virus towards osteosarcoma cells was compared in vitro with that of two variants, Del H-1PV and DM H-1PV, previously described as fitness variants displaying higher infectivity and spreading in human transformed cell lines of different origins. Surprisingly, wild-type H-1PV displayed the strongest cytostatic and cytotoxic effects in this analysis and thus seems the most promising for the next preclinical validation steps in vivo.

  1. Preclinical Testing of an Oncolytic Parvovirus: Standard Protoparvovirus H-1PV Efficiently Induces Osteosarcoma Cell Lysis In Vitro

    Directory of Open Access Journals (Sweden)

    Carsten Geiss

    2017-10-01

    Full Text Available Osteosarcoma is the most frequent malignant disease of the bone. On the basis of early clinical experience in the 1960s with H-1 protoparvovirus (H-1PV in osteosarcoma patients, this effective oncolytic virus was selected for systematic preclinical testing on various osteosarcoma cell cultures. A panel of five human osteosarcoma cell lines (CAL 72, H-OS, MG-63, SaOS-2, U-2OS was tested. Virus oncoselectivity was confirmed by infecting non-malignant human neonatal fibroblasts and osteoblasts used as culture models of non-transformed mesenchymal cells. H-1PV was found to enter osteosarcoma cells and to induce viral DNA replication, transcription of viral genes, and translation to viral proteins. After H-1PV infection, release of infectious viral particles from osteosarcoma cells into the supernatant indicated successful viral assembly and egress. Crystal violet staining revealed progressive cytomorphological changes in all osteosarcoma cell lines. Infection of osteosarcoma cell lines with the standard H-1PV caused an arrest of the cell cycle in the G2 phase, and these lines had a limited capacity for standard H-1PV virus replication. The cytotoxicity of wild-type H-1PV virus towards osteosarcoma cells was compared in vitro with that of two variants, Del H-1PV and DM H-1PV, previously described as fitness variants displaying higher infectivity and spreading in human transformed cell lines of different origins. Surprisingly, wild-type H-1PV displayed the strongest cytostatic and cytotoxic effects in this analysis and thus seems the most promising for the next preclinical validation steps in vivo.

  2. Histamine response and local cooling in the human skin: involvement of H1- and H2-receptors.

    Science.gov (United States)

    Grossmann, M; Jamieson, M J; Kirch, W

    1999-08-01

    Histamine may contribute locally to cutaneous blood flow control under normal and pathologic conditions. The objective of this study was to observe the influence of skin temperature on histamine vasodilation, and the roles of H1-and H2-receptors using novel noninvasive methods. Eleven healthy subjects received, double-blind, single doses of the H1-receptor antagonist cetirizine (10 mg), cetirizine (10 mg) plus the H2-receptor antagonist cimetidine (400 mg), or placebo on separate occasions. Histamine was dosed cumulatively by iontophoresis to the forearm skin at 34 degrees C and 14 degrees C. Laser-Doppler flux (LDF) was measured at the same sites using customised probeholder/iontophoretic chambers with Peltier cooling elements. Finger mean arterial pressure (MAP) was measured and cutaneous vascular conductance calculated as LDF/MAP. Histamine vasodilation was reduced in cold skin. Cetirizine shifted the histamine dose-response at both temperatures: statistically significantly at 14 degrees C only. Combined H1- and H2-receptor antagonism shifted the response significantly at both temperatures. H1- and H2-receptors mediate histamine-induced skin vasodilation. The sensitivity of these receptors, particularly the H1- receptor, is attenuated at low skin temperature. Whether the reduced effect in cold skin represents specific receptor or postreceptor desensitization, or nonspecific attenuation of cutaneous vasodilation remains to be elucidated.

  3. Experiment prediction for Loft Nonnuclear Experiment L1-4

    International Nuclear Information System (INIS)

    White, J.R.; Berta, V.T.; Holmstrom, H.L.O.

    1977-04-01

    A computer analysis, using the WHAM and RELAP4 computer codes, was performed to predict the LOFT system thermal-hydraulic response for Experiment L1-4 of the nonnuclear (isothermal) test series. Experiment L1-4 will simulate a 200 percent double-ended offset shear in the cold leg of a four-loop large pressurized water reactor. A core simulator will be used to provide a reactor vessel pressure drop representative of the LOFT nuclear core. Experiment L1-4 will be initiated with a nominal isothermal primary coolant temperature of 282.2 0 C, a pressurizer pressure of 15.51 MPa, and a primary coolant flow of 270.9 kg/s. In general, the predictions of saturated blowdown for Experiment Ll-4 are consistent with the expected system behavior, and predicted trends agree with results from Semiscale Test S-01-4A, which simulated the Ll-4 experiment conditions

  4. The data acquisition system for the HERA H1 experiment

    International Nuclear Information System (INIS)

    Haynes, W.J.

    1990-06-01

    The HERA ep collider will set new challenges for the acquisition of data from large particle physics experiments. Short bunch-crossing times combined with high data rates imply sophisticated designs based on current technology. This paper describes how a multi-microprocessor system is being used at the H1 experiment. (author)

  5. The H^{-1}-norm of tubular neighbourhoods of curves

    NARCIS (Netherlands)

    Gennip, van Y.; Peletier, M.A.

    2011-01-01

    We study the H^{-1}-norm of the function 1 on tubular neighbourhoods of curves in R^2. We take the limit of small thickness epsilon, and we prove two different asymptotic results. The first is an asymptotic development for a fixed curve in the limit epsilon to 0, containing contributions from the

  6. Spread of H1N1 within Households

    Centers for Disease Control (CDC) Podcasts

    This podcast describes an investigation into how H1N1 was spreading within households during the initial days of the pandemic in Texas. CDC's Dr. Oliver Morgan discusses what investigators learned about the role that children played in introducing the virus into households and spreading flu.

  7. Influenza A (H1N1) pneumonia: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Amorim, Viviane Brandao; Rodrigues, Rosana Souza; Barreto, Miriam Menna; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Zanetti, Glaucia [Escola de Medicina de Petropolis, RJ (Brazil); Hochhegger, Bruno [Santa Casa de Misericordia de Porto Alegre, RS (Brazil)

    2013-11-01

    Objective: to describe aspects found on HRCT scans of the chest in patients infected with the influenza A (H1N1) virus. Methods: we retrospectively analyzed the HRCT scans of 71 patients (38 females and 33 males) with H1N1 infection, confirmed through laboratory tests, between July and September of 2009. The HRCT scans were interpreted by two thoracic radiologists independently, and in case of disagreement, the decisions were made by consensus. Results: the most common HRCT findings were ground-glass opacities (85%), consolidation (64%), or a combination of ground-glass opacities and consolidation (58%). Other findings were airspace nodules (25%), bronchial wall thickening (25%), interlobular septal thickening (21%), crazy-paving pattern (15%), perilobular pattern (3%), and air trapping (3%). The findings were frequently bilateral (89%), with a random distribution (68%). Pleural effusion, when observed, was typically minimal. No lymphadenopathy was identified. Conclusions: the most common findings were ground-glass opacities and consolidations, or a combination of both. Involvement was commonly bilateral with no axial or cranio caudal predominance in the distribution. Although the major tomographic findings in H1N1 infection are nonspecific, it is important to recognize such findings in order to include infection with the H1N1 virus in the differential diagnosis of respiratory symptoms. (author)

  8. Charge transfer in H2+-H(1s) collisions

    International Nuclear Information System (INIS)

    Errea, L.F.; Macias, A.; Mendez, L.; Rabadan, I.; Riera, A.

    2005-01-01

    We present an ab initio study of H 2 + +H(1s) collisions at H 2 + impact energies between 0.4 and 50keV. Cross sections are obtained within the sudden approximation for rotation and vibration of the diatomic molecule. We have found that anisotropy effects are crucial to correctly describe this system in this energy range

  9. H1N1 Influenza A hos mennesker og svin

    DEFF Research Database (Denmark)

    Larsen, Lars Erik

    2009-01-01

    Den nye pandemiske influenza A stamme H1N1 er hovedsagelig et nyt virus, som spredes mellem mennesker, men virusset er formodentlig opstået ved blanding af to svineinfluenza-virus og har derfor bibeholdt evnen til at kunne smitte fra mennesker til svin og fra svin til svin. Det er derfor vigtigt...

  10. Pneumococcal Pneumonia and Pandemic H1N1

    Centers for Disease Control (CDC) Podcasts

    2012-06-06

    Dr. George Nelson, a CDC medical officer, discusses the relationship between pneumococcal pneumonia and Pandemic H1N1.  Created: 6/6/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 6/6/2012.

  11. Development of the H1 backward silicon strip detector

    International Nuclear Information System (INIS)

    Eick, W.; Hansen, K.; Lange, W.; Prell, S.; Zimmermann, W.; Bullough, M.A.; Greenwood, N.M.; Lucas, A.D.; Newton, A.M.; Wilburn, C.D.; Horisberger, R.; Pitzl, D.; Haynes, W.J.; Noyes, G.

    1996-10-01

    The development and first results are described of a silicon strip detector telescope for the HERA experiment H1 designed to measure the polar angle of deep inelastic scattered electrons at small Bjorken x and low momentum transfers Q 2 . (orig.)

  12. Development of the H1 backward silicon strip detector

    International Nuclear Information System (INIS)

    Eick, W.; Hansen, K.; Lange, W.; Prell, S.; Zimmermann, W.; Bullough, M.A.; Greenwood, N.M.; Lucas, A.D.; Newton, A.M.; Wilburn, C.D.; Horisberger, R.; Pitzl, D.; Haynes, W.J.; Noyes, G.

    1997-01-01

    The development and first results are described of a silicon strip detector telescope for the HERA experiment H1 designed to measure the polar angle of deep inelastic scattered electrons at small Bjorken x and low momentum transfers Q 2 . (orig.)

  13. Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.

    Science.gov (United States)

    Gianotti, Massimo; Botta, Maurizio; Brough, Stephen; Carletti, Renzo; Castiglioni, Emiliano; Corti, Corrado; Dal-Cin, Michele; Delle Fratte, Sonia; Korajac, Denana; Lovric, Marija; Merlo, Giancarlo; Mesic, Milan; Pavone, Francesca; Piccoli, Laura; Rast, Slavko; Roscic, Maja; Sava, Anna; Smehil, Mario; Stasi, Luigi; Togninelli, Andrea; Wigglesworth, Mark J

    2010-11-11

    Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.

  14. Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs, United States.

    Science.gov (United States)

    Ali, Ahmed; Khatri, Mahesh; Wang, Leyi; Saif, Yehia M; Lee, Chang-Won

    2012-07-06

    In October and November 2010, novel H1N2 reassortant influenza viruses were identified from pigs showing mild respiratory signs that included cough and depression. Sequence and phylogenetic analysis showed that the novel H1N2 reassortants possesses HA and NA genes derived from recent H1N2 swine isolates similar to those isolated from Midwest. Compared to the majority of reported reassortants, both viruses preserved human-like host restrictive and putative antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA, and NS were similar to the contemporary swine triple reassortant viruses' internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants were derived from the 2009 pandemic H1N1. The NP and M proteins of the two isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino acid changes in the M2 and NP proteins, respectively. Similar amino acid changes were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other reassortant viruses reported in the U.S. Thus the role of those amino acids in relation to host adaptation need to be further investigated. The reassortments of pandemic H1N1 with swine influenza viruses and the potential of interspecies transmission of these reassortants from swine to other species including human indicate the importance of systematic surveillance of swine population to determine the origin, the prevalence of similar reassortants in the U.S. and their impact on both swine production and public health. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. The Influence of histamine H1-receptor on liver functions in immunized rabbits.

    Science.gov (United States)

    Tripathi, Trivendra; Shahid, Mohammad; Khan, Haris M; Khan, Rahat Ali; Siddiqui, Mashiatullah; Mahdi, Abbas Ali

    2011-10-01

    This study was designed to investigate the functional roles of histamine and histamine H1-receptor agonist and antagonist in the development of liver function impairment in immunized rabbits. The study comprised of six groups containing 18 rabbits each. Group III-VI received histamine (100 μg/kg, s.c.), H1R-agonist (HTMT, 10 μg/kg, s.c.), H1R-antagonist (pheniramine, 10 mg/kg, i.m.), and H1R-antagonist (pheniramine, 10 mg/kg, i.m.) plus histamine (100 μg/kg, s.c.), respectively, b.i.d. for 10 days. Group I (negative control) and group II (positive control) received sterile distilled water intramuscularly b.i.d. for 10 days. Groups II-VI were immunized on day 3 with intravenous injection of SRBC (1 × 10(9) cells/ml). Blood samples were collected on pre-immunization day 0, as well as on days 7-, 14-, 21-, 28-, and 58-post-immunization. Biochemical parameters AST, ALT, alkaline phosphatase and bilirubin [total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB)] were determined. On each experimental day, the mean values of serum enzymes and bilirubin in group I and group II showed no significant changes while in group III, IV, V, and VI, these enzymes and bilirubin levels showed significant changes (p pheniramine, and combination of histamine + pheniramine cause hepatic function impairment in terms of altered serum enzymes and bilirubin levels. The present findings suggest that HTMT causes moderate liver function impairment while others show mild impairment.

  16. L 1 Generalized Procrustes 2D Shape Alignment

    DEFF Research Database (Denmark)

    Larsen, Rasmus

    2008-01-01

    on the orientation of the coordinate system, i.e. it is not rotationally invariant. However, by simultaneously minimizing the city block distances in a series of rotated coordinate systems we are able to approximate the circular equidistance curves of Euclidean distances with a regular polygonal equidistance curve...... to the precision needed. Using 3 coordinate systems rotated 30 degrees we get a 12 sided regular polygon, with which we achieve deviations from Euclidean distances less than 2 % over all directions. This new formulation allows for minimization in the L1-norm using LP. We demonstrate that the use of the L1-norm...

  17. Molecular treatment of the ion-pair formation reaction in H(1s) + H(1s) collisions

    Energy Technology Data Exchange (ETDEWEB)

    Borondo, F.; Martin, F.; Yaez, M.

    1987-01-01

    All the available theoretical calculations of the cross section for the ion-pair formation reaction H(1s)+H(1s)..-->..H/sup +/H/sup -/(1s/sup 2/) have been performed using methods that are only valid at high collision energies. They get good agreement with the experiments for impact energies greater than 25 keV, but fail completely at smaller energies. In this work we report the cross section for this reaction at impact energies less than 10 keV, calculated in the framework of the impact-parameter approximation and using the molecular method with a common translation factor.

  18. Modulation of in vivo immunoglobulin production by endogenous histamine and H1R and H2R agonists and antagonists.

    Science.gov (United States)

    Tripathi, Trivendra; Shahid, Mohammad; Khan, Haris M; Negi, Mahendra Pal Singh; Siddiqui, Mashiatullah; Khan, Rahat A

    2010-01-01

    The present study was designed to delineate the immunomodulatory role of histamine receptors (H1R and H2R) and their antibody generation in a rabbit model. Six groups containing 18 rabbits each received either vehicle (sterile distilled water, 1 ml/kg x b.i.d), histamine (100 μg/kg x b.i.d.), H1R agonist (HTMT, 10 μg/kg x b.i.d.), H2R agonist (amthamine, 10 μg/kg x b.i.d.), H1R antagonist (pheniramine, 10 mg/kg x b.i.d.) or H2R antagonist (ranitidine, 10 mg/kg x b.i.d.). All animals were subsequently immunized with an intravenous injection of sheep red blood cells (SRBC). Estimations of total serum immunoglobulins (Igs), immunoglobulin M (IgM) and immunoglobulin G (IgG) were performed by ELISA and hemagglutination assay (HA) at days 0 (pre-immunization), 7, 14, 21, 28 and 58 (post-immunization). Both the ELISA and the HA showed similar production of Igs, IgM and IgG but the results were found comparatively more significant by ELISA as opposed to HA. Results showed that histamine could influence a detectable antibody response to SRBC early (i.e., at day 7), which lasted until day 58. Immunomodulatory processes showed suppression of an Ig generation in the H1R-antagonist group with enhancement in the H2R-antagonist group. The H1R-agonist group showed an increased Ig production in comparison to the H2R-agonist group. The IgM production was inhibited in the H1R-antagonist group as compared to the H2R-antagonist group, and it was also suppressed in H1R-agonist group as compared to H2R-agonist group. IgG production was inhibited in the H1R-antagonist group as opposed to the H2R-antagonist group. In contrast, the H1R-agonist group increased IgG production as compared to the H2R-agonist group. All the results were found to be statistically significant (p < 0.05 or p < 0.01). In conclusion, histamine and its receptor (H1R and H2R) agonists enhance antibody production by triggering the histamine receptors (H1R and H2R), and both the H1R antagonist and the H2R antagonist

  19. Imaging MOSS tomographic system for H-1NF

    International Nuclear Information System (INIS)

    Glass, F.; Howard, J.

    1999-01-01

    A tomographic diagnostic utilising the Modulated Optical Solid-State spectrometer (MOSS) is planned for the H-1NF stellarator at the ANU. It is designed to create two-dimensional temperature or velocity maps of a poloidal cross-section of the high temperature plasma of H-1NF. The introduction of the MOSS spectrometers has enabled the development of several diagnostics to be used on the H-1NF stellerator. The MOSS spectrometer allows calculations of the plasma temperature and bulk velocity based on a line-integrated measurement of light emitted from electronic transitions within the plasma. A tomographic system utilising a rotatable multi-view ring apparatus and spatial multiplexing through a MOSS spectrometer is currently being developed. The ring apparatus is placed inside the H-1NF vessel and encircles the plasma. Multiple line-of-sight views collect light through a poloidal cross-section of the plasma and the emitted light is coupled into large core optical fibres. The transmitted light, via the optical fibre bundle, is then imaged through a large aperture MOSS spectrometer and onto another optical fibre array. Each fibre is then fed into a photomultiplier tube for signal detection. Characterisation of the properties of the lithium niobate (LiNbO 3 ) crystal used for modulation in the MOSS spectrometer is being undertaken to account for ray divergence in the imaging system. Tomographic techniques enable the construction of a temperature or velocity map of the poloidal cross-section. Rotating the ring apparatus to a new viewing position for the next pulse of plasma should allow an accurate picture to be built up based on the reproducibility of the plasma pulses. It is expected that initial testing of the system will begin in May when H-1NF begins operations at 0.5 Telsa field strength

  20. Evidence from adult L1 Afrikaans L2 French

    African Journals Online (AJOL)

    results of this study show that a large number of the L2 learners had indeed acquired ... position in V2-languages (such as German) and in third position in non-V2 ... L1, allows construction types x and y but he will have no problem acquiring .... Modern Foreign Languages at Stellenbosch University at the time of testing.

  1. Discourse Connectives in L1 and L2 Argumentative Writing

    Science.gov (United States)

    Hu, Chunyu; Li, Yuanyuan

    2015-01-01

    Discourse connectives (DCs) are multi-functional devices used to connect discourse segments and fulfill interpersonal levels of discourse. This study investigates the use of selected 80 DCs within 11 categories in the argumentative essays produced by L1 and L2 university students. The analysis is based on the International Corpus Network of Asian…

  2. Biodegradation of alkaline lignin by Bacillus ligniniphilus L1

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Daochen; Zhang, Peipei; Xie, Changxiao; Zhang, Weimin; Sun, Jianzhong; Qian, Wei-Jun; Yang, Bin

    2017-02-21

    Background: Lignin is the most abundant aromatic biopolymer in the biosphere and it comprises up to 30% of plant biomass. Although lignin is the most recalcitrant component of the plant cell wall, still there are microorganisms able to decompose it or degrade it. Fungi are recognized as the most widely used microbes for lignin degradation. However, bacteria have also been known to be able to utilize lignin as a carbon or energy source. Bacillus ligniniphilus L1 was selected in this study due to its capability to utilize alkaline lignin as a single carbon or energy source and its excellent ability to survive in extreme environments. Results: To investigate the aromatic metabolites of strain L1 decomposing alkaline lignin, GC-MS analyze was performed and fifteen single phenol ring aromatic compounds were identified. The dominant absorption peak included phenylacetic acid, 4-hydroxy-benzoicacid, and vanillic acid with the highest proportion of metabolites resulting in 42%. Comparison proteomic analysis were carried out for further study showed that approximately 1447 kinds of proteins were produced, 141 of which were at least 2-fold up-regulated with alkaline lignin as the single carbon source. The up-regulated proteins contents different categories in the biological functions of protein including lignin degradation, ABC transport system, environmental response factors, protein synthesis and assembly, etc. Conclusions: GC-MS analysis showed that alkaline lignin degradation of strain L1 produced 15 kinds of aromatic compounds. Comparison proteomic data and metabolic analysis showed that to ensure the degradation of lignin and growth of strain L1, multiple aspects of cells metabolism including transporter, environmental response factors, and protein synthesis were enhanced. Based on genome and proteomic analysis, at least four kinds of lignin degradation pathway might be present in strain L1, including a Gentisate pathway, the benzoic acid pathway and the

  3. Citrullination regulates pluripotency and histone H1 binding to chromatin

    DEFF Research Database (Denmark)

    Christophorou, Maria A; Castelo-Branco, Gonçalo; Halley-Stott, Richard P

    2014-01-01

    citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune...... and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel...... PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic...

  4. Data storage and data access at H1

    International Nuclear Information System (INIS)

    Gerhards, R.; Kleinwort, C.; Kruener-Marquis, U.; Niebergall, F.

    1996-01-01

    The electron proton collider HERA at the DESY laboratory in Hamburg and the H1 experiment are now in successful operation for more than three years. The H1 experiment is logging data at an average rate of 500KB/s which results in a yearly raw data volume of several Terabytes. The data are reconstructed with a delay of only a few hours, also yielding several Terabytes of reconstructed data after physics oriented event classification. Physics analysis is performed on a SGI Challenge computer, equipped with about 500 GB of disk and, since a couple of months, direct access to a Storage Tek ACS 4400 silo. The disk space is mainly devoted to store the reconstructed data in very compressed format (typically 5 to 10 KB per event). This allows for very efficient and fast physics analysis. Monte Carlo data, on the other hand, are kept in the ACS silo and staged to disk on demand. (author)

  5. The readout system of the new H1 silicon detectors

    International Nuclear Information System (INIS)

    Buerger, J.; Hansen, K.; Lange, W.; Prell, S.; Zimmermann, W.; Henschel, H.; Haynes, W.J.; Noyes, G.W.; Joensson, L.; Gabathuler, K.; Horisberger, R.; Wagener, M.; Eichler, R.; Erdmann, W.; Niggli, H.; Pitzl, D.

    1995-03-01

    The H1 detector at HERA at DESY undergoes presently a major upgrade. In this context silicon strip detectors have been installed at beginning of 1995. The high bunch crossing frequency of HERA (10.4 MHz) demands a novel readout architecture which includes pipelining, signal processing and data reduction at a very early stage. The front end readout is hierarchically organized. The detector elements are read out by the APC chip which contains an analog pipeline and performs first background subtraction. Up to five readout chips are controlled by a Decoder Chip. The readout processor module (OnSiRoC) operates the detectors, controls the Decoder Chips and performs a first level data reduction. The paper describes the readout architecture of the H1 Silicon Detectors and performance data of the complete readout chain. (orig.)

  6. Ten years of Object-Oriented analysis on H1

    International Nuclear Information System (INIS)

    Laycock, Paul

    2012-01-01

    Over a decade ago, the H1 Collaboration decided to embrace the object-oriented paradigm and completely redesign its data analysis model and data storage format. The event data model, based on the ROOT framework, consists of three layers - tracks and calorimeter clusters, identified particles and finally event summary data - with a singleton class providing unified access. This original solution was then augmented with a fourth layer containing user-defined objects. This contribution will summarise the history of the solutions used, from modifications to the original design, to the evolution of the high-level end-user analysis object framework which is used by H1 today. Several important issues are addressed - the portability of expert knowledge to increase the efficiency of data analysis, the flexibility of the framework to incorporate new analyses, the performance and ease of use, and lessons learned for future projects.

  7. Results from the H1 experiment at HERA

    International Nuclear Information System (INIS)

    Krasny, M.W.

    1993-01-01

    Results obtained by the H1 collaboration at HERA from the analysis of the data collected in 1992 - the first year of HERA operation are presented. Measurements of the total photoproduction cross-section and the inclusive jet cross-section in γp scattering, the structure function F 2 (x,Q 2 ) and the jet rates in deep inelastic ep scattering, and results of direct searches for leptoquarks are discussed. (author) 37 refs., 6 figs

  8. Underreporting of 2009 H1N1 Influenza Cases

    Centers for Disease Control (CDC) Podcasts

    Influenza cases are difficult to track because many people don't go to the doctor or get tested for flu when they're sick. The first months of the 2009 H1N1 influenza pandemic were no different. In this podcast, CDC's Dr. Carrie Reed discusses a study in the December issue of Emerging Infectious Diseases that looked at the actual number of cases reported and estimated the true number of cases when correcting for underreporting.

  9. Spread of H1N1 within Households

    Centers for Disease Control (CDC) Podcasts

    2010-03-29

    This podcast describes an investigation into how H1N1 was spreading within households during the initial days of the pandemic in Texas. CDC's Dr. Oliver Morgan discusses what investigators learned about the role that children played in introducing the virus into households and spreading flu.  Created: 3/29/2010 by Emerging Infectious Diseases.   Date Released: 3/29/2010.

  10. Contextualizing ethics: ventilators, H1N1 and marginalized populations.

    Science.gov (United States)

    Silva, Diego S; Nie, Jason X; Rossiter, Kate; Sahni, Sachin; Upshur, Ross E G

    2010-01-01

    If the H1N1 pandemic worsens, there may not be enough ventilated beds to care for all persons with respiratory failure. To date, researchers who explicitly discuss the ethics of intensive care unit admission and the allocation of ventilators during an influenza pandemic have based criteria predominantly on the principles of utility and efficiency, that is, promoting actions that maximize the greatest good for the greatest number of people. However, haphazardly applying utility and efficiency potentially disadvantages marginalized populations who might be at increased risk of severe reactions to H1N1. In Canada, Aboriginals represent 3% of Canadians, yet 11% of H1N1 cases requiring hospitalization involve Aboriginal persons. Aboriginal persons suffer from high rates of obesity due to socio-economic inequalities. Obesity is also a risk factor for severe H1N1 reactions. Yet, since obesity is found to increase the duration of stay in ventilated beds and a long stay is not considered an optimal use of ventilators, applying the principles of utility and efficiency may magnify existing social inequalities. Although promoting utility and efficiency is important, other ethical principles, such as equity and need, require thoughtful consideration and implementation. Furthermore, since public resources are being used to address a public health hazard, the viewpoints of the public, and specifically stakeholders who will be disproportionately affected, should inform decision-makers. Finally, giving attention to the needs and rights of marginalized populations means that ventilators should not be allocated based on criteria that exacerbate the social injustices faced by these groups of people.

  11. The H1 calorimetry: Performance and upgrade program

    International Nuclear Information System (INIS)

    Borras, K.

    1995-04-01

    The energies of particles are measured in the H1 detector with four different calorimeters. Their designs, which are optimized for their particular requirements, are briefly described. Their performance is characterized in terms of their operational stability, the precision of their energy scale and their trigger functionality. The most important among the four calorimeters is the large liquid argon calorimeter and therefore most emphasis is given to the description of this component. (orig.)

  12. Sedation and memory: studies with a histamine H-1 receptor antagonist.

    Science.gov (United States)

    Turner, Claire; Handford, Alison D F; Nicholson, Anthony N

    2006-07-01

    The influence of sedation on the effect of an H-1 receptor antagonist on various cognitive functions, including memory, were evaluated. Diphenhydramine (50, 75 and 100 mg) and lorazepam (0.5 and 1.5 mg) were given on single occasions to 12 healthy volunteers (six males, six females) aged 20-33 (mean 23.4) years. Subjective assessments of sedation, sleep latencies, digit symbol substitution, choice reaction time, sustained attention and memory recall were studied 1.0 h before and 0.5, 2.0 and 3.5 h after drug ingestion. The study was double blind, placebo controlled and with a crossover design. With all doses of diphenhydramine there was subjective sedation, reduced sleep latencies and impairments in performance on the digit symbol substitution, choice reaction time and sustained attention tasks. No effects were observed with 0.5 mg lorazepam. With 1.5 mg lorazepam there was subjective sedation, fewer digit symbol substitutions, slowed choice reaction time, impaired attention and memory, but no effect on sleep latencies. Contrast analysis of data measured at all time points showed that although there was no difference in the effect of diphenhydramine (100 mg) and lorazepam (1.5 mg) on those tasks without a memory component, response times were slower with lorazepam on those tasks with a memory component. However, both 100 mg diphenhydramine and 1.5 mg lorazepam impaired prompted recall measured at 2 h post-ingestion only. It is considered that impaired memory is not necessarily associated with sedation, and that impairment of memory with drugs that lead to sedation may be effected through neuronal systems independent of those that affect arousal.

  13. The H1 SPACAL time-to-digital converter system

    International Nuclear Information System (INIS)

    Eisenhandler, E.; Landon, M.; Thompson, G.

    1995-01-01

    This paper describes a pipelined 1,400-channel Time-to-Digital Converter (TDC) system for the H1 Scintillating Fiber Calorimeter, which will soon be installed in the H1 experiment at DESY. The main task of the TDC system is to determine the time of arrival of energy depositions, and send this information from bunch crossings that satisfy the event trigger into the H1 data acquisition system. In addition, the TDC system must monitor the timing trigger, which vetoes bunch crossings that contain too much background energy. Products of the interaction are separated from background on the basis of their different times of arrival with respect to the bunch crossing clock. For this monitoring the TDC system uses automatic on-board histogramming hardware that produces a family of histograms for each of 1,400 channels. The TDC function is performed by the TMC1004 ASIC. The system digitizes over a range of 32ns per bunch crossing with 1ns bins and a precision of 1ns. Because of the way the TMC1004 is designed, it is possible to vary the size of the bins between 0.6ns and 3ns by trading off measurement range for bin size. The system occupies two 9U VME crates

  14. Critical electrolyte concentration of spermatozoal chromatin containing histone H1 variants

    Directory of Open Access Journals (Sweden)

    J.R.P. Falco

    1999-06-01

    Full Text Available The critical electrolyte concentrations (CEC of sperm chromatin from animal species known or suspected to contain histone H1 variants were compared by examining the affinity of their DNA-protein complexes for toluidine blue in the presence of Mg2+. Bullfrog, sea urchin, bee and bumblebee spermatozoa were studied. The CEC for Rana catesbeiana and two sea urchin species were similar to that of histone H5-containing chromatin from chicken erythrocytes, thus confirming the biochemical and structural similarities of these DNA-protein complexes. The CEC for bees and the bumblebee, Bombus atratus, showed no particular phylogenetic relationship. We concluded that the CEC of histone H1-containing sperm cell chromatin is a useful indicator of variability in DNA-protein complexes but is of little phylogenetic value.Valores de concentração crítica de eletrólitos (CEC da cromatina de espermatozóides de espécies conhecidas ou suspeitas de apresentarem variantes da histona H1 foram comparados entre si. O objetivo foi estabelecer semelhanças ou diferenças nos complexos DNA-proteína de espermatozóides dessas espécies em nível citoquímico. A afinidade por moléculas de azul de toluidina em condições de competição com íons Mg2+ foi investigada nos espermatozóides do sapo boi e de ouriços do mar, abelhas e mamangava. Uma íntima relação entre os valores de CEC de Rana catesbeiana e de duas espécies de ouriço do mar com os da cromatina de eritrócitos de frango, que contém a histona H5, foi vista estar de acordo com certas semelhanças bioquímicas e estruturais entre seus complexos DNA-proteína. Quanto aos dados para abelhas e para a mamangava Bombus atratus, não se pôde associar a variabilidade em valores de CEC com a posição das espécies na respectiva árvore filogenética. Conclui-se, portanto, que a CEC de cromatina de espermatozóides que contêm histona H1 é um indicador útil da influência de variantes de H1 na organiza

  15. Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

    Science.gov (United States)

    Brahmer, Julie R.; Tykodi, Scott S.; Chow, Laura Q.M.; Hwu, Wen-Jen; Topalian, Suzanne L.; Hwu, Patrick; Drake, Charles G.; Camacho, Luis H.; Kauh, John; Odunsi, Kunle; Pitot, Henry C.; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M.; Alaparthy, Suresh; Grosso, Joseph F.; Korman, Alan J.; Parker, Susan M.; Agrawal, Shruti; Goldberg, Stacie M.; Pardoll, Drew M.; Gupta, Ashok; Wigginton, Jon M.

    2013-01-01

    BACKGROUND Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host’s immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non–small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.) PMID:22658128

  16. Conditions for l =1 Pomeranchuk instability in a Fermi liquid

    Science.gov (United States)

    Wu, Yi-Ming; Klein, Avraham; Chubukov, Andrey V.

    2018-04-01

    We perform a microscopic analysis of how the constraints imposed by conservation laws affect q =0 Pomeranchuk instabilities in a Fermi liquid. The conventional view is that these instabilities are determined by the static interaction between low-energy quasiparticles near the Fermi surface, in the limit of vanishing momentum transfer q . The condition for a Pomeranchuk instability is set by Flc (s )=-1 , where Flc (s ) (a Landau parameter) is a properly normalized partial component of the antisymmetrized static interaction F (k ,k +q ;p ,p -q ) in a charge (c) or spin (s) subchannel with angular momentum l . However, it is known that conservation laws for total spin and charge prevent Pomeranchuk instabilities for l =1 spin- and charge-current order parameters. Our study aims to understand whether this holds only for these special forms of l =1 order parameters or is a more generic result. To this end we perform a diagrammatic analysis of spin and charge susceptibilities for charge and spin density order parameters, as well as perturbative calculations to second order in the Hubbard U . We argue that for l =1 spin-current and charge-current order parameters, certain vertex functions, which are determined by high-energy fermions, vanish at Fl=1 c (s )=-1 , preventing a Pomeranchuk instability from taking place. For an order parameter with a generic l =1 form factor, the vertex function is not expressed in terms of Fl=1 c (s ), and a Pomeranchuk instability may occur when F1c (s )=-1 . We argue that for other values of l , a Pomeranchuk instability may occur at Flc (s )=-1 for an order parameter with any form factor.

  17. Anti-PD-L1 Treatment Induced Central Diabetes Insipidus.

    Science.gov (United States)

    Zhao, Chen; Tella, Sri Harsha; Del Rivero, Jaydira; Kommalapati, Anuhya; Ebenuwa, Ifechukwude; Gulley, James; Strauss, Julius; Brownell, Isaac

    2018-02-01

    Immune checkpoint inhibitors, including anti-programmed cell death protein 1 (PD-1), anti-programmed cell death protein ligand 1 (PD-L1), and anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) monoclonal antibodies, have been widely used in cancer treatment. They are known to cause immune-related adverse events (irAEs), which resemble autoimmune diseases. Anterior pituitary hypophysitis with secondary hypopituitarism is a frequently reported irAE, especially in patients receiving anti-CTLA4 treatment. In contrast, posterior pituitary involvement, such as central diabetes insipidus (DI), is relatively rare and is unreported in patients undergoing PD-1/PD-L1 blockade. We describe a case of a 73-year-old man with Merkel cell carcinoma who received the anti-PD-L1 monoclonal antibody avelumab and achieved partial response. The patient developed nocturia, polydipsia, and polyuria 3 months after starting avelumab. Further laboratory testing revealed central DI. Avelumab was held and he received desmopressin for the management of central DI. Within 6 weeks after discontinuation of avelumab, the patient's symptoms resolved and he was eventually taken off desmopressin. The patient remained off avelumab and there were no signs or symptoms of DI 2 months after the discontinuation of desmopressin. To our knowledge, this is the first report of central DI associated with anti-PD-L1 immunotherapy. The patient's endocrinopathy was successfully managed by holding treatment with the immune checkpoint inhibitor. This case highlights the importance of early screening and appropriate management of hormonal irAEs in subjects undergoing treatment with immune checkpoint inhibitors to minimize morbidity and mortality. Copyright © 2017 Endocrine Society

  18. Selection of regularization parameter for l1-regularized damage detection

    Science.gov (United States)

    Hou, Rongrong; Xia, Yong; Bao, Yuequan; Zhou, Xiaoqing

    2018-06-01

    The l1 regularization technique has been developed for structural health monitoring and damage detection through employing the sparsity condition of structural damage. The regularization parameter, which controls the trade-off between data fidelity and solution size of the regularization problem, exerts a crucial effect on the solution. However, the l1 regularization problem has no closed-form solution, and the regularization parameter is usually selected by experience. This study proposes two strategies of selecting the regularization parameter for the l1-regularized damage detection problem. The first method utilizes the residual and solution norms of the optimization problem and ensures that they are both small. The other method is based on the discrepancy principle, which requires that the variance of the discrepancy between the calculated and measured responses is close to the variance of the measurement noise. The two methods are applied to a cantilever beam and a three-story frame. A range of the regularization parameter, rather than one single value, can be determined. When the regularization parameter in this range is selected, the damage can be accurately identified even for multiple damage scenarios. This range also indicates the sensitivity degree of the damage identification problem to the regularization parameter.

  19. Preclinical Testing of an Oncolytic Parvovirus: Standard Protoparvovirus H-1PV Efficiently Induces Osteosarcoma Cell Lysis In Vitro

    OpenAIRE

    Carsten Geiss; Zoltán Kis; Barbara Leuchs; Monika Frank-Stöhr; Jörg R. Schlehofer; Jean Rommelaere; Christiane Dinsart; Jeannine Lacroix

    2017-01-01

    Osteosarcoma is the most frequent malignant disease of the bone. On the basis of early clinical experience in the 1960s with H-1 protoparvovirus (H-1PV) in osteosarcoma patients, this effective oncolytic virus was selected for systematic preclinical testing on various osteosarcoma cell cultures. A panel of five human osteosarcoma cell lines (CAL 72, H-OS, MG-63, SaOS-2, U-2OS) was tested. Virus oncoselectivity was confirmed by infecting non-malignant human neonatal fibroblasts and osteoblasts...

  20. Pulmonary function in patients with pandemic H1N1

    Directory of Open Access Journals (Sweden)

    Soraia Koppe

    Full Text Available Abstract Introduction: The influenza A (H1N1 was responsible for the 2009 pandemic, especially with severe pulmonary complications. Objective: To describe characteristics of patients in a university hospital in Curitiba - PR with laboratory diagnosis of influenza A (H1N1 and its post hospital discharge in the 2009 lung function pandemic. Methodology: A retrospective observational study. It was used as a data source the institution Epidemiology Service (SEPIH and spirometry tests of patients who were admitted in 2009, 18 years without lung disease associated and non-pregnant. Descriptive statistics were used and applied Fisher's exact test for relationship between comorbidity and spirometry tests. Results: There were 84 confirmed cases, of these 11 were eligible for the study with a mean age of 44.27 years (± 9.63 and 63.63% males. 54.54% of the 11 patients had comorbidities associated with systemic arterial hypertension (54.54%, diabetes (18.18% and late postoperative period of kidney transplantation (18.18% were the most frequent. Most patients (81.81% had BMI ≥ 25kg / m². The Spirometry test was performed approximately 40.09 (± 15.27 days after discharge, of these, 5 had restrictive pattern and all had abnormal chest radiograph results. There was no statistically significant difference between the results of Spirometry and comorbidities (p=0.24. Conclusions: The group evaluated in this research did not show a direct relationship between Spirometry and comorbidities, but changes in Spirometry in some patients after hospital discharge stood out, suggesting changes in lung function due to influenza A (H1N1.

  1. The H1 forward proton spectrometer at HERA

    International Nuclear Information System (INIS)

    Esch, P. van; Kapichine, M.; Morozov, A.; Spaskov, V.; Bartel, W.; List, B.; Mahlke-Krueger, H.; Schroeder, V.; Wilksen, T.; Buesser, F.W.; Geske, K.; Karschnik, O.; Niebergall, F.; Riege, H.; Schuett, J.; Staa, R. van; Wittek, C.; Dau, D.; Newton, D.; Kotelnikov, S.K.; Lebedev, A.; Rusakov, S.; Astvatsatourov, A.; Baehr, J.; Harder, U.; Hiller, K.; Hoffmann, B.; Luedecke, H.; Nahnhauer, R.

    2000-01-01

    The forward proton spectrometer is part of the H1 detector at the HERA collider. Protons with energies above 500 GeV and polar angles below 1 mrad can be detected by this spectrometer. The main detector components are scintillating fiber detectors read out by position-sensitive photo-multipliers. These detectors are housed in the so-called Roman Pots which allow them to be moved close to the circulating proton beam. Four Roman Pot stations are located at distances between 60 and 90 m from the interaction point

  2. The H1 forward proton spectrometer at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Esch, P. van; Kapichine, M.; Morozov, A.; Spaskov, V.; Bartel, W.; List, B.; Mahlke-Krueger, H.; Schroeder, V.; Wilksen, T.; Buesser, F.W.; Geske, K.; Karschnik, O.; Niebergall, F.; Riege, H.; Schuett, J.; Staa, R. van; Wittek, C.; Dau, D.; Newton, D.; Kotelnikov, S.K.; Lebedev, A.; Rusakov, S.; Astvatsatourov, A.; Baehr, J.; Harder, U.; Hiller, K. E-mail: hiller@ifh.de; Hoffmann, B.; Luedecke, H.; Nahnhauer, R

    2000-05-21

    The forward proton spectrometer is part of the H1 detector at the HERA collider. Protons with energies above 500 GeV and polar angles below 1 mrad can be detected by this spectrometer. The main detector components are scintillating fiber detectors read out by position-sensitive photo-multipliers. These detectors are housed in the so-called Roman Pots which allow them to be moved close to the circulating proton beam. Four Roman Pot stations are located at distances between 60 and 90 m from the interaction point.

  3. Underreporting of 2009 H1N1 Influenza Cases

    Centers for Disease Control (CDC) Podcasts

    2009-12-08

    Influenza cases are difficult to track because many people don't go to the doctor or get tested for flu when they're sick. The first months of the 2009 H1N1 influenza pandemic were no different. In this podcast, CDC's Dr. Carrie Reed discusses a study in the December issue of Emerging Infectious Diseases that looked at the actual number of cases reported and estimated the true number of cases when correcting for underreporting.  Created: 12/8/2009 by Emerging Infectious Diseases.   Date Released: 12/8/2009.

  4. L1 French learning of L2 Spanish past tenses: L1 transfer versus aspect and interface issues

    Directory of Open Access Journals (Sweden)

    José Amenós Pons

    2017-09-01

    Full Text Available This paper examines the process of acquiring L2s that are closely related to the L1 through data on how adult French speakers learning L2 Spanish in a formal setting develop knowledge and use of past tenses in this L2. We consider the role of transfer and simplification in acquiring mental representations of the L2 grammar, specifically in the area of tense and aspect, and how learners deal with integrating grammatically encoded, lexical and discursive information, including mismatching feature combinations leading to particular inferential effects on interpretation. Data is presented on the Spanish past tenses (simple and compound past, pluperfect, imperfect and progressive forms from two tasks, an oral production filmretell and a multiple-choice interpretation task, completed by learners at A2, B1, B2 and C1 CEFR levels (N = 20-24 per level. L1 influence is progressively attenuated as proficiency increases. Difficulties were not always due to negative L1 transfer, but related also to grammar-discourse interface issues when integrating linguistic and pragmatic information in the interpretation process. This has clear implications for the teaching of closely related languages: instruction should not only focus on crosslinguistic contrasts, but also prioritize uses requiring complex interface integration, which are harder to process.

  5. The H1 lead/scintillating-fibre calorimeter

    International Nuclear Information System (INIS)

    Appuhn, R.D.; Arndt, C.; Barrelet, E.

    1996-08-01

    The backward region of the H1 detector has been upgraded in order to provide improved measurement of the scattered electron in deep inelastic scattering events. The centerpiece of the upgrade is a high-resolution lead/scintillating-fibre calorimeter. The main design goals of the calorimeter are: good coverage of the region close to the beam pipe, high angular resolution and energy resolution of better than 2% for 30 GeV electrons. The calorimeter should be capable of providing coarse hadronic energy measurement and precise time information to suppress out-of-time background events at the first trigger level. It must be compact due to space restrictions. These requirements were fulfilled by constructing two separate calorimeter sections. The inner electromagnetic section is made of 0.5 mm scintillating plastic fibres embedded in a lead matrix. Its lead-to-fibre ratio is 2.3:1 by volume. The outer hadronic section consists of 1.0 mm diameter fibres with a lead-to-fibre ratio of 3.4:1. The mechanical construction of the new calorimeter and its assembly in the H1 detector are described. (orig.)

  6. The H1 lead/scintillating-fibre calorimeter

    International Nuclear Information System (INIS)

    Appuhn, R.-D.; Arndt, C.; Barrelet, E.

    1997-01-01

    The backward region of the H1 detector has been upgraded in order to provide improved measurement of the scattered electron in deep inelastic scattering events. The centerpiece of the upgrade is a high-resolution lead/scintillating-fibre calorimeter. The main design goals of the calorimeter are: good coverage of the region close to the beam pipe, high angular resolution and energy resolution of better than 2% for 30 GeV electrons. The calorimeter should be capable of providing coarse hadronic energy measurement and precise time information to suppress out-of-time background events at the first trigger level. It must be compact due to space restrictions. These requirements were fulfilled by constructing two separate calorimeter sections. The inner electromagnetic section is made of 0.5 mm scintillating plastic fibres embedded in a lead matrix. Its lead-to-fibre ratio is 2.3:1 by volume. The outer hadronic section consists of 1.0 mm diameter fibres with a lead-to-fibre ratio of 3.4:1. The mechanical construction of the new calorimeter and its assembly in the H1 detector are described. (orig.)

  7. Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses

    OpenAIRE

    Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub

    2014-01-01

    Background The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. Findings The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decrease...

  8. The L1-shell ionisation of atoms by relativistic particles

    International Nuclear Information System (INIS)

    Moiseiwitsch, B.L.; Norrington, P.H.

    1979-01-01

    An expression for the L 1 -shell ionisation cross sections of atoms by high-energy particles has been derived using the relativistic plane-wave Born approximation. The incident and scattered particles are described by Dirac plane waves while Darwin hydrogenic wavefunctions are used for the atomic electrons. A comparison is made with experimental total cross sections for incident electrons in the energy range 1-2 MeV. The agreement is a considerable improvement on that obtained using the non-relativistic planewave Born approximation. (author)

  9. About a significance of the avian linker histone (H1) polymorphic ...

    Indian Academy of Sciences (India)

    60

    structural disorder may specify histone H1 interaction with both DNA and partnering proteins through ... from the studies conducted on mammalian model, including the human H1 variants. However ..... Thus, the disparate layout of histone H1.

  10. House dust mite induces expression of intercellular adhesion molecule-1 in EoL-1 human eosinophilic leukemic cells.

    Science.gov (United States)

    Kwon, Byoung Chul; Sohn, Myung Hyun; Kim, Kyung Won; Kim, Eun Soo; Kim, Kyu-Earn; Shin, Myeong Heon

    2007-10-01

    The house dust mite (HDM) is considered to be the most common indoor allergen associated with bronchial asthma. In this study, we investigated whether crude extract of the HDM Dermatophagoides farinae could activate human eosinophilic leukemic cells (EoL-1) to induce upregulation of cell-surface adhesion molecules. When EoL-1 cells were incubated with D. farinae extract, expression of intercellular adhesion molecule-1 (ICAM-1) significantly increased on the cell surfaces compared to cells incubated with medium alone. In contrast, surface expression of CD11b and CD49d in EoL-1 cells was not affected by D. farinae extract. In addition, pretreatment of cells with NF-kappaB inhibitor (MG-132) or JNK inhibitor (SP600125) significantly inhibited ICAM-1 expression promoted by HDM extract. However, neither p38 MAP kinase inhibitor nor MEK inhibitor prevented HDM-induced ICAM-1 expression in EoL-1 cells. These results suggest that crude extract of D. farinae induces ICAM-1 expression in EoL-1 cells through signaling pathways involving both NF-kappaB and JNK.

  11. Experiences at HERA with the H1 data acquisition system

    International Nuclear Information System (INIS)

    Haynes, W.J.

    1992-09-01

    The recently commissioned HERA collider provides a significant pointer to the problems that have to be surmounted in data acquisition systems at the next generation of hadron machines. With bunch crossings, between 30 GeV electrons and 820 GeV protons, 96 nanoseconds apart, the H1 experiment illustrates the application of sophisticated pipelining solutions in the readout of several hundred thousand electronic channels. A modular, multiprocessor design structure emphasis the architectural concepts necessary to cope with large data throughput and yet remain flexible enough to exploit ongoing technological advances in both hardware and software. The range of techniques implemented will be surveyed, covering various digitisation solutions at the front-end through to embedded microprocessor arrays in standard busses controlled by graphics-based stations executing object- orientated code. The experiences gained in developing such a system are also discussed. (orig.)

  12. H1N1 pandemic preparedness and business continuity plan

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    SaskPower's H1N1 pandemic preparedness and business continuity plan was designed to prepare SaskPower employees for elevated levels of absenteeism during a potential pandemic. Emergency management and business continuity will be facilitated if critical duties and essential services are maintained without interruption. A layered approach was used to develop a range of response measures designed to meet a range of possible pandemic threats. The plan identified essential activities, tasks and functions and outlined methods of mitigating supply disruptions and possible shortages. Methods of minimizing illness in employees were discussed, as well as methods of maintaining a safe and secure work environment. The measures were developed in accordance with the World Health Organization (WHO) 6 phases of pandemic alert. The plan was also designed to be read by SaskPower's key suppliers in order to ensure their pandemic readiness. 5 tabs.

  13. Results from the H1 experiment at HERA

    International Nuclear Information System (INIS)

    Roeck, A. de

    1994-01-01

    New results from the H1 experiment at HERA on photoproduction, deep inelastic scattering and search for exotic particles are presented. Clear evidence is found for hard scattering in photoproduction interactions. Jets have been observed and used to examine the x γ distribution, indicating the need for a gluonic component in the photon. Hadronic final states and jet cross sections have been measured in deep inelastic scattering. A class of deep inelastic events with diffractive characteristics has been observed. The proton structure function F 2 (x, Q 2 ) has been measured in the new Bjorken-x region 10 -4 -2 and is found to rise with decreasing x. New limits for leptoquarks, squarks and excited electrons have been deduced. (orig.)

  14. Technicon H*1 Hematology System: Optical Design Considerations

    Science.gov (United States)

    Colella, G. M.; Tycko, D. H.; Groner, W.

    1988-06-01

    The Technicon H*1 systemTM is a clinical laboratory flow cytometer which performs a complete hematology profile, providing quantitative information on the various types of cells in a blood sample. A light-scattering method, using a HeNe laser, determines in a single flow channel the red cell count, platelet count, and the distributions of red cell volume, red cell hemoglobin concentration, and platelet volume. To accomplish this the scattered light from each red cell in the sample is measured in real time at two angular intervals. The cell volume and the hemoglobin concentration within the cell are derived from these two measurements. Severe accuracy and precision specifications are placed on the medically important red cell count (RBC) and the mean red cell volume (MCV). From the point of view of optical system design, the dominant factor is the requirement that RBC and MCV have precision and accuracy of the order of 2%. Signal-to-noise and scattering-angle definition requirements dictated the choice of a HeNe laser light source. The optics includes an illumination system for producing a sharply defined, uniformly illuminated scattering region and a detection system which must accurately define the accepted scattering angles. In previous cytometric methods for determining MCV only a single quantity was measured for each cell. Such methods cannot disentangle the independent effects of cell size and hemoglobin concentration on the measurement, thus compromising MCV accuracy. The present double-angle scattering method overcomes this accuracy problem. The H*1 red cell method, the supporting optical design and data demonstrating that the use of this technique eliminates interference between the observed red cell indices are presented.

  15. Ophthalmic antihistamines and H1-H4 receptors.

    Science.gov (United States)

    Wade, Laurie; Bielory, Leonard; Rudner, Shara

    2012-10-01

    Antihistamines exert pharmacologic effects by binding to four histamine receptors (H1-H4) at different affinities, producing variable effects depending on the receptor they predominantly bind to. This review's purpose is to determine the relative potency of antihistamines by comparing their binding affinities to these receptors. Studies on binding affinities of antihistamines to histamine receptors were reviewed and the dissociation constant for inhibitor binding (Ki) analyzed to determine the most and least potent antihistamine for each receptor. We retrieved the binding affinities for nineteen antihistamines. For H1 receptors, pyrilamine exhibited the highest affinity (Ki = 0.8 nM), and thioperamide the lowest (Ki = 280, 000 nM). For H2 receptors, ranitidine exhibited the highest affinity (Ki = 187 nM), and olopatadine the lowest (Ki = 100 ,000 nM). For the recently discovered H3 and H4 receptors, thioperamide exhibited the highest affinity (Ki = 1.1 nM), and olopatadine exhibited the lowest (Ki = 79 ,400 nM), to H3. Data on binding affinities to the H4 receptor exist for: ketotifen, pheniramine, ranitidine, cimetidine and thioperamide. Of these, thioperamide exhibited the highest affinity (Ki = 27 nM), whereas cimetidine and ranitidine exhibited the lowest affinity (Ki = >10, 000 nM) for H4 receptors. This review summarizes the relative potency of antihistamines based on their binding affinities to the four histamine receptors. Although data on binding affinities of antihistamines to the H4 receptor are sparse, it is apparent that further research on these histamine subtypes may open new venues for more direct treatment with a higher therapeutic efficacy on allergic disorders including those affecting the ocular surface.

  16. L1 Adaptive Control for a Vertical Rotor Orientation System

    Directory of Open Access Journals (Sweden)

    Sijia Liu

    2016-08-01

    Full Text Available Bottom-fixed vertical rotating devices are widely used in industrial and civilian fields. The free upside of the rotor will cause vibration and lead to noise and damage during operation. Meanwhile, parameter uncertainties, nonlinearities and external disturbances will further deteriorate the performance of the rotor. Therefore, in this paper, we present a rotor orientation control system based on an active magnetic bearing with L 1 adaptive control to restrain the influence of the nonlinearity and uncertainty and reduce the vibration amplitude of the vertical rotor. The boundedness and stability of the adaptive system are analyzed via a theoretical derivation. The impact of the adaptive gain is discussed through simulation. An experimental rig based on dSPACE is designed to test the validity of the rotor orientation system. The experimental results show that the relative vibration amplitude of the rotor using the L 1 adaptive controller will be reduced to ∼50% of that in the initial state, which is a 10% greater reduction than can be achieved with the nonadaptive controller. The control approach in this paper is of some significance to solve the orientation control problem in a low-speed vertical rotor with uncertainties and nonlinearities.

  17. L1 track finding for a time multiplexed trigger

    Energy Technology Data Exchange (ETDEWEB)

    Cieri, D., E-mail: davide.cieri@bristol.ac.uk [University of Bristol, Bristol (United Kingdom); Rutherford Appleton Laboratory, Didcot (United Kingdom); Brooke, J.; Grimes, M. [University of Bristol, Bristol (United Kingdom); Newbold, D. [University of Bristol, Bristol (United Kingdom); Rutherford Appleton Laboratory, Didcot (United Kingdom); Harder, K.; Shepherd-Themistocleous, C.; Tomalin, I. [Rutherford Appleton Laboratory, Didcot (United Kingdom); Vichoudis, P. [CERN, Geneva (Switzerland); Reid, I. [Brunel University, London (United Kingdom); Iles, G.; Hall, G.; James, T.; Pesaresi, M.; Rose, A.; Tapper, A.; Uchida, K. [Imperial College, London (United Kingdom)

    2016-07-11

    At the HL-LHC, proton bunches will cross each other every 25 ns, producing an average of 140 pp-collisions per bunch crossing. To operate in such an environment, the CMS experiment will need a L1 hardware trigger able to identify interesting events within a latency of 12.5 μs. The future L1 trigger will make use also of data coming from the silicon tracker to control the trigger rate. The architecture that will be used in future to process tracker data is still under discussion. One interesting proposal makes use of the Time Multiplexed Trigger concept, already implemented in the CMS calorimeter trigger for the Phase I trigger upgrade. The proposed track finding algorithm is based on the Hough Transform method. The algorithm has been tested using simulated pp-collision data. Results show a very good tracking efficiency. The algorithm will be demonstrated in hardware in the coming months using the MP7, which is a μTCA board with a powerful FPGA capable of handling data rates approaching 1 Tb/s.

  18. Aspartame downregulates 3T3-L1 differentiation.

    Science.gov (United States)

    Pandurangan, Muthuraman; Park, Jeongeun; Kim, Eunjung

    2014-10-01

    Aspartame is an artificial sweetener used as an alternate for sugar in several foods and beverages. Since aspartame is 200 times sweeter than traditional sugar, it can give the same level of sweetness with less substance, which leads to lower-calorie food intake. There are reports that consumption of aspartame-containing products can help obese people lose weight. However, the potential role of aspartame in obesity is not clear. The present study investigated whether aspartame suppresses 3T3-L1 differentiation, by downregulating phosphorylated peroxisome proliferator-activated receptor γ (p-PPARγ), peroxisome proliferator-activated receptor γ (PPARγ), fatty acid-binding protein 4 (FABP4), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1), which are critical for adipogenesis. The 3T3-L1 adipocytes were cultured and differentiated for 6 d in the absence and presence of 10 μg/ml of aspartame. Aspartame reduced lipid accumulation in differentiated adipocytes as evidenced by Oil Red O staining. qRT-PCR analysis showed that the PPARγ, FABP4, and C/EBPα mRNA expression was significantly reduced in the aspartame-treated adipocytes. Western blot analysis showed that the induction of p-PPARγ, PPARγ, SREBP1, and adipsin was markedly reduced in the aspartame-treated adipocytes. Taken together, these data suggest that aspartame may be a potent substance to alter adipocyte differentiation and control obesity.

  19. L1 Track Finding for a Time Multiplexed Trigger

    CERN Document Server

    AUTHOR|(CDS)2090481; Grimes, M.; Newbold, D.; Harder, K.; Shepherd-Themistocleous, C.; Tomalin, I.; Vichoudis, P.; Reid, I.; Iles, G.; Hall, G.; James, T.; Pesaresi, M.; Rose, A.; Tapper, A.; Uchida, K.

    2016-01-01

    At the HL-LHC, proton bunches will cross each other every 25 ns, producing an average of 140 p p-collisions per bunch crossing. To operate in such an environment, the CMS experiment will need a L1 hardware trigger able to identify interesting events within a latency of 12.5 us. The future L1 trigger will make use also of data coming from the silicon tracker to control the trigger rate. The architecture that will be used in future to process tracker data is still under discussion. One interesting proposal makes use of the Time Multiplexed Trigger concept, already implemented in the CMS calorimeter trigger for the Phase I trigger upgrade. The proposed track finding algorithm is based on the Hough Transform method. The algorithm has been tested using simulated pp-collision data. Results show a very good tracking efficiency. The algorithm will be demonstrated in hardware in the coming months using the MP7, which is a uTCA board with a powerful FPGA capable of handling data rates approaching 1 Tb/s.

  20. Safety and efficacy of bilastine: a new H(1)-antihistamine for the treatment of allergic rhinoconjunctivitis and urticaria.

    Science.gov (United States)

    Church, Martin K

    2011-09-01

    New H(1)-antihistamines should be effective in relieving the symptoms of allergic disease, should have a rapid onset and long duration of action and should neither cause sedation nor interact with cytochrome P450. A review of bilastine was undertaken to determine whether this newer H(1)-antihistamine meets these requirements. A Medline search was conducted to identify preclinical and clinical studies of bilastine. This was supplemented with additional articles or abstracts cited in reference lists and/or obtained from online sources and internal reports supplied by Faes Farma. Review of these data indicated that bilastine has high selectivity for H(1)-receptors, is rapidly and effectively absorbed, undergoes negligible metabolism and is a substrate for P-glycoprotein, which limits its passage across the blood-brain barrier. At the recommended dose of 20 mg, bilastine is non-sedative, does not enhance the effects of alcohol or CNS sedatives, does not impair actual driving tests, shows no cardiotoxicity and has a similar efficacy to other second-generation H(1)-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria. In view of its favorable pharmacological and clinical characteristics, bilastine is likely to have particular benefit in urticaria for which guidelines recommend increasing the dosage of H(1)-antihistamines up to fourfold if standard dosing is ineffective.

  1. The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation.

    Science.gov (United States)

    Bardhan, Kankana; Anagnostou, Theodora; Boussiotis, Vassiliki A

    2016-01-01

    The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (T Regs ). These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programed cell death 1 (PD-1) receptor (CD279) and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273) plays an important role in the induction and maintenance of peripheral tolerance and for the maintenance of the stability and the integrity of T cells. However, the PD-1:PD-L1/L2 pathway also mediates potent inhibitory signals to hinder the proliferation and function of T effector cells and have inimical effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events regulated by PD-1 engagement, and their consequences on the function of T effector cells.

  2. The PD1: PD-L1/2 pathway from discovery to clinical implementation

    Directory of Open Access Journals (Sweden)

    Kankana Bardhan

    2016-12-01

    Full Text Available The immune system has the difficult challenge of discerning and defending against a diversity of microbial pathogens, while simultaneously avoiding self-reactivity. T lymphocytes function as effectors and regulators of the immune system. While central tolerance mechanism results in deletion of the majority of self-reactive T lymphocytes during thymic selection, a fraction of self reactive lymphocytes escapes to the periphery and retains the potential to inflict destructive autoimmune pathology. The immune system evolved various mechanisms to restrain such auto-reactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs. These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programmed cell death 1 (PD-1 receptor (CD279 and its ligands PD-L1 (B7-H1, CD274 and PD-L2 (B7-DC; CD273 plays a vital role in the induction and maintenance of peripheral tolerance and for the maintenance of T cell homeostasis. In contrast to its beneficial role in self-tolerance, the PD-1: PD-L1/L2 pathway mediates potent inhibitory signals that prevent the expansion and function of T effector cells and have detrimental effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events that are regulated by PD-1 triggering, and their consequences on the function of T effector cells.

  3. La influenza A (H1N1: estado actual del conocimiento Influenza A (H1N1 virus: current information

    Directory of Open Access Journals (Sweden)

    Laura Margarita González Valdés

    2010-03-01

    Full Text Available Se revisó la bibliografía actualizada sobre el tema a partir de los principales buscadores, y reuniones internacionales realizadas sobre la pandemia de la influenza A (H1N1. Se tratan los aspectos relacionados con la historia, la aparición de la pandemia, la biología de la enfermedad, la epidemiología, el cuadro clínico, el tratamiento y el pronóstico y la prevención. La gripe A (H1N1 es una pandemia causada por una variante nueva del virus de la Influenza A que ha sufrido cambios antigénicos en la hemaglutinina y la neuraminidasa. Esto hace que la población sea altamente vulnerable a la infección y produce una sobrecarga temporal enorme a los servicios de salud. El virus se trasmite como otros virus Influenza. Su letalidad es similar a la de la influenza estacional, pero puede incrementarse en personas con factores de riesgo y en adultos jóvenes sanos. El asma y el embarazo parecen ser condiciones de base importantes para incrementar la severidad de la infección. Puede existir cierta protección por inmunidad cruzada con cepas que circularon en el pasado. El espectro clínico va desde personas asintomáticas hasta las formas graves que requieren internación en cuidados intensivos, con rápido deterioro hasta llegar a la insuficiencia respiratoria en un plazo de 24 horas. La vacunación durante la pandemia no parece ser suficientemente efectiva. Son necesarios antivirales (oseltamivir y zanamivir, y las medidas preventivas higiénico-sanitarias son muy eficaces.An updated review using the main search motors and international meetings already celebrated related to Influenza A H1N1 pandemics. Items related to the history, the appearance of the pandemics, the biology of the disease, its epidemiology, clinics, treatment, prognosis and prevention. Grippe A H1N1 is a pandemic caused by a new variant of the Influenza A virus that has suffered antigenic changes in haemaglutinin and neuraminidase. This turns populations more susceptible to

  4. Effects of oral cetirizine, a selective H1 antagonist, on allergen- and exercise-induced bronchoconstriction in subjects with asthma.

    LENUS (Irish Health Repository)

    Gong, H

    1990-03-01

    The protective efficacy of oral cetirizine, a selective and potent H1-receptor antagonist, against the immediate bronchoconstrictive response to allergen inhalation and exercise challenge was evaluated in 16 subjects with stable, predominantly mild asthma. The subjects underwent double-blind, crossover pretreatments in randomized order in two separate protocols with (1) three daily oral doses of 20 mg of cetirizine and placebo, followed by allergen inhalation, and (2) single oral doses of cetirizine (5, 10, and 20 mg), albuterol (4 mg), and placebo, followed by exercise with cold-air inhalation. Cetirizine failed to decrease bronchial sensitivity to inhaled allergen in eight of 10 subjects. Neither cetirizine nor albuterol uniformly inhibited exercise-induced bronchoconstriction. Serum concentrations of cetirizine were consistent with systemic H1-blocking activity. Modest bronchodilation occurred after administration of cetirizine and albuterol before exercise but not after the third dose of cetirizine in the allergen protocol. One subject developed moderate drowsiness during multiple dosing with cetirizine. Thus, cetirizine, in the doses studied, is not uniformly effective in preventing allergen- or exercise-induced bronchoconstriction. Histamine is one of many mediators participating in immediate asthmatic responses, and selective H1 antagonists do not completely block these airway events. However, cetirizine may still clinically benefit some patients with asthma, such as patients with allergic rhinitis or urticaria.

  5. Solar and Heliospheric Data Requirements: Going Further Than L1

    Science.gov (United States)

    Szabo, A.

    2011-01-01

    Current operational space weather forecasting relies on solar wind observations made by the ACE spacecraft located at the L1 point providing 30-40 minutes warning time. Some use is also made of SOHO and STEREO solar imaging that potentially can give multiple days of warning time. However, our understanding of the propagation and evolution of solar wind transients is still limited resulting in a typical timing uncertainty of approximately 10 hours. In order to improve this critical understanding, a number of NASA missions are being planned. Specifically the Solar Probe Plus and Solar Orbiter missions will investigate the inner Heliospheric evolution of coronal mass ejections and the acceleration and propagation of solar energetic particles. In addition, a number of multi-spacecraft concepts have been studied that have the potential to significantly improve the accuracy of long-term space weather forecasts.

  6. l=1,2 high-beta stellarator

    International Nuclear Information System (INIS)

    Bartsch, R.R.; Cantrell, E.L.; Gribble, R.F.; Klare, K.A.; Kutac, K.J.; Miller, G.; Siemon, R.E.

    1978-01-01

    The final scyllac experiments are described. These experiments utilized a feedback-stabilized, l=1,2 high-beta stellarator configuration and like the previous feedback-stabilization experiments were carried out in a toroidal sector, rather than a complete torus. The energy confinement time, obtained from excluded flux measurements, agrees with a two-dimensional calculation of particle end loss from a straight theta pinch. Because simple end loss was dominant, the energy confinement time was independent of whether equilibrium adjustment or feedback stabilization fields were applied. The dynamical characteristics of the toroidal equilibrium were improved by elimination of the l=0 field used previously, as expected from theory. A modal rather than local feedback control algorithm was used. Although feedback clearly decreased the m=1 motion of the plasma, the experimental test of modal feedback, which is expected from theory to be superior to local feedback, is considered inconclusive because of the limitations imposed by the sector configuration

  7. Identification of Human H1N2 and Human-Swine Reassortant H1N2 and H1N1 Influenza A Viruses among Pigs in Ontario, Canada (2003 to 2005)†

    OpenAIRE

    Karasin, Alexander I.; Carman, Suzanne; Olsen, Christopher W.

    2006-01-01

    Since 2003, three novel genotypes of H1 influenza viruses have been recovered from Canadian pigs, including a wholly human H1N2 virus and human-swine reassortants. These isolates demonstrate that human-lineage H1N2 viruses are infectious for pigs and that viruses with a human PB1/swine PA/swine PB2 polymerase complex can replicate in pigs.

  8. Purification and H-1 NMR spectroscopic characterization of phase II metabolites of tolfenamic acid

    DEFF Research Database (Denmark)

    Sidelmann, U. G.; Christiansen, E.; Krogh, L.

    1997-01-01

    samples obtained on days 7 to 10 from a human volunteer after oral administration of 200 mg of the drug three times per day (steady-state plasma concentration). The metabolites of tolfenamic acid were initially concentrated by preparative solid phase extraction (PSPE) chromatography, thereby removing...... the endogenous polar compounds that are present in the urine. The individual metabolites were purified by preparative high performance liquid chromatography (HPLC) and then identified using H-1 NMR, Both one- and two-dimensional NMR experiments were performed to identify the phase II metabolites of tolfenamic......), and N-(2-methyl-4-hydroxyphenyl)-anthranilic acid (11) were identified. The phase II metabolites (5-11) had not previously been identified in urine from humans administered tolfenamic acid. The phase I metabolites of the glucuronides 7, 8, 10, and 11 were identified here for the first time. An HPLC...

  9. Physics from the first year of H1 at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Kiesling, C. [Max-Planck-Institut fuer Physik, Muenchen (Germany)

    1994-12-01

    In this report the author summarizes the results from the H1 experiment at HERA, using the data from the first year of running, 1992, when an integrated luminosity of 25 nb{sup {minus}1} has been recorded. These results include photoproduction, the measurement of the deep inelastic scattering, both for neutral current reactions and the search for physics beyond the Standard Model. Apart from the measurement of a moderate rise in the total photoproduction cross section, clear evidence is seen for hard interactions in single particle spectra and jet production, requiring a {open_quotes}resolved{close_quotes} photon as expected in QCD. The investigation of the global properties of hadronic final states in deep inelastic scattering demonstrates the need for further improvement of present QCD models. Evidence is found for a class of events with diffractive characteristics, exhibiting a large gap of hadronic energy flow about the proton direction. The proton structure function F{sub 2}{sup p}(x, Q{sup 2}) has been measured for neutral current events for Bjorken x in the range 10{sup {minus}4} - 10{sup {minus}2} and Q{sup 2} > 5 GeV{sup 2}, showing a steep rise towards small x. Furthermore, using 1993 data, a measurement of the cross section for charged current events is presented, clearly demonstrating, for the first time, the propagator effect of the W boson. Finally, new limits on leptoquarks, leptogluons, and excited electrons have been determined.

  10. Data acquisition system realization for H1 experiment

    International Nuclear Information System (INIS)

    Del Buono, L.

    1989-06-01

    The acquisition and trigger system for H1 liquid argon calorimeter deals with severe constraints which have to be taken into account. We describe the system which results from these constraints, emphasizing the solutions adopted to meet the specificities of the detector and the difficult experimental conditions at HERA: high physical background (10 4-5 Hz), physics and background events pile up (10%), large crossing frequency of proton and electron bunches (10.4 MHz). Next, we present a detailed description of the acquisition and online control scheme used during the calorimetry tests in SPS beam, at CERN. This test system, prefiguring the final one (which will start to work at the end of 1989), includes a fast frontal processor CAB (taking charge of the electronics read out and sequencing, and furthermore producing simple histograms). The CAB is controlled by a Micro Vax computer which realizes the user interface, allowing a quick visualisation and verification of the acquired data, these functions being performed in multitasking environment [fr

  11. Physics from the first year of H1 at HERA

    International Nuclear Information System (INIS)

    Kiesling, C.

    1994-08-01

    In this report we summarize the results from the H1 experiment at HERA, using the data from the first year of running, 1992, where an integrated luminosity of 25 nb -1 has been recorded. These results include photoproduction, the measurement of the deep inelastic scattering, both for neutral current reactions, and the search for physics beyond the standard model. Apart from the measurement of a moderate rise in the total photoproduction cross section, clear evidence is seen for hard interactions in single particle spectra and jet production, requiring a ''resolved'' photon as expected is QCD. The investigation of the global properties of hadronic final states in deep inelastic scattering demonstrates the need for further improvement of present QCD models. Evidence is found for a class of events with diffractive characteristics, exhibiting a large gap of hadronic energy flow about the proton direction. The proton structure function F 2 p (x,Q 2 ) has been measured for neutral current events for Bjorken x in the range 10 -4 - 10 -2 and Q 2 > 5 GeV 2 , showing a steep rise towards small x. Furthermore, using 1993 data, a measurement of the cross section for charged current events is presented, clearly demonstrating, for the first time, the propagator effect of the W boson. Finally, new limits on leptoquarks, leptogluons, and excited electrons have been determined. (orig.)

  12. Recent results from the H1 collaboration at HERA

    International Nuclear Information System (INIS)

    Feltesse, J.

    1994-01-01

    New results from the H1 experiment at the electron-proton collider HERA are reported. Evidence for hard scattering in gamma diffraction in photoproduction events is presented. The hadronic final state in low x deep inelastic scattering (DIS) events has been analyzed. Transverse energy flow and cross section for production of jets at high x j are compared to the expectations of present Monte Carlo programs and to analytical calculations based on the BFKL evolution equation. DIS interactions with no hadronic energy flow in a large interval of rapidity around the incident proton direction are presented. The data are compared to models based on deep inelastic pomeron scattering or on MVD contributions. Measured cross sections for the production of multijet in DIS events at HERA are used to provide a preliminary measurement of the strong coupling constant alpha s , together with the first direct measurement of the gluon density in the proton. The cross section of the charged current process e - p → ν e + hadrons is measured. The effects of the W propagator term is visible for the first time. New limits on leptoquarks, leptogluons, Squarks from R-parity violating supersymmetry and on excited leptons are given. (author). 20 figs., 34 refs

  13. Analysis of Ca and Mg in blood of golden hamster using NAA technique

    International Nuclear Information System (INIS)

    Aguiar, Rodrigo O.; Zamboni, Cibele B.; Medeiros, Jose A.G.

    2009-01-01

    Neutron activation analysis (NAA) technique has been used to determine simultaneously Ca and Mg concentrations in whole blood of Golden Hamster. The reference values for Ca (0.17 - 0.29 gL -1 ) and Mg (0.042 - 0.074 gL -1 ) can be used to performed biochemistry investigation using whole blood. (author)

  14. Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses.

    Science.gov (United States)

    Chung, Jee-Eun; Lee, Kyung Eun; Chang, Byung Chul; Gwak, Hye Sun

    2018-01-30

    The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements. The rs4072879 of VKORC1L1 (A>G) was significantly associated with stable warfarin doses; wild homozygote carriers (AA) required significantly lower stable warfarin doses than those with the variant G allele (5.02±1.56 vs. 5.96±2.01mg; p=0.001). Multivariate analysis showed that EPHX1 rs1877724 and VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability. Adding EPHX1 and VKORC1L1 SNPs to the base model including non-genetic variables (operation age, body weight and the therapy of ACEI or ARB) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 34. This study showed that polymorphisms of EPHX1 and VKORC1L1 could be determinants of stable warfarin doses. Copyright © 2017. Published by Elsevier B.V.

  15. A monoclonal antibody-based ELISA for differential diagnosis of 2009 pandemic H1N1

    Science.gov (United States)

    The swine-origin 2009 pandemic H1N1 virus (pdmH1N1) is genetically related to North American swine H1 influenza viruses and unrelated to human seasonal H1 viruses. Currently, specific diagnosis of pdmH1N1 relies on RT-PCR. In order to develop an assay that does not rely in amplification of the viral...

  16. Dicarbonyl Induced Structural Perturbations Make Histone H1 Highly Immunogenic and Generate an Auto-Immune Response in Cancer.

    Directory of Open Access Journals (Sweden)

    Abdul Rouf Mir

    Full Text Available Increased oxidative stress under hyperglycemic conditions, through the interaction of AGEs with RAGE receptors and via activation of interleukin mediated transcription signalling, has been reported in cancer. Proteins modifications are being explored for their roles in the development and progression of cancer and autoantibody response against them is gaining interest as a probe for early detection of the disease. This study has analysed the changes in histone H1 upon modification by methylglyoxal (MG and its implications in auto-immunopathogenesis of cancer. Modified histone showed modifications in the aromatic residues, changed tyrosine microenvironment, intermolecular cross linking and generation of AGEs. It showed masking of hydrophobic patches and a hypsochromic shift in the in ANS specific fluorescence. MG aggressively oxidized histone H1 leading to the accumulation of reactive carbonyls. Far UV CD measurements showed di-carbonyl induced enhancement of the alpha structure and the induction of beta sheet conformation; and thermal denaturation (Tm studies confirmed the thermal stability of the modified histone. FTIR analysis showed amide I band shift, generation of a carboxyethyl group and N-Cα vibrations in the modified histone. LCMS analysis confirmed the formation of Nε-(carboxyethyllysine and electron microscopic studies revealed the amorphous aggregate formation. The modified histone showed altered cooperative binding with DNA. Modified H1 induced high titre antibodies in rabbits and the IgG isolated form sera of rabbits immunized with modified H1 exhibited specific binding with its immunogen in Western Blot analysis. IgG isolated from the sera of patients with lung cancer, prostate cancer, breast cancer and cancer of head and neck region showed better recognition for neo-epitopes on the modified histone, reflecting the presence of circulating autoantibodies in cancer. Since reports suggest a link between AGE-RAGE axis and

  17. Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses.

    Science.gov (United States)

    Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub

    2014-09-24

    The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decreased. Both the H1N1 and H1N2 infected pigs lacked gross lesions at PID 2, but they showed moderate to severe pneumonia on PID 4, 7 and 14. The pigs infected with H1N1 had significant scores of gross and histopathological lesions when compared with the other pigs infected with H1N2, H3N2, and mock at PID 14. Mean SIV antigen-positive scores were rarely detected for pigs infected with H1N2 and H3N2 from PID 7, whereas a significantly increased amount of viral antigens were found in the bronchioles and alveolar epithelium of the H1N1infected pigs at PID 14. We demonstrated that Korean SIV subtypes had different pulmonary pathologic patterns. The Korean H3N2 rapidly induced acute lung lesions such as broncho-interstitial pneumonia, while the Korean H1N1 showed longer course of infection as compared to other strains.

  18. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    Science.gov (United States)

    Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  19. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    Directory of Open Access Journals (Sweden)

    Helena Grgić

    Full Text Available The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1pdm09. One H1N2 isolate had hemagglutinin (HA, polymerase A (PA and non-structural (NS genes closely related to A(H1N1pdm09, and neuraminidase (NA, matrix (M, polymerase B1 (PB1, polymerase B2 (PB2, and nucleoprotein (NP genes originating from a triple-reassortant H3N2 virus (tr H3N2. The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  20. In vitro reassortment between endemic H1N2 and 2009 H1N1 pandemic swine influenza viruses generates attenuated viruses.

    Directory of Open Access Journals (Sweden)

    Ben M Hause

    Full Text Available The pandemic H1N1 (pH1N1 influenza virus was first reported in humans in the spring of 2009 and soon thereafter was identified in numerous species, including swine. Reassortant viruses, presumably arising from the co-infection of pH1N1 and endemic swine influenza virus (SIV, were subsequently identified from diagnostic samples collected from swine. In this study, co-infection of swine testicle (ST cells with swine-derived endemic H1N2 (MN745 and pH1N1 (MN432 yielded two reassortant H1N2 viruses (R1 and R2, both possessing a matrix gene derived from pH1N1. In ST cells, the reassortant viruses had growth kinetics similar to the parental H1N2 virus and reached titers approximately 2 log(10 TCID(50/mL higher than the pH1N1 virus, while in A549 cells these viruses had similar growth kinetics. Intranasal challenge of pigs with H1N2, pH1N1, R1 or R2 found that all viruses were capable of infecting and transmitting between direct contact pigs as measured by real time reverse transcription PCR of nasal swabs. Lung samples were also PCR-positive for all challenge groups and influenza-associated microscopic lesions were detected by histology. Interestingly, infectious virus was detected in lung samples for pigs challenged with the parental H1N2 and pH1N1 at levels significantly higher than either reassortant virus despite similar levels of viral RNA. Results of our experiment suggested that the reassortant viruses generated through in vitro cell culture system were attenuated without gaining any selective growth advantage in pigs over the parental lineages. Thus, reassortant influenza viruses described in this study may provide a good system to study genetic basis of the attenuation and its mechanism.

  1. Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.

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    Naoya Maekawa

    Full Text Available Programmed death 1 (PD-1, an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1, its ligand, together induce the "exhausted" status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1-expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed.

  2. Mechanism for the decrease in the FIP1L1-PDGFRalpha protein level in EoL-1 cells by histone deacetylase inhibitors.

    Science.gov (United States)

    Ishihara, Kenji; Kaneko, Motoko; Kitamura, Hajime; Takahashi, Aki; Hong, Jang Ja; Seyama, Toshio; Iida, Koji; Wada, Hiroshi; Hirasawa, Noriyasu; Ohuchi, Kazuo

    2008-01-01

    Acetylation and deacetylation of proteins occur in cells in response to various stimuli, and are reversibly catalyzed by histone acetyltransferase and histone deacetylase (HDAC), respectively. EoL-1 cells have an FIP1L1-PDGFRA fusion gene that causes transformation of eosinophilic precursor cells into leukemia cells. The HDAC inhibitors apicidin and n-butyrate suppress the proliferation of EoL-1 cells and induce differentiation into eosinophils by a decrease in the protein level of FIP1L1-PDGFRalpha without affecting the mRNA level for FIP1L1-PDGFRA. In this study, we analyzed the mechanism by which the protein level of FIP1L1-PDGFRalpha is decreased by apicidin and n-butyrate. EoL-1 cells were incubated in the presence of the HDAC inhibitors apicidin, trichostatin A or n-butyrate. The protein levels of FIP1L1-PDGFRalpha and phosphorylated eIF-2alpha were determined by Western blotting. Actinomycin D and cycloheximide were used to block RNA synthesis and protein synthesis, respectively, in the chasing experiment of the amount of FIP1L1-PDGFRalpha protein. When apicidin- and n-butyrate-treated EoL-1 cells were incubated in the presence of actinomycin D, the decrease in the protein level of FIP1L1-PDGFRalpha was significantly enhanced when compared with controls. In contrast, the protein levels were not changed by cycloheximide among these groups. Apicidin and n-butyrate induced the continuous phosphorylation of eIF-2alpha for up to 8 days. The decrease in the level of FIP1L1-PDGFRalpha protein by continuous inhibition of HDAC may be due to the decrease in the translation rate of FIP1L1-PDGFRA. Copyright 2008 S. Karger AG, Basel.

  3. Prediction of LOFT L1-4 experiment

    International Nuclear Information System (INIS)

    Soda, Kunihisa; Sasaki, Shinobu; Akimoto, Masayuki; Koizumi, Yasuo; Araya, Fumimasa

    1977-10-01

    LOFT L1-4 experimental results were predicted by LOFT Analysis Group and Code Development Group using RELAP-4J and ALARM-P1 respectively. The input data prepared by the former group were used in both the analyses. Thus any differences in the results should stem from the differences in code performance characteristics of the two codes. (1) The coolant behaviors predicted by RELAP-4J and ALARM-P1 are in good agreement although some differences do exist between these two calculation models. (2) Large difference is seen in coolant flow rate across the pump. The coast down and the flow rate by ALARM-P1 are larger and smaller respectively than by RELAP-4J. (3) An explicit method of the ALARM-P1 leads to unstable calculation at a T shaped junction when one of the two volumes connected by the junction is filled with subcooled water. (4) Coolant flow in the downcomer, heat transfer to and from the steam generator secondary and suppression tank behavior must be modified to better predict the experimental results. (5) Additional instrumentation in reflood assist and ECC injection lines are necessary to better nderstand the coolant behavior. (auth.)

  4. On Recursive Modification in Child L1 French

    Directory of Open Access Journals (Sweden)

    Yves Roberge

    2018-03-01

    Full Text Available This paper investigates nominal recursive modification (RM in the L1 acquisition of French. Although recursion is considered the fundamental property of human languages, recursive self-embedding is found to be difficult for children in a variety of languages and constructions. Despite these challenges, the acquisition of RM proves to be resilient; acquirable even under severely degraded input conditions. From a minimalist perspective on the operations of narrow syntax, recursive embedding is essentially the application of a sequence of Merge operations (Chomsky 1995; Trotzke and Zwart 2014; therefore, given the universality of Merge, we do not expect to find cross-linguistic differences in how difficult recursion is. But if the challenging nature of recursion stems from factors which might differ from language to language, we expect different outcomes cross-linguistically. We compare new data from French to existing English data (Pérez-Leroux et al. 2012 in order to examine to what extent language-specific properties of RM structures determine the acquisition path. While children’s production differs significantly from their adult’s counterparts, we find no differences between French-speaking and English-speaking children. Our findings suggest that the challenging nature of recursion does not stem from the grammar itself and that what shapes the acquisition path is the interaction between universal properties of language and considerations not specific to language, namely computational efficiency.

  5. Status of the ESA L1 mission candidate ATHENA

    Science.gov (United States)

    Rando, N.; Martin, D.; Lumb, D.; Verhoeve, P.; Oosterbroek, T.; Bavdaz, M.; Fransen, S.; Linder, M.; Peyrou-Lauga, R.; Voirin, T.; Braghin, M.; Mangunsong, S.; van Pelt, M.; Wille, E.

    2012-09-01

    ATHENA (Advanced Telescope for High Energy Astrophysics) was an L class mission candidate within the science programme Cosmic Vision 2015-2025 of the European Space Agency, with a planned launch by 2022. ATHENA was conceived as an ESA-led project, open to the possibility of focused contributions from JAXA and NASA. By allowing astrophysical observations between 100 eV and 10 keV, it would represent the new generation X-ray observatory, following the XMM-Newton, Astro-H and Chandra heritage. The main scientific objectives of ATHENA include the study of large scale structures, the evolution of black holes, strong gravity effects, neutron star structure as well as investigations into dark matter. The ATHENA mission concept would be based on focal length of 12m achieved via a rigid metering tube and a twoaperture, x-ray telescope. Two identical x-ray mirrors would illuminate fixed focal plane instruments: a cryogenic imaging spectrometer (XMS) and a wide field imager (WFI). The S/C is designed to be fully compatible with Ariane 5 ECA. The observatory would operate at SE-L2, with a nominal lifetime of 5 yr. This paper provides a summary of the reformulation activities, completed in December 2011. An overview of the spacecraft design and of the payload is provided, including both telescope and instruments. Following the ESA Science Programme Committee decision on the L1 mission in May 2012, ATHENA was not selected to enter Definition Phase.

  6. Reference payload of the ESA L1 mission candidate ATHENA

    Science.gov (United States)

    Martin, Didier; Rando, Nicola; Lumb, David; Verhoeve, Peter; Oosterbroek, Tim; Bavdaz, Marcos

    2012-09-01

    The Advanced Telescope for High ENergy Astrophysics (ATHENA) is one of the three candidates that competed for the first large-class mission (L1) in ESA’s Cosmic Vision 2015-2025 programme, with a launch planned by 2022 and is the result of the IXO reformulation activities. ATHENA is an ESA-led project and is conceived as the next generation X-ray observatory. It is meant to address fundamental questions about accretion around black-holes, reveal the physics underpinning cosmic feedback, trace the large scale structure of baryons in galaxy clusters and the cosmic as well as a large number of astrophysics and fundamental physics phenomena. The observatory consists of two identical mirrors each illuminating a fixed focal plane instrument, providing collectively 1 m2 effective area at 1 keV. The reference payload consists of a medium resolution wide field imager (WFI) and a high resolution X-ray micro-calorimeter spectrometer (XMS). The WFI is based on a monolithic Si DepFET array providing imaging over a 24 × 24 arcmin2 field of view and a good PSF oversampling. The sensor will measure X-rays in the range 0.1-15 keV and provides near Fano limited energy resolution (150eV at 6keV). The XMS is based on a micro-calorimeter array operating at its transition temperature of ~100mK and provides Definition Phase.

  7. Seroprevalence of H1N1, H3N2 and H1N2 influenza viruses in pigs in seven European countries in 2002-2003.

    Science.gov (United States)

    Van Reeth, Kristien; Brown, Ian H; Dürrwald, Ralf; Foni, Emanuela; Labarque, Geoffrey; Lenihan, Patrick; Maldonado, Jaime; Markowska-Daniel, Iwona; Pensaert, Maurice; Pospisil, Zdenek; Koch, Guus

    2008-05-01

    Avian-like H1N1 and human-like H3N2 swine influenza viruses (SIV) have been considered widespread among pigs in Western Europe since the 1980s, and a novel H1N2 reassortant with a human-like H1 emerged in the mid 1990s. This study, which was part of the EC-funded 'European Surveillance Network for Influenza in Pigs 1', aimed to determine the seroprevalence of the H1N2 virus in different European regions and to compare the relative prevalences of each SIV between regions. Laboratories from Belgium, the Czech Republic, Germany, Italy, Ireland, Poland and Spain participated in an international serosurvey. A total of 4190 sow sera from 651 farms were collected in 2002-2003 and examined in haemagglutination inhibition tests against H1N1, H3N2 and H1N2. In Belgium, Germany, Italy and Spain seroprevalence rates to each of the three SIV subtypes were high (> or =30% of the sows seropositive) to very high (> or =50%), except for a lower H1N2 seroprevalence rate in Italy (13.8%). Most sows in these countries with high pig populations had antibodies to two or three subtypes. In Ireland, the Czech Republic and Poland, where swine farming is less intensive, H1N1 was the dominant subtype (8.0-11.7% seropositives) and H1N2 and H3N2 antibodies were rare (0-4.2% seropositives). Thus, SIV of H1N1, H3N2 and H1N2 subtype are enzootic in swine producing regions of Western Europe. In Central Europe, SIV activity is low and the circulation of H3N2 and H1N2 remains to be confirmed. The evolution and epidemiology of SIV throughout Europe is being further monitored through a second 'European Surveillance Network for Influenza in Pigs'.

  8. Seroprevalence of H1N1, H3N2 and H1N2 influenza viruses in pigs in seven European countries in 2002-2003

    NARCIS (Netherlands)

    Reeth, K.; Brown, I.H.; Durrwald, R.; Foni, E.; Labarque, G.; Lenihan, P.; Maldonado, J.; Markowska-Daniel, I.; Pensaert, M.; Pospisil, Z.; Koch, G.

    2008-01-01

    Objectives Avian-like H1N1 and human-like H3N2 swine influenza viruses (SIV) have been considered widespread among pigs in Western Europe since the 1980s, and a novel H1N2 reassortant with a human-like H1 emerged in the mid 1990s. This study, which was part of the EC-funded 'European Surveillance

  9. Novel reassortant influenza A(H1N2) virus derived from A(H1N1)pdm09 virus isolated from swine, Japan, 2012.

    Science.gov (United States)

    Kobayashi, Miho; Takayama, Ikuyo; Kageyama, Tsutomu; Tsukagoshi, Hiroyuki; Saitoh, Mika; Ishioka, Taisei; Yokota, Yoko; Kimura, Hirokazu; Tashiro, Masato; Kozawa, Kunihisa

    2013-12-01

    We isolated a novel influenza virus A(H1N2) strain from a pig on January 13, 2012, in Gunma Prefecture, Japan. Phylogenetic analysis showed that the strain was a novel type of double-reassortant virus derived from the swine influenza virus strains H1N1pdm09 and H1N2, which were prevalent in Gunma at that time.

  10. Regioselectivity in the Thermal Rearrangement of Unsymmetrical 4-Methyl-4H-1,2,4-triazoles to 1-Methyl-1H-1,2,4-triazoles

    Directory of Open Access Journals (Sweden)

    Per H.J. Carlsen

    2001-11-01

    Full Text Available The rearrangement of 4-methyl-3,5-diaryl-4H-1,2,4-triazoles to the corresponding 1-methyl-3,5-diaryl-1H-1,2,4-triazoles showed regioselectivity comparable to that observed for the alkylation of 3,5-diaryl-1H-1,2,4-triazoles. This lends support to a proposed mechanism for the rearrangement that involves consecutive nucleophilic displacements steps.

  11. Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

    Science.gov (United States)

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-01-01

    INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T

  12. Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.

    Science.gov (United States)

    Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María

    2010-01-01

    The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains. © INRA, EDP Sciences, 2010.

  13. Characterization of a newly emerged genetic cluster of H1N1 and H1N2 swine influenza virus in the United States.

    Science.gov (United States)

    Vincent, Amy L; Ma, Wenjun; Lager, Kelly M; Gramer, Marie R; Richt, Juergen A; Janke, Bruce H

    2009-10-01

    H1 influenza A viruses that were distinct from the classical swine H1 lineage were identified in pigs in Canada in 2003–2004; antigenic and genetic characterization identified the hemagglutinin (HA) as human H1 lineage. The viruses identified in Canadian pigs were human lineage in entirety or double (human–swine) reassortants. Here, we report the whole genome sequence analysis of four human-like H1 viruses isolated from U.S. swine in 2005 and 2007. All four isolates were characterized as triple reassortants with an internal gene constellation similar to contemporary U.S. swine influenza virus (SIV), with HA and neuraminidase (NA) most similar to human influenza virus lineages. A 2007 human-like H1N1 was evaluated in a pathogenesis and transmission model and compared to a 2004 reassortant H1N1 SIV isolate with swine lineage HA and NA. The 2007 isolate induced disease typical of influenza virus and was transmitted to contact pigs; however, the kinetics and magnitude differed from the 2004 H1N1 SIV. This study indicates that the human-like H1 SIV can efficiently replicate and transmit in the swine host and now co-circulates with contemporary SIVs as a distinct genetic cluster of H1 SIV.

  14. Antiviral therapy and outcomes of patients with pneumonia caused by influenza A pandemic (H1N1 virus.

    Directory of Open Access Journals (Sweden)

    Shi-gui Yang

    Full Text Available BACKGROUND: There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1 pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset. METHODS: During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models. RESULTS: 920 adults and 541 children with pneumonia who didn't receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2% than those with who received oseltamivir ≤ 2 days (2.9%, between 2-5 days (4.6% and >5 days after illness onset (4.9%, p5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO(2/FiO(23.8 mg/kg/d did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05. CONCLUSIONS: Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14-60 years, and patients with PaO(2/FiO(2<200.

  15. Histamine Excites Rat Superior Vestibular Nuclear Neurons via Postsynaptic H1 and H2 Receptors in vitro

    Directory of Open Access Journals (Sweden)

    Qian-Xing Zhuang

    2012-09-01

    Full Text Available The superior vestibular nucleus (SVN, which holds a key position in vestibulo-ocular reflexes and nystagmus, receives direct hypothalamic histaminergic innervations. By using rat brainstem slice preparations and extracellular unitary recordings, we investigated the effect of histamine on SVN neurons and the underlying receptor mechanisms. Bath application of histamine evoked an excitatory response of the SVN neurons, which was not blocked by the low-Ca2+/high-Mg2+ medium, indicating a direct postsynaptic effect of the amine. Selective histamine H1 receptor agonist 2-pyridylethylamine and H2 receptor agonist dimaprit, rather than VUF8430, a selective H4 receptor agonist, mimicked the excitation of histamine on SVN neurons. In addition, selective H1 receptor antagonist mepyramine and H2 receptor antagonist ranitidine, but not JNJ7777120, a selective H4 receptor antagonist, partially blocked the excitatory response of SVN neurons to histamine. Moreover, mepyramine together with ranitidine nearly totally blocked the histamine-induced excitation. Immunostainings further showed that histamine H1 and H2 instead of H4 receptors existed in the SVN. These results demonstrate that histamine excites the SVN neurons via postsynaptic histamine H1 and H2 receptors, and suggest that the central histaminergic innervation from the hypothalamus may actively bias the SVN neuronal activity and subsequently modulate the SVN-mediated vestibular functions and gaze control.

  16. Adaptive L1/2 Shooting Regularization Method for Survival Analysis Using Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Xiao-Ying Liu

    2013-01-01

    Full Text Available A new adaptive L1/2 shooting regularization method for variable selection based on the Cox’s proportional hazards mode being proposed. This adaptive L1/2 shooting algorithm can be easily obtained by the optimization of a reweighed iterative series of L1 penalties and a shooting strategy of L1/2 penalty. Simulation results based on high dimensional artificial data show that the adaptive L1/2 shooting regularization method can be more accurate for variable selection than Lasso and adaptive Lasso methods. The results from real gene expression dataset (DLBCL also indicate that the L1/2 regularization method performs competitively.

  17. A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects.

    Science.gov (United States)

    Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

    2009-03-01

    To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). Five H(1) receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. The median clearance (CL), apparent volume of distribution (V(d)) and apparent terminal elimination half-life (t(1/2)) of diphenhydramine after an i.v. microdose were 24.7 l h(-1), 302 l and 9.3 h, and the oral C(max) and AUC(0-infinity) were 0.195 ng ml(-1) and 1.52 ng h ml(-1), respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection.

  18. Reviving the dead: history and reactivation of an extinct l1.

    Science.gov (United States)

    Yang, Lei; Brunsfeld, John; Scott, LuAnn; Wichman, Holly

    2014-06-01

    Although L1 sequences are present in the genomes of all placental mammals and marsupials examined to date, their activity was lost in the megabat family, Pteropodidae, ∼24 million years ago. To examine the characteristics of L1s prior to their extinction, we analyzed the evolutionary history of L1s in the genome of a megabat, Pteropus vampyrus, and found a pattern of periodic L1 expansion and quiescence. In contrast to the well-characterized L1s in human and mouse, megabat genomes have accommodated two or more simultaneously active L1 families throughout their evolutionary history, and major peaks of L1 deposition into the genome always involved multiple families. We compared the consensus sequences of the two major megabat L1 families at the time of their extinction to consensus L1s of a variety of mammalian species. Megabat L1s are comparable to the other mammalian L1s in terms of adenosine content and conserved amino acids in the open reading frames (ORFs). However, the intergenic region (IGR) of the reconstructed element from the more active family is dramatically longer than the IGR of well-characterized human and mouse L1s. We synthesized the reconstructed element from this L1 family and tested the ability of its components to support retrotransposition in a tissue culture assay. Both ORFs are capable of supporting retrotransposition, while the IGR is inhibitory to retrotransposition, especially when combined with either of the reconstructed ORFs. We dissected the inhibitory effect of the IGR by testing truncated and shuffled versions and found that length is a key factor, but not the only one affecting inhibition of retrotransposition. Although the IGR is inhibitory to retrotransposition, this inhibition does not account for the extinction of L1s in megabats. Overall, the evolution of the L1 sequence or the quiescence of L1 is unlikely the reason of L1 extinction.

  19. Reviving the dead: history and reactivation of an extinct l1.

    Directory of Open Access Journals (Sweden)

    Lei Yang

    2014-06-01

    Full Text Available Although L1 sequences are present in the genomes of all placental mammals and marsupials examined to date, their activity was lost in the megabat family, Pteropodidae, ∼24 million years ago. To examine the characteristics of L1s prior to their extinction, we analyzed the evolutionary history of L1s in the genome of a megabat, Pteropus vampyrus, and found a pattern of periodic L1 expansion and quiescence. In contrast to the well-characterized L1s in human and mouse, megabat genomes have accommodated two or more simultaneously active L1 families throughout their evolutionary history, and major peaks of L1 deposition into the genome always involved multiple families. We compared the consensus sequences of the two major megabat L1 families at the time of their extinction to consensus L1s of a variety of mammalian species. Megabat L1s are comparable to the other mammalian L1s in terms of adenosine content and conserved amino acids in the open reading frames (ORFs. However, the intergenic region (IGR of the reconstructed element from the more active family is dramatically longer than the IGR of well-characterized human and mouse L1s. We synthesized the reconstructed element from this L1 family and tested the ability of its components to support retrotransposition in a tissue culture assay. Both ORFs are capable of supporting retrotransposition, while the IGR is inhibitory to retrotransposition, especially when combined with either of the reconstructed ORFs. We dissected the inhibitory effect of the IGR by testing truncated and shuffled versions and found that length is a key factor, but not the only one affecting inhibition of retrotransposition. Although the IGR is inhibitory to retrotransposition, this inhibition does not account for the extinction of L1s in megabats. Overall, the evolution of the L1 sequence or the quiescence of L1 is unlikely the reason of L1 extinction.

  20. Antibody fragments directed against different portions of the human neural cell adhesion molecule L1 act as inhibitors or activators of L1 function.

    Directory of Open Access Journals (Sweden)

    Yan Wang

    Full Text Available The neural cell adhesion molecule L1 plays important roles in neuronal migration and survival, neuritogenesis and synaptogenesis. L1 has also been found in tumors of different origins, with levels of L1 expression correlating positively with the metastatic potential of tumors. To select antibodies targeting the varied functions of L1, we screened the Tomlinson library of recombinant human antibody fragments to identify antibodies binding to recombinant human L1 protein comprising the entire extracellular domain of human L1. We obtained four L1 binding single-chain variable fragment antibodies (scFvs, named I4, I6, I13, and I27 and showed by enzyme-linked immunosorbent assay (ELISA that scFvs I4 and I6 have high affinity to the immunoglobulin-like (Ig domains 1-4 of L1, while scFvs I13 and I27 bind strongly to the fibronectin type III homologous (Fn domains 1-3 of L1. Application of scFvs I4 and I6 to human SK-N-SH neuroblastoma cells reduced proliferation and transmigration of these cells. Treatment of SK-N-SH cells with scFvs I13 and I27 enhanced cell proliferation and migration, neurite outgrowth, and protected against the toxic effects of H(2O(2 by increasing the ratio of Bcl-2/Bax. In addition, scFvs I4 and I6 inhibited and scFvs I13 and I27 promoted phosphorylation of src and Erk. Our findings indicate that scFvs reacting with the immunoglobulin-like domains 1-4 inhibit L1 functions, whereas scFvs interacting with the fibronectin type III domains 1-3 trigger L1 functions of cultured neuroblastoma cells.

  1. 20 CFR 655.705 - What Federal agencies are involved in the H-1B and H-1B1 programs, and what are the...

    Science.gov (United States)

    2010-04-01

    ... Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and... whether the individual is a fashion model of distinguished merit and ability, and whether the... § 655.700(d)(4). Each employer seeking an H-1B nonimmigrant in a specialty occupation or as a fashion...

  2. Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam.

    Science.gov (United States)

    Takemae, Nobuhiro; Nguyen, Tung; Ngo, Long Thanh; Hiromoto, Yasuaki; Uchida, Yuko; Pham, Vu Phong; Kageyama, Tsutomu; Kasuo, Shizuko; Shimada, Shinichi; Yamashita, Yasutaka; Goto, Kaoru; Kubo, Hideyuki; Le, Vu Tri; Van Vo, Hung; Do, Hoa Thi; Nguyen, Dang Hoang; Hayashi, Tsuyoshi; Matsuu, Aya; Saito, Takehiko

    2013-04-01

    The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.

  3. PD-L1 expression by neurons nearby tumors indicates better prognosis in glioblastoma patients

    DEFF Research Database (Denmark)

    Liu, Yawei; Carlsson, Robert; Ambjørn, Malene

    2013-01-01

    Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. In general, tumor growth requires disruption of the tissue microenvironment, yet how this affects glioma progression is unknown. We studied program death-ligand (PD-L)1 in neurons and gliomas in tumors from GBM patients...... and associated the findings with clinical outcome. Remarkably, we found that upregulation of PD-L1 by neurons in tumor-adjacent brain tissue (TABT) associated positively with GBM patient survival, whereas lack of neuronal PD-L1 expression was associated with high PD-L1 in tumors and unfavorable prognosis...... in GBM patients, better survival in wild-type mice was associated with high neuronal PD-L1 in TABT and downregulation of PD-L1 in tumors, which was defective in Ifnb-/- mice. Our data indicated that neuronal PD-L1 signaling in brain cells was important for GBM patient survival. Reciprocal PD-L1...

  4. H1DS: A new web-based data access system

    Energy Technology Data Exchange (ETDEWEB)

    Pretty, D.G., E-mail: david.pretty@anu.edu.au; Blackwell, B.D.

    2014-05-15

    Highlights: • We present H1DS, a new RESTful web service for accessing fusion data. • We examine the scalability and extensibility of H1DS. • We present a fast and user friendly web browser client for the H1DS web service. • A summary relational database is presented as an application of the H1DS API. - Abstract: A new data access system, H1DS, has been developed and deployed for the H-1 Heliac at the Australian Plasma Fusion Research Facility. The data system provides access to fusion data via a RESTful web service. With the URL acting as the API to the data system, H1DS provides a scalable and extensible framework which is intuitive to new users, and allows access from any internet connected device. The H1DS framework, originally designed to work with MDSplus, has a modular design which can be extended to provide access to alternative data storage systems.

  5. H1DS: A new web-based data access system

    International Nuclear Information System (INIS)

    Pretty, D.G.; Blackwell, B.D.

    2014-01-01

    Highlights: • We present H1DS, a new RESTful web service for accessing fusion data. • We examine the scalability and extensibility of H1DS. • We present a fast and user friendly web browser client for the H1DS web service. • A summary relational database is presented as an application of the H1DS API. - Abstract: A new data access system, H1DS, has been developed and deployed for the H-1 Heliac at the Australian Plasma Fusion Research Facility. The data system provides access to fusion data via a RESTful web service. With the URL acting as the API to the data system, H1DS provides a scalable and extensible framework which is intuitive to new users, and allows access from any internet connected device. The H1DS framework, originally designed to work with MDSplus, has a modular design which can be extended to provide access to alternative data storage systems

  6. A novel PKD2L1 C-terminal domain critical for trimerization and channel function.

    Science.gov (United States)

    Zheng, Wang; Hussein, Shaimaa; Yang, JungWoo; Huang, Jun; Zhang, Fan; Hernandez-Anzaldo, Samuel; Fernandez-Patron, Carlos; Cao, Ying; Zeng, Hongbo; Tang, Jingfeng; Chen, Xing-Zhen

    2015-03-30

    As a transient receptor potential (TRP) superfamily member, polycystic kidney disease 2-like-1 (PKD2L1) is also called TRPP3 and has similar membrane topology as voltage-gated cation channels. PKD2L1 is involved in hedgehog signaling, intestinal development, and sour tasting. PKD2L1 and PKD1L3 form heterotetramers with 3:1 stoichiometry. C-terminal coiled-coil-2 (CC2) domain (G699-W743) of PKD2L1 was reported to be important for its trimerization but independent studies showed that CC2 does not affect PKD2L1 channel function. It thus remains unclear how PKD2L1 proteins oligomerize into a functional channel. By SDS-PAGE, blue native PAGE and mutagenesis we here identified a novel C-terminal domain called C1 (K575-T622) involved in stronger homotrimerization than the non-overlapping CC2, and found that the PKD2L1 N-terminus is critical for dimerization. By electrophysiology and Xenopus oocyte expression, we found that C1, but not CC2, is critical for PKD2L1 channel function. Our co-immunoprecipitation and dynamic light scattering experiments further supported involvement of C1 in trimerization. Further, C1 acted as a blocking peptide that inhibits PKD2L1 trimerization as well as PKD2L1 and PKD2L1/PKD1L3 channel function. Thus, our study identified C1 as the first PKD2L1 domain essential for both PKD2L1 trimerization and channel function, and suggest that PKD2L1 and PKD2L1/PKD1L3 channels share the PKD2L1 trimerization process.

  7. L1 Korean and L1 Mandarin L2 English Learners' Acquisition of the Count/Mass Distinction in English

    Science.gov (United States)

    Choi, Sea Hee; Ionin, Tania; Zhu, Yeqiu

    2018-01-01

    This study investigates the second language (L2) acquisition of the English count/mass distinction by speakers of Korean and Mandarin Chinese, with a focus on the semantics of atomicity. It is hypothesized that L1-Korean and L1-Mandarin L2-English learners are influenced by atomicity in the use of the count/mass morphosyntax in English. This…

  8. Do L2 Writing Courses Affect the Improvement of L1 Writing Skills via Skills Transfer from L2 to L1?

    Science.gov (United States)

    Gonca, Altmisdort

    2016-01-01

    This study investigates the relationship of second language (L2) writing skills proficiency with the first language (L1) writing skills, in light of the language transfer. The study aims to analyze the positive effects of L2 writing proficiency on L1 writing proficiency. Forty native Turkish-speaking university students participated in the study.…

  9. Isolation and genetic characterization of avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China.

    Science.gov (United States)

    Yu, Hai; Zhang, Peng-Chao; Zhou, Yan-Jun; Li, Guo-Xin; Pan, Jie; Yan, Li-Ping; Shi, Xiao-Xiao; Liu, Hui-Li; Tong, Guang-Zhi

    2009-08-21

    As pigs are susceptible to both human and avian influenza viruses, they have been proposed to be intermediate hosts or mixing vessels for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. In this study, we reported avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China. Homology and phylogenetic analyses showed that the H1N1 virus (A/swine/Zhejiang/1/07) was closely to avian-like H1N1 viruses and seemed to be derived from the European swine H1N1 viruses, which was for the first time reported in China; and the two H1N2 viruses (A/swine/Shanghai/1/07 and A/swine/Guangxi/13/06) were novel ressortant H1N2 influenza viruses containing genes from the classical swine (HA, NP, M and NS), human (NA and PB1) and avian (PB2 and PA) lineages, which indicted that the reassortment among human, avian, and swine influenza viruses had taken place in pigs in China and resulted in the generation of new viruses. The isolation of avian-like H1N1 influenza virus originated from the European swine H1N1 viruses, especially the emergence of two novel ressortant H1N2 influenza viruses provides further evidence that pigs serve as intermediate hosts or "mixing vessels", and swine influenza virus surveillance in China should be given a high priority.

  10. Syntheses and modulations in the chromatin contents of histones H1/sup o/ and H1 during G1 and S phases in Chinese hamsters cells

    International Nuclear Information System (INIS)

    D'Anna, J.A.; Gurley, L.R.; Tobey, R.A.

    1982-01-01

    Flow cytometry, conventional autoradiography, and autoradiography employing high concentrations of high specific activity [ 3 H]thymidine indicate that (1) treatment of Chinese hamster ovary (line CHO) cells with butyrate truly blocks cells in G 1 and (2) cells blocked in G 1 by isoleucine deprivation remain blocked in G 1 when they are released into complete medium containing butyrate. Measurements of H1/sup o/ content relative to core histones and H1/sup o/:H1 ratios indicate that H1/sup o/ is enhanced somewhat in G 1 cells arrested by isoleucine deprivation; however, (1) treatment with butyrate greatly increases the H1/sup o/ content in G 1 -blocked cells, and (2) the enhancement is very sensitive to butyrate concentration. Measurements of relative histone contents in the isolated chromatin of synchronized cultures also suggest that the acid-soluble content of histone H1 (relative to core histones) becomes greatly depleted in the isolated chromatin when synchronized cells are blocked in early S phase by sequential use of isoleucine deprivation and hydroxyurea blockade. We also have measured [ 3 H]lysine incorporation, various protein ratios, and relative rates of deposition of newly synthesized H1/sup o/, H1, and H4 onto chromatin during G 1 and S in the absence of butyrate. The results suggest a dynamic picture of chromatin organization in which (1) newly synthesized histone H1/sup o/ binds to chromatin during traverse of G 1 and S phases and (2) histone H1 dissociates from (or becomes loosely bound to) chromatin during prolonged early S-phase block with hydroxyurea

  11. Metacognitive Online Reading Strategy Use: Readers' Perceptions in L1 and L2

    Science.gov (United States)

    Taki, Saeed

    2016-01-01

    This study aimed to explore whether first-language (L1) readers of different language backgrounds would employ similar metacognitive online reading strategies and whether reading online in a second language (L2) could be influenced by L1 reading strategies. To this end, 52 Canadian college students as English L1 readers and 38 Iranian university…

  12. PD-L1 expression in non-small cell lung cancer : Correlations with genetic alterations

    NARCIS (Netherlands)

    Scheel, Andreas H.; Ansen, Sascha; Schultheis, Anne M.; Scheffler, Matthias; Fischer, Rieke N.; Michels, Sebastian; Hellmich, Martin; George, Julie; Zander, Thomas; Brockmann, Michael; Stoelben, Erich; Groen, Harry; Timens, Wim; Perner, Sven; von Bergwelt-Baildon, Michael; Buettner, Reinhard; Wolf, Juergen

    2016-01-01

    Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects of PD-L1 prevalence and

  13. Mechanism for the differentiation of EoL-1 cells into eosinophils by histone deacetylase inhibitors.

    Science.gov (United States)

    Kaneko, Motoko; Ishihara, Kenji; Takahashi, Aki; Hong, Jangja; Hirasawa, Noriyasu; Zee, Okpyo; Ohuchi, Kazuo

    2007-01-01

    EoL-1 cells have a FIP1L1-PDGFRA fusion gene which causes the transformation of eosinophilic precursor cells into leukemia cells. Recently, we suggested that the induction of differentiation of EoL-1 cells into eosinophils by the HDAC inhibitors apicidin and n-butyrate is due to the continuous inhibition of HDACs. However, neither apicidin nor n-butyrate inhibited the expression of FIP1L1-PDGFRA mRNA, although both these inhibitors suppressed cell proliferation. Therefore, in this study, we analyzed whether the levels of FIP1L1-PDGFRalpha protein and phosphorylated-Stat5 involved in the signaling for the proliferation of EoL-1 cells are attenuated by HDAC inhibitors. EoL-1 cells were incubated in the presence of apicidin, TSA or n-butyrate. FIP1L1-PDGFRalpha and phosphorylated-Stat5 were detected by Western blotting. Treatment of EoL-1 cells with apicidin at 100 nM or n-butyrate at 500 microM decreased the levels of FIP1L1-PDGFRalpha protein and phosphorylated-Stat5, while that with trichostatin A at 30 nM did not. The decrease in the level of FIP1L1-PDGFRalpha protein caused by apicidin and n-butyrate might be one of the mechanisms by which EoL-1 cells are induced to differentiate into eosinophils by these HDAC inhibitors.

  14. The Influence of Schema and Cultural Difference on L1 and L2 Reading

    Science.gov (United States)

    Yang, Shi-sheng

    2010-01-01

    Reading in L1 shares numerous basic elements with reading in L2, and the processes also differ greatly. Intriguing questions involve whether there are two parallel cognitive processes at work, or whether there are processing strategies that accommodate both L1 and L2. This paper examines how reading in L1 is different from and similar to reading…

  15. 26 CFR 1.1402(h)-1 - Members of certain religious groups opposed to insurance.

    Science.gov (United States)

    2010-04-01

    ... insurance. 1.1402(h)-1 Section 1.1402(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Tax on Self-Employment Income § 1.1402(h)-1... 1402(h) and this section refer does not include liability insurance of a kind that provides only for...

  16. 26 CFR 1.643(h)-1 - Distributions by certain foreign trusts through intermediaries.

    Science.gov (United States)

    2010-04-01

    ... intermediaries. 1.643(h)-1 Section 1.643(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.643(h)-1... section, FT is deemed to have distributed XYZ stock with a value of 85X to C on December 1, 2001. (h...

  17. 76 FR 62455 - Announcement of Updated Funding Availability for H-1B Technical Skills Training Grants

    Science.gov (United States)

    2011-10-07

    ... 10-13] Announcement of Updated Funding Availability for H-1B Technical Skills Training Grants AGENCY... the availability of $240 million for the H-1B Technical Skills Training Grants to be awarded through a... additional applicants to apply for the H-1B Technical Skills Training Grants competition that will close on...

  18. Factors Influencing School Closure and Dismissal Decisions: Influenza A (H1N1), Michigan 2009

    Science.gov (United States)

    Dooyema, Carrie A.; Copeland, Daphne; Sinclair, Julie R.; Shi, Jianrong; Wilkins, Melinda; Wells, Eden; Collins, Jim

    2014-01-01

    Background: In fall 2009, many US communities experienced school closures during the influenza A H1N1 pandemic (pH1N1) and the state of Michigan reported 567 closures. We conducted an investigation in Michigan to describe pH1N1-related school policies, practices, and identify factors related to school closures. Methods: We distributed an online…

  19. Antigenic and genetic evolution of contemporary swine H1 influenza viruses in the United States.

    Science.gov (United States)

    Rajao, Daniela S; Anderson, Tavis K; Kitikoon, Pravina; Stratton, Jered; Lewis, Nicola S; Vincent, Amy L

    2018-05-01

    Several lineages of influenza A viruses (IAV) currently circulate in North American pigs. Genetic diversity is further increased by transmission of IAV between swine and humans and subsequent evolution. Here, we characterized the genetic and antigenic evolution of contemporary swine H1N1 and H1N2 viruses representing clusters H1-α (1A.1), H1-β (1A.2), H1pdm (1A.3.3.2), H1-γ (1A.3.3.3), H1-δ1 (1B.2.2), and H1-δ2 (1B.2.1) currently circulating in pigs in the United States. The δ1-viruses diversified into two new genetic clades, H1-δ1a (1B.2.2.1) and H1-δ1b (1B.2.2.2), which were also antigenically distinct from the earlier H1-δ1-viruses. Further characterization revealed that a few key amino acid changes were associated with antigenic divergence in these groups. The continued genetic and antigenic evolution of contemporary H1 viruses might lead to loss of vaccine cross-protection that could lead to significant economic impact to the swine industry, and represents a challenge to public health initiatives that attempt to minimize swine-to-human IAV transmission. Published by Elsevier Inc.

  20. Data of evolutionary structure change: 1CR9H-1RUPH [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1CR9H-1RUPH 1CR9 1RUP H H KVKLQQSGAELVRSGASVKLSCTASGFNIKDY-YIQWVK...ine> TYR CA 299 TRP CA 347 1RUP... H 1RUPH YCAGLLWYDGGAGS...2550649642944336 1 1RUP H 1RUPH GYINY-SGFTS

  1. The average effective dose of 4-amino-5-(furan-2-yl-4H-1 ,2,4-triazole-3-thiol in experimental hepatitis

    Directory of Open Access Journals (Sweden)

    I. M. Belay

    2014-04-01

    Full Text Available The work presents the research of the average effective dose of 4-amino-5-(furan-2-yl-4H-1,2,4-triazole-3-thiol in experimental hepatitis. Recalculations conducted for the human with the sensitivity coefficient, average effective dose for human is 13,87 mg/kg.

  2. Reviving the Dead: History and Reactivation of an Extinct L1

    OpenAIRE

    Yang, Lei; Brunsfeld, John; Scott, LuAnn; Wichman, Holly

    2014-01-01

    Although L1 sequences are present in the genomes of all placental mammals and marsupials examined to date, their activity was lost in the megabat family, Pteropodidae, ∼24 million years ago. To examine the characteristics of L1s prior to their extinction, we analyzed the evolutionary history of L1s in the genome of a megabat, Pteropus vampyrus, and found a pattern of periodic L1 expansion and quiescence. In contrast to the well-characterized L1s in human and mouse, megabat genomes have accomm...

  3. Epigenetics and autism spectrum disorder: A report of an autism case with mutation in H1 linker histone HIST1H1e and literature review.

    Science.gov (United States)

    Duffney, Lara J; Valdez, Purnima; Tremblay, Martine W; Cao, Xinyu; Montgomery, Sarah; McConkie-Rosell, Allyn; Jiang, Yong-Hui

    2018-04-27

    Genetic mutations in genes encoding proteins involved in epigenetic machinery have been reported in individuals with autism spectrum disorder (ASD), intellectual disability, congenital heart disease, and other disorders. H1 histone linker protein, the basic component in nucleosome packaging and chromatin organization, has not been implicated in human disease until recently. We report a de novo deleterious mutation of histone cluster 1 H1 family member e (HIST1H1E; c.435dupC; p.Thr146Hisfs*50), encoding H1 histone linker protein H1.4, in a 10-year-old boy with autism and intellectual disability diagnosed through clinical whole exome sequencing. The c.435dupC at the 3' end of the mRNA leads to a frameshift and truncation of the positive charge in the carboxy-terminus of the protein. An expression study demonstrates the mutation leads to reduced protein expression, supporting haploinsufficiency of HIST1H1E protein and loss of function as an underlying mechanism of dysfunction in the brain. Taken together with other recent cases with mutations of HIST1H1E in intellectual disability, the evidence supporting the link to causality in disease is strong. Our finding implicates the deficiency of H1 linker histone protein in autism. The systematic review of candidate genes implicated in ASD revealed that 42 of 215 (19.5%) genes are directly involved in epigenetic regulations and the majority of these genes belong to histone writers, readers, and erasers. While the mechanism of how haploinsufficiency of HIST1H1E causes autism is entirely unknown, our report underscores the importance of further study of the function of this protein and other histone linker proteins in brain development. © 2018 Wiley Periodicals, Inc.

  4. G1- and S-phase syntheses of histones H1 and H1o in mitotically selected CHO cells: utilization of high-performance liquid chromatography

    International Nuclear Information System (INIS)

    D'Anna, J.A.; Thayer, M.M.; Tobey, R.A.; Gurley, L.R.

    1985-01-01

    The authors have employed high-performance liquid chromatography (HPLC) to investigate the syntheses of histones H1 and H1o as synchronized cells traverse from mitosis to S phase. Chinese hamster (line CHO) cells were synchronized by mitotic selection, and, at appropriate times, they were pulse labeled for 1 h with [ 3 H]lysine. Histones H1 and H1o were extracted by blending radiolabeled and carrier cells directly in 0.83 M HC1O 4 ; the total HC1O 4 -soluble, Cl 3 CCO 2 H-precipitable proteins were then separated by a modification of an HPLC system employing three mu Bondapak reversed-phase columns. These procedures (1) produce minimally perturbed populations of synchronized proliferating cells and (2) maximize the recovery of radiolabeled histones during isolation and analysis. Measurements of rates of synthesis indicate that the rate of H1 synthesis increases as cells traverse from early to mid G1; as cells enter S phase, the rate of H1 synthesis increases an additional congruent to 22-fold and is proportional to the number of S-phase cells. In contrast to H1, the rate of H1o synthesis is nearly constant throughout G1. As cells progress into S phase, the rate of H1o synthesis increases so that it also appears to be proportional to the number of S-phase cells. Except for the first 1-2 h after mitotic selection, these results are similar to those obtained when cells are synchronized in G1 with the isoleucine deprivation procedure

  5. Influenza A (H1N1) neuraminidase inhibitors from Vitis amurensis

    DEFF Research Database (Denmark)

    Nguyen, Ngoc Anh; Dao, Trong Tuan; Tung, Bui Thanh

    2011-01-01

    Recently, a novel H1N1 influenza A virus (H1N1/09 virus) was identified and considered a strong candidate for a novel influenza pandemic. As part of an ongoing anti-influenza screening programme on natural products, eight oligostilbenes were isolated as active principles from the methanol extract...... of Vitis amurensis. This manuscript reports the isolation, structural elucidation, and anti-viral activities of eight compounds on various neuraminidases from influenza A/PR/8/34 (H1N1), novel swine-origin influenza A (H1N1), and oseltamivir-resistant novel H1N1 (H274Y) expressed in 293T cells...

  6. Identification of reassortant pandemic H1N1 influenza virus in Korean pigs.

    Science.gov (United States)

    Han, Jae Yeon; Park, Sung Jun; Kim, Hye Kwon; Rho, Semi; Nguyen, Giap Van; Song, Daesub; Kang, Bo Kyu; Moon, Hyung Jun; Yeom, Min Joo; Park, Bong Kyun

    2012-05-01

    Since the 2009 pandemic human H1N1 influenza A virus emerged in April 2009, novel reassortant strains have been identified throughout the world. This paper describes the detection and isolation of reassortant strains associated with human pandemic influenza H1N1 and swine influenza H1N2 (SIV) viruses in swine populations in South Korea. Two influenza H1N2 reassortants were detected, and subtyped by PCR. The strains were isolated using Madin- Darby canine kidney (MDCK) cells, and genetically characterized by phylogenetic analysis for genetic diversity. They consisted of human, avian, and swine virus genes that were originated from the 2009 pandemic H1N1 virus and a neuraminidase (NA) gene from H1N2 SIV previously isolated in North America. This identification of reassortment events in swine farms raises concern that reassortant strains may continuously circulate within swine populations, calling for the further study and surveillance of pandemic H1N1 among swine.

  7. Apolipoprotein L1 confers pH-switchable ion permeability to phospholipid vesicles.

    Science.gov (United States)

    Bruno, Jonathan; Pozzi, Nicola; Oliva, Jonathan; Edwards, John C

    2017-11-03

    Apolipoprotein L1 (ApoL1) is a human serum protein conferring resistance to African trypanosomes, and certain ApoL1 variants increase susceptibility to some progressive kidney diseases. ApoL1 has been hypothesized to function like a pore-forming colicin and has been reported to have permeability effects on both intracellular and plasma membranes. Here, to gain insight into how ApoL1 may function in vivo , we used vesicle-based ion permeability, direct membrane association, and intrinsic fluorescence to study the activities of purified recombinant ApoL1. We found that ApoL1 confers chloride-selective permeability to preformed phospholipid vesicles and that this selectivity is strongly pH-sensitive, with maximal activity at pH 5 and little activity above pH 7. When ApoL1 and lipid were allowed to interact at low pH and were then brought to neutral pH, chloride permeability was suppressed, and potassium permeability was activated. Both chloride and potassium permeability linearly correlated with the mass of ApoL1 in the reaction mixture, and both exhibited lipid selectivity, requiring the presence of negatively charged lipids for activity. Potassium, but not chloride, permease activity required the presence of calcium ions in both the association and activation steps. Direct assessment of ApoL1-lipid associations confirmed that ApoL1 stably associates with phospholipid vesicles, requiring low pH and the presence of negatively charged phospholipids for maximal binding. Intrinsic fluorescence of ApoL1 supported the presence of a significant structural transition when ApoL1 is mixed with lipids at low pH. This pH-switchable ion-selective permeability may explain the different effects of ApoL1 reported in intracellular and plasma membrane environments. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Histone H1x is highly expressed in human neuroendocrine cells and tumours

    International Nuclear Information System (INIS)

    Warneboldt, Julia; Haller, Florian; Horstmann, Olaf; Danner, Bernhard C; Füzesi, László; Doenecke, Detlef; Happel, Nicole

    2008-01-01

    Histone H1x is a ubiquitously expressed member of the H1 histone family. H1 histones, also called linker histones, stabilize compact, higher order structures of chromatin. In addition to their role as structural proteins, they actively regulate gene expression and participate in chromatin-based processes like DNA replication and repair. The epigenetic contribution of H1 histones to these mechanisms makes it conceivable that they also take part in malignant transformation. Based on results of a Blast data base search which revealed an accumulation of expressed sequence tags (ESTs) of H1x in libraries from neuroendocrine tumours (NETs), we evaluated the expression of H1x in NETs from lung and the gastrointestinal tract using immunohistochemisty. Relative protein and mRNA levels of H1x were analysed by Western blot analysis and quantitative real-time RT-PCR, respectively. Since several reports describe a change of the expression level of the replacement subtype H1.0 during tumourigenesis, the analysis of this subtype was included in this study. We found an increased expression of H1x but not of H1.0 in NET tissues in comparison to corresponding normal tissues. Even though the analysed NETs were heterogenous regarding their grade of malignancy, all except one showed a considerably higher protein amount of H1x compared with corresponding non-neoplastic tissue. Furthermore, double-labelling of H1x and chromogranin A in sections of pancreas and small intestine revealed that H1x is highly expressed in neuroendocrine cells of these tissues. We conclude that the high expression of histone H1x in NETs is probably due to the abundance of this protein in the cells from which these tumours originate

  9. The N-terminal domain determines the affinity and specificity of H1 binding to chromatin

    International Nuclear Information System (INIS)

    Öberg, Christine; Belikov, Sergey

    2012-01-01

    Highlights: ► wt Human histone H1.4 and hH1.4 devoid of N-terminal domain, ΔN-hH1.4, were compared. ► Both histones bind to chromatin, however, ΔN-hH1.4 displays lower binding affinity. ► Interaction of ΔN-hH1.4 with chromatin includes a significant unspecific component. ► N-terminal domain is a determinant of specificity of histone H1 binding to chromatin. -- Abstract: Linker histone H1, one of the most abundant nuclear proteins in multicellular eukaryotes, is a key component of the chromatin structure mainly due to its role in the formation and maintenance of the 30 nm chromatin fiber. It has a three-domain structure; a central globular domain flanked by a short N-terminal domain and a long, highly basic C-terminal domain. Previous studies have shown that the binding abilities of H1 are at large determined by the properties of the C-terminal domain; much less attention has been paid to role of the N-terminal domain. We have previously shown that H1 can be reconstituted via cytoplasmic mRNA injection in Xenopus oocytes, cells that lack somatic H1. The heterologously expressed H1 proteins are incorporated into in vivo assembled chromatin at specific sites and the binding event is monitored as an increase in nucleosomal repeat length (NRL). Using this setup we have here compared the binding properties of wt-H1.4 and hH1.4 devoid of its N-terminal domain (ΔN-hH1.4). The ΔN-hH1.4 displays a drastically lower affinity for chromatin binding as compared to the wild type hH1.4. Our data also indicates that ΔN-hH1.4 is more prone to unspecific chromatin binding than the wild type. We conclude that the N-terminal domain of H1 is an important determinant of affinity and specificity of H1-chromatin interactions.

  10. Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Tomomi Tsubai

    2017-02-01

    Full Text Available Clozapine, a second-generation antipsychotic (SGA, is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT2C and histamine H1 receptors in the central nervous system has been reported as a mechanism of the weight gain caused by clozapine. In the present study, we investigated the direct pharmacological action of clozapine on the 3T3-L1 adipocytes and compared it to that of blonanserin, an SGA with low affinity for both receptors. Short-term exposure to clozapine decreased secretion and mRNA expression of leptin. Long-term exposure decreased leptin as well as adiponectin secretion, and further increased lipid droplets accumulation. However, short- and long-term exposures to blonanserin did not affect these parameters. A selective serotonin 5-HT2C, but not a histamine H1, receptor antagonist enhanced the decreased secretion of leptin induced by short-term exposure to clozapine, but did not affect the increased accumulation of lipid droplets. Our findings indicate that clozapine, but not blonanserin, strongly and directly affected the secretion of adipokines, such as leptin, in adipocytes and caused adipocyte enlargement.

  11. Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus.

    Science.gov (United States)

    O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice N; Wei, Chih-Jen; Nabel, Gary J; Subbarao, Kanta

    2012-08-01

    Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.

  12. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

    OpenAIRE

    Dirix, Luc Y.; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E.; Somer, Robert; Smakal, Martin; Emens, Leisha A.; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja

    2017-01-01

    Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 week...

  13. Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin

    Directory of Open Access Journals (Sweden)

    Mora Xavier

    2007-05-01

    Full Text Available Abstract Background Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes in physiological salt (0.14 M NaCl at constant stoichiometry. Results The H1 complement of native chromatin was perturbed by adding an additional amount of one of the subtypes. A certain amount of SAR (scaffold-associated region DNA was present in the mixture to avoid precipitation of chromatin by excess H1. SAR DNA also provided a set of reference relative affinities, which were needed to estimate the relative affinities of the subtypes for chromatin from the distribution of the subtypes between the SAR and the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so as to keep the stoichiometry of perturbed chromatin similar to that of native chromatin. H1 molecules freely exchanged between the chromatin and SAR binding sites. In conditions of free exchange, H1a was the subtype of lowest affinity, H1b and H1c had intermediate affinities and H1d, H1e and H1° the highest affinities. Subtype affinities for chromatin differed by up to 19-fold. The relative affinities of the subtypes for chromatin were equivalent to those estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5 had an affinity ~12-fold higher than H1e for both DNA and chromatin. Conclusion H1 subtypes freely exchange in vitro between chromatin binding sites in physiological salt (0.14 M NaCl. The large differences in relative affinity of the H1 subtypes for

  14. Predicting H1N1 vaccine uptake and H1N1-related health beliefs: the role of individual difference in consideration of future consequences.

    Science.gov (United States)

    Nan, Xiaoli; Kim, Jarim

    2014-01-01

    This research examines the influence of individual difference in consideration of future consequences on H1N1 vaccine uptake and H1N1-related health beliefs (i.e., perceived susceptibility to and severity of the H1N1 flu, perceived efficacy and safety of the H1N1 vaccine, and perceived self-efficacy in obtaining the H1N1 vaccine). A survey of 411 college students showed that consideration of future consequences had no direct effect on vaccine uptake, but higher consideration of future consequences was associated with greater perceived severity of the flu, higher perceived effectiveness of the vaccine, and greater perceived self-efficacy. Additional analysis suggested that consideration of future consequences had a significant indirect effect on vaccine uptake through perceived vaccine efficacy. Results of the study also revealed gender and racial differences in some of the H1N1-related health beliefs. Implications of the findings for vaccine risk communication are discussed.

  15. Mitochondrial haplogroup H1 in north Africa: an early holocene arrival from Iberia.

    Directory of Open Access Journals (Sweden)

    Claudio Ottoni

    Full Text Available The Tuareg of the Fezzan region (Libya are characterized by an extremely high frequency (61% of haplogroup H1, a mitochondrial DNA (mtDNA haplogroup that is common in all Western European populations. To define how and when H1 spread from Europe to North Africa up to the Central Sahara, in Fezzan, we investigated the complete mitochondrial genomes of eleven Libyan Tuareg belonging to H1. Coalescence time estimates suggest an arrival of the European H1 mtDNAs at about 8,000-9,000 years ago, while phylogenetic analyses reveal three novel H1 branches, termed H1v, H1w and H1x, which appear to be specific for North African populations, but whose frequencies can be extremely different even in relatively close Tuareg villages. Overall, these findings support the scenario of an arrival of haplogroup H1 in North Africa from Iberia at the beginning of the Holocene, as a consequence of the improvement in climate conditions after the Younger Dryas cold snap, followed by in situ formation of local H1 sub-haplogroups. This process of autochthonous differentiation continues in the Libyan Tuareg who, probably due to isolation and recent founder events, are characterized by village-specific maternal mtDNA lineages.

  16. Effects of ethanol and NAP on cerebellar expression of the neural cell adhesion molecule L1.

    Directory of Open Access Journals (Sweden)

    Devon M Fitzgerald

    Full Text Available The neural cell adhesion molecule L1 is critical for brain development and plays a role in learning and memory in the adult. Ethanol inhibits L1-mediated cell adhesion and neurite outgrowth in cerebellar granule neurons (CGNs, and these actions might underlie the cerebellar dysmorphology of fetal alcohol spectrum disorders. The peptide NAP potently blocks ethanol inhibition of L1 adhesion and prevents ethanol teratogenesis. We used quantitative RT-PCR and Western blotting of extracts of cerebellar slices, CGNs, and astrocytes from postnatal day 7 (PD7 rats to investigate whether ethanol and NAP act in part by regulating the expression of L1. Treatment of cerebellar slices with 20 mM ethanol, 10(-12 M NAP, or both for 4 hours, 24 hours, and 10 days did not significantly affect L1 mRNA and protein levels. Similar treatment for 4 or 24 hours did not regulate L1 expression in primary cultures of CGNs and astrocytes, the predominant cerebellar cell types. Because ethanol also damages the adult cerebellum, we studied the effects of chronic ethanol exposure in adult rats. One year of binge drinking did not alter L1 gene and protein expression in extracts from whole cerebellum. Thus, ethanol does not alter L1 expression in the developing or adult cerebellum; more likely, ethanol disrupts L1 function by modifying its conformation and signaling. Likewise, NAP antagonizes the actions of ethanol without altering L1 expression.

  17. Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1-PDGFRα

    International Nuclear Information System (INIS)

    Ishihara, Kenji; Kitamura, Hajime; Hiraizumi, Kenji; Kaneko, Motoko; Takahashi, Aki; Zee, OkPyo; Seyama, Toshio; Hong, JangJa; Ohuchi, Kazuo; Hirasawa, Noriyasu

    2008-01-01

    The constitutively activated tyrosine kinase Fip1-like 1 (FIP1L1)-platelet-derived growth factor receptor α (PDGFRα) causes eosinophilic leukemia EoL-1 cells to proliferate. Recently, we demonstrated that histone deacetylase inhibitors suppressed this proliferation and induced the differentiation of EoL-1 cells into eosinophils in parallel with a decrease in the level of FIP1L1-PDGFRα. In this study, we analyzed the mechanism by which FIP1L1-PDGFRα induces the proliferation and whether the suppression of cell proliferation triggers the differentiation into eosinophils. The FIP1L1-PDGFRα inhibitor imatinib inhibited the proliferation of EoL-1 cells and decreased the level of the oncoprotein c-Myc as well as the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK). The proliferation of EoL-1 cells and expression of c-Myc were also inhibited by the MEK inhibitor U0126 and JNK inhibitor SP600125. The expression of the eosinophilic differentiation marker CCR3 was not induced by imatinib. These findings suggest that FIP1L1-PDGFRα induces the proliferation of EoL-1 cells through the induction of c-Myc expression via ERK and JNK signaling pathways, but is not involved in the inhibition of differentiation toward mature eosinophils

  18. Histone H1 heterogeneity in the midge, Chironomus thummi. Structural comparison of the H1 variants in an organism where their intrachromosomal localization is possible.

    Science.gov (United States)

    Hoyer-Fender, S; Grossbach, U

    1988-09-01

    1. Seven subfractions of histone H1 have been isolated and purified from larvae of Chironomus thummi (Diptera). They have been denominated I-1, II-1, II-2, II-3, III-1, III-2, and III-3, according to the order of migration in two steps of preparative electrophoresis. 2. The amino acid compositions are similar to those of other H1 histones. Subfractions I-1 and II-1 were found to contain one methionine and two tyrosine residues, II-2 contained two methionine and three tyrosine residues, and III-1 one methionine and three tyrosine residues. The other subfractions contained one or two methionine and two or three tyrosine residues. For subfractions I-1 and II-1 a chain length of about 252 amino acids was estimated. 3. Peptide pattern analyses after chemical cleavage at the methionine and tyrosine residues, and enzymatic cleavage with thrombin and chymotrypsin, respectively, showed that all subfractions have different individual primary structures. A comparison of peptide sizes and of the positions in the peptide patterns of epitopes recognized by monoclonal antibodies was made to check whether some of the subfractions could arise by proteolytic degradation of others. This possibility can be excluded for five of the subfractions and is very improbable for the two others. Treatment of C. thummi H1 with alkaline phosphatase did not change the pattern of subfractions, while the phosphorylated subfraction of histone H2A disappeared after this treatment. Most and very probably all subfractions are thus H1 sequence variants. 4. Inbred strains and individual larvae of C. thummi were found to comprise all seven variants. The H1 heterogeneity can therefore not be due to allelic polymorphism. Salivary gland nuclei were found to contain variant I-1 and at least some of the other variants. 5. H1 from Drosophila melanogaster and from calf thymus were used as reference molecules in all cleavage experiments and yielded the peptide patterns expected from the sequence. The comparison

  19. PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells

    International Nuclear Information System (INIS)

    Kan-o, Keiko; Matsumoto, Koichiro; Asai-Tajiri, Yukari; Fukuyama, Satoru; Hamano, Saaka; Seki, Nanae; Nakanishi, Yoichi; Inoue, Hiromasa

    2013-01-01

    Highlights: •Double-stranded RNA upregulates B7-H1 on BEAS-2B airway epithelial cells. •The upregulation of B7-H1 is attenuated by inhibition of PI3Kδ isoform. •PI3Kδ-mediated upregulation of B7-H1 is independent of NF-κB activation. •Inhibition of PI3Kδ may prevent persistent viral infection induced by B7-H1. -- Abstract: Airway viral infection disturbs the health-related quality of life. B7-H1 (also known as PD-L1) is a coinhibitory molecule associated with the escape of viruses from the mucosal immunity, leading to persistent infection. Most respiratory viruses generate double-stranded (ds) RNA during replication. The stimulation of cultured airway epithelial cells with an analog of viral dsRNA, polyinosinic-polycytidylic acid (poly IC) upregulates the expression of B7-H1 via activation of the nuclear factor κB(NF-κB). The mechanism of upregulation was investigated in association with phosphatidylinositol 3-kinases (PI3Ks). Poly IC-induced upregulation of B7-H1 was profoundly suppressed by a pan-PI3K inhibitor and partially by an inhibitor or a small interfering (si)RNA for PI3Kδ in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110δ was detected by Western blot and suppressed by pretreatment with PI3Kδ siRNA. The activation of PI3Kδ is typically induced by oxidative stress. The generation of reactive oxygen species was increased by poly IC. Poly IC-induced upregulation of B7-H1 was attenuated by N-acetyl-L-cysteine, an antioxidant, or by oxypurinol, an inhibitor of xanthine oxidase. Poly IC-induced activation of NF-κB was suppressed by a pan-PI3K inhibitor but not by a PI3Kδ inhibitor. These results suggest that PI3Kδ mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-κB

  20. Night-time sedating H1 -antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial.

    Science.gov (United States)

    Staevska, M; Gugutkova, M; Lazarova, C; Kralimarkova, T; Dimitrov, V; Zuberbier, T; Church, M K; Popov, T A

    2014-07-01

    Many physicians believe that the most effective way to treat chronic urticaria is to take a nonsedating second-generation H1 -antihistamine in the morning and a sedating first-generation H1 -antihistamine, usually hydroxyzine, at night to enhance sleep. But is this belief well founded? To test this belief by comparing the effectiveness and prevalence of unwanted sedative effects when treating patients with chronic spontaneous urticaria (CSU) with levocetirizine 15 mg daily plus hydroxyzine 50 mg at night (levocetirizine plus hydroxyzine) vs. levocetirizine 20 mg daily (levocetirizine monotherapy). In this randomized, double-blind, cross-over study, 24 patients with difficult-to-treat CSU took levocetirizine plus hydroxyzine or levocetirizine monotherapy for periods of 5 days each. At the end of each treatment period, assessments were made of quality of life (Chronic Urticaria Quality of Life Questionnaire, CU-Q2 oL), severity of urticaria symptoms (Urticaria Activity Score, UAS), sleep disturbance during the night and daytime somnolence. Both treatments significantly decreased UAS, night-time sleep disturbances and CU-Q2 oL scores (P generation H1 -antihistamine, usually hydroxyzine, at night is not supported. These results are in line with the urticaria guidelines, which state that first-line treatment for urticaria should be new-generation, nonsedating H1 -antihistamines only. © 2014 The Authors. British Association of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

  1. Histones H10a and H10b are the same as CHO histones H1(III) and H1(IV):new features of H10 phosphorylation during the cell cycle

    International Nuclear Information System (INIS)

    D'Anna, J.A.; Gurley, L.R.; Becker, R.R.

    1981-01-01

    Two histone H1 fractions [H1(I) and H1(II) and two histone H1 0 fractions (H1 0 a and H1 0 b) have been isolated from butyrate-treated Chinese hamster (line CHO) cells by guanidine hydrochloride gradient chromatography on Bio-Rex 70 ion-exchange resin. The fractions have been identified by electrophoresis and amino acid analyses. Electrophoretic analysis of cyanogen bromide treated H1 0 in long acid-urea-polyacrylamide gels suggests that H1 0 a and H1 0 b differ, at least, within the 20-30 residue fragment(s) removed by the cyanogen bromide clevage. Shallow-gradient Bio-Rex 70 chromatography indicates that histones H1 0 a and H1 0 b are the same as the respective CHO histones, H1(III) and H1(IV). This identification and the phosphate incorporation data of Gurley et al. (1975) reveal new features about H1 0 phosphorylation: (1) following release from G 1 arrest, H1 0 a and H1 0 b become phosphorylated in late G 1 prior to DNA synthesis; (2) H1 0 a and H1 0 b are phosphorylated at similar rates throughout the cell cycle. These and other data demonstrate that histone H1 0 is phosphorylated in a cell cycle dependent fashion which mimics that of histone H1

  2. The H1 linker histones: multifunctional proteins beyond the nucleosomal core particle.

    Science.gov (United States)

    Hergeth, Sonja P; Schneider, Robert

    2015-11-01

    The linker histone H1 family members are a key component of chromatin and bind to the nucleosomal core particle around the DNA entry and exit sites. H1 can stabilize both nucleosome structure and higher-order chromatin architecture. In general, H1 molecules consist of a central globular domain with more flexible tail regions at both their N- and C-terminal ends. The existence of multiple H1 subtypes and a large variety of posttranslational modifications brings about a considerable degree of complexity and makes studying this protein family challenging. Here, we review recent progress in understanding the function of linker histones and their subtypes beyond their role as merely structural chromatin components. We summarize current findings on the role of H1 in heterochromatin formation, transcriptional regulation and embryogenesis with a focus on H1 subtypes and their specific modifications. © 2015 The Authors.

  3. Thermodynamical study of interaction of histone H1 chromosomal protein and mitoxantrone anticancer drug

    International Nuclear Information System (INIS)

    Jafargholizadeh, Naser; Zargar, Seyed Jalal; Safarian, Shahrokh; Habibi-Rezaei, Mehran

    2012-01-01

    Highlights: ► For the first time, our results show mitoxantrone anticancer drug binds to histone H1, via hydrophobic, hydrogen, van der Waals and electrostatic interactions. ► Binding of mitoxantrone molecules to histone H1 is positive cooperative. ► Histone H1 may be considered as a new target for mitoxantrone at the chromatin level. - Using ultraviolet spectroscopy technique, we have investigated the interaction of anticancer drug, mitoxantrone with calf thymus histone H1 chromosomal protein in 100 mM phosphate buffer, pH 7.0, at temperatures 300 and 310 K. UV spectroscopy results show interactions between mitoxantrone and histone H1 with a positive cooperative binding process which was confirmed by Scatchard plot. According to the obtained results, it is concluded that histone H1 can be considered as a target for mitoxantrone binding at the chromatin level.

  4. Subband Adaptive Filtering with l1-Norm Constraint for Sparse System Identification

    Directory of Open Access Journals (Sweden)

    Young-Seok Choi

    2013-01-01

    Full Text Available This paper presents a new approach of the normalized subband adaptive filter (NSAF which directly exploits the sparsity condition of an underlying system for sparse system identification. The proposed NSAF integrates a weighted l1-norm constraint into the cost function of the NSAF algorithm. To get the optimum solution of the weighted l1-norm regularized cost function, a subgradient calculus is employed, resulting in a stochastic gradient based update recursion of the weighted l1-norm regularized NSAF. The choice of distinct weighted l1-norm regularization leads to two versions of the l1-norm regularized NSAF. Numerical results clearly indicate the superior convergence of the l1-norm regularized NSAFs over the classical NSAF especially when identifying a sparse system.

  5. Characteristics of atopic children with pandemic H1N1 influenza viral infection: pandemic H1N1 influenza reveals 'occult' asthma of childhood.

    Science.gov (United States)

    Hasegawa, Shunji; Hirano, Reiji; Hashimoto, Kunio; Haneda, Yasuhiro; Shirabe, Komei; Ichiyama, Takashi

    2011-02-01

    The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment. © 2011 John Wiley & Sons A/S.

  6. Comparative analyses of pandemic H1N1 and seasonal H1N1, H3N2, and influenza B infections depict distinct clinical pictures in ferrets.

    Directory of Open Access Journals (Sweden)

    Stephen S H Huang

    Full Text Available Influenza A and B infections are a worldwide health concern to both humans and animals. High genetic evolution rates of the influenza virus allow the constant emergence of new strains and cause illness variation. Since human influenza infections are often complicated by secondary factors such as age and underlying medical conditions, strain or subtype specific clinical features are difficult to assess. Here we infected ferrets with 13 currently circulating influenza strains (including strains of pandemic 2009 H1N1 [H1N1pdm] and seasonal A/H1N1, A/H3N2, and B viruses. The clinical parameters were measured daily for 14 days in stable environmental conditions to compare clinical characteristics. We found that H1N1pdm strains had a more severe physiological impact than all season strains where pandemic A/California/07/2009 was the most clinically pathogenic pandemic strain. The most serious illness among seasonal A/H1N1 and A/H3N2 groups was caused by A/Solomon Islands/03/2006 and A/Perth/16/2009, respectively. Among the 13 studied strains, B/Hubei-Wujiagang/158/2009 presented the mildest clinical symptoms. We have also discovered that disease severity (by clinical illness and histopathology correlated with influenza specific antibody response but not viral replication in the upper respiratory tract. H1N1pdm induced the highest and most rapid antibody response followed by seasonal A/H3N2, seasonal A/H1N1 and seasonal influenza B (with B/Hubei-Wujiagang/158/2009 inducing the weakest response. Our study is the first to compare the clinical features of multiple circulating influenza strains in ferrets. These findings will help to characterize the clinical pictures of specific influenza strains as well as give insights into the development and administration of appropriate influenza therapeutics.

  7. A pharmacokinetic evaluation of five H1 antagonists after an oral and intravenous microdose to human subjects

    Science.gov (United States)

    Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

    2009-01-01

    AIMS To evaluate the pharmacokinetics (PK) of five H1 receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). METHODS Five H1 receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. RESULTS The median clearance (CL), apparent volume of distribution (Vd) and apparent terminal elimination half-life (t1/2) of diphenhydramine after an i.v. microdose were 24.7 l h−1, 302 l and 9.3 h, and the oral Cmax and AUC0–∞ were 0.195 ng ml−1 and 1.52 ng h ml−1, respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. CONCLUSIONS Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection. PMID:19523012

  8. Classical and semi-classical treatments of Li3+, Ne10++H(1s) collisions

    International Nuclear Information System (INIS)

    Errea, L F; Illescas, Clara; Mendez, L; Pons, B; Riera, A; Suarez, J

    2004-01-01

    We perform molecular close-coupling and impact-parameter classical trajectory Monte Carlo calculations of total and partial cross sections for capture and ionization in collisions of highly charged ions on H(1s). We first consider Li 3+ +H(1s) as a benchmark to ascertain the complementarity of the methods, and then Ne 10+ +H(1s), which has been scarcely studied up to now, and has recently become of interest for fusion plasma research

  9. How Does L1 and L2 Exposure Impact L1 Performance in Bilingual Children? Evidence from Polish-English Migrants to the United Kingdom

    Directory of Open Access Journals (Sweden)

    Ewa Haman

    2017-09-01

    Full Text Available Most studies on bilingual language development focus on children’s second language (L2. Here, we investigated first language (L1 development of Polish-English early migrant bilinguals in four domains: vocabulary, grammar, phonological processing, and discourse. We first compared Polish language skills between bilinguals and their Polish non-migrant monolingual peers, and then investigated the influence of the cumulative exposure to L1 and L2 on bilinguals’ performance. We then examined whether high exposure to L1 could possibly minimize the gap between monolinguals and bilinguals. We analyzed data from 233 typically developing children (88 bilingual and 145 monolingual aged 4;0 to 7;5 (years;months on six language measures in Polish: receptive vocabulary, productive vocabulary, receptive grammar, productive grammar (sentence repetition, phonological processing (non-word repetition, and discourse abilities (narration. Information about language exposure was obtained via parental questionnaires. For each language task, we analyzed the data from the subsample of bilinguals who had completed all the tasks in question and from monolinguals matched one-on-one to the bilingual group on age, SES (measured by years of mother’s education, gender, non-verbal IQ, and short-term memory. The bilingual children scored lower than monolinguals in all language domains, except discourse. The group differences were more pronounced on the productive tasks (vocabulary, grammar, and phonological processing and moderate on the receptive tasks (vocabulary and grammar. L1 exposure correlated positively with the vocabulary size and phonological processing. Grammar scores were not related to the levels of L1 exposure, but were predicted by general cognitive abilities. L2 exposure negatively influenced productive grammar in L1, suggesting possible L2 transfer effects on L1 grammatical performance. Children’s narrative skills benefitted from exposure to two languages

  10. Equilibrium, stability and transport in L=1 compact helical axis configuration

    International Nuclear Information System (INIS)

    Kikuchi, Hitoshi; Ueno, Hikaru; Aizawa, Masamitsu; Suzuki, Kiyomitsu; Gesso, Hirokazu; Saito, Katsunori; Kawakami, Ichiro; Shiina, Shoichi

    1990-01-01

    The L=1 torsatron is modified by two methods to improve the plasma stability. First one is the negative pitch modulation of coil winding. Second is the superposition of a relatively weak L=-1 torsatron field. These modification give rise to a local magnetic well keeping a positive magnetic shear. The equilibrium, stability and transport of plasma in these modified L=1 torsatrons are described and discussed. (author)

  11. Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance.

    Science.gov (United States)

    Martin, A M; Nirschl, T R; Nirschl, C J; Francica, B J; Kochel, C M; van Bokhoven, A; Meeker, A K; Lucia, M S; Anders, R A; DeMarzo, A M; Drake, C G

    2015-12-01

    Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation--constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss. Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples. In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss. These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.

  12. Purification and Characterization of Recombinant Vaccinia L1R Protein from Escherichia coli

    Science.gov (United States)

    2016-08-01

    RECOMBINANT VACCINIA L1R PROTEIN FROM ESCHERICHIA COLI 1. INTRODUCTION 1.1 Background Vaccinia virus (VACV) is the active component of the...the preparation of the recombinant VACV L1R protein fragment by denaturing , refolding, and purifying material expressed into inclusion bodies in...PURIFICATION AND CHARACTERIZATION OF RECOMBINANT VACCINIA L1R PROTEIN FROM ESCHERICHIA COLI ECBC-TR-1370

  13. The first Swedish H1N2 swine influenza virus isolate represents an uncommon reassortant

    OpenAIRE

    Renström Lena HM; Isaksson Mats; Berg Mikael; Zohari Siamak; Widén Frederik; Metreveli Giorgi; Bálint Ádám; Wallgren Per; Belák Sándor; Segall Thomas; Kiss István

    2009-01-01

    Abstract The European swine influenza viruses (SIVs) show considerable diversity comprising different types of H1N1, H3N2, and H1N2 strains. The intensifying full genome sequencing efforts reveal further reassortants within these subtypes. Here we report the identification of an uncommon reassortant variant of H1N2 subtype influenza virus isolated from a pig in a multisite herd where H1N2 swine influenza was diagnosed for the first time in Sweden during the winter of 2008-2009. The majority o...

  14. Two genotypes of H1N2 swine influenza viruses appeared among pigs in China.

    Science.gov (United States)

    Xu, Chuantian; Zhu, Qiyun; Yang, Huanliang; Zhang, Xiumei; Qiao, Chuanling; Chen, Yan; Xin, Xiaoguang; Chen, Hualan

    2009-10-01

    H1N2 is one of the main subtypes of influenza, which circulates in swine all over the world. To investigate the prevalence and genetic of H1N2 in swine of China. Two H1N2 swine influenza viruses were isolated from Tianjin and Guangdong province of China in 2004 and 2006, respectively. The molecular evolution of eight gene segments was analyzed. A/Swine/Tianjin/1/2004 has low identity with A/Swine/Guangdong/2006; in the phylogenetic tree of PA gene, A/Swine/Guangdong/1/2006 and A/Swine/Guangxi/1/2006 along with the H1N2 swine isolates of North America formed a cluster; and A/Swine/Tianjin/2004 and A/Swine/Zhejiang/2004, along with the classical H1N1 swine isolates formed another cluster; except that NA gene of A/Swine/Tianjin/1/2004 fell into the cluster of the H3N2 human influenza virus, indicating the reassortment between H3N2 human and H1N1 swine influenza viruses. Two different genotypes of H1N2 appeared among pigs in China. A/swine/Guangdong/1/06 was probably from H1N2 swine influenza viruses of North America; while A/swine/Tianjin/1/04 maybe come from reassortments of classical H1N1 swine and H3N2 human viruses prevalent in North America.

  15. A reverse genetic analysis of human Influenza A virus H1N2

    OpenAIRE

    Anton, Aline

    2010-01-01

    Reassortment between influenza A viruses of different subtypes rarely appears. Even in a community where H1N1 and H3N2 viruses co-circulate, reassortment to produce persistent viruses of mixed gene segments does not readily occur. H1N2 viruses, that circulated between 2001-2003 were considered to have arisen through the reassortment of the two human influenza subtypes H1N1 and H3N2. Due to the fact they make such a rare appearance, H1N2 viruses used to have new characteristics compared to the...

  16. Reasons for Low Pandemic H1N1 2009 Vaccine Acceptance within a College Sample

    Directory of Open Access Journals (Sweden)

    Russell D. Ravert

    2012-01-01

    Full Text Available This study examined health beliefs associated with novel influenza A (H1N1 immunization among US college undergraduates during the 2009-2010 pandemic. Undergraduates (ages 18–24 years from a large Midwestern University were invited to complete an online survey during March, 2010, five months after H1N1 vaccines became available. Survey items measured H1N1 vaccine history and H1N1-related attitudes based on the health belief literature. Logistic regression was used to identify attitudes associated with having received an H1N1 vaccine, and thematic analysis of student comments was conducted to further understand influences on vaccine decisions. Among the 296 students who participated in the survey, 15.2% reported having received an H1N1 vaccine. In regression analysis, H1N1 immunization was associated with seasonal flu vaccine history, perceived vaccine effectiveness, perceived obstacles to vaccination, and vaccine safety concerns. Qualitative results illustrate the relationship of beliefs to vaccine decisions, particularly in demonstrating that students often held concerns that vaccine could cause H1N1 or side effects. Vaccine safety, efficacy, and obstacles to immunization were major considerations in deciding whether to accept the H1N1 pandemic vaccine. Therefore, focusing on those aspects might be especially useful in future vaccine efforts within the college population.

  17. Histone H1 phosphorylation is associated with transcription by RNA polymerases I and II

    Science.gov (United States)

    Zheng, Yupeng; John, Sam; Pesavento, James J.; Schultz-Norton, Jennifer R.; Schiltz, R. Louis; Baek, Sonjoon; Nardulli, Ann M.; Hager, Gordon L.; Kelleher, Neil L.

    2010-01-01

    Histone H1 phosphorylation affects chromatin condensation and function, but little is known about how specific phosphorylations impact the function of H1 variants in higher eukaryotes. In this study, we show that specific sites in H1.2 and H1.4 of human cells are phosphorylated only during mitosis or during both mitosis and interphase. Antisera generated to individual H1.2/H1.4 interphase phosphorylations reveal that they are distributed throughout nuclei and enriched in nucleoli. Moreover, interphase phosphorylated H1.4 is enriched at active 45S preribosomal RNA gene promoters and is rapidly induced at steroid hormone response elements by hormone treatment. Our results imply that site-specific interphase H1 phosphorylation facilitates transcription by RNA polymerases I and II and has an unanticipated function in ribosome biogenesis and control of cell growth. Differences in the numbers, structure, and locations of interphase phosphorylation sites may contribute to the functional diversity of H1 variants. PMID:20439994

  18. Efficacy and Safety of Omalizumab in Patients with Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic on H1 Antihistamines: A Randomized, Placebo-Controlled Study

    Science.gov (United States)

    Saini, Sarbjit S; Bindslev-Jensen, Carsten; Maurer, Marcus; Grob, Jean-Jacques; Bülbül Baskan, Emel; Bradley, Mary S; Canvin, Janice; Rahmaoui, Abdelkader; Georgiou, Panayiotis; Alpan, Oral; Spector, Sheldon; Rosén, Karin

    2015-01-01

    ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12–75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional 2.96 points (95% confidence interval (CI): −4.71 to −1.21; P=0.0010), 2.95 points (95% CI: −4.72 to −1.18; P=0.0012), and 5.80 points (95% CI: −7.49 to −4.10; Pomalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups (n=81), respectively. The omalizumab 300-mg group met all nine secondary end points, including a significant decrease in the duration of time to reach minimally important difference response (⩾5-point decrease) in weekly ISS (Pomalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a serious adverse event. Omalizumab 300 mg administered subcutaneously every 4 weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU patients who remained symptomatic despite treatment with approved doses of H1 antihistamines. PMID:25046337

  19. Combining Amplification Typing of L1 Active Subfamilies (ATLAS) with High-Throughput Sequencing.

    Science.gov (United States)

    Rahbari, Raheleh; Badge, Richard M

    2016-01-01

    With the advent of new generations of high-throughput sequencing technologies, the catalog of human genome variants created by retrotransposon activity is expanding rapidly. However, despite these advances in describing L1 diversity and the fact that L1 must retrotranspose in the germline or prior to germline partitioning to be evolutionarily successful, direct assessment of de novo L1 retrotransposition in the germline or early embryogenesis has not been achieved for endogenous L1 elements. A direct study of de novo L1 retrotransposition into susceptible loci within sperm DNA (Freeman et al., Hum Mutat 32(8):978-988, 2011) suggested that the rate of L1 retrotransposition in the germline is much lower than previously estimated (ATLAS L1 display technique (Badge et al., Am J Hum Genet 72(4):823-838, 2003) to investigate de novo L1 retrotransposition in human genomes. In this chapter, we describe how we combined a high-coverage ATLAS variant with high-throughput sequencing, achieving 11-25× sequence depth per single amplicon, to study L1 retrotransposition in whole genome amplified (WGA) DNAs.

  20. Hepatic NPC1L1 overexpression ameliorates glucose metabolism in diabetic mice via suppression of gluconeogenesis.

    Science.gov (United States)

    Kurano, Makoto; Hara, Masumi; Satoh, Hiroaki; Tsukamoto, Kazuhisa

    2015-05-01

    Inhibition of intestinal NPC1L1 by ezetimibe has been demonstrated to improve glucose metabolism in rodent models; however, the role of hepatic NPC1L1 in glucose metabolism has not been elucidated. In this study, we analyzed the effects of hepatic NPC1L1 on glucose metabolism. We overexpressed NPC1L1 in the livers of lean wild type mice, diet-induced obesity mice and db/db mice with adenoviral gene transfer. We found that in all three mouse models, hepatic NPC1L1 overexpression lowered fasting blood glucose levels as well as blood glucose levels on ad libitum; in db/db mice, hepatic NPC1L1 overexpression improved blood glucose levels to almost the same as those found in lean wild type mice. A pyruvate tolerance test revealed that gluconeogenesis was suppressed by hepatic NPC1L1 overexpression. Further analyses revealed that hepatic NPC1L1 overexpression decreased the expression of FoxO1, resulting in the reduced expression of G6Pase and PEPCK, key enzymes in gluconeogenesis. These results indicate that hepatic NPC1L1 might have distinct properties of suppressing gluconeogenesis via inhibition of FoxO1 pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Negative Transfer of L1 on English Grammar Learning in SLA

    Institute of Scientific and Technical Information of China (English)

    马秀琳

    2015-01-01

    At present,many scholars pay more attention to the positive transfer of native language on the English learning,while ignoring the negative transfer of L1 on English grammar learning.Therefore native transfer of L1 often appears on English grammar learning.This paper aims to point out that the negative transfer of L1 has a profound and vast influence on the English grammar learning,to find out the countermeasures to reduce the influence of negative transfer of L1 and finally to bring the benefits to the following relative studies.

  2. HPV-16 L1 genes with inactivated negative RNA elements induce potent immune responses

    International Nuclear Information System (INIS)

    Rollman, Erik; Arnheim, Lisen; Collier, Brian; Oeberg, Daniel; Hall, Haakan; Klingstroem, Jonas; Dillner, Joakim; Pastrana, Diana V.; Buck, Chris B.; Hinkula, Jorma; Wahren, Britta; Schwartz, Stefan

    2004-01-01

    Introduction of point mutations in the 5' end of the human papillomavirus type 16 (HPV-16) L1 gene specifically inactivates negative regulatory RNA processing elements. DNA vaccination of C57Bl/6 mice with the mutated L1 gene resulted in improved immunogenicity for both neutralizing antibodies as well as for broad cellular immune responses. Previous reports on the activation of L1 by codon optimization may be explained by inactivation of the regulatory RNA elements. The modified HPV-16 L1 DNA that induced anti-HPV-16 immunity may be seen as a complementary approach to protein subunit immunization against papillomavirus

  3. Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

    Science.gov (United States)

    Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn

    2012-01-01

    There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

  4. Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

    Directory of Open Access Journals (Sweden)

    Charles Nfon

    Full Text Available There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI. In addition, heterologous cell mediated immunity (CMI was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

  5. Tunable magnetic properties by interfacial manipulation of L1(0)-FePt perpendicular ultrathin film with island-like structures.

    Science.gov (United States)

    Feng, C; Wang, S G; Yang, M Y; Zhang, E; Zhan, Q; Jiang, Y; Li, B H; Yu, G H

    2012-02-01

    Based on interfacial manipulation of the MgO single crystal substrate and non-magnetic AIN compound, a L1(0)-FePt perpendicular ultrathin film with the structure of MgO/FePt-AIN/Ta was designed, prepared, and investigated. The film is comprised of L1(0)-FePt "magnetic islands," which exhibits a perpendicular magnetic anisotropy (PMA), tunable coercivity (Hc), and interparticle exchange coupling (IEC). The MgO substrate promotes PMA of the film because of interfacial control of the FePt lattice orientation. The AIN compound is doped to increase the difference of surface energy between FePt layer and MgO substrate and to suppress the growth of FePt grains, which takes control of island growth mode of FePt atoms. The AIN compound also acts as isolator of L1(0)-FePt islands to pin the sites of FePt domains, resulting in the tunability of Hc and IEC of the films.

  6. Appearance of reassortant European avian-origin H1 influenza A viruses of swine in Vietnam.

    Science.gov (United States)

    Takemae, N; Nguyen, P T; Le, V T; Nguyen, T N; To, T L; Nguyen, T D; Pham, V P; Vo, H V; Le, Q V T; Do, H T; Nguyen, D T; Uchida, Y; Saito, T

    2018-03-06

    Three subtypes-H1N1, H1N2 and H3N2-of influenza A viruses of swine (IAVs-S) are currently endemic in swine worldwide, but there is considerable genotypic diversity among each subtype and limited geographical distribution. Through IAVs-S monitoring in Vietnam, two H1N2 influenza A viruses were isolated from healthy pigs in Ba Ria-Vung Tau Province, Southern Vietnam, on 2 December 2016. BLAST and phylogenetic analyses revealed that their HA and NA genes were derived from those of European avian-like H1N2 IAVs-S that contained avian-origin H1 and human-like N2 genes, and were particularly closely related to those of IAVs-S circulating in the Netherlands, Germany or Denmark. In addition, the internal genes of these Vietnamese isolates were derived from human A(H1N1)pdm09 viruses, suggesting that the Vietnamese H1N2 IAVs-S are reassortants between European H1N2 IAVs-S and human A(H1N1)pdm09v. The appearance of European avian-like H1N2 IAVs-S in Vietnam marks their first transmission outside Europe. Our results and statistical analyses of the number of live pigs imported into Vietnam suggest that the European avian-like H1N2 IAVs-S may have been introduced into Vietnam with their hosts through international trade. These findings highlight the importance of quarantining imported pigs to impede the introduction of new IAVs-S. © 2018 Blackwell Verlag GmbH.

  7. Predictors of H1N1 influenza in the emergency department: proposition for a modified H1N1 case definition.

    Science.gov (United States)

    Flick, H; Drescher, M; Prattes, J; Tovilo, K; Kessler, H H; Vander, K; Seeber, K; Palfner, M; Raggam, R B; Avian, A; Krause, R; Hoenigl, M

    2014-02-01

    Reliable and rapid diagnosis of influenza A H1N1 is essential to initiate appropriate antiviral therapy and preventive measures. We analysed the differences in clinical presentation and laboratory parameters between emergency department patients with PCR-confirmed H1N1 influenza infection (n = 199) and those with PCR-negative influenza-like illness (ILI; n = 252). Cough, wheezing, leucopenia, eosinopenia and a lower C-reactive protein remained significant predictors of H1N1 influenza. Proposed combinations of clinical symptoms with simple laboratory parameters (e.g. reported or measured fever and either cough or leucocytes definitions that use clinical criteria alone. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  8. Method for the preparation of cellulose acetate flat sheet composite membranes for forward osmosis—Desalination using MgSO4 draw solution

    KAUST Repository

    Sairam, M.; Sereewatthanawut, E.; Li, K.; Bismarck, A.; Livingston, A.G.

    2011-01-01

    A lab scale method for the preparation of defect free flat sheet composite membranes for forward osmosis (FO) has been developed. Membranes containing a thin layer of cellulose acetate (CA) cast on a nylon fabric of 50μm thick were prepared by phase inversion in water. Cellulose acetate (CA) membranes with an overall thickness of 70-80μm have been prepared with lactic acid, maleic acid and zinc chloride as pore forming agents, at different annealing temperatures, for forward osmosis. These membranes have been tested in the desalination of saline feeds (35g·L-1 of NaCl) using magnesium sulphate solution (150g·L-1) as the draw solution. The water flux, and rejection of NaCl, were compared with those of commercially available membranes tested under the same FO conditions. The commercially available FO membrane from Hydration Technologies Inc, OR (M1) has a permeability of 0.13L·h-1·m-2·bar-1 with a NaCl rejection of 97% when tested with 150g·L-1 of MgSO4 in the draw solution. Another commercially available membrane for FO from Hydration Technologies Inc, OR, M2 has a water permeability of 0.014L·h-1·m-2·bar-1 with NaCl rejection of 100%. The flux and rejection of the CA membranes prepared in this work are found to be dependent on the nature of the pore forming agent, and annealing temperature. Impregnation of an inorganic filler, sodium montmorrillonite in CA membranes and coating of CA membranes with hydrophilic PVA did not enhance the flux of base CA membranes. Cellulose acetate membranes cast from dope solutions containing acetone/isopropanol and lactic acid, maleic acid and zinc chloride as pore forming agents have water permeabilities of 0.13, 0.09 and 0.68L·h-1·m-2·bar-1 respectively, with NaCl rejections of 97.7, 99.3 and 88% when annealed at 50°C. CA membranes prepared with zinc chloride as a pore forming agent have good permeability of 0.27L·h-1·m-2·bar-1 with a NaCl rejection of 95% when annealed at 70°C. © 2011.

  9. Method for the preparation of cellulose acetate flat sheet composite membranes for forward osmosis—Desalination using MgSO4 draw solution

    KAUST Repository

    Sairam, M.

    2011-06-01

    A lab scale method for the preparation of defect free flat sheet composite membranes for forward osmosis (FO) has been developed. Membranes containing a thin layer of cellulose acetate (CA) cast on a nylon fabric of 50μm thick were prepared by phase inversion in water. Cellulose acetate (CA) membranes with an overall thickness of 70-80μm have been prepared with lactic acid, maleic acid and zinc chloride as pore forming agents, at different annealing temperatures, for forward osmosis. These membranes have been tested in the desalination of saline feeds (35g·L-1 of NaCl) using magnesium sulphate solution (150g·L-1) as the draw solution. The water flux, and rejection of NaCl, were compared with those of commercially available membranes tested under the same FO conditions. The commercially available FO membrane from Hydration Technologies Inc, OR (M1) has a permeability of 0.13L·h-1·m-2·bar-1 with a NaCl rejection of 97% when tested with 150g·L-1 of MgSO4 in the draw solution. Another commercially available membrane for FO from Hydration Technologies Inc, OR, M2 has a water permeability of 0.014L·h-1·m-2·bar-1 with NaCl rejection of 100%. The flux and rejection of the CA membranes prepared in this work are found to be dependent on the nature of the pore forming agent, and annealing temperature. Impregnation of an inorganic filler, sodium montmorrillonite in CA membranes and coating of CA membranes with hydrophilic PVA did not enhance the flux of base CA membranes. Cellulose acetate membranes cast from dope solutions containing acetone/isopropanol and lactic acid, maleic acid and zinc chloride as pore forming agents have water permeabilities of 0.13, 0.09 and 0.68L·h-1·m-2·bar-1 respectively, with NaCl rejections of 97.7, 99.3 and 88% when annealed at 50°C. CA membranes prepared with zinc chloride as a pore forming agent have good permeability of 0.27L·h-1·m-2·bar-1 with a NaCl rejection of 95% when annealed at 70°C. © 2011.

  10. Nephrogenic diabetes insipidus in a patient with L1 syndrome: a new report of a contiguous gene deletion syndrome including L1CAM and AVPR2.

    Science.gov (United States)

    Knops, Noël B B; Bos, Krista K; Kerstjens, Mieke; van Dael, Karin; Vos, Yvonne J

    2008-07-15

    We report on an infant boy with congenital hydrocephalus due to L1 syndrome and polyuria due to diabetes insipidus. We initially believed his excessive urine loss was from central diabetes insipidus and that the cerebral malformation caused a secondary insufficient pituitary vasopressin release. However, he failed to respond to treatment with a vasopressin analogue, which pointed to nephrogenic diabetes insipidus (NDI). L1 syndrome and X-linked NDI are distinct clinical disorders caused by mutations in the L1CAM and AVPR2 genes, respectively, located in adjacent positions in Xq28. In this boy we found a deletion of 61,577 basepairs encompassing the entire L1CAM and AVPR2 genes and extending into intron 7 of the ARHGAP4 gene. To our knowledge this is the first description of a patient with a deletion of these three genes. He is the second patient to be described with L1 syndrome and NDI. During follow-up he manifested complications from the hydrocephalus and NDI including global developmental delay and growth failure with low IGF-1 and hypothyroidism. 2008 Wiley-Liss, Inc.

  11. The Expression and Biological Significance of PD-L1 on Lung Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Cheng CHEN

    2009-08-01

    Full Text Available Background and objective Tumor-associated PD-L1 expression was recently shown to promote T-cell apoptosis and proposed as a potential mechanism of immune evasion by tumors. On the basis of the ability of tumor-associated PD-L1 to mediate activated T-cell death, it is likely that manipulation of the PD-L1 pathway at defined time points during the development of the T-cell antitumor immune response can enhance the efficacy of T-cell-based immunotherapy. Here, the levels of expression of PD-L1 on lung cancer cell lines and its role in interaction of CTL and target cells was investigated. Methods Human PBMC derived DCs were loaded with apoptotic tumor cells and stimulated by CD40 mAb (5C11. Tumor specific CTL was generated in vitro by autologous T cells co-cultured with mature DCs. Expression of PD-L1 on lung cancer cell lines H1299 and A549 were analyzed by FCM. JAM assay was used to detect the cytolytic activity of CTL with or without blocking PD-L1 by PD-L1 mAb respectively. The concentrations of IFN-γ in supernatants from distinct groups were analyzed by ELISA. Results Tumor cells-loaded mature DCs could induce the generation of the tumor specific CTL. Expression of PD-L1 was low on A549 cell, but high on H1299 cell. Blockade of PD-L1 on A549 could not improve cytolytic effect of CTL on target cells and IFN-γ production, but fragmentation of H1299 cells and IFN-γ production were significantly enhanced by the combination of PD-L1 mAb and CTL. Conclusion Expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells.

  12. The specificity and flexibility of l1 reverse transcription priming at imperfect T-tracts.

    Directory of Open Access Journals (Sweden)

    Clément Monot

    2013-05-01

    Full Text Available L1 retrotransposons have a prominent role in reshaping mammalian genomes. To replicate, the L1 ribonucleoprotein particle (RNP first uses its endonuclease (EN to nick the genomic DNA. The newly generated DNA end is subsequently used as a primer to initiate reverse transcription within the L1 RNA poly(A tail, a process known as target-primed reverse transcription (TPRT. Prior studies demonstrated that most L1 insertions occur into sequences related to the L1 EN consensus sequence (degenerate 5'-TTTT/A-3' sites and frequently preceded by imperfect T-tracts. However, it is currently unclear whether--and to which degree--the liberated 3'-hydroxyl extremity on the genomic DNA needs to be accessible and complementary to the poly(A tail of the L1 RNA for efficient priming of reverse transcription. Here, we employed a direct assay for the initiation of L1 reverse transcription to define the molecular rules that guide this process. First, efficient priming is detected with as few as 4 matching nucleotides at the primer 3' end. Second, L1 RNP can tolerate terminal mismatches if they are compensated within the 10 last bases of the primer by an increased number of matching nucleotides. All terminal mismatches are not equally detrimental to DNA extension, a C being extended at higher levels than an A or a G. Third, efficient priming in the context of duplex DNA requires a 3' overhang. This suggests the possible existence of additional DNA processing steps, which generate a single-stranded 3' end to allow L1 reverse transcription. Based on these data we propose that the specificity of L1 reverse transcription initiation contributes, together with the specificity of the initial EN cleavage, to the distribution of new L1 insertions within the human genome.

  13. Molecular identification of the ompL1 gene within Leptospira interrogans standard serovars.

    Science.gov (United States)

    Dezhbord, Mehrangiz; Esmaelizad, Majid; Khaki, Pejvak; Fotohi, Fariba; Zarehparvar Moghaddam, Athena

    2014-06-11

    Leptospirosis, caused by infection with pathogenic Leptospira species, is one of the most prevalent zoonotic diseases in the world. Current leptospiral vaccines are mainly multivalent dead whole-cell mixtures made of several local dominant serovars. Therefore, design and construction of an efficient recombinant vaccine for leptospirosis control is very important. OmpL1 is an immunogenic porin protein that could be of special significance in vaccination and serodiagnosis for leptospirosis. Three strains belonging to pathogenic L. interrogans were analyzed. The specific primers for proliferation of the ompL1 gene were designed. The amplified gene was cloned. In order to investigate the ompL1 nucleotide sequence and homological analysis of this gene, ompL1 genes cloned from standard vaccinal Leptospira serovars prevalent in Iran were sequenced and cloned. PCR amplification of the ompL1 gene using the designed primers resulted in a 963 bp ompL1 gene product. The PCR based on the ompL1 gene detected all pathogenic reference serovars of Leptospira spp. tested. Based on alignment and phylogenetic analysis, although the ompL1 nucleotide sequence was slightly different within three vaccinal serovars (100%-85% identity), amino acid alignment of the OmpL1 proteins revealed that there would be inconsiderable difference among them. The ompL1 gene of the three isolates was well conserved, differing only by a total of 6 bp and the proteins by 2 amino acids. The cloned gene could be further used for expression and recombinant OmpL1 as an efficient and conserved antigen, and may be a useful vaccine candidate against leptospirosis in our region.

  14. The specificity and flexibility of l1 reverse transcription priming at imperfect T-tracts.

    Science.gov (United States)

    Monot, Clément; Kuciak, Monika; Viollet, Sébastien; Mir, Ashfaq Ali; Gabus, Caroline; Darlix, Jean-Luc; Cristofari, Gaël

    2013-05-01

    L1 retrotransposons have a prominent role in reshaping mammalian genomes. To replicate, the L1 ribonucleoprotein particle (RNP) first uses its endonuclease (EN) to nick the genomic DNA. The newly generated DNA end is subsequently used as a primer to initiate reverse transcription within the L1 RNA poly(A) tail, a process known as target-primed reverse transcription (TPRT). Prior studies demonstrated that most L1 insertions occur into sequences related to the L1 EN consensus sequence (degenerate 5'-TTTT/A-3' sites) and frequently preceded by imperfect T-tracts. However, it is currently unclear whether--and to which degree--the liberated 3'-hydroxyl extremity on the genomic DNA needs to be accessible and complementary to the poly(A) tail of the L1 RNA for efficient priming of reverse transcription. Here, we employed a direct assay for the initiation of L1 reverse transcription to define the molecular rules that guide this process. First, efficient priming is detected with as few as 4 matching nucleotides at the primer 3' end. Second, L1 RNP can tolerate terminal mismatches if they are compensated within the 10 last bases of the primer by an increased number of matching nucleotides. All terminal mismatches are not equally detrimental to DNA extension, a C being extended at higher levels than an A or a G. Third, efficient priming in the context of duplex DNA requires a 3' overhang. This suggests the possible existence of additional DNA processing steps, which generate a single-stranded 3' end to allow L1 reverse transcription. Based on these data we propose that the specificity of L1 reverse transcription initiation contributes, together with the specificity of the initial EN cleavage, to the distribution of new L1 insertions within the human genome.

  15. Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: an ecological study.

    Science.gov (United States)

    Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R

    2012-01-01

    The influenza A (H1N1) pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality. Country-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders. After adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR) = 0.84 per log increase in oseltamivir supply). While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase). While there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics.

  16. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.

    Science.gov (United States)

    Dirix, Luc Y; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E; Somer, Robert; Smakal, Martin; Emens, Leisha A; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja; Grote, Hans Juergen; Chin, Kevin; Hamilton, Erika P

    2018-02-01

    Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

  17. H1N1 Flu & U.S. Schools: Answers to Frequently Asked Questions

    Science.gov (United States)

    US Department of Education, 2009

    2009-01-01

    A severe form of influenza known as H1N1, commonly being called swine flu, has health officials around the world concerned. In the United States, the outbreak of H1N1 has prompted school closures and cancellation of school-related events. As the flu spreads, the Department of Education encourages school leaders, parents and students to know how to…

  18. Outcomes of Oseltamivir Treatment for H1N1 Infection During Pregnancy: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Nermin Akdemir

    2011-04-01

    CONCLUSION: In this retrospective, study, we found that, H1N1 infection during pregnancy has a good prognosis and without complication for maternal health. Although oseltamivir therapy is safe in pregnant women, it can be associated with cardiac structural cardiac malformations in H1N1 infected pregnancy newborns

  19. Digested Ara h 1 Loses Sensitizing Capacity When Separated into Fractions

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Barkholt, Vibeke; Rigby, Neil M.

    2012-01-01

    The major peanut allergen Ara h 1 is an easily digestible protein under physiological conditions. The present study revealed that pepsin digestion products of Ara h 1 retained the sensitizing potential in a Brown Norway rat model, while this sensitizing capacity was lost by separating the digest...

  20. Novel reassortant of swine influenza H1N2 virus in Germany.

    Science.gov (United States)

    Zell, Roland; Motzke, Susann; Krumbholz, Andi; Wutzler, Peter; Herwig, Volker; Dürrwald, Ralf

    2008-01-01

    European porcine H1N2 influenza viruses arose after multiple reassortment steps involving a porcine influenza virus with avian-influenza-like internal segments and human H1N1 and H3N2 viruses in 1994. In Germany, H1N2 swine influenza viruses first appeared in 2000. Two German H1N2 swine influenza virus strains isolated from pigs with clinical symptoms of influenza are described. They were characterized by the neutralization test, haemagglutination inhibition (HI) test and complete sequencing of the viral genomes. The data demonstrate that these viruses represent a novel H1N2 reassortant. The viruses showed limited neutralization by sera raised against heterologous A/sw/Bakum/1,832/00-like H1N2 viruses. Sera pools from recovered pigs showed a considerably lower HI reaction, indicative of diagnostic difficulties in using the HI test to detect these viruses with A/sw/Bakum/1,832/00-like H1N2 antigens. Genome sequencing revealed the novel combination of the human-like HAH1 gene of European porcine H1N2 influenza viruses and the NAN2 gene of European porcine H3N2 viruses.

  1. A historical perspective of influenza A(H1N2) virus.

    Science.gov (United States)

    Komadina, Naomi; McVernon, Jodie; Hall, Robert; Leder, Karin

    2014-01-01

    The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals.

  2. Outbreak of pandemic influenza A/H1N1 2009 in Nepal.

    Science.gov (United States)

    Adhikari, Bal Ram; Shakya, Geeta; Upadhyay, Bishnu Prasad; Prakash Kc, Khagendra; Shrestha, Sirjana Devi; Dhungana, Guna Raj

    2011-03-23

    The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Out of 609 collected samples, 302 (49.6%) were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3%) were positive for Pandemic influenza A/H1N1 and 130 (21.3%) were Seasonal influenza A. Most of the pandemic cases (53%) were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1)v type. The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1)v type.

  3. Adoption of Preventive Measures and Attitudes toward the H1N1 Influenza Pandemic in Schools

    Science.gov (United States)

    Pérez, Anna; Rodríguez, Tània; López, Maria José; Continente, Xavier; Nebot, Manel

    2016-01-01

    Background: This study describes the perceived impact of H1N1 influenza and the adoption of the recommended measures to address the pandemic in schools. Methods: A cross-sectional self-reported survey was conducted in 433 schools in Barcelona addressed to the school principal or the H1N1 influenza designated person. A descriptive analysis was…

  4. Pandemic H1N1 2009 virus in Danish pigs: Diagnosis and lack of surveillance

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Nielsen, L. P.; Breum, Solvej Østergaard

    In March-April 2009, a novel pandemic H1N1 virus (H1N1v) of likely swine origin emerged in the human population globally. The first case in pigs was reported from Canada in May 2009 and presently almost all countries with pig production have reported cases. The emergence of a new influenza subtype...

  5. Safety of pandemic H1N1 vaccines in children and adolescents

    NARCIS (Netherlands)

    E.G. Wijnans (Leonoor); S. de Bie (Sandra); J.P. Dieleman (Jeanne); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

    2011-01-01

    textabstractDuring the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of

  6. Hospitalizations for Pandemic (H1N1) 2009 among Maori and Pacific Islanders, New Zealand

    Science.gov (United States)

    Verrall, Ayesha; Norton, Katherine; Rooker, Serena; Dee, Stephen; Olsen, Leeanne; Tan, Chor Ee; Paull, Sharon; Allen, Richard

    2010-01-01

    Community transmission of influenza A pandemic (H1N1) 2009 was followed by high rates of hospital admissions in the Wellington region of New Zealand, particularly among Maori and Pacific Islanders. These findings may help health authorities anticipate the effects of pandemic (H1N1) 2009 in other communities. PMID:20031050

  7. Function and coding in the blowfly H1 neuron during naturalistic optic flow

    NARCIS (Netherlands)

    Hateren, J.H. van; Kern, R.; Schwerdtfeger, G.; Egelhaaf, M.

    2005-01-01

    Naturalistic stimuli, reconstructed from measured eye movements of flying blowflies, were replayed on a panoramic stimulus device. The directional movement-sensitive H1 neuron was recorded from blowflies watching these stimuli. The response of the H1 neuron is dominated by the response to fast

  8. Application of independent component analysis to H-1 MR spectroscopic imaging exams of brain tumours

    NARCIS (Netherlands)

    Szabo de Edelenyi, F.; Simonetti, A.W.; Postma, G.; Huo, R.; Buydens, L.M.C.

    2005-01-01

    The low spatial resolution of clinical H-1 MRSI leads to partial volume effects. To overcome this problem, we applied independent component analysis (ICA) on a set of H-1 MRSI exams of brain turnours. With this method, tissue types that yield statistically independent spectra can be separated. Up to

  9. Role of H1 linker histones in mammalian development and stem cell differentiation.

    Science.gov (United States)

    Pan, Chenyi; Fan, Yuhong

    2016-03-01

    H1 linker histones are key chromatin architectural proteins facilitating the formation of higher order chromatin structures. The H1 family constitutes the most heterogeneous group of histone proteins, with eleven non-allelic H1 variants in mammals. H1 variants differ in their biochemical properties and exhibit significant sequence divergence from one another, yet most of them are highly conserved during evolution from mouse to human. H1 variants are differentially regulated during development and their cellular compositions undergo dramatic changes in embryogenesis, gametogenesis, tissue maturation and cellular differentiation. As a group, H1 histones are essential for mouse development and proper stem cell differentiation. Here we summarize our current knowledge on the expression and functions of H1 variants in mammalian development and stem cell differentiation. Their diversity, sequence conservation, complex expression and distinct functions suggest that H1s mediate chromatin reprogramming and contribute to the large variations and complexity of chromatin structure and gene expression in the mammalian genome. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. 78 FR 69539 - Removal of Attestation Process for Facilities Using H-1A Registered Nurses

    Science.gov (United States)

    2013-11-20

    ... of Attestation Process for Facilities Using H-1A Registered Nurses AGENCY: Employment and Training... registered nurses under the H-1A visa program. These subparts became obsolete after the authorizing statute... nonimmigrant classification exclusively for the temporary admission and employment of registered nurses, which...

  11. Influenza A(H1N1)pdm09 in critically ill children admitted to a ...

    African Journals Online (AJOL)

    tes. Fig. 1. The prevalence of seasonal and pandemic H1N1 (pH1N1) influenza A at RCWMCH and ... Full approval for the study was obtained from the Human Research ... respiratory virus infection, had not received prophylactic oseltamivir,.

  12. Age as Risk Factor for Death from Pandemic (H1N1) 2009, Chile

    Science.gov (United States)

    Dabanch, Jeannette; Nájera, Manuel; González, Claudia; Guerrero, Andrea; Olea, Andrea; Fasce, Rodrigo; Morales, Cecilia; Vega, Jeanette

    2011-01-01

    Pandemic (H1N1) 2009 affected Chile during the winter of 2009. The hospitalization rate was 0.56% overall and 3.47% for persons >60 years of age at risk for severe disease and death independent of concurrent conditions. Age >60 years was the major risk factor for death from pandemic (H1N1) 2009. PMID:21762580

  13. Outbreak of pandemic influenza A/H1N1 2009 in Nepal

    Directory of Open Access Journals (Sweden)

    Shrestha Sirjana

    2011-03-01

    Full Text Available Abstract Background The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Results Out of 609 collected samples, 302 (49.6% were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3% were positive for Pandemic influenza A/H1N1 and 130 (21.3% were Seasonal influenza A. Most of the pandemic cases (53% were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1v type. Conclusion The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1v type.

  14. A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma.

    Science.gov (United States)

    Maekawa, Naoya; Konnai, Satoru; Takagi, Satoshi; Kagawa, Yumiko; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Deguchi, Tatsuya; Nakajima, Chie; Kato, Yukinari; Yamamoto, Keiichi; Uemura, Hidetoshi; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

    2017-08-21

    Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.

  15. Complete Genome Sequence of Bacillus velezensis L-1, Which Has Antagonistic Activity against Pear Diseases

    OpenAIRE

    Sun, Pingping; Cui, Jianchao; Jia, Xiaohui; Wang, Wenhui

    2017-01-01

    ABSTRACT Bacillus velezensis L-1 is an effective biocontrol agent against pear diseases. Here, we report the complete genome sequence of B. velezensis L-1 in which clusters related to the biosynthesis of secondary metabolites were predicted. This genome provides insights into the possible biocontrol mechanisms and furthers application of this specific bacterium.

  16. Complete Genome Sequence of Bacillus velezensis L-1, Which Has Antagonistic Activity against Pear Diseases.

    Science.gov (United States)

    Sun, Pingping; Cui, Jianchao; Jia, Xiaohui; Wang, Wenhui

    2017-11-30

    Bacillus velezensis L-1 is an effective biocontrol agent against pear diseases. Here, we report the complete genome sequence of B. velezensis L-1 in which clusters related to the biosynthesis of secondary metabolites were predicted. This genome provides insights into the possible biocontrol mechanisms and furthers application of this specific bacterium. Copyright © 2017 Sun et al.

  17. Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade.

    Science.gov (United States)

    Zhang, Fei; Wei, Hudie; Wang, Xiaoxiao; Bai, Yu; Wang, Pilin; Wu, Jiawei; Jiang, Xiaoyong; Wang, Yugang; Cai, Haiyan; Xu, Ting; Zhou, Aiwu

    2017-01-01

    The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids. This loop forms two short helices and develops key hydrophobic and ionic interactions with PD-L1 residues, such as Ile54, Tyr56 and Arg113, which are also involved in PD-1 binding. The detailed mutagenesis study identified the hotspot residues of the PD-L1 surface and provides an explanation for the stronger (~1 000-fold) binding of KN035 to PD-L1 than PD-1 and its lack of binding to PD-L2. Overall, this study reveals how a single immunoglobulin-variable scaffold of KN035 or PD-1 can bind to a flat protein surface through either a single surface loop or beta-sheet strands; and provides a basis for designing new immune checkpoint blockers and generating bi-specific antibodies for combination therapy.

  18. [Regulatory Mechanisms of PD-L1 Expression and Its Role in Immune Evasion].

    Science.gov (United States)

    Kataoka, Keisuke

    2017-11-01

    Immune checkpoint blockade therapy using anti-PD-1 or anti-PD-L1 antibodies can unleash anti-tumor immunity and induce durable remission in a variety ofhuman cancers. However, the regulatory mechanisms of PD-L1 expression mediating immune evasion ofcancer cells have not been fully elucidated, including the genetic alterations causing PD-L1 overexpression. Recently, we have reported a novel genetic mechanism ofimmune evasion associated with structural variations(SVs)disrupting the 3'-untranslated region(UTR)ofthe PD-L1 gene in various malignancies, such as aggressive lymphomas and gastrointestinal cancers. Despite a heterogenous nature ofthese SVs, they are closely associated with a marked upregulation of PD-L1 expression, which augments tumor growth and escape from anti-tumor immunity. Here we present an overview of the regulatory mechanisms of PD-L1 expression in cancer cells, highlighting the genetic mechanisms of PD-L1 constitutive activation, with specific focus on PD-L1 3'-UTR disruption.

  19. Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1.

    Science.gov (United States)

    Cartier, Anna E; Djakovic, Stevan N; Salehi, Afshin; Wilson, Scott M; Masliah, Eliezer; Patrick, Gentry N

    2009-06-17

    Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We found that UCH-L1 activity is rapidly upregulated by NMDA receptor activation, which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of presynaptic and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1-inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner.

  20. L1-L2 Transfer in the Narrative Styles of Chinese EFL Learners' Written Personal Narratives

    Science.gov (United States)

    Su, I-Ru; Chou, Yi-Chun

    2016-01-01

    Most of the research on second language (L2) narratives has focused on whether or how L2 learners carry their L1 narrative styles into L2 narration; few studies have explored whether L2 learners' knowledge of the L2 also in turn affects their L1 narrative performance. The present study attempted to probe the issue of cultural transfer in narrative…

  1. L1 Differences and L2 Similarities: Teaching Verb Tenses in English

    Science.gov (United States)

    Collins, Laura

    2007-01-01

    In making decisions regarding the focus for grammar teaching, ESL instructors may take into consideration errors that appear to result from the influence of their students' first language(s) (L1). There is also evidence from language acquisition research suggesting that for some grammatical features, learners of different L1 backgrounds may face…

  2. L1 and L2 Strategy Use in Reading Comprehension of Chinese EFL Readers

    Science.gov (United States)

    Tsai, Yea-Ru; Ernst, Cheryl; Talley, Paul C.

    2010-01-01

    This study revealed the relationship between L1 (Mandarin Chinese) and L2 (English) strategy use in L2 reading comprehension by focusing on the correlation of L1 reading ability, L2 proficiency and employed reading strategies. The participants, 222 undergraduates learning English as a foreign language (EFL), were classified into skilled and…

  3. Modeling of the structure of ribosomal protein L1 from the archaeon Haloarcula marismortui

    Science.gov (United States)

    Nevskaya, N. A.; Kljashtorny, V. G.; Vakhrusheva, A. V.; Garber, M. B.; Nikonov, S. V.

    2017-07-01

    The halophilic archaeon Haloarcula marismortui proliferates in the Dead Sea at extremely high salt concentrations (higher than 3 M). This is the only archaeon, for which the crystal structure of the ribosomal 50S subunit was determined. However, the structure of the functionally important side protuberance containing the abnormally negatively charged protein L1 (HmaL1) was not visualized. Attempts to crystallize HmaL1 in the isolated state or as its complex with RNA using normal salt concentrations (≤500 mM) failed. A theoretical model of HmaL1 was built based on the structural data for homologs of the protein L1 from other organisms, and this model was refined by molecular dynamics methods. Analysis of this model showed that the protein HmaL1 can undergo aggregation due to the presence of a cluster of positive charges unique for proteins L1. This cluster is located at the RNA-protein interface, which interferes with the crystallization of HmaL1 and the binding of the latter to RNA.

  4. L2 Word Recognition: Influence of L1 Orthography on Multi-Syllabic Word Recognition

    Science.gov (United States)

    Hamada, Megumi

    2017-01-01

    L2 reading research suggests that L1 orthographic experience influences L2 word recognition. Nevertheless, the findings on multi-syllabic words in English are still limited despite the fact that a vast majority of words are multi-syllabic. The study investigated whether L1 orthography influences the recognition of multi-syllabic words, focusing on…

  5. X-linked hydrocephalus : A novel missense mutation in the L1CAM gene

    NARCIS (Netherlands)

    Sztriha, L; Vos, YJ; Verlind, E; Johansen, J; Berg, B

    2002-01-01

    X-linked hydrocephalus is associated with mutations in the L1 neuronal cell adhesion molecule gene. L1 protein plays a key role in neurite outgrowth, axonal guidance, and pathfinding during the development of the nervous system. A male is described with X-linked hydrocephalus who had multiple small

  6. Equilibrium and stability of high-beta plasma in a finite l=+-1 toroidal system

    International Nuclear Information System (INIS)

    Shiina, S.; Saito, K.; Todoroki, J.; Hamada, S.; Gesso, H.; Nogi, Y.; Osanai, Y.; Yoshimura, H.

    1983-01-01

    The equilibrium and stability are theoretically and experimentally investigated of high-beta plasma in the Modified Bumpy Torus, which is an asymmetric closed-line system with fairly large l=0 and l=+-1 field components. The finiteness of the l=+-1 component induces significant stabilizing effects due both to self formation of a magnetic well and to the conducting wall. (author)

  7. The Status of the Auxiliary "Do" in L1 and L2 English Negative Clauses

    Science.gov (United States)

    Perales, Susana

    2010-01-01

    This paper addresses the issue of whether negative sentences containing auxiliary "do" in L1 and L2 English share the same underlying syntactic representation. To this end, I compare the negative sentences produced by 77 bilingual (Spanish/Basque) L2 learners of English with the corresponding data available for L1 acquirers reported on in Schutze…

  8. Ternary Weighted Function and Beurling Ternary Banach Algebra l1ω(S

    Directory of Open Access Journals (Sweden)

    Mehdi Dehghanian

    2011-01-01

    Full Text Available Let S be a ternary semigroup. In this paper, we introduce our notation and prove some elementary properties of a ternary weight function ω on S. Also, we make ternary weighted algebra l1ω(S and show that l1ω(S is a ternary Banach algebra.

  9. CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer.

    NARCIS (Netherlands)

    Guo, Z.; Linn, J.F.; Wu, G.; Anzick, S.L.; Eisenberger, C.F.; Halachmi, S.; Cohen, Y.; Fomenkov, A.; Hoque, M.O.; Okami, K.; Steiner, G.; Engles, J.M.; Osada, M.; Moon, C.; Ratovitski, E.; Trent, J.M.; Meltzer, P.S.; Westra, W.H.; Kiemeney, L.A.L.M.; Schoenberg, M.P.; Sidransky, D.; Trink, B.

    2004-01-01

    Genomic amplification at 20q11-13 is a common event in human cancers. We isolated a germline translocation breakpoint at 20q11 from a bladder cancer patient. We identified CDC91L1, the gene encoding CDC91L1 (also called phosphatidylinositol glycan class U (PIG-U), a transamidase complex unit in the

  10. Enhanced spatial resolution in fluorescence molecular tomography using restarted L1-regularized nonlinear conjugate gradient algorithm.

    Science.gov (United States)

    Shi, Junwei; Liu, Fei; Zhang, Guanglei; Luo, Jianwen; Bai, Jing

    2014-04-01

    Owing to the high degree of scattering of light through tissues, the ill-posedness of fluorescence molecular tomography (FMT) inverse problem causes relatively low spatial resolution in the reconstruction results. Unlike L2 regularization, L1 regularization can preserve the details and reduce the noise effectively. Reconstruction is obtained through a restarted L1 regularization-based nonlinear conjugate gradient (re-L1-NCG) algorithm, which has been proven to be able to increase the computational speed with low memory consumption. The algorithm consists of inner and outer iterations. In the inner iteration, L1-NCG is used to obtain the L1-regularized results. In the outer iteration, the restarted strategy is used to increase the convergence speed of L1-NCG. To demonstrate the performance of re-L1-NCG in terms of spatial resolution, simulation and physical phantom studies with fluorescent targets located with different edge-to-edge distances were carried out. The reconstruction results show that the re-L1-NCG algorithm has the ability to resolve targets with an edge-to-edge distance of 0.1 cm at a depth of 1.5 cm, which is a significant improvement for FMT.

  11. Code-Switching: L1-Coded Mediation in a Kindergarten Foreign Language Classroom

    Science.gov (United States)

    Lin, Zheng

    2012-01-01

    This paper is based on a qualitative inquiry that investigated the role of teachers' mediation in three different modes of coding in a kindergarten foreign language classroom in China (i.e. L2-coded intralinguistic mediation, L1-coded cross-lingual mediation, and L2-and-L1-mixed mediation). Through an exploratory examination of the varying effects…

  12. L1 effects on the processing of grammatical gender in L2

    NARCIS (Netherlands)

    Sabourin, L; Foster-Cohen, S.; Nizegorodcew, A.

    2001-01-01

    This paper explores L1 effects on the L2 off-line processing of Dutch (grammatical gender) agreement The L2 participants had either German, English or a Romance language as their L1. Non-gender agreement (finiteness and agreement) was tested to ascertain the level of proficiency of the participants

  13. L1 and L2 Distance Effects in Learning L3 Dutch

    Science.gov (United States)

    Schepens, Job J.; der Slik, Frans; Hout, Roeland

    2016-01-01

    Many people speak more than two languages. How do languages acquired earlier affect the learnability of additional languages? We show that linguistic distances between speakers' first (L1) and second (L2) languages and their third (L3) language play a role. Larger distances from the L1 to the L3 and from the L2 to the L3 correlate with lower…

  14. Heterologous production of human papillomavirus type-16 L1 protein by a lactic acid bacterium

    Directory of Open Access Journals (Sweden)

    Bermúdez-Humarán Luis G

    2009-08-01

    Full Text Available Abstract Background The expression of vaccine antigens in lactic acid bacteria (LAB is a safe and cost-effective alternative to traditional expression systems. In this study, we investigated i the expression of Human papillomavirus type 16 (HPV-16 L1 major capsid protein in the model LAB Lactococcus lactis and ii the ability of the resulting recombinant strain to produce either capsomer-or virus-like particles (VLPs. Results and conclusion HPV-16 L1 gene was cloned into two vectors, pCYT and pSEC, designed for controlled intra- or extracellular heterologous expression in L. lactis, respectively. The capacity of L. lactis harboring either pCYT:L1 or pSEC:L1 plasmid to accumulate L1 in the cytoplasm and supernatant samples was confirmed by Western blot assays. Electron microscopy analysis suggests that, L1 protein produced by recombinant lactococci can self-assemble into structures morphologically similar to VLPs intracellularly. The presence of conformational epitopes on the L. lactis-derived VLPs was confirmed by ELISA using an anti-HPV16 L1 capsid antigen antibody. Our results support the feasibility of using recombinant food-grade LAB, such as L. lactis, for the production of L1-based VLPs and open the possibility for the development of a new safe mucosal vector for HPV-16 prophylactic vaccination.

  15. Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication.

    Science.gov (United States)

    Holmes, J Bradley; Akman, Gokhan; Wood, Stuart R; Sakhuja, Kiran; Cerritelli, Susana M; Moss, Chloe; Bowmaker, Mark R; Jacobs, Howard T; Crouch, Robert J; Holt, Ian J

    2015-07-28

    Encoding ribonuclease H1 (RNase H1) degrades RNA hybridized to DNA, and its function is essential for mitochondrial DNA maintenance in the developing mouse. Here we define the role of RNase H1 in mitochondrial DNA replication. Analysis of replicating mitochondrial DNA in embryonic fibroblasts lacking RNase H1 reveals retention of three primers in the major noncoding region (NCR) and one at the prominent lagging-strand initiation site termed Ori-L. Primer retention does not lead immediately to depletion, as the persistent RNA is fully incorporated in mitochondrial DNA. However, the retained primers present an obstacle to the mitochondrial DNA polymerase γ in subsequent rounds of replication and lead to the catastrophic generation of a double-strand break at the origin when the resulting gapped molecules are copied. Hence, the essential role of RNase H1 in mitochondrial DNA replication is the removal of primers at the origin of replication.

  16. The first Swedish H1N2 swine influenza virus isolate represents an uncommon reassortant

    Directory of Open Access Journals (Sweden)

    Renström Lena HM

    2009-10-01

    Full Text Available Abstract The European swine influenza viruses (SIVs show considerable diversity comprising different types of H1N1, H3N2, and H1N2 strains. The intensifying full genome sequencing efforts reveal further reassortants within these subtypes. Here we report the identification of an uncommon reassortant variant of H1N2 subtype influenza virus isolated from a pig in a multisite herd where H1N2 swine influenza was diagnosed for the first time in Sweden during the winter of 2008-2009. The majority of the European H1N2 swine influenza viruses described so far possess haemagglutinin (HA of the human-like H1N2 SIV viruses and the neuraminidase (NA of either the European H1N2 or H3N2 SIV-like viruses. The Swedish isolate has an avian-like SIV HA and a H3N2 SIV-like NA, which is phylogenetically more closely related to H3N2 SIV NAs from isolates collected in the early '80s than to the NA of H3N2 origin of the H1N2 viruses isolated during the last decade, as depicted by some German strains, indicative of independent acquisition of the NA genes for these two types of reassortants. The internal genes proved to be entirely of avian-like SIV H1N1 origin. The prevalence of this SIV variant in pig populations needs to be determined, as well as the suitability of the routinely used laboratory reagents to analyze this strain. The description of this H1N2 SIV adds further information to influenza epidemiology and supports the necessity of surveillance for influenza viruses in pigs.

  17. The first Swedish H1N2 swine influenza virus isolate represents an uncommon reassortant.

    Science.gov (United States)

    Bálint, Adám; Metreveli, Giorgi; Widén, Frederik; Zohari, Siamak; Berg, Mikael; Isaksson, Mats; Renström, Lena Hm; Wallgren, Per; Belák, Sándor; Segall, Thomas; Kiss, István

    2009-10-28

    The European swine influenza viruses (SIVs) show considerable diversity comprising different types of H1N1, H3N2, and H1N2 strains. The intensifying full genome sequencing efforts reveal further reassortants within these subtypes. Here we report the identification of an uncommon reassortant variant of H1N2 subtype influenza virus isolated from a pig in a multisite herd where H1N2 swine influenza was diagnosed for the first time in Sweden during the winter of 2008-2009. The majority of the European H1N2 swine influenza viruses described so far possess haemagglutinin (HA) of the human-like H1N2 SIV viruses and the neuraminidase (NA) of either the European H1N2 or H3N2 SIV-like viruses. The Swedish isolate has an avian-like SIV HA and a H3N2 SIV-like NA, which is phylogenetically more closely related to H3N2 SIV NAs from isolates collected in the early '80s than to the NA of H3N2 origin of the H1N2 viruses isolated during the last decade, as depicted by some German strains, indicative of independent acquisition of the NA genes for these two types of reassortants. The internal genes proved to be entirely of avian-like SIV H1N1 origin. The prevalence of this SIV variant in pig populations needs to be determined, as well as the suitability of the routinely used laboratory reagents to analyze this strain.The description of this H1N2 SIV adds further information to influenza epidemiology and supports the necessity of surveillance for influenza viruses in pigs.

  18. L1{sub 0} phase transition in FePt thin films via direct interface reaction

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaohong; Sun Hongyu; Wang Fengqing; Li Wei; Zhang Xiangyi [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, 066004 Qinhuangdao (China); Liu Baoting; Guo Jianxin [College of Physics Science and Technology, Hebei University, 071002 Baoding (China)], E-mail: xyzh66@ysu.edu.cn

    2008-12-07

    Lowering the L1{sub 0} ordering temperature of FePt films is of great significance for their application as an ultrahigh density magnetic recording medium. In this study, the L1{sub 0} ordering process of FePt thin films deposited directly on Si substrates has been significantly accelerated by the interface reaction between the thin film and the Si substrate, and thus the thin films show a low L1{sub 0} ordering temperature of T = 310 deg. C as compared with those deposited on Si/SiO{sub 2} substrates. The accelerated L1{sub 0} ordering transition is predominantly dependent on the rapid growth of the ordered domains during the interface reaction. The film thickness has an important effect on the interface reaction and thus can be used to tune the L1{sub 0} ordering process of the FePt films.

  19. Exonization of active mouse L1s: a driver of transcriptome evolution?

    Directory of Open Access Journals (Sweden)

    Badge Richard

    2007-10-01

    Full Text Available Abstract Background Long interspersed nuclear elements (LINE-1s, L1s have been recently implicated in the regulation of mammalian transcriptomes. Results Here, we show that members of the three active mouse L1 subfamilies (A, GF and TF contain, in addition to those on their sense strands, conserved functional splice sites on their antisense strands, which trigger multiple exonization events. The latter is particularly intriguing in the light of the strong antisense orientation bias of intronic L1s, implying that the toleration of antisense insertions results in an increased potential for exonization. Conclusion In a genome-wide analysis, we have uncovered evidence suggesting that the mobility of the large number of retrotransposition-competent mouse L1s (~2400 potentially active L1s in NCBIm35 has significant potential to shape the mouse transcriptome by continuously generating insertions into transcriptional units.

  20. Identification of CREB3L1 as a Biomarker Predicting Doxorubicin Treatment Outcome.

    Directory of Open Access Journals (Sweden)

    Bray Denard

    Full Text Available Doxorubicin has been shown to inhibit proliferation of cancer cells through proteolytic activation of CREB3L1 (cAMP response element binding protein 3-like 1, a transcription factor synthesized as a membrane-bound precursor. Upon doxorubicin treatment, CREB3L1 is cleaved so that the N-terminal domain of the protein can reach the nucleus where it activates transcription of genes that inhibit cell proliferation. These results suggest that the level of CREB3L1 in cancer cells may determine their sensitivity to doxorubicin.Mice transplanted with 6 lines of renal cell carcinoma (RCC were injected with doxorubicin to observe the effect of the chemotherapy on tumor growth. Immunohistochemistry and bioinformatics analyses were performed to compare CREB3L1 levels in types of cancer known to respond to doxorubicin versus those resistant to doxorubicin.Higher levels of CREB3L1 protein are correlated with increased doxorubicin sensitivity of xenograft RCC tumors (p = 0.017 by Pearson analysis. From patient tumor biopsies we analyzed, CREB3L1 was expressed in 19% of RCC, which is generally resistant to doxorubicin, but in 70% of diffuse large B-cell lymphoma that is sensitive to doxorubicin. Doxorubicin is used as the standard treatment for cancers that express the highest levels of CREB3L1 such as osteosarcoma and malignant fibrous histiocytoma but is not generally used to treat those that express the lowest levels of CREB3L1 such as RCC.Identification of CREB3L1 as the biomarker for doxorubicin sensitivity may markedly improve the doxorubicin response rate by applying doxorubicin only to patients with cancers expressing CREB3L1.

  1. PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma.

    Science.gov (United States)

    Nguyen, Bella Hai; Montgomery, Renn; Fadia, Mitali; Wang, Jiali; Ali, Sayed

    2018-02-01

    There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome. Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity. Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484). Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time. © 2017 John Wiley & Sons Australia, Ltd.

  2. 20 CFR 655.700 - What statutory provisions govern the employment of H-1B, H-1B1, and E-3 nonimmigrants and how do...

    Science.gov (United States)

    2010-04-01

    ... Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in... occupations or certain fashion models from any country, the INA, as amended, provides as follows: (1... work in a “specialty occupation” or as a fashion model of distinguished merit and ability in the United...

  3. Molecular characterization of pandemic H1N1 influenza viruses isolated from turkeys and pathogenicity of a human pH1N1 isolate in turkeys.

    Science.gov (United States)

    Berhane, Yohannes; Ojkic, Davor; Neufeld, James; Leith, Marsha; Hisanaga, Tamiko; Kehler, Helen; Ferencz, Arpad; Wojcinski, Helen; Cottam-Birt, Colleen; Suderman, Matthew; Handel, Katherine; Alexandersen, Soren; Pasick, John

    2010-12-01

    Suspected human-to-animal transmission of the 2009 pandemic H1N1 (pH1N1) virus has been reported in several animal species, including pigs, dogs, cats, ferrets, and turkeys. In this study we describe the genetic characterization of pH1N1 viruses isolated from breeder turkeys that was associated with a progressive drop in egg production. Sequence analysis of all eight gene segments from three viruses isolated from this outbreak demonstrated homology with other human and swine pH1N1 isolates. The susceptibility of turkeys to a human pH1N1 isolate was further evaluated experimentally. The 50% turkey infectious dose (TID50) for the human isolate A/Mexico/LnDRE/4487/2009 was determined by inoculating groups of 8-10-week-old turkeys with serial 10-fold dilutions of virus by oronasal and cloacal routes. We estimated the TID50 to be between 1 x 10(5) and 1 x 10(6) TCID50. The pathogenesis of pH1N1 in oronasally or cloacally inoculated juvenile turkeys was also examined. None of the turkeys exhibited clinical signs, and no significant difference in virus shedding or seroconversion was observed between the two inoculation groups. More than 50% of the turkeys in both oronasal and cloacal groups shed virus beginning at 2 days postinoculation (dpi). All birds that actively shed virus seroconverted by 14 dpi. Virus antigen was demonstrated by immunohistochemistry in the cecal tonsils and bursa of Fabricius in two of the birds that were infected by the cloacal route. Virus transmission to naive contact turkeys was at best doubtful. This report provides additional evidence that pH1N1 can cross the species barrier and cause disease outbreaks in domestic turkeys. However, it appears that the reproductive status of the host as well as environmental factors such as concurrent infections, stress, the presence or absence of litter, and stocking density may also contribute to efficient infection and transmission of this agent.

  4. Multiplex RT-PCR assay for differentiating European swine influenza virus subtypes H1N1, H1N2 and H3N2.

    Science.gov (United States)

    Chiapponi, Chiara; Moreno, Ana; Barbieri, Ilaria; Merenda, Marianna; Foni, Emanuela

    2012-09-01

    In Europe, three major swine influenza viral (SIV) subtypes (H1N1, H1N2 and H3N2) have been isolated in pigs. Developing a test that is able to detect and identify the subtype of the circulating strain rapidly during an outbreak of respiratory disease in the pig population is of essential importance. This study describes two multiplex RT-PCRs which distinguish the haemagglutinin (HA) gene and the neuraminidase (NA) gene of the three major subtypes of SIV circulating in Europe. The HA PCR was able to identify the lineage (avian or human) of the HA of H1 subtypes. The analytical sensitivity of the test, considered to be unique, was assessed using three reference viruses. The detection limit corresponded to 1×10(-1) TCID(50)/200μl for avian-like H1N1, 1×10(0) TCID(50)/200μl for human-like H1N2 and 1×10(1) TCID(50)/200μl for H3N2 SIV. The multiplex RT-PCR was first carried out on a collection of 70 isolated viruses showing 100% specificity and then on clinical samples, from which viruses had previously been isolated, resulting in an 89% positive specificity of the viral subtype. Finally, the test was able to identify the viral subtype correctly in 56% of influenza A positive samples, from which SIV had not been isolated previously. It was also possible to identify mixed viral infections and the circulation of a reassortant strain before performing genomic studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Design, synthesis and anticonvulsant activity evaluation of 7-substituted-4H-[1,2,4]triazino[3,4-alpha]phthalazin-4-one derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xian-Yu; Quan, Zhe-Shan [Yanbian Univ., Yanji, Jilin (China). Key Lab. of Organism Functional Factors of the Changbai Mountain; Yanbian Univ., Yanji, Jilin (China). Coll. of Pharmacy; Guan, Li-Ping; Zhang, Lei; Wei, Cheng-Xi; Piao, Hu-Ri [Yanbian Univ., Yanji, Jilin (China). Key Lab. of Organism Functional Factors of the Changbai Mountain

    2009-07-01

    In this study, a novel series of 7-substituted-4H-[1,2,4]triazino[3,4-a]phthalazin-4-one derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that 7-hexyloxy-4H-[1,2,4]triazino[3,4-alpha]phthalazin-4-one 4e was the most potent with median effective dose (ED{sub 50}) value of 6.6 mg kg-1, median toxicity dose (TD{sub 50}) of 39.4 mg kg{sup -1}, providing a protective index (PI=TD{sub 50} /ED{sub 50}) value of 6.0. (author)

  6. Vaccine potential of recombinant cathepsinL1G against Fasciola gigantica in mice.

    Science.gov (United States)

    Changklungmoa, Narin; Phoinok, Natthacha; Yencham, Chonthicha; Sobhon, Prasert; Kueakhai, Pornanan

    2016-08-15

    In this study, we characterized and investigated the vaccine potential of FgCatL1G against Fasciola gigantica infection in mice. Recombinant mature FgCatL1G (rmFgCatL1G) was expressed in Escherichia coli BL21. The vaccination was performed in Imprinting Control Region (ICR) mice (n=10) by subcutaneous injection with 50μg of rmFgCatL1G combined with Freund's adjuvant. Two weeks after the second boost, mice were infected with 15 metacercariae by the oral route. The percents of protection of rmFgCatL1G vaccine were estimated to be 56.5% and 58.3% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. Antibodies in the immune sera of vaccinated mice were shown by immunoblot to react with the native FgCatL1s in the extract of all stages of parasites and rmFgCatL1H, recombinant pro - FgCatL1 (rpFgCatL1). By immunohistochemistry, the immune sera also reacted with FgCatL1s in the caecal epithelial cells of the parasites. The levels of IgG1 and IgG2a in the immune sera, which are indicative of Th2 and Th1 immune responses, were also increased with IgG1 predominating. The levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in rmFgCatL1G-immunized group showed no significant difference from the control groups, but pathological lesions of livers in rmFgCatL1G-immunized group showed significant decrease when compared to the control groups. This study indicates that rmFgCatL1G has a vaccine potential against F. gigantica in mice, and this potential will be tested in larger livestock animals. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1.

    Science.gov (United States)

    Maher, Christina M; Thomas, Jeffrey D; Haas, Derick A; Longen, Charles G; Oyer, Halley M; Tong, Jane Y; Kim, Felix J

    2018-02-01

    Emerging evidence suggests that Sigma1 ( SIGMAR1 , also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small-molecule modulators of Sigma1 alter endoplasmic reticulum (ER)-associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type I integral membrane glycoprotein that is cotranslationally inserted into the ER and is processed and transported through the secretory pathway. Once at the surface of cancer cells, PD-L1 acts as a T-cell inhibitory checkpoint molecule and suppresses antitumor immunity. Here, we demonstrate that in Sigma1-expressing triple-negative breast and androgen-independent prostate cancer cells, PD-L1 protein levels were suppressed by RNAi knockdown of Sigma1 and by small-molecule inhibition of Sigma1. Sigma1-mediated action was confirmed by pharmacologic competition between Sigma1-selective inhibitor and activator ligands. When administered alone, the Sigma1 inhibitor decreased cell surface PD-L1 expression and suppressed functional interaction of PD-1 and PD-L1 in a coculture of T cells and cancer cells. Conversely, the Sigma1 activator increased PD-L1 cell surface expression, demonstrating the ability to positively and negatively modulate Sigma1 associated PD-L1 processing. We discovered that the Sigma1 inhibitor induced degradation of PD-L1 via autophagy, by a mechanism distinct from bulk macroautophagy or general ER stress-associated autophagy. Finally, the Sigma1 inhibitor suppressed IFNγ-induced PD-L1. Our data demonstrate that small-molecule Sigma1 modulators can be used to regulate PD-L1 in cancer cells and trigger its degradation by selective autophagy. Implications: Sigma1 modulators sequester and eliminate PD-L1 by autophagy, thus preventing functional PD-L1 expression at the cell surface. This

  8. rno-miR-665 targets BCL2L1 (Bcl-xl) and increases vulnerability to propofol in developing astrocytes.

    Science.gov (United States)

    Sun, Wen-Chong; Pei, Ling

    2016-07-01

    Propofol exerts a cytotoxic influence over immature neurocytes. Our previous study revealed that clinically relevant doses of propofol accelerated apoptosis of primary cultured astrocytes of developing rodent brains via rno-miR-665 regulation. However, the role of rno-miR-665 during the growth spurt of neonatal rodent brains in vivo is still uncertain. Post-natal day 7 (P7) rats received a single injection of propofol 30 mg/kg intraperitoneally (i.p.), and neuroapoptosis of hippocampal astrocytes was analyzed by immunofluorescence and scanning electron microscopy. The differential expression of rno-miR-665, BCL2L1 (Bcl-xl), and cleaved caspase 3 (CC3) was surveyed by qRT-PCR and western blotting. In addition, the utility of A-1155463, a highly potent and BCL2L1-selective antagonist, was aimed to assess the contribution of BCL2L1 for neuroglial survival. Following the intraventricular injection of lentivirus rno-miR-665, neuroprotection was detected by 5-point scale measurement. The single dose of propofol 30 mg/kg triggered dose-dependent apoptosis of developing hippocampal astrocytes. Meanwhile, propofol triggered both rno-miR-665 and CC3, and depressed BCL2L1, which was predicted as one target gene of rno-miR-665. Combination treatment with A-1155463 and propofol induced lower mRNA and protein levels of BCL2L1 and more CC3 activation than propofol treatment alone in vivo. The lentivirus-mediated knockdown of rno-miR-665 elevated BCL2L1 and attenuated CC3 levels, whereas up-regulation of rno-miR-665 suppressed BCL2L1 and induced CC3 expression in vivo. More importantly, rno-miR-665 antagomir infusion improved neurological outcomes of pups receiving propofol during the brain growth spurt. Rno-miR-665, providing a potential target for alternative therapeutics for pediatric anesthesia, is susceptible to propofol by negatively targeting antiapoptotic BCL2L1. Relatively little is known about the association between exposure of astrocytes to brief propofol

  9. Immunotherapeutic Potential of Oncolytic H-1 Parvovirus: Hints of Glioblastoma Microenvironment Conversion towards Immunogenicity.

    Science.gov (United States)

    Angelova, Assia L; Barf, Milena; Geletneky, Karsten; Unterberg, Andreas; Rommelaere, Jean

    2017-12-15

    Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV), show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01), H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients. The virus was able to cross the blood-brain (tumor) barrier after intravenous infusion. Importantly, H-1PV treatment of glioblastoma patients was associated with immunogenic changes in the tumor microenvironment. Tumor infiltration with activated cytotoxic T cells, induction of cathepsin B and inducible nitric oxide (NO) synthase (iNOS) expression in tumor-associated microglia/macrophages (TAM), and accumulation of activated TAM in cluster of differentiation (CD) 40 ligand (CD40L)-positive glioblastoma regions was detected. These are the first-in-human observations of H-1PV capacity to switch the immunosuppressed tumor microenvironment towards immunogenicity. Based on this pilot study, we present a tentative model of H-1PV-mediated modulation of glioblastoma microenvironment and propose a combinatorial therapeutic approach taking advantage of H-1PV-induced microglia/macrophage activation for further (pre)clinical testing.

  10. Dynamic behavior of histone H1 microinjected into HeLa cells

    International Nuclear Information System (INIS)

    Wu, L.H.; Kuehl, L.; Rechsteiner, M.

    1986-01-01

    Histone H1 was purified from bovine thymus and radiolabeled with tritium by reductive methylation or with 125 I using chloramine-T. Red blood cell-mediated microinjection was then used to introduce the labeled H1 molecules into HeLa cells synchronized in S phase. The injected H1 molecules rapidly entered HeLa nuclei, and a number of tests indicate that their association with chromatin was equivalent to that of endogenous histone H1. The injected molecules copurified with HeLa cell nucleosomes, exhibited a half-life of ∼100h, and were hyperphosphorylated at mitosis. When injected HeLa cells were fused with mouse 3T3 fibroblasts < 10% of the labeled H1 molecules migrated to mouse nuclei during the next 48 h. Despite their slow rate of migration between nuclei, the injected H1 molecules were evenly distributed on mouse and human genomes soon after mitosis of HeLa-3T3 heterokaryons. These results suggest that although most histone H1 molecules are stably associated with interphase chromatin, they undergo extensive redistribution after mitosis

  11. Characterization of monomeric DNA-binding protein Histone H1 in Leishmania braziliensis.

    Science.gov (United States)

    Carmelo, Emma; González, Gloria; Cruz, Teresa; Osuna, Antonio; Hernández, Mariano; Valladares, Basilio

    2011-08-01

    Histone H1 in Leishmania presents relevant differences compared to higher eukaryote counterparts, such as the lack of a DNA-binding central globular domain. Despite that, it is apparently fully functional since its differential expression levels have been related to changes in chromatin condensation and infectivity, among other features. The localization and the aggregation state of L. braziliensis H1 has been determined by immunolocalization, mass spectrometry, cross-linking and electrophoretic mobility shift assays. Analysis of H1 sequences from the Leishmania Genome Database revealed that our protein is included in a very divergent group of histones H1 that is present only in L. braziliensis. An antibody raised against recombinant L. braziliensis H1 recognized specifically that protein by immunoblot in L. braziliensis extracts, but not in other Leishmania species, a consequence of the sequence divergences observed among Leishmania species. Mass spectrometry analysis and in vitro DNA-binding experiments have also proven that L. braziliensis H1 is monomeric in solution, but oligomerizes upon binding to DNA. Finally, despite the lack of a globular domain, L. braziliensis H1 is able to form complexes with DNA in vitro, with higher affinity for supercoiled compared to linear DNA.

  12. Dialogic spaces of knowledge construction in research article Conclusion sections written by English L1, English L2 and Spanish L1 writers

    Directory of Open Access Journals (Sweden)

    Elena Sheldon

    2018-04-01

    Full Text Available While vast research efforts have been directed to the identification of moves and their constituent steps in research articles (RA, less attention has been paid to the social negotiation of knowledge, in particular in the Conclusion section of RAs. In this paper, I examine the Conclusion sections of RAs in English and Spanish, including RA Conclusions written in English by Spanish-background speakers in the field of applied linguistics. This study brings together two complementary frameworks, genre-based knowledge and evaluative stance, drawing on Swales’s (1990, 2004 move analysis framework and on the engagement system in Martin and White’s (2005 Appraisal framework. The results indicate that the English L1 group negotiates a consistent space for readers to approve or disapprove the writers’ propositions. However, the Spanish L1 group aligns with readers, using a limited space through contracting resources, which may be because this group addresses a smaller audience in comparison to the English L1 group which addresses an international readership. On the other hand, the English L2 group tends to move towards English rhetorical international practice, but without fully abandoning their SpL1. These results contribute to gaining a better understanding of how successful scholarly writing in English is achieved, and offers important insights for teaching multilingual researchers.

  13. Evolutionary trends of A(H1N1 influenza virus hemagglutinin since 1918.

    Directory of Open Access Journals (Sweden)

    Jun Shen

    2009-11-01

    Full Text Available The Pandemic (H1N1 2009 is spreading to numerous countries and causing many human deaths. Although the symptoms in humans are mild at present, fears are that further mutations in the virus could lead to a potentially more dangerous outbreak in subsequent months. As the primary immunity-eliciting antigen, hemagglutinin (HA is the major agent for host-driven antigenic drift in A(H3N2 virus. However, whether and how the evolution of HA is influenced by existing immunity is poorly understood for A(H1N1. Here, by analyzing hundreds of A(H1N1 HA sequences since 1918, we show the first evidence that host selections are indeed present in A(H1N1 HAs. Among a subgroup of human A(H1N1 HAs between 1918 approximately 2008, we found strong diversifying (positive selection at HA(1 156 and 190. We also analyzed the evolutionary trends at HA(1 190 and 225 that are critical determinants for receptor-binding specificity of A(H1N1 HA. Different A(H1N1 viruses appeared to favor one of these two sites in host-driven antigenic drift: epidemic A(H1N1 HAs favor HA(1 190 while the 1918 pandemic and swine HAs favor HA(1 225. Thus, our results highlight the urgency to understand the interplay between antigenic drift and receptor binding in HA evolution, and provide molecular signatures for monitoring future antigenically drifted 2009 pandemic and seasonal A(H1N1 influenza viruses.

  14. The Neurological Manifestations of H1N1 Influenza Infection; Diagnostic Challenges and Recommendations

    Directory of Open Access Journals (Sweden)

    Ali Akbar Asadi-Pooya

    2011-03-01

    Full Text Available Background: World Health Organization declared pandemic phase of human infection with novel influenza A (H1N1 in April 2009. There are very few reports about the neurological complications of H1N1 virus infection in the literature. Occasionally, these complications are severe and even fatal in some individuals. The aims of this study were to report neurological complaints and/or complications associated with H1N1 virus infection. Methods: The medical files of all patients with H1N1 influenza infection admitted to a specified hospital in the city of Shiraz, Iran from October through November 2009 were reviewed. More information about the patients were obtained by phone calls to the patients or their care givers. All patients had confirmed H1N1 virus infection with real-time PCR assay. Results: Fifty-five patients with H1N1 infection were studied. Twenty-three patients had neurological signs and/or symptoms. Mild neurological complaints may be reported in up to 42% of patients infected by H1N1 virus. Severe neurological complications occurred in 9% of the patients. The most common neurological manifestations were headache, numbness and paresthesia, drowsiness and coma. One patient had a Guillain-Barre syndrome-like illness, and died in a few days. Another patient had focal status epilepticus and encephalopathy. Conclusions: The H1N1 infection seems to have been quite mild with a self-limited course in much of the world, yet there appears to be a subset, which is severely affected. We recommend performing diagnostic tests for H1N1influenza virus in all patients with respiratory illness and neurological signs/symptoms. We also recommend initiating treatment with appropriate antiviral drugs as soon as possible in those with any significant neurological presentation accompanied with respiratory illness and flu-like symptoms

  15. Potent, nonsteroidal selective androgen receptor modulators (SARMs) based on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones.

    Science.gov (United States)

    Higuchi, Robert I; Thompson, Anthony W; Chen, Jyun-Hung; Caferro, Thomas R; Cummings, Marquis L; Deckhut, Charlotte P; Adams, Mark E; Tegley, Christopher M; Edwards, James P; López, Francisco J; Kallel, E Adam; Karanewsky, Donald S; Schrader, William T; Marschke, Keith B; Zhi, Lin

    2007-10-01

    A series of androgen receptor modulators based on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones was synthesized and evaluated in an androgen receptor transcriptional activation assay. The most potent analogues from the series exhibited single-digit nanomolar potency in vitro. Compound 18h demonstrated full efficacy in the maintenance of muscle weight, at 10 mg/kg, with reduced activity in prostate weight in an in vivo model of androgen action.

  16. Regulation of Synaptic Structure by the Ubiquitin C-terminal Hydrolase UCH-L1

    Science.gov (United States)

    Cartier, Anna E.; Djakovic, Stevan N.; Salehi, Afshin; Wilson, Scott M.; Masliah, Eliezer; Patrick, Gentry N.

    2009-01-01

    UCH-L1 is a de-ubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We have found that UCH-L1 activity is rapidly up-regulated by NMDA receptor activation which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of pre and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1 inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner. PMID:19535597

  17. Novel functions for the endocytic regulatory proteins MICAL-L1 and EHD1 in mitosis.

    Science.gov (United States)

    Reinecke, James B; Katafiasz, Dawn; Naslavsky, Naava; Caplan, Steve

    2015-01-01

    During interphase, recycling endosomes mediate the transport of internalized cargo back to the plasma membrane. However, in mitotic cells, recycling endosomes are essential for the completion of cytokinesis, the last phase of mitosis that promotes the physical separation the two daughter cells. Despite recent advances, our understanding of the molecular determinants that regulate recycling endosome dynamics during cytokinesis remains incomplete. We have previously demonstrated that Molecule Interacting with CasL Like-1 (MICAL-L1) and C-terminal Eps15 Homology Domain protein 1 (EHD1) coordinately regulate receptor transport from tubular recycling endosomes during interphase. However, their potential roles in controlling cytokinesis had not been addressed. In this study, we show that MICAL-L1 and EHD1 regulate mitosis. Depletion of either protein resulted in increased numbers of bi-nucleated cells. We provide evidence that bi-nucleation in MICAL-L1- and EHD1-depleted cells is a consequence of impaired recycling endosome transport during late cytokinesis. However, depletion of MICAL-L1, but not EHD1, resulted in aberrant chromosome alignment and lagging chromosomes, suggesting an EHD1-independent function for MICAL-L1 earlier in mitosis. Moreover, we provide evidence that MICAL-L1 and EHD1 differentially influence microtubule dynamics during early and late mitosis. Collectively, our new data suggest several unanticipated roles for MICAL-L1 and EHD1 during the cell cycle. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. L1-norm kernel discriminant analysis via Bayes error bound optimization for robust feature extraction.

    Science.gov (United States)

    Zheng, Wenming; Lin, Zhouchen; Wang, Haixian

    2014-04-01

    A novel discriminant analysis criterion is derived in this paper under the theoretical framework of Bayes optimality. In contrast to the conventional Fisher's discriminant criterion, the major novelty of the proposed one is the use of L1 norm rather than L2 norm, which makes it less sensitive to the outliers. With the L1-norm discriminant criterion, we propose a new linear discriminant analysis (L1-LDA) method for linear feature extraction problem. To solve the L1-LDA optimization problem, we propose an efficient iterative algorithm, in which a novel surrogate convex function is introduced such that the optimization problem in each iteration is to simply solve a convex programming problem and a close-form solution is guaranteed to this problem. Moreover, we also generalize the L1-LDA method to deal with the nonlinear robust feature extraction problems via the use of kernel trick, and hereafter proposed the L1-norm kernel discriminant analysis (L1-KDA) method. Extensive experiments on simulated and real data sets are conducted to evaluate the effectiveness of the proposed method in comparing with the state-of-the-art methods.

  19. Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1.

    Science.gov (United States)

    Su, Qiang; Hu, Feizhuo; Liu, Yuxia; Ge, Xiaofei; Mei, Changlin; Yu, Shengqiang; Shen, Aiwen; Zhou, Qiang; Yan, Chuangye; Lei, Jianlin; Zhang, Yanqing; Liu, Xiaodong; Wang, Tingliang

    2018-03-22

    PKD2L1, also termed TRPP3 from the TRPP subfamily (polycystic TRP channels), is involved in the sour sensation and other pH-dependent processes. PKD2L1 is believed to be a nonselective cation channel that can be regulated by voltage, protons, and calcium. Despite its considerable importance, the molecular mechanisms underlying PKD2L1 regulations are largely unknown. Here, we determine the PKD2L1 atomic structure at 3.38 Å resolution by cryo-electron microscopy, whereby side chains of nearly all residues are assigned. Unlike its ortholog PKD2, the pore helix (PH) and transmembrane segment 6 (S6) of PKD2L1, which are involved in upper and lower-gate opening, adopt an open conformation. Structural comparisons of PKD2L1 with a PKD2-based homologous model indicate that the pore domain dilation is coupled to conformational changes of voltage-sensing domains (VSDs) via a series of π-π interactions, suggesting a potential PKD2L1 gating mechanism.

  20. PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice.

    Directory of Open Access Journals (Sweden)

    Dongxia Ma

    Full Text Available Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM. However, immune rejection, especially that induced by the alloreactive T-cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1 is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time.Glucose Stimulation Assays were performed to evaluate whether PD-L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT mice (C57BL/6j were implanted beneath the renal capsule of streptozotocin (STZ-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients.PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity.This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses.

  1. Differentiation of eosinophilic leukemia EoL-1 cells into eosinophils induced by histone deacetylase inhibitors.

    Science.gov (United States)

    Ishihara, Kenji; Takahashi, Aki; Kaneko, Motoko; Sugeno, Hiroki; Hirasawa, Noriyasu; Hong, JangJa; Zee, OkPyo; Ohuchi, Kazuo

    2007-03-06

    EoL-1 cells differentiate into eosinophils in the presence of n-butyrate, but the mechanism has remained to be elucidated. Because n-butyrate can inhibit histone deacetylases, we hypothesized that the inhibition of histone deacetylases induces the differentiation of EoL-1 cells into eosinophils. In this study, using n-butyrate and two other histone deacetylase inhibitors, apicidin and trichostatin A, we have analyzed the relationship between the inhibition of histone deacetylases and the differentiation into eosinophils in EoL-1 cells. It was demonstrated that apicidin and n-butyrate induced a continuous acetylation of histones H4 and H3, inhibited the proliferation of EoL-1 cells without attenuating the level of FIP1L1-PDGFRA mRNA, and induced the expression of markers for mature eosinophils such as integrin beta7, CCR1, and CCR3 on EoL-1 cells, while trichostatin A evoked a transient acetylation of histones and induced no differentiation into eosinophils. These findings suggest that the continuous inhibition of histone deacetylases in EoL-1 cells induces the differentiation into mature eosinophils.

  2. L1 arrest, daf-16/FoxO and nonautonomous control of post-embryonic development.

    Science.gov (United States)

    Kaplan, Rebecca E W; Baugh, L Ryan

    2016-01-01

    Post-embryonic development is governed by nutrient availability. L1 arrest, dauer formation and aging illustrate how starvation, anticipation of starvation and caloric restriction have profound influence on C. elegans development, respectively. Insulin-like signaling through the Forkhead box O transcription factor daf-16/FoxO regulates each of these processes. We recently reported that ins-4, ins-6 and daf-28 promote L1 development from the intestine and chemosensory neurons, similar to their role in dauer development. daf-16 functions cell-nonautonomously in regulation of L1 arrest, dauer development and aging. Discrepancies in daf-16 sites of action have been reported in each context, but the consensus implicates epidermis, intestine and nervous system. We suggest technical limitations of the experimental approach responsible for discrepant results. Steroid hormone signaling through daf-12/NHR is known to function downstream of daf-16 in control of dauer development, but signaling pathways mediating cell-nonautonomous effects of daf-16 in aging and L1 arrest had not been identified. We recently showed that daf-16 promotes L1 arrest by inhibiting daf-12/NHR and dbl-1/TGF-β Sma/Mab signaling, two pathways that promote L1 development in fed larvae. We will review these results on L1 arrest and speculate on why there are so many signals and signaling centers regulating post-embryonic development.

  3. Hospitalizations Associated with Pandemic Influenza A (H1N1) 2009 in Asthmatic Children in Japan

    OpenAIRE

    Toshio Katsunuma; Takehiko Matsui; Tsutomu Iwata; Mitsuhiko Nambu; Naomi Kondo

    2012-01-01

    Background: The pandemic influenza A (H1N1) 2009 [pdm (H1N1) 2009] spread through the world in 2009, producing a serious epidemic in Japan. Since it was suggested early that asthma is a risk factor for an increased severity of the infection, the Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI) organized a working group for countermeasures, and investigated asthmatic children admitted to the hospitals for pdm (H1N1) 2009 infection. Methods: An appeal was made on the ho...

  4. A Historical Perspective of Influenza A(H1N2) Virus

    OpenAIRE

    Komadina, Naomi; McVernon, Jodie; Hall, Robert; Leder, Karin

    2014-01-01

    The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase ...

  5. Three-decade epidemiological analysis of Escherichia coli O15:K52:H1

    DEFF Research Database (Denmark)

    Olesen, Bente; Scheutz, Flemming; Menard, Megan

    2009-01-01

    The successful Escherichia coli O15:K52:H1 clonal group provides a case study for the emergence of multiresistant clonal groups of Enterobacteriaceae generally. Accordingly, we tested the hypotheses that, over time, the O15:K52:H1 clonal group has become increasingly (i) virulent and (ii) resistant...... to antibiotics. One hundred archived international E. coli O15:K52:[H1] clinical isolates from 100 unique patients (1975 to 2006) were characterized for diverse phenotypic and molecular traits. All 100 isolates derived from phylogenetic group D and, presumptively, sequence type ST393. They uniformly carried...

  6. West syndrome associated with administration of a histamine H1 antagonist, oxatomide.

    Science.gov (United States)

    Yamashita, Yushiro; Isagai, Takeo; Seki, Yoshitaka; Ohya, Takashi; Nagamitsu, Shinichiro; Matsuishi, Toyojiro

    2004-01-01

    We report a 4-month-old female infant who developed West syndrome eleven days after administration of a histamine H1 antagonist, oxatomide, for atopic dermatitis. It has been reported that some histamine H1 antagonists induce seizures in epileptic patients. The age, the interval between oxatomide administration, and the onset of West syndrome and its clinical course were similar to two previously reported 3-month-old infants with West syndrome associated with ketotifen administration. We should be cautious in using the histamine H1 antagonists, oxatomide and ketotifen, in young infants because such agents could potentially disturb the anticonvulsive central histaminergic system.

  7. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Peng-Yeh [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Tsai, Chong-Bin [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC (China); Tseng, Min-Jen, E-mail: biomjt@ccu.edu.tw [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China)

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  8. Characterization of new cell line stably expressing CHI3L1 oncogene

    Directory of Open Access Journals (Sweden)

    Chekhonin V. P.

    2011-06-01

    Full Text Available Aim. To characterize the immortalized 293 cell line after stable transfection with human oncogene (CHI3L1. Methods. 293 cells, stably transfected with pcDNA3.1_CHI3L1, and 293 cells, stably transfected with pcDNA3.1 as a negative control, were used throughout all experiments. The clones of CHI3L1-expressing 293 cells and 293 cells, transfected with pcDNA3.1, were analyzed by immunofluorescence and confocal microscopy. Cell proliferation was measured using MTT assay; analyses of ERK1/2 and AKT activation and their cellular localization were performed with anti-phospho-ERK and anti-phospho-AKT antibodies. Specific activation of MAP and PI3 kinases was measured by densitometric analysis of Western-blot signals. Results. The obtained results show quite modest ability of CHI3L1 to stimulate cell growth and reflect rather an improved cellular plating efficiency of the 293 cells stably transfected with pcDNA3.1_CHI3L1 as compared to the 293 cells transfected with an «empty» vector. ERK1/2 and AKT are activated in the 293_CHI3L1 cells. In these cells phosphorylated ERK1/2 were localized in both cell cytoplasm and nuclei while AKT only in cytoplasm. The 293_CHI3L1 cells differed from the 293 cells, transfected with an «empty» vector, in their size and ability to adhere to the culture plates. Conclusions. The overexpression of CHI3L1 is likely to have an important role in tumorigenesis via a mechanism which involves activation of PI3K and ERK1/2 pathways. The tumors which can be induced by orthotopic implantation of the transformed human cells with overexpressed human oncogene CHI3L1 into the rat brain can be used as a target for anticancer drug development.

  9. Localization and role of NPC1L1 in cholesterol absorption in human intestine.

    Science.gov (United States)

    Sané, Alain Théophile; Sinnett, Daniel; Delvin, Edgard; Bendayan, Moise; Marcil, Valérie; Ménard, Daniel; Beaulieu, Jean-François; Levy, Emile

    2006-10-01

    Recent studies have documented the presence of Niemann-Pick C1-Like 1 (NPC1L1) in the small intestine and its capacity to transport cholesterol in mice and rats. The current investigation was undertaken to explore the localization and function of NPC1L1 in human enterocytes. Cell fractionation experiments revealed an NPC1L1 association with apical membrane of the enterocyte in human jejunum. Signal was also detected in lysosomes, endosomes, and mitochondria. Confirmation of cellular NPC1L1 distribution was obtained by immunocytochemistry. Knockdown of NPC1L1 caused a decline in the ability of Caco-2 cells to capture micellar [(14)C]free cholesterol. Furthermore, this NPC1L1 suppression resulted in increased and decreased mRNA levels and activity of HMG-CoA reductase, the rate-limiting step in cholesterol synthesis, and of ACAT, the key enzyme in cholesterol esterification, respectively. An increase was also noted in the transcriptional factor sterol-regulatory element binding protein that modulates cholesterol homeostasis. Efforts were devoted to define the impact of NPC1L1 knockdown on other mediators of cholesterol uptake. RT-PCR evidence is presented to show the significant decrease in the levels of scavenger receptor class B type I (SR-BI) with no changes in ABCA1, ABCG5, and cluster determinant 36 in NPC1L1-deficient Caco-2 cells. Together, our data suggest that NPC1L1 contributes to intestinal cholesterol homeostasis and possibly cooperates with SR-BI to mediate cholesterol absorption in humans.

  10. Prognostic Value of PD-L1 in Breast Cancer: A Meta-Analysis.

    Science.gov (United States)

    Wang, Changjun; Zhu, Hanjiang; Zhou, Yidong; Mao, Feng; Lin, Yan; Pan, Bo; Zhang, Xiaohui; Xu, Qianqian; Huang, Xin; Sun, Qiang

    2017-07-01

    Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies. Publication bias was evaluated by funnel plot and Begg's test. Overall, nine relevant studies with 8583 patients were included. PD-L1 overexpression was found in 25.8% of breast cancer patients. PD-L1 (+) associated with several high-risk prognostic indicators, such as ductal cancer (p = 0.037), high tumor grade (p = 0.000), ER negativity (p = 0.000), PR negativity (p = 0.000), HER2 positivity (p = 0.001) and aggressive molecular subtypes (HER2-rich and Basal-like p = 0.000). PD-L1 overexpression had no significant impact on metastasis-free survival (HR 0.924, 95% CI = 0.747-1.141, p = 0.462), disease-free survival (HR 1.122, 95% CI = 0.878-1.434, p = 0.357) and overall specific survival (HR 0.837, 95% CI = 0.640-1.093, p = 0.191), but significantly correlated with shortened overall survival (HR 1.573, 95% CI = 1.010-2.451, p = 0.045). PD-L1 overexpression in breast cancer associates with multiple clinicopathological parameters that indicated poor outcome, and may increase the risk for mortality. Further standardization of PD-L1 assessment assay and well-controlled clinical trials are warranted to clarify its prognostic and therapeutic value. © 2017 Wiley Periodicals, Inc.

  11. Modelling and L1 Adaptive Control of pH in Bioethanol Enzymatic Process

    DEFF Research Database (Denmark)

    Prunescu, Remus Mihail; Blanke, Mogens; Sin, Gürkan

    2013-01-01

    for pH level regulation: one is a classical PI controller; the other an L1 adaptive output feedback controller. Model-based feed-forward terms are added to the controllers to enhance their performances. A new tuning method of the L1 adaptive controller is also proposed. Further, a new performance...... function is formulated and tailored to this type of processes and is used to monitor the performances of the process in closed loop. The L1 design is found to outperform the PI controller in all tests....

  12. Effect of L1-ORF2 on senescence of GES-1 cells and its molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Ying-nan LI

    2016-06-01

    Full Text Available Objective  To investigate the effect of long interspersed nuclear elements 1 open reading frame 2(L1-ORF2 gene on the senescence of GES-1 cells and its mechanism of molecular regulation. Methods  Cell culture of high glucose was used to construct stable model of senescent GES-1 cells. L1-ORF2 siRNA vector was constructed and then transfected into normal GES1 and senescent ones with liposome transfection reagents for transient expression. Forty eight hours after transfection, cell growth curves were drawn to show the speed of cell proliferation, flow cytometry was used to analyze the cell cycle, β-galactosidase staining to detect cell aging and Western blotting to detect the expressions of L1-ORF2, P53 and P21proteins. Results  Senescent GES-1 cell model and L1-ORF2 siRNA vector were constructed. Compared with negative control group, the L1-ORF2 expression decreased in normal and senescent GES-1 cells transfected with L1-ORF2 siRNA vector. There was a faster proliferation of senescent GES1 cells (P<0.05 and lower ratio of β-galactosidase (56% vs 69%, P<0.05 and G0/G1 phase (34.2% vs 39.3%, P<0.05 in senescent GES-1 cells transfected with L1-ORE2 siRNA vector than those transfected with negative control vector, while there was no obvious difference between normal GES-1 cells transfected with L1-ORF2 siRNA vector and negative control vector (P>0.05. P53 protein was expressed only in senescent GES-1 cell, while P21 protein was expressed in both normal and senescent GES-1 cells, and the latter had a higher expression level (P<0.05. The GES-1 cells transfected with L1-ORF2 siRNA vector showed lower expressions of P53 and P21 proteins than those transfected with negative control vector (P<0.05. Conclusions  L1-ORF2-siRNA vector could down-regulate the expression of L1-ORF2 protein in normal and senescent GES-1 cells and promote the proliferation of senescent GES-1 cells. P21 and P53 proteins participate in the process of L1-ORF2 regulating

  13. Degradation of fifteen emerging contaminants at microg L(-1) initial concentrations by mild solar photo-Fenton in MWTP effluents.

    Science.gov (United States)

    Klamerth, N; Rizzo, L; Malato, S; Maldonado, Manuel I; Agüera, A; Fernández-Alba, A R

    2010-01-01

    The degradation of 15 emerging contaminants (ECs) at low concentrations in simulated and real effluent of municipal wastewater treatment plant with photo-Fenton at unchanged pH and Fe=5 mg L(-1) in a pilot-scale solar CPC reactor was studied. The degradation of those 15 compounds (Acetaminophen, Antipyrine, Atrazine, Caffeine, Carbamazepine, Diclofenac, Flumequine, Hydroxybiphenyl, Ibuprofen, Isoproturon, Ketorolac, Ofloxacin, Progesterone, Sulfamethoxazole and Triclosan), each with an initial concentration of 100 microg L(-1), was found to depend on the presence of CO(3)(2-) and HCO(3)(-) (hydroxyl radicals scavengers) and on the type of water (simulated water, simulated effluent wastewater and real effluent wastewater), but is relatively independent of pH, the type of acid used for release of hydroxyl radicals scavengers and the initial H(2)O(2) concentration used. Toxicity tests with Vibrio fisheri showed that degradation of the compounds in real effluent wastewater led to toxicity increase. (c) 2009 Elsevier Ltd. All rights reserved.

  14. Inhibitory effects and related molecular mechanisms of total flavonoids in Mosla chinensis Maxim against H1N1 influenza virus.

    Science.gov (United States)

    Zhang, Xiao-Xia; Wu, Qiao-Feng; Yan, Yun-Liang; Zhang, Feng-Ling

    2018-02-01

    The Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly contain luteolin and apigenin. The study aims to examine the inhibitory effects of STF on anti-H1N1 influenza virus and its related molecular mechanisms in pneumonia mice. The viral pneumonia mice were treated with Ribavirin or various doses of STF. We observed histological changes of lung by immunohistochemistry and measured lung index to value anti-influenza virus effects of STF. The concentrations of inflammatory cytokines and anti-oxidant factors were detected by ELISA. RT-PCR and western blot assays were used to determine the expression level of TLR pathway's key genes and proteins in lung tissues. We found that the pathological changes of lung in the viral pneumonia mice obviously alleviated by STF treatments and the STF (288 or 576 mg/kg) could significantly decrease lung indices. Moreover, the up-regulation (IL-6, TNF-α, IFN-γ, and NO) and down-regulation (IL-2, SOD and GSH) of inflammatory cytokines and anti-oxidant factors were associated with higher clearance of virus and reduction of inflammatory lung tissue damage. Meanwhile, the expression levels of TLR3, TLR7, MyD88, TRAF3 and NF-κB p65 of the TLR pathway were reduced by STF treatment. This study suggested that STF may be a promising candidate for treating H1N1 influenza and subsequent viral pneumonia.

  15. Mg2BIV: Narrow Bandgap Thermoelectric Semiconductors

    Science.gov (United States)

    Kim, Il-Ho

    2018-05-01

    Thermoelectric materials can convert thermal energy directly into electric energy and vice versa. The electricity generation from waste heat via thermoelectric devices can be considered as a new energy source. For instance, automotive exhaust gas and all industrial processes generate an enormous amount of waste heat that can be converted to electricity by using thermoelectric devices. Magnesium compound Mg2BIV (BIV = Si, Ge or Sn) has a favorable combination of physical and chemical properties and can be a good base for the development of new efficient thermoelectrics. Because they possess similar properties to those of group BIV elemental semiconductors, they have been recognized as good candidates for thermoelectric applications. Mg2Si, Mg2Ge and Mg2Sn with an antifluorite structure are narrow bandgap semiconductors with indirect band gaps of 0.77 eV, 0.74 eV, and 0.35 eV, respectively. Mg2BIV has been recognized as a promising material for thermoelectric energy conversion at temperatures ranging from 500 K to 800 K. Compared to other thermoelectric materials operating in the similar temperature range, such as PbTe and filled skutterudites, the important aspects of Mg2BIV are non-toxic and earth-abundant elements. Based on classical thermoelectric theory, the material factor β ( m* / m e)3/2μκ L -1 can be utilized as the criterion for thermoelectric material selection, where m* is the density-of-states effective mass, me is the mass of an electron, μ is the carrier mobility, and κL is the lattice thermal conductivity. The β for magnesium silicides is 14, which is very high compared to 0.8 for iron silicides, 1.4 for manganese silicides, and 2.6 for silicon-germanium alloys. In this paper, basic phenomena of thermoelectricity and transport parameters for thermoelectric materials were briefly introduced, and thermoelectric properties of Mg2BIV synthesized by using a solid-state reaction were reviewed. In addition, various Mg2BIV compounds were discussed

  16. trans-2-Phenyl-4-thiophenoxy-3,4-dihydro-2H-1-benzothiopyran

    Directory of Open Access Journals (Sweden)

    Rammohan Pal

    2011-02-01

    Full Text Available Iodine-catalyzed cyclocondensation of cinnamaldehyde and thiophenol yields rapidly trans-2-phenyl-4-thiophenoxy-3,4-dihydro-2H-1-benzothiopyran in excellent yield with very high diastereoselectivity.

  17. MSX1 cooperates with histone H1b for inhibition of transcription and myogenesis.

    Science.gov (United States)

    Lee, Hansol; Habas, Raymond; Abate-Shen, Cory

    2004-06-11

    During embryogenesis, differentiation of skeletal muscle is regulated by transcription factors that include members of the Msx homeoprotein family. By investigating Msx1 function in repression of myogenic gene expression, we identified a physical interaction between Msx1 and H1b, a specific isoform of mouse histone H1. We found that Msx1 and H1b bind to a key regulatory element of MyoD, a central regulator of skeletal muscle differentiation, where they induce repressed chromatin. Moreover, Msx1 and H1b cooperate to inhibit muscle differentiation in cell culture and in Xenopus animal caps. Our findings define a previously unknown function for "linker" histones in gene-specific transcriptional regulation.

  18. H1N1 infection in emergency surgery: A cautionary tale.

    LENUS (Irish Health Repository)

    Galbraith, J G

    2010-01-01

    Pandemic 2009 influenza A H1N1 has spread rapidly since its first report in Mexico in March 2009. This is the first influenza pandemic in over 40 years and it atypically affects previously healthy young adults, with higher rates of morbidity and mortality. The medical literature has been inundated with reports of H1N1 infection, the majority found in critical care and internal medicine journals with a relative paucity in the surgical literature. Despite this, it remains an important entity that can impact greatly on acute surgical emergencies. We present a case of previously healthy 31-year-old male who underwent open appendectomy. His post-operative recovery was complicated by acute respiratory distress syndrome secondary to H1N1 infection. This case report highlights the impact that H1N1 virus can have on acute surgical emergencies and how it can complicate the post-operative course.

  19. Pediatric Healthcare Response to Pandemic (H1N1) 2009 Influenza Stakeholder Meeting - Summary of Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    HCTT CHE

    2010-01-01

    The goal of the meeting was to bring together subject matter experts to develop tools and resources for use by the pediatric healthcare community in response to 2009 (H1N1) pandemic influenza activity during the 2009 influenza season.

  20. 20 CFR 655.736 - What are H-1B-dependent employers and willful violators?

    Science.gov (United States)

    2010-04-01

    ... Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in... not include bona fide consultants and independent contractors. For purposes of this section, the...

  1. Ethnic differences in susceptibilities to A(H1N1) flu: An epidemic ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-12-29

    Dec 29, 2009 ... ... Center, the Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, .... countries including Mexico, the country of the A (H1N1) outbreak origin. The ... precious resources used more effectively for specific.

  2. 26 CFR 1.642(h)-1 - Unused loss carryovers on termination of an estate or trust.

    Science.gov (United States)

    2010-04-01

    ... estate or trust. 1.642(h)-1 Section 1.642(h)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF....642(h)-1 Unused loss carryovers on termination of an estate or trust. (a) If, on the final termination...(h)(1) to the beneficiaries succeeding to the property of the estate or trust. See § 1.641(b)-3 for...

  3. The seroprevalence of pandemic influenza H1N1 (2009 virus in China.

    Directory of Open Access Journals (Sweden)

    Cuiling Xu

    2011-04-01

    Full Text Available Mainland China experienced pandemic influenza H1N1 (2009 virus (pH1N1 with peak activity during November-December 2009. To understand the geographic extent, risk factors, and attack rate of pH1N1 infection in China we conducted a nationwide serological survey to determine the prevalence of antibodies to pH1N1.Stored serum samples (n = 2,379 collected during 2006-2008 were used to estimate baseline serum reactogenicity to pH1N1. In January 2010, we used a multistage-stratified random sampling method to select 50,111 subjects who met eligibility criteria and collected serum samples and administered a standardized questionnaire. Antibody response to pH1N1 was measured using haemagglutination inhibition (HI assay and the weighted seroprevalence was calculated using the Taylor series linearization method. Multivariable logistic regression analyses were used to examine risk factors for pH1N1 seropositivity. Baseline seroprevalence of pH1N1 antibody (HI titer ≥40 was 1.2%. The weighted seroprevalence of pH1N1 among the Chinese population was 21.5%(vaccinated: 62.0%; unvaccinated: 17.1%. Among unvaccinated participants, those aged 6-15 years (32.9% and 16-24 years (30.3% had higher seroprevalence compared with participants aged 25-59 years (10.7% and ≥60 years (9.9%, P<0.0001. Children in kindergarten and students had higher odds of seropositivity than children in family care (OR: 1.36 and 2.05, respectively. We estimated that 207.7 million individuals (15.9% experienced pH1N1 infection in China.The Chinese population had low pre-existing immunity to pH1N1 and experienced a relatively high attack rate in 2009 of this virus. We recommend routine control measures such as vaccination to reduce transmission and spread of seasonal and pandemic influenza viruses.

  4. Eviction of linker histone H1 by NAP-family histone chaperones enhances activated transcription.

    Science.gov (United States)

    Zhang, Qian; Giebler, Holli A; Isaacson, Marisa K; Nyborg, Jennifer K

    2015-01-01

    In the Metazoan nucleus, core histones assemble the genomic DNA to form nucleosome arrays, which are further compacted into dense chromatin structures by the linker histone H1. The extraordinary density of chromatin creates an obstacle for accessing the genetic information. Regulation of chromatin dynamics is therefore critical to cellular homeostasis, and histone chaperones serve as prominent players in these processes. In the current study, we examined the role of specific histone chaperones in negotiating the inherently repressive chromatin structure during transcriptional activation. Using a model promoter, we demonstrate that the human nucleosome assembly protein family members hNap1 and SET/Taf1β stimulate transcription in vitro during pre-initiation complex formation, prior to elongation. This stimulatory effect is dependent upon the presence of activators, p300, and Acetyl-CoA. We show that transcription from our chromatin template is strongly repressed by H1, and that both histone chaperones enhance RNA synthesis by overcoming H1-induced repression. Importantly, both hNap1 and SET/Taf1β directly bind H1, and function to enhance transcription by evicting the linker histone from chromatin reconstituted with H1. In vivo studies demonstrate that SET/Taf1β, but not hNap1, strongly stimulates activated transcription from the chromosomally-integrated model promoter, consistent with the observation that SET/Taf1β is nuclear, whereas hNap1 is primarily cytoplasmic. Together, these observations indicate that SET/Taf1β may serve as a critical regulator of H1 dynamics and gene activation in vivo. These studies uncover a novel function for SET that mechanistically couples transcriptional derepression with H1 dynamics. Furthermore, they underscore the significance of chaperone-dependent H1 displacement as an essential early step in the transition of a promoter from a dense chromatin state into one that is permissive to transcription factor binding and robust

  5. H1 Grid production tool for large scale Monte Carlo simulation

    Energy Technology Data Exchange (ETDEWEB)

    Lobodzinski, B; Wissing, Ch [DESY, Hamburg (Germany); Bystritskaya, E; Vorobiew, M [ITEP, Moscow (Russian Federation); Karbach, T M [University of Dortmund (Germany); Mitsyn, S [JINR, Moscow (Russian Federation); Mudrinic, M, E-mail: bogdan.lobodzinski@desy.d [VINS, Belgrad (Serbia)

    2010-04-01

    The H1 Collaboration at HERA has entered the period of high precision analyses based on the final data sample. These analyses require a massive production of simulated Monte Carlo (MC) events. The H1 MC framework (H1MC) is a software for mass MC production on the LCG Grid infrastructure and on a local batch system created by H1 Collaboration. The aim of the tool is a full automatisation of the MC production workflow including management of the MC jobs on the Grid down to copying of the resulting files from the Grid to the H1 mass storage tape device. The H1 MC framework has modular structure, delegating a specific task to each module, including task specific to the H1 experiment: Automatic building of steer and input files, simulation of the H1 detector, reconstruction of particle tracks and post processing calculation. Each module provides data or functionality needed by other modules via a local database. The Grid jobs created for detector simulation and reconstruction from generated MC input files are fully independent and fault-tolerant for 32 and 64-bit LCG Grid architecture and in Grid running state they can be continuously monitored using Relational Grid Monitoring Architecture (R-GMA) service. To monitor the full production chain and detect potential problems, regular checks of the job state are performed using the local database and the Service Availability Monitoring (SAM) framework. The improved stability of the system has resulted in a dramatic increase in the production rate, which exceeded two billion MC events in 2008.

  6. Mutational analysis of the antagonist-binding site of the histamine H(1) receptor.

    Science.gov (United States)

    Wieland, K; Laak, A M; Smit, M J; Kühne, R; Timmerman, H; Leurs, R

    1999-10-15

    We combined in a previously derived three-dimensional model of the histamine H(1) receptor (Ter Laak, A. M., Timmerman, H., Leurs, H., Nederkoorn, P. H. J., Smit, M. J., and Donne-Op den Kelder, G. M. (1995) J. Comp. Aid. Mol. Design. 9, 319-330) a pharmacophore for the H(1) antagonist binding site (Ter Laak, A. M., Venhorst, J., Timmerman, H., and Donné-Op de Kelder, G. M. (1994) J. Med. Chem. 38, 3351-3360) with the known interacting amino acid residue Asp(116) (in transmembrane domain III) of the H(1) receptor and verified the predicted receptor-ligand interactions by site-directed mutagenesis. This resulted in the identification of the aromatic amino acids Trp(167), Phe(433), and Phe(436) in transmembrane domains IV and VI of the H(1) receptor as probable interaction points for the trans-aromatic ring of the H(1) antagonists. Subsequently, a specific interaction of carboxylate moieties of two therapeutically important, zwitterionic H(1) antagonists with Lys(200) in transmembrane domain V was predicted. A Lys(200) --> Ala mutation results in a 50- (acrivastine) to 8-fold (d-cetirizine) loss of affinity of these zwitterionic antagonists. In contrast, the affinities of structural analogs of acrivastine and cetirizine lacking the carboxylate group, triprolidine and meclozine, respectively, are unaffected by the Lys(200) --> Ala mutation. These data strongly suggest that Lys(200), unique for the H(1) receptor, acts as a specific anchor point for these "second generation" H(1) antagonists.

  7. In vitro H1-receptor antagonist activity of methanolic extract of tuber of Stephania glabra

    Directory of Open Access Journals (Sweden)

    Nisar Ahmad Khan

    2010-06-01

    Full Text Available In the present study, methanolic extract of tuber of Stephania glabra was evaluated for H1-bloker activity by employing in vitro screening models of guinea pig ileum and goat tracheal chain preparation. Goat isolated trachea and guinea pig ileum contracted to histamine in a dose-dependent manner while chlorpheniramine blocked this effect. The methanolic extract produced significant dose-dependent H1-receptor antagonist activity by blocking histamine-induced contraction.

  8. Obstetricians and the 2009-2010 H1N1 vaccination effort: implications for future pandemics.

    Science.gov (United States)

    Clark, Sarah J; Cowan, Anne E; Wortley, Pascale M

    2013-09-01

    Our objective was to describe the experiences of obstetricians during the 2009-2010 H1N1 vaccination campaign in order to identify possible improvements for future pandemic situations. We conducted a cross-sectional mail survey of a national random sample of 4,000 obstetricians, fielded in Summer 2010. Survey items included availability, recommendation, and patient acceptance of H1N1 vaccine; prioritization of H1N1 vaccine when supply was limited; problems with H1N1 vaccination; and likelihood of providing vaccine during a future influenza pandemic. Response rate was 66 %. Obstetricians strongly recommended H1N1 vaccine during the second (85 %) and third (86 %) trimesters, and less often during the first trimester (71 %) or the immediate postpartum period (76 %); patient preferences followed a similar pattern. H1N1 vaccine was typically available in outpatient obstetrics clinics (80 %). Overall vaccine supply was a major problem for 30 % of obstetricians, but few rated lack of thimerosal-free vaccine as a major problem (12 %). Over half of obstetricians had no major problems with the H1N1 vaccine campaign. Based on this experience, 74 % would be "very likely" and 12 % "likely" to provide vaccine in the event of a future influenza pandemic. Most obstetricians strongly recommended H1N1 vaccine, had few logistical problems beyond limited vaccine supply, and are willing to vaccinate in a future pandemic. Addressing concerns about first-trimester vaccination, developing guidance for prioritization of vaccine in the event of severe supply constraints, and continued facilitation of the logistical aspects of vaccination should be emphasized in future influenza pandemics.

  9. Nodal-dependent mesendoderm specification requires the combinatorial activities of FoxH1 and Eomesodermin.

    Directory of Open Access Journals (Sweden)

    Christopher E Slagle

    2011-05-01

    Full Text Available Vertebrate mesendoderm specification requires the Nodal signaling pathway and its transcriptional effector FoxH1. However, loss of FoxH1 in several species does not reliably cause the full range of loss-of-Nodal phenotypes, indicating that Nodal signals through additional transcription factors during early development. We investigated the FoxH1-dependent and -independent roles of Nodal signaling during mesendoderm patterning using a novel recessive zebrafish FoxH1 mutation called midway, which produces a C-terminally truncated FoxH1 protein lacking the Smad-interaction domain but retaining DNA-binding capability. Using a combination of gel shift assays, Nodal overexpression experiments, and genetic epistasis analyses, we demonstrate that midway more accurately represents a complete loss of FoxH1-dependent Nodal signaling than the existing zebrafish FoxH1 mutant schmalspur. Maternal-zygotic midway mutants lack notochords, in agreement with FoxH1 loss in other organisms, but retain near wild-type expression of markers of endoderm and various nonaxial mesoderm fates, including paraxial and intermediate mesoderm and blood precursors. We found that the activity of the T-box transcription factor Eomesodermin accounts for specification of these tissues in midway embryos. Inhibition of Eomesodermin in midway mutants severely reduces the specification of these tissues and effectively phenocopies the defects seen upon complete loss of Nodal signaling. Our results indicate that the specific combinations of transcription factors available for signal transduction play critical and separable roles in determining Nodal pathway output during mesendoderm patterning. Our findings also offer novel insights into the co-evolution of the Nodal signaling pathway, the notochord specification program, and the chordate branch of the deuterostome family of animals.

  10. Are Portable Stereophotogrammetric Devices Reliable in Facial Imaging? A Validation Study of VECTRA H1 Device.

    Science.gov (United States)

    Gibelli, Daniele; Pucciarelli, Valentina; Cappella, Annalisa; Dolci, Claudia; Sforza, Chiarella

    2018-01-31

    Modern 3-dimensional (3D) image acquisition systems represent a crucial technologic development in facial anatomy because of their accuracy and precision. The recently introduced portable devices can improve facial databases by increasing the number of applications. In the present study, the VECTRA H1 portable stereophotogrammetric device was validated to verify its applicability to 3D facial analysis. Fifty volunteers underwent 4 facial scans using portable VECTRA H1 and static VECTRA M3 devices (2 for each instrument). Repeatability of linear, angular, surface area, and volume measurements was verified within the device and between devices using the Bland-Altman test and the calculation of absolute and relative technical errors of measurement (TEM and rTEM, respectively). In addition, the 2 scans obtained by the same device and the 2 scans obtained by different devices were registered and superimposed to calculate the root mean square (RMS; point-to-point) distance between the 2 surfaces. Most linear, angular, and surface area measurements had high repeatability in M3 versus M3, H1 versus H1, and M3 versus H1 comparisons (range, 82.2 to 98.7%; TEM range, 0.3 to 2.0 mm, 0.4° to 1.8°; rTEM range, 0.2 to 3.1%). In contrast, volumes and RMS distances showed evident differences in M3 versus M3 and H1 versus H1 comparisons and reached the maximum when scans from the 2 different devices were compared. The portable VECTRA H1 device proved reliable for assessing linear measurements, angles, and surface areas; conversely, the influence of involuntary facial movements on volumes and RMS distances was more important compared with the static device. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  11. Evolution and adaptation of the pandemic A/H1N1 2009 influenza virus

    Directory of Open Access Journals (Sweden)

    Ducatez MF

    2011-07-01

    Full Text Available Mariette F Ducatez, Thomas P Fabrizio, Richard J WebbyDepartment of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USAAbstract: The emergence of the 2009 H1N1 pandemic influenza virus [A(H1N1pdm09] has provided the public health community with many challenges, but also the scientific community with an opportunity to monitor closely its evolution through the processes of drift and shift. To date, and despite having circulated in humans for nearly two years, little antigenic variation has been observed in the A(H1N1pdm09 viruses. However, as the A(H1N1pdm09 virus continues to circulate and the immunologic pressure within the human population increases, future antigenic change is almost a certainty. Several coinfections of A(H1N1pdm09 and seasonal A(H1N1 or A(H3N2 viruses have been observed, but no reassortant viruses have been described in humans, suggesting a lack of fitness of reassortant viruses or a lack of opportunities for interaction of different viral lineages. In contrast, multiple reassortment events have been detected in swine populations between A(H1N1 pdm09 and other endemic swine viruses. Somewhat surprisingly, many of the well characterized influenza virus virulence markers appear to have limited impact on the phenotype of the A(H1N1pdm09 viruses when they have been introduced into mutant viruses in laboratory settings. As such, it is unclear what the evolutionary path of the pandemic virus will be, but the monitoring of any changes in the circulating viruses will remain a global public and animal health priority.Keywords: influenza, pandemic, evolution, adaptation

  12. Kompliceret influenza A (H1N1) hos gravid i andet trimester

    DEFF Research Database (Denmark)

    Ersboell, Anne Schjoedt; Hesselvig, Anne Brun; Hedegaard, Morten

    2012-01-01

    A 27-year-old woman at 25 weeks of gestation was admitted to hospital due to bilateral pneumonia with increasing hypoxia. She was tested positive for influenza A (H1N1) and successfully treated with oral oseltamivir. Nine days after the admission pathological umbilical flows were recorded...... and an emergency caesarean was performed at 26 weeks + 2 days of gestation. The neonatal period was uncomplicated. Influenza A (H1N1) is especially dangerous in pregnant women and vaccination is important....

  13. Radiologic Findings of Influenza A (H1N1) Pneumonia: Report of Two Cases

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jin Kyoung; Ahn, Myeong Im; Jung, Jung Im; Han, Dae Hee; Park, Seog Hee; Park, Chan Kwon; Kim, Young Kyoon [Seoul St. Mary' s Hospital, Seoul (Korea, Republic of)

    2010-08-15

    Novel influenza A (H1N1) infection is a highly infectious disease, which has been rapidly spreading worldwide since it was first documented in March of 2009 in Mexico. We experienced and report two cases of Influenza A (H1N1) pneumonia, accompanied by chest radiographic and CT findings. The chest radiographs revealed diffuse haziness and extensive airspace consolidation, whereas the CT scans demonstrated multifocal areas of ground glass opacity and airspace consolidation with a CT halo sign.

  14. Extracellular vesicles shed by melanoma cells contain a modified form of H1.0 linker histone and H1.0 mRNA-binding proteins.

    Science.gov (United States)

    Schiera, Gabriella; Di Liegro, Carlo Maria; Puleo, Veronica; Colletta, Oriana; Fricano, Anna; Cancemi, Patrizia; Di Cara, Gianluca; Di Liegro, Italia

    2016-11-01

    Extracellular vesicles (EVs) are now recognized as a fundamental way for cell-to-cell horizontal transfer of properties, in both physiological and pathological conditions. Most of EV-mediated cross-talk among cells depend on the exchange of proteins, and nucleic acids, among which mRNAs, and non-coding RNAs such as different species of miRNAs. Cancer cells, in particular, use EVs to discard molecules which could be dangerous to them (for example differentiation-inducing proteins such as histone H1.0, or antitumor drugs), to transfer molecules which, after entering the surrounding cells, are able to transform their phenotype, and even to secrete factors, which allow escaping from immune surveillance. Herein we report that melanoma cells not only secrete EVs which contain a modified form of H1.0 histone, but also transport the corresponding mRNA. Given the already known role in tumorigenesis of some RNA binding proteins (RBPs), we also searched for proteins of this class in EVs. This study revealed the presence in A375 melanoma cells of at least three RBPs, with apparent MW of about 65, 45 and 38 kDa, which are able to bind H1.0 mRNA. Moreover, we purified one of these proteins, which by MALDI-TOF mass spectrometry was identified as the already known transcription factor MYEF2.

  15. Signature of an h1 state in the J/ψ→ηh1→ηK⁎0K¯⁎0 decay

    International Nuclear Information System (INIS)

    Xie, Ju-Jun; Albaladejo, M.; Oset, E.

    2014-01-01

    The BES data on the J/ψ→ηK ⁎0 K ¯⁎0 reaction show a clear enhancement in the K ⁎0 K ¯⁎0 mass distribution close to the threshold of this channel. Such an enhancement is usually a signature of an L=0 resonance around threshold, which in this case would correspond to an h 1 state with quantum numbers I G (J PC )=0 − (1 +− ). A state around 1800MeV results from the interaction of the K ⁎ K ¯⁎ using the local hidden gauge approach. We show that the peak observed in J/ψ→ηK ⁎0 K ¯⁎0 naturally comes from the creation of this h 1 state with mass and width around 1830MeV and 110MeV, respectively. A second analysis, model independent, corroborates the first result, confirming the relationship of the enhancement in the invariant mass spectrum with the h 1 resonance

  16. Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.

    Science.gov (United States)

    Weber, Lea; Schulz, Wolfgang A; Philippou, Stathis; Eckardt, Josephine; Ubrig, Burkhard; Hoffmann, Michéle J; Tannapfel, Andrea; Kalbe, Benjamin; Gisselmann, Günter; Hatt, Hanns

    2018-01-01

    Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca 2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

  17. Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Lea Weber

    2018-05-01

    Full Text Available Olfactory receptors (ORs are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

  18. Numerical Analysis of an H1-Galerkin Mixed Finite Element Method for Time Fractional Telegraph Equation

    Directory of Open Access Journals (Sweden)

    Jinfeng Wang

    2014-01-01

    Full Text Available We discuss and analyze an H1-Galerkin mixed finite element (H1-GMFE method to look for the numerical solution of time fractional telegraph equation. We introduce an auxiliary variable to reduce the original equation into lower-order coupled equations and then formulate an H1-GMFE scheme with two important variables. We discretize the Caputo time fractional derivatives using the finite difference methods and approximate the spatial direction by applying the H1-GMFE method. Based on the discussion on the theoretical error analysis in L2-norm for the scalar unknown and its gradient in one dimensional case, we obtain the optimal order of convergence in space-time direction. Further, we also derive the optimal error results for the scalar unknown in H1-norm. Moreover, we derive and analyze the stability of H1-GMFE scheme and give the results of a priori error estimates in two- or three-dimensional cases. In order to verify our theoretical analysis, we give some results of numerical calculation by using the Matlab procedure.

  19. EX1004L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1004L1: Exploration Indonesia - Guam to...

  20. IceBridge NSERC L1B Geolocated Meteorologic and Surface Temperature Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge National Suborbital Education & Research Center (NSERC) L1B Geolocated Meteorologic and Surface Temperature (IAMET1B) data set is a collection of...

  1. IceBridge NSERC L1B Geolocated Meteorologic and Surface Temperature Data, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge National Suborbital Education & Research Center (NSERC) L1B Geolocated Meteorologic and Surface Temperature (IAMET1B) data set is a collection of...

  2. IceBridge LVIS POS/AV L1B Corrected Position and Attitude Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge LVIS POS/AV L1B Corrected Position and Attitude Data (IPPLV1B) data set contains georeferencing data from the Applanix 510 and 610 POS AV systems flown...

  3. IceBridge POS/AV L1B Corrected Position and Attitude Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge POS/AV L1B Corrected Position and Attitude (IPAPP1B) data set contains georeferencing data from the Applanix 510 POS AV system flown with the Digital...

  4. EX1205L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1205L1: Exploration, Blake Plateau...

  5. EX1502L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1502L1: Caribbean Exploration (Mapping)...

  6. EX1504L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1504L1: CAPSTONE NWHI & Johnston...

  7. SMAP L1B Radiometer Half-Orbit Time-Ordered Brightness Temperatures V003

    Data.gov (United States)

    National Aeronautics and Space Administration — This Level-1B (L1B) product provides calibrated estimates of time-ordered geolocated brightness temperatures measured by the Soil Moisture Active Passive (SMAP)...

  8. EX1503L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1503L1: Tropical Exploration (Mapping I)...

  9. Okeanos Explorer (EX1402L1): Gulf of Mexico Mapping and Exploration

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — During EX1402L1, multibeam,single beam, and subbottom data will be collected 24 hours a day and XBT casts will be conducted at an interval defined by prevailing...

  10. An optimal L1-minimization algorithm for stationary Hamilton-Jacobi equations

    KAUST Repository

    Guermond, Jean-Luc; Popov, Bojan

    2009-01-01

    We describe an algorithm for solving steady one-dimensional convex-like Hamilton-Jacobi equations using a L1-minimization technique on piecewise linear approximations. For a large class of convex Hamiltonians, the algorithm is proven

  11. ASTER Expedited L1A Reconstructed Unprocessed Instrument Data V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The ASTER Expedited L1A Reconstructed Unprocessed Instrument Data is produced with the express purpose of providing the ASTER Science Team members and others, data...

  12. Assay for the pattern recognition molecule collectin liver 1 (CL-L1)

    DEFF Research Database (Denmark)

    Axelgaard, Esben; Jensenius, Jens Christian; Thiel, Steffen

    Collectin liver 1 (also termed collectin 10 and CL-L1) is a C-type lectin that functions as a pattern recognition molecule (PRM) in the innate immune system1. We have produced antibodies against CL-L1 and have developed a sandwich-type time-resolved immuno-fluorometric assay (TRIFMA...... to co-purify with MASPs, possibly rendering it a role in complement. CL-L1 showed binding activity towards mannose-TSK beads in a Ca2+-dependent manner. This binding could be inhibited by mannose and glucose, but not by galactose, indicating that CL-L1 binds via its carbohydrate-recognition domain (CRD)....

  13. MODIS/Aqua Raw Radiances in Counts 5-Min L1A Swath V006

    Data.gov (United States)

    National Aeronautics and Space Administration — The MODIS/Aqua Raw Radiances in Counts 5-Min L1A Swath (MYD01) product contains reformatted and packaged raw instrument data. MODIS instrument data, in packetized...

  14. IceBridge Riegl Laser Altimeter L1B Time-Tagged Laser Ranges

    Data.gov (United States)

    National Aeronautics and Space Administration — The NASA IceBridge Riegl Laser Altimeter L1B Time-Tagged Laser Ranges (ILUTP1B) data set contains laser ranges, returned pulses, and deviation for returned pulses in...

  15. EX1402L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1402L1: Gulf of Mexico Mapping and...

  16. Hydrography - MO 2014 Class L1 Lake Watersheds WQS TableG (SHP)

    Data.gov (United States)

    NSGIC State | GIS Inventory — This feature class contains watersheds for Class L1 lakes listed in Table G - Lake Classifications and Use Designations of the Water Quality Standards rule published...

  17. IceBridge Scintrex CS-3 Cesium Magnetometer L1B Geolocated Magnetic Anomalies, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — The NASA IceBridge Scintrex CS-3 Cesium Magnetometer L1B Geolocated Magnetic Anomalies (IMCS31B) data set contains magnetic field readings taken over Greenland using...

  18. YKL-40 and genetic status of CHI3L1 in a large group of asthmatics

    DEFF Research Database (Denmark)

    Hansen, Jakob W; Thomsen, Simon F; Porsbjerg, Celeste

    2015-01-01

    BACKGROUND: Studies have shown a relationship between asthma, serum YKL-40, and the single nucleotide polymorphism (SNP) (-131 C/G, rs4950928) in the CHI3L1 gene that codes for YKL-40. However, the findings differ. We studied the relationship between clinical asthma phenotypes, serum YKL-40...... to clarify the relationship between different asthma phenotypes, YKL-40, and CHI3L1....

  19. High-dose Resveratrol Inhibits Insulin Signaling Pathway in 3T3-L1 Adipocytes

    OpenAIRE

    Lee, Haemi; Kim, Jae-woo

    2013-01-01

    Background Insulin resistance is a major factor in the development of metabolic syndrome and is associated with central obesity and glucose intolerance. Resveratrol, a polyphenol found in fruits, has been shown to improve metabolic conditions. Although it has been widely studied how resveratrol affects metabolism, little is known about how resveratrol regulates lipogenesis with insulin signaling in 3T3-L1 adipocytes. Methods: We treated differentiated 3T3-L1 adipocytes with resveratrol to obs...

  20. L1 Use in EFL Classes with English-only Policy: Insights from Triangulated Data

    Directory of Open Access Journals (Sweden)

    Seyyed Hatam Tamimi Sa’d

    2015-06-01

    Full Text Available This study examines the role of the use of the L1 in EFL classes from the perspective of EFL learners. The triangulated data were collected using class observations, focus group semi-structured interviews and the learners’ written reports of their perceptions and attitudes in a purpose-designed questionnaire. The participants consisted of sixty male Iranian EFL learners who constituted three classes. The results indicated a strong tendency among the participants toward L1 and its positive effects on language learning; while only a minority of the learners favoured an English-only policy, the majority supported the judicious, limited and occasional use of the L1, particularly on the part of the teacher. The participants mentioned the advantages as well as the disadvantages of the use/non-use of the L1. While the major advantage and the main purpose of L1 use was said to be the clarification and intelligibility of instructions, grammatical and lexical items, the main advantages of avoiding it were stated as being the improvement of speaking and listening skills, aximizing learners’ exposure to English and their becoming accustomed to it. The study concludes that, overall and in line with the majority of the previous research studies, a judicious, occasional and limited use of the L1 is a better approach to take in EFL classes than to include or exclude it totally. In conclusion, a re-examination of the English-only policy and a reconsideration of the role of the L1 are recommended. Finally, the commonly held assumption that L1 is a hindrance and an impediment to the learners’ language learning is challenged.

  1. Multiplexed Immunofluorescence Reveals Potential PD-1/PD-L1 Pathway Vulnerabilities in Craniopharyngioma.

    Science.gov (United States)

    Coy, Shannon; Rashid, Rumana; Lin, Jia-Ren; Du, Ziming; Donson, Andrew M; Hankinson, Todd C; Foreman, Nicholas K; Manley, Peter E; Kieran, Mark W; Reardon, David A; Sorger, Peter K; Santagata, Sandro

    2018-03-02

    Craniopharyngiomas are neoplasms of the sellar/parasellar region that are classified into adamantinomatous (ACP) and papillary (PCP) subtypes. Surgical resection of craniopharyngiomas is challenging, and recurrence is common, frequently leading to profound morbidity. BRAF V600E mutations render PCP susceptible to BRAF/MEK inhibitors, but effective targeted therapies are needed for ACP. We explored the feasibility of targeting the PD-1/PD-L1 immune checkpoint pathway in ACP and PCP. We mapped and quantified PD-L1 and PD-1 expression in ACP and PCP resections using immunohistochemistry, immunofluorescence, and RNA in situ hybridization. We used tissue-based cyclic immunofluorescence (t-CyCIF) to map the spatial distribution of immune cells and characterize cell cycle and signaling pathways in ACP tumor cells which intrinsically express PD-1. All ACP (15±14% of cells, n=23, average±S.D.) and PCP (35±22% of cells, n=18) resections expressed PD-L1. In ACP, PD-L1 was predominantly expressed by tumor cells comprising the cyst-lining. In PCP, PD-L1 was highly-expressed by tumor cells surrounding the stromal fibrovascular cores. ACP also exhibited tumor cell-intrinsic PD-1 expression in whorled epithelial cells with nuclear-localized beta-catenin. These cells exhibited evidence of elevated mTOR and MAPK signaling. Profiling of immune populations in ACP and PCP showed a modest density of CD8+ T-cells. ACP exhibit PD-L1 expression in the tumor cyst-lining and intrinsic PD-1 expression in cells proposed to comprise an oncogenic stem-like population. In PCP, proliferative tumor cells express PD-L1 in a continuous band at the stromal-epithelial interface. Targeting PD-L1 and/or PD-1 in both subtypes of craniopharyngioma might therefore be an effective therapeutic strategy.

  2. PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules.

    Science.gov (United States)

    Geng, Qiaohong; Jiao, Peifu; Jin, Peng; Su, Gaoxing; Dong, Jinlong; Yan, Bing

    2018-02-12

    The recent regulatory approvals of immune checkpoint protein inhibitors, such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab ushered a new era in cancer therapy. These inhibitors do not attack tumor cells directly but instead mobilize the immune system to re-recognize and eradicate tumors, which endows them with unique advantages including durable clinical responses and substantial clinical benefits. PD-1/PD-L1 inhibitors, a pillar of immune checkpoint protein inhibitors, have demonstrated unprecedented clinical efficacy in more than 20 cancer types. Besides monoclonal antibodies, diverse PD- 1/PD-L1 inhibiting candidates, such as peptides, small molecules have formed a powerful collection of weapons to fight cancer. The goal of this review is to summarize and discuss the current PD-1/PD-L1 inhibitors including candidates under clinical development, their molecular interactions with PD-1 or PD-L1, the disclosed structureactivity relationships of peptides and small molecules as inhibitors. Current PD-1/PD-L1 inhibitors under clinical development are exclusively dominated by antibodies. The molecular interactions of therapeutic antibodies with PD-1 or PD-L1 have been gradually elucidated for the design of novel inhibitors. Various peptides and traditional small molecules have been investigated in preclinical model to discover novel PD-1/PD-L1 inhibitors. Peptides and small molecules may play an important role in immuno-oncology because they may bind to multiple immune checkpoint proteins via rational design, opening opportunity for a new generation of novel PD-1/PD-L1 inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Actoprotective properties of 7'-((3-thio-4-methyl-4H-1,2,4-triazole-5-ylmethyltheophylline derivatives

    Directory of Open Access Journals (Sweden)

    A. S. Gotsulya

    2016-06-01

    Full Text Available The aim of this work was the study of actoprotective activity of compounds, which combine sintons of 1,2,4-triazole-3-thiol and theophylline. Materials and methods. The first time synthesized 7'-((3-thio-4-phenyl-4H-1,2,4-triazole-5-ylmethyltheophylline derivatives have been used for the research. The systemic toxicity and the acute toxicity of the studied compounds have been performed by the rapid method of Prozorovskiy to determine the optimal conditions for dispensing substances. Experiments have been conducted on a group of white nonlinear rats, 159–221 g weight. During the study of actoprotective activity the method of forced immersion in water with a load of 10% by weight of the rats has been used. The substances were administered at a dose 1/10 of LD50, and the reference drug «Riboxin» at a dose of 100 mg/kg. The swim time was recorded in seconds. The control group of animals was used for comparison; these animals received saline solution intraperitoneally 20 minutes before immersion. The obtained results were statistically processed using the standard software package of Microsoft Office 2007 and «STATISTICA@ for Windows 6.0». Results. According to the results of conducted researches it has been established that the most active compound among the studied was 7'-((5-(2-hydroxyethylthio-4-phenyl-4H-1,2,4-triazole-3-ylmethyltheophylline, which increased the duration of swimming by 14.31% comparing to control group, whereas the reference drug increased it by 20.57%. It has been established that 2-((5-((theophylline-7'-ylmethyl-4-phenyl-4H-1,2,4-triazol-3-ylthio-N'-(3,4-difluorobenzylideneacetohydrazide also increases the duration of swimming. Conclusion. The study of actoprotective activity of 13 first time synthesized compounds has been conducted. 7'-((5-(2-Hydroxyethylthio-4-phenyl-4H-1,2,4-triazole-3-ylmethyltheophylline has been detected as the most active compound among the studied ones.

  4. Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

    DEFF Research Database (Denmark)

    Rojkó, Lívia; Reiniger, Lilla; Téglási, Vanda

    2018-01-01

    Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unkn...... expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.......Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression...... is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. Materials and methods: We...

  5. Improved l1-SPIRiT using 3D walsh transform-based sparsity basis.

    Science.gov (United States)

    Feng, Zhen; Liu, Feng; Jiang, Mingfeng; Crozier, Stuart; Guo, He; Wang, Yuxin

    2014-09-01

    l1-SPIRiT is a fast magnetic resonance imaging (MRI) method which combines parallel imaging (PI) with compressed sensing (CS) by performing a joint l1-norm and l2-norm optimization procedure. The original l1-SPIRiT method uses two-dimensional (2D) Wavelet transform to exploit the intra-coil data redundancies and a joint sparsity model to exploit the inter-coil data redundancies. In this work, we propose to stack all the coil images into a three-dimensional (3D) matrix, and then a novel 3D Walsh transform-based sparsity basis is applied to simultaneously reduce the intra-coil and inter-coil data redundancies. Both the 2D Wavelet transform-based and the proposed 3D Walsh transform-based sparsity bases were investigated in the l1-SPIRiT method. The experimental results show that the proposed 3D Walsh transform-based l1-SPIRiT method outperformed the original l1-SPIRiT in terms of image quality and computational efficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1.

    Science.gov (United States)

    de Oliveira Mann, Carina C; Kiefersauer, Reiner; Witte, Gregor; Hopfner, Karl-Peter

    2016-06-08

    The exceptionally conserved metazoan MAB21 proteins are implicated in cell fate decisions and share considerable sequence homology with the cyclic GMP-AMP synthase. cGAS is the major innate immune sensor for cytosolic DNA and produces the second messenger 2'-5', 3'-5' cyclic GMP-AMP. Little is known about the structure and biochemical function of other proteins of the cGAS-MAB21 subfamily, such as MAB21L1, MAB21L2 and MAB21L3. We have determined the crystal structure of human full-length MAB21L1. Our analysis reveals high structural conservation between MAB21L1 and cGAS but also uncovers important differences. Although monomeric in solution, MAB21L1 forms a highly symmetric double-pentameric oligomer in the crystal, raising the possibility that oligomerization could be a feature of MAB21L1. In the crystal, MAB21L1 is in an inactive conformation requiring a conformational change - similar to cGAS - to develop any nucleotidyltransferase activity. Co-crystallization with NTP identified a putative ligand binding site of MAB21 proteins that corresponds to the DNA binding site of cGAS. Finally, we offer a structure-based explanation for the effects of MAB21L2 mutations in patients with eye malformations. The underlying residues participate in fold-stabilizing interaction networks and mutations destabilize the protein. In summary, we provide a first structural framework for MAB21 proteins.

  7. Systemic Immunization with Papillomavirus L1 Protein Completely Prevents the Development of Viral Mucosal Papillomas

    Science.gov (United States)

    Suzich, Joann A.; Ghim, Shin-Je; Palmer-Hill, Frances J.; White, Wendy I.; Tamura, James K.; Bell, Judith A.; Newsome, Joseph A.; Bennett Jenson, A.; Schlegel, Richard

    1995-12-01

    Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.

  8. Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and mitochondrial network fragmentation.

    Science.gov (United States)

    Hartmann, Bianca; Wai, Timothy; Hu, Hao; MacVicar, Thomas; Musante, Luciana; Fischer-Zirnsak, Björn; Stenzel, Werner; Gräf, Ralph; van den Heuvel, Lambert; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Langer, Thomas; Kaindl, Angela M

    2016-08-06

    Mitochondriopathies often present clinically as multisystemic disorders of primarily high-energy consuming organs. Assembly, turnover, and surveillance of mitochondrial proteins are essential for mitochondrial function and a key task of AAA family members of metalloproteases. We identified a homozygous mutation in the nuclear encoded mitochondrial escape 1-like 1 gene YME1L1, member of the AAA protease family, as a cause of a novel mitochondriopathy in a consanguineous pedigree of Saudi Arabian descent. The homozygous missense mutation, located in a highly conserved region in the mitochondrial pre-sequence, inhibits cleavage of YME1L1 by the mitochondrial processing peptidase, which culminates in the rapid degradation of YME1L1 precursor protein. Impaired YME1L1 function causes a proliferation defect and mitochondrial network fragmentation due to abnormal processing of OPA1. Our results identify mutations in YME1L1 as a cause of a mitochondriopathy with optic nerve atrophy highlighting the importance of YME1L1 for mitochondrial functionality in humans.

  9. Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and mitochondrial network fragmentation

    Science.gov (United States)

    Hartmann, Bianca; Wai, Timothy; Hu, Hao; MacVicar, Thomas; Musante, Luciana; Fischer-Zirnsak, Björn; Stenzel, Werner; Gräf, Ralph; van den Heuvel, Lambert; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Langer, Thomas; Kaindl, Angela M

    2016-01-01

    Mitochondriopathies often present clinically as multisystemic disorders of primarily high-energy consuming organs. Assembly, turnover, and surveillance of mitochondrial proteins are essential for mitochondrial function and a key task of AAA family members of metalloproteases. We identified a homozygous mutation in the nuclear encoded mitochondrial escape 1-like 1 gene YME1L1, member of the AAA protease family, as a cause of a novel mitochondriopathy in a consanguineous pedigree of Saudi Arabian descent. The homozygous missense mutation, located in a highly conserved region in the mitochondrial pre-sequence, inhibits cleavage of YME1L1 by the mitochondrial processing peptidase, which culminates in the rapid degradation of YME1L1 precursor protein. Impaired YME1L1 function causes a proliferation defect and mitochondrial network fragmentation due to abnormal processing of OPA1. Our results identify mutations in YME1L1 as a cause of a mitochondriopathy with optic nerve atrophy highlighting the importance of YME1L1 for mitochondrial functionality in humans. DOI: http://dx.doi.org/10.7554/eLife.16078.001 PMID:27495975

  10. Effects of Larval Density on Gene Regulation in Caenorhabditis elegans During Routine L1 Synchronization.

    Science.gov (United States)

    Chan, Io Long; Rando, Oliver J; Conine, Colin C

    2018-05-04

    Bleaching gravid C. elegans followed by a short period of starvation of the L1 larvae is a routine method performed by worm researchers for generating synchronous populations for experiments. During the process of investigating dietary effects on gene regulation in L1 stage worms by single-worm RNA-Seq, we found that the density of resuspended L1 larvae affects expression of many mRNAs. Specifically, a number of genes related to metabolism and signaling are highly expressed in worms arrested at low density, but are repressed at higher arrest densities. We generated a GFP reporter strain based on one of the most density-dependent genes in our dataset - lips-15 - and confirmed that this reporter was expressed specifically in worms arrested at relatively low density. Finally, we show that conditioned media from high density L1 cultures was able to downregulate lips-15 even in L1 animals arrested at low density, and experiments using daf-22 mutant animals demonstrated that this effect is not mediated by the ascaroside family of signaling pheromones. Together, our data implicate a soluble signaling molecule in density sensing by L1 stage C. elegans , and provide guidance for design of experiments focused on early developmental gene regulation. Copyright © 2018 Chan et al.

  11. Asynchronous L1-gain control of uncertain switched positive linear systems with dwell time.

    Science.gov (United States)

    Li, Yang; Zhang, Hongbin

    2018-04-01

    In this paper, dwell time (DT) stability, L 1 -gain performance analysis and asynchronous L 1 -gain controller design problems of uncertain switched positive linear systems (SPLSs) are investigated. Via a time-scheduled multiple linear co-positive Lyapunov function (TSMLCLF) approach, convex sufficient conditions of DT stability and L 1 -gain performance of SPLSs with interval and polytopic uncertainties are presented. Furthermore, by utilizing the feature that the TSMLCLF keeps decreasing even if the controller is running asynchronously with the system, the asynchronous L 1 -gain controller design problem of SPLSs with interval and polytopic uncertainties is investigated. Convex sufficient conditions of the existence of time-varying asynchronous state-feedback controller which can ensure the closed-loop system's positivity, stability and L 1 -gain performance are established, and the controller gain matrices can be calculated instantaneously online. The obtained L 1 -gain in the paper is standard. All the results are presented in terms of linear programming. A practical example is provided to show the effectiveness of the results. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  12. Inhibitory effects of ethyl acetate-soluble fraction from morus alba on lipid accumulation in 3T3-L1 cells.

    Science.gov (United States)

    Park, Hee-Sook; Shim, Soon-Mi; Kim, Gun-Hee

    2013-11-01

    Fruits of mulberry (Morus alba) have been widely used for therapeutic purposes in Asian countries for centuries. Treatment of 3T3-L1 cells with ethanolic extracts of M. alba decreased adipocyte differentiation at 100 microg/mL by 18.6%. Treatment suppressed mRNA levels of PPARgamma and C/EBPalpha expression in 3T3-L1 cells. However, the extract did not change free glycerol release from mature adipocytes. Thus, M. alba inhibited lipid accumulation by regulating transcription factors in 3T3-L1 adipocytes without a lipolytic effect. Among the soluble- fractions, the ethyl acetate-soluble fraction had the highest antiadipogenic effects on 3T3-L1 cells. This fraction decreasing intracellular lipid accumulation by 38.5% in response to treatment with 100 microg/mL. In addition, HPLC analysis of the ethyl acetate-soluble fraction of M. alba contained 167.7 microM of protocatechulic acid in 1 mg/mL of fraction, which inhibited lipid accumulation by 44.8% in response to treatment with 100 microM. From these results, M. alba is a possible candidate for regulating lipid accumulation in obesity.

  13. Highly (001) oriented L1{sub 0}-CoPt/TiN multilayer films on glass substrates with perpendicular magnetic anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    An, Hongyu; Sannomiya, Takumi; Muraishi, Shinji; Nakamura, Yoshio; Shi, Ji, E-mail: shi.j.aa@m.titech.ac.jp [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro-ku, Tokyo 152-8552 (Japan); Xie, Qian; Zhang, Zhengjun [Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Wang, Jian [National Institute for Materials Science (NIMS), Sengen 1-2-1, Tsukuba, Ibaraki 305-0047 (Japan)

    2015-03-15

    To obtain strong perpendicular magnetic anisotropy (PMA) based on L1{sub 0} structure for magnetic storage devices, costly single crystalline substrates are generally required to achieve (001) texture. Recently, various studies also have focused on depositing different kinds of seed layers on glass or other amorphous substrates to promote (001) preferred orientation of L1{sub 0} CoPt and FePt. TiN is a very promising seed layer material because of its cubic crystalline structure (similar to MgO) and excellent diffusion barring property even at high temperatures. In the present work, highly (001) oriented L1{sub 0}-CoPt/TiN multilayer films have been successfully deposited on glass substrates. After annealing at 700 °C, the film exhibits PMA, and a strong (001) peak is detected from the x-ray diffraction profiles, indicating the ordering transformation of CoPt layers from fcc (A1) to L1{sub 0} structure. It also is found that alternate deposition of cubic TiN and CoPt effectively improves the crystallinity and (001) preferred orientation of CoPt layers. This effect is verified by the substantial enhancement of (001) reflection and PMA with increasing the period number of the multilayer films.

  14. Genomic characterization of H1N2 swine influenza viruses in Italy.

    Science.gov (United States)

    Moreno, Ana; Chiapponi, Chiara; Boniotti, Maria Beatrice; Sozzi, Enrica; Foni, Emanuela; Barbieri, Ilaria; Zanoni, Maria Grazia; Faccini, Silvia; Lelli, Davide; Cordioli, Paolo

    2012-05-04

    Three subtypes (H1N1, H1N2, and H3N2) are currently diffused worldwide in pigs. The H1N2 subtype was detected for the first time in Italian pigs in 1998. To investigate the genetic characteristics and the molecular evolution of this subtype in Italy, we conducted a phylogenetic analysis of whole genome sequences of 26 strains isolated from 1998 to 2010. Phylogenetic analysis of HA and NA genes showed differences between the older (1998-2003) and the more recent strains (2003-2010). The older isolates were closely related to the established European H1N2 lineage, whereas the more recent isolates possessed a different NA deriving from recent human H3N2 viruses. Two other reassortant H1N2 strains have been detected: A/sw/It/22530/02 has the HA gene that is closely related to H1N1 viruses; A/sw/It/58769/10 is an uncommon strain with an HA that is closely related to H1N1 and an NA similar to H3N2 SIVs. Amino acid analysis revealed interesting features: a deletion of two amino acids (146-147) in the HA gene of the recent isolates and two strains isolated in 1998; the presence of the uncommon aa change (N66S), in the PB1-F2 protein in strains isolated from 2009 to 2010, which is said to have contributed to the increased virulence. These results demonstrate the importance of pigs as mixing vessels for animal and human influenza and show the presence and establishment of reassortant strains involving human viruses in pigs in Italy. These findings also highlighted different genomic characteristics of the NA gene the recent Italian strains compared to circulating European viruses. Published by Elsevier B.V.

  15. Abundance of intrinsic structural disorder in the histone H1 subtypes.

    Science.gov (United States)

    Kowalski, Andrzej

    2015-12-01

    The intrinsically disordered proteins consist of partially structured regions linked to the unstructured stretches, which consequently form the transient and dynamic conformational ensembles. They undergo disorder to order transition upon binding their partners. Intrinsic disorder is attributed to histones H1, perceived as assemblers of chromatin structure and the regulators of DNA and proteins activity. In this work, the comparison of intrinsic disorder abundance in the histone H1 subtypes was performed both by the analysis of their amino acid composition and by the prediction of disordered stretches, as well as by identifying molecular recognition features (MoRFs) and ANCHOR protein binding regions (APBR) that are responsible for recognition and binding. Both human and model organisms-animals, plants, fungi and protists-have H1 histone subtypes with the properties typical of disordered state. They possess a significantly higher content of hydrophilic and charged amino acid residues, arranged in the long regions, covering over half of the whole amino acid residues in chain. Almost complete disorder corresponds to histone H1 terminal domains, including MoRFs and ANCHOR. Those motifs were also identified in a more ordered histone H1 globular domain. Compared to the control (globular and fibrous) proteins, H1 histones demonstrate the increased folding rate and a higher proportion of low-complexity segments. The results of this work indicate that intrinsic disorder is an inherent structural property of histone H1 subtypes and it is essential for establishing a protein conformation which defines functional outcomes affecting on DNA- and/or partner protein-dependent cell processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Clinical profile and outcome of critically ill pregnant females with H1N1 influenza

    Directory of Open Access Journals (Sweden)

    Minal Shastri

    2016-12-01

    Full Text Available Background Record based review of the 2009 H1N1 Influenza pandemic suggests that pregnant women are at higher risk for hospitalization and death due to H1N1 Influenza. Aims To study the clinical profile and outcome of critically ill pregnant females admitted in intensive care unit (ICU with real-time recombinant polymerase chain reaction (rRT-PCR proven positive H1N1 cases. Methods A retrospective record-review based study was conducted at Sir SayajiRao General Hospital (SSGH and Medical College, Vadodara on data of confirmed rRT-PCR H1N1 pregnant females admitted during the pandemics of 2010and 2015. Demographics, clinical profile and laboratory investigations were recorded and outcomes (survived or expired were analysed. Results There were a total of 20 H1N1 positive pregnant females requiring ICU admission. With equal demographic distribution among rural and urban population, cough and fever were the most common presenting complaints. 65 per cent were in third trimester, the subgroup which also had the highest mortality. Mean days from onset until presentation was 5.05 days. 12 (60 per cent patients’ required invasive mode of ventilation and all died. Average hospital stay was 7 days. Foetus had favourable outcome in patients who recovered from H1N1 acute illness. Conclusion Pregnant females in our study had 60 per cent mortality. Thus, awareness, early diagnosis and treatment should be provided to them. Guidelines, policy changes and government protocols are required specifically for pregnant females with H1N1 Influenza A infection. Our study was an observational study and comparisons with non-pregnant females were not done, conclusions applicable to entire pregnant population was not derived.

  17. Lessons learned from H1N1 epidemic: The role of mass media in informing physicians

    Directory of Open Access Journals (Sweden)

    Jaleh Gholami

    2011-01-01

    Full Text Available Objectives: Preparedness and response at the time of pandemic range from writing programs to conducting procedures as well as informing the target population. The present study was conducted to evaluate the awareness of general practitioners in Tehran, at the time of H1N1 pan-demic. It also aimed to identify the main sources used for gathering information at each alert level. Methods: Two telephone surveys were conducted with a 4 month interval, at the beginning of H1N1 pandemic alert level 5 and 6, on 90 and 100 general practitioners, respectively. The knowledge of these physicians on the symptoms of H1N1 flu, the transmission methods, the preventative measures, and existing treatments along with the sources used for gathering information were assessed. Results: While mass media was the main source of gathering informa-tion in the H1N1 pandemic alert level 5, more professional sources were used at the H1N1 pandemic alert level 6. Despite the acceptable improvement noted in the knowledge of the physicians during the two phases of the study, their understanding of the disease was believed to be less than the expected level based on H1N1 pandemic alert level. Conclusions: The routine use of mass media as one of the main sources of information gathering at the two stages of the study points out its importance in providing physicians with the required informa-tion at the time of H1N1 pandemic. Using adequate, up-to-date, but non-specialized media can fill the gap in information gathering, re-quired for fighting pandemic.

  18. Inactivation of influenza A virus H1N1 by disinfection process.

    Science.gov (United States)

    Jeong, Eun Kyo; Bae, Jung Eun; Kim, In Seop

    2010-06-01

    Because any patient, health care worker, or visitor is capable of transmitting influenza to susceptible persons within hospitals, hospital-acquired influenza has been a clinical concern. Disinfection and cleaning of medical equipment, surgical instruments, and hospital environment are important measures to prevent transmission of influenza virus from hospitals to individuals. This study was conducted to evaluate the efficacy of disinfection processes, which can be easily operated at hospitals, in inactivating influenza A virus H1N1 (H1N1). The effects of 0.1 mol/L NaOH, 70% ethanol, 70% 1-propanol, solvent/detergent (S/D) using 0.3% tri (n-butyl)-phosphate and 1.0% Triton X-100, heat, and ethylene oxide (EO) treatments in inactivating H1N1 were determined. Inactivation of H1N1 was kinetically determined by the treatment of disinfectants to virus solution. Also, a surface test method, which involved drying an amount of virus on a surface and then applying the inactivation methods for 1 minute of contact time, was used to determine the virucidal activity. H1N1 was completely inactivated to undetectable levels in 1 minute of 70% ethanol, 70% 1-propanol, and solvent/detergent treatments in the surface tests as well as in the suspension tests. H1N1 was completely inactivated in 1 minute of 0.1 mol/L NaOH treatment in the suspension tests and also effectively inactivated in the surface tests with the log reduction factor of 3.7. H1N1 was inactivated to undetectable levels within 5 minutes, 2.5 minutes, and 1 minute of heat treatment at 70, 80, and 90 degrees C, respectively in the suspension tests. Also, H1N1 was completely inactivated by EO treatment in the surface tests. Common disinfectants, heat, and EO tested in this study were effective at inactivating H1N1. These results would be helpful in implementing effective disinfecting measures to prevent hospital-acquired infections. Copyright 2010 Association for Professionals in Infection Control and Epidemiology, Inc

  19. UCH-L1-containing exosomes mediate chemotherapeutic resistance transfer in breast cancer.

    Science.gov (United States)

    Ning, Kuan; Wang, Teng; Sun, Xu; Zhang, Pengfei; Chen, Yun; Jin, Jian; Hua, Dong

    2017-06-01

    Chemotherapy resistance has become a serious challenge in the treatment of breast cancer. Previous studies showed cells can transfer proteins, including those responsible for drug resistance to adjacent cells via exosomes. The switches of drug resistance via exosomes transfer were assessed by CellTiter-Blue Viability assay, flow cytometry, and immunostaining analysis. Relative protein levels of Ubiquitin carboxyl terminal hydrolase-L1 (UCH-L1), P-glycoprotein (P-gp), extracellular-signal regulated protein kinase1/2 (ERK1/2), and phospho-extracellular-signal regulated protein kinase1/2 (p-ERK1/2) were measured by Western blot. Immunohistochemistry was performed on 93 breast cancer samples to assess the associations of UCH-L1 levels with immunofluorescence value of UCH-L1 in circulating exosomes. The Adriamycin-resistant human breast cancer cells (MCF7/ADM) secreted exosomes carrying UCH-L1 and P-gp proteins into the extracellular microenvironment then integrated into Adriamycin-sensitive human breast cancer cells (MCF7/WT) in a time-dependent manner, transferring the chemoresistance phenotype. Notably, in blood samples from patients with breast cancer, the level of exosomes carrying UCH-L1 before chemotherapy was significantly negatively correlated with prognosis. Our study demonstrated that UCH-L1-containing exosomes can transfer chemoresistance to recipient cells and these exosomes may be useful as non-invasive diagnostic biomarkers for detection of chemoresitance in breast cancer patients, achieving more effective and individualized chemotherapy. © 2017 Wiley Periodicals, Inc.

  20. OmpL1 is an extracellular matrix- and plasminogen-interacting protein of Leptospira spp.

    Science.gov (United States)

    Fernandes, Luis G V; Vieira, Monica L; Kirchgatter, Karin; Alves, Ivy J; de Morais, Zenaide M; Vasconcellos, Silvio A; Romero, Eliete C; Nascimento, Ana L T O

    2012-10-01

    Leptospirosis is a zoonosis with multisystem involvement caused by pathogenic strains of the genus Leptospira. OmpL1 is an outer membrane protein of Leptospira spp. that is expressed during infection. In this work, we investigated novel features of this protein. We describe that OmpL1 is a novel leptospiral extracellular matrix (ECM)-binding protein and a plasminogen (PLG) receptor. The recombinant protein was expressed in Escherichia coli BL21(DE3) Star/pLysS as inclusion bodies, refolded, and purified by metal-chelating chromatography. The protein presented a typical β-strand secondary structure, as evaluated by circular dichroism spectroscopy. The recombinant protein reacted with antibodies in serum samples from convalescent leptospirosis patients with a high specificity compared to serum samples from individuals with unrelated diseases. These data strengthen the usefulness of OmpL1 as a diagnostic marker of leptospirosis. The characterization of the immunogenicity of recombinant OmpL1 in inoculated BALB/c mice showed that the protein has the capacity to elicit humoral and cellular immune responses, as denoted by high antibody titers and the proliferation of lymphocytes. We demonstrate that OmpL1 has the ability to mediate attachment to laminin and plasma fibronectin, with K(D) (equilibrium dissociation constant) values of 2,099.93 ± 871.03 nM and 1,239.23 ± 506.85 nM, respectively. OmpL1 is also a PLG receptor, with a K(D) of 368.63 ± 121.23 nM, capable of generating enzymatically active plasmin. This is the first report that shows and characterizes OmpL1 as an ECM-interacting and a PLG-binding protein of Leptospira spp. that may play a role in bacterial pathogenesis when expressed during infection.

  1. L1-norm locally linear representation regularization multi-source adaptation learning.

    Science.gov (United States)

    Tao, Jianwen; Wen, Shiting; Hu, Wenjun

    2015-09-01

    In most supervised domain adaptation learning (DAL) tasks, one has access only to a small number of labeled examples from target domain. Therefore the success of supervised DAL in this "small sample" regime needs the effective utilization of the large amounts of unlabeled data to extract information that is useful for generalization. Toward this end, we here use the geometric intuition of manifold assumption to extend the established frameworks in existing model-based DAL methods for function learning by incorporating additional information about the target geometric structure of the marginal distribution. We would like to ensure that the solution is smooth with respect to both the ambient space and the target marginal distribution. In doing this, we propose a novel L1-norm locally linear representation regularization multi-source adaptation learning framework which exploits the geometry of the probability distribution, which has two techniques. Firstly, an L1-norm locally linear representation method is presented for robust graph construction by replacing the L2-norm reconstruction measure in LLE with L1-norm one, which is termed as L1-LLR for short. Secondly, considering the robust graph regularization, we replace traditional graph Laplacian regularization with our new L1-LLR graph Laplacian regularization and therefore construct new graph-based semi-supervised learning framework with multi-source adaptation constraint, which is coined as L1-MSAL method. Moreover, to deal with the nonlinear learning problem, we also generalize the L1-MSAL method by mapping the input data points from the input space to a high-dimensional reproducing kernel Hilbert space (RKHS) via a nonlinear mapping. Promising experimental results have been obtained on several real-world datasets such as face, visual video and object. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Swine Influenza Virus (H1N2) Characterization and Transmission in Ferrets, Chile.

    Science.gov (United States)

    Bravo-Vasquez, Nicolás; Karlsson, Erik A; Jimenez-Bluhm, Pedro; Meliopoulos, Victoria; Kaplan, Bryan; Marvin, Shauna; Cortez, Valerie; Freiden, Pamela; Beck, Melinda A; Hamilton-West, Christopher; Schultz-Cherry, Stacey

    2017-02-01

    Phylogenetic analysis of the influenza hemagglutinin gene (HA) has suggested that commercial pigs in Chile harbor unique human seasonal H1-like influenza viruses, but further information, including characterization of these viruses, was unavailable. We isolated influenza virus (H1N2) from a swine in a backyard production farm in Central Chile and demonstrated that the HA gene was identical to that in a previous report. Its HA and neuraminidase genes were most similar to human H1 and N2 viruses from the early 1990s and internal segments were similar to influenza A(H1N1)pdm09 virus. The virus replicated efficiently in vitro and in vivo and transmitted in ferrets by respiratory droplet. Antigenically, it was distinct from other swine viruses. Hemagglutination inhibition analysis suggested that antibody titers to the swine Chilean H1N2 virus were decreased in persons born after 1990. Further studies are needed to characterize the potential risk to humans, as well as the ecology of influenza in swine in South America.

  3. New Onset Refractory Status Epilepticus in a Young Man with H1N1 Infection

    Directory of Open Access Journals (Sweden)

    Faisal Ibrahim

    2014-01-01

    Full Text Available Objective. To report a case of refractory status epilepticus (SE as an unusual early manifestation of H1N1 influenza infection. Introduction. H1N1 neurological complications have been reported and consist mainly of seizures or encephalopathy occurring in children. However, we only found a single report of an adult developing complex partial SE with H1N1 infection. Case Report. A 21-year-old previously healthy man was brought to the emergency room (ER after a witnessed generalized tonic clonic seizure (GTCS. He was fully alert and afebrile upon ER arrival, but a second GTCS prompted treatment with Lorazepam and Fosphenytoin. The initial EEG showed diffuse slowing, but a repeat one requested as the patient failed to regain consciousness revealed recurrent focal seizures of independent bihemispheric origin, fulfilling the criteria for nonconvulsive SE. Chest X-ray, followed by chest CT scan, showed a left upper lobe consolidation. H1N1 infection was confirmed with PCR on bronchoalveolar lavage material. Despite aggressive treatment with Midazolam, Propofol, and multiple high dose antiepileptic drugs, the electrographic seizures recurred at every attempt to reduce the intravenous sedative drugs. The patient died two weeks after his initial presentation. Conclusion. H1N1 should be added to the list of rare causes of refractory SE, regardless of the patient’s age.

  4. Genetic and pathogenic characteristics of H1 avian and swine influenza A viruses.

    Science.gov (United States)

    Kang, Hyun-Mi; Lee, Eun-Kyoung; Song, Byung-Min; Jeong, Jipseol; Kim, Hye-Ryoung; Choi, Eun-Jin; Shin, Yeun-Kyung; Lee, Hee-Soo; Lee, Youn-Jeong

    2014-10-01

    This study examined the potential for cross-species transmission of influenza viruses by comparing the genetic and pathogenic characteristics of H1 avian influenza viruses (AIVs) with different host origins in Korea. Antigenic and phylogenetic analyses of H1 AIVs circulating in Korea provided evidence of genetic similarity between viruses that infect domestic ducks and those that infect wild birds, although there was no relationship between avian and swine viruses. However, there were some relationships between swine and human viral genes. The replication and pathogenicity of the H1 viruses was assessed in chickens, domestic ducks and mice. Viral shedding in chickens was relatively high. Virus was recovered from both oropharyngeal and cloacal swabs up to 5-10 days post-inoculation. The titres of domestic duck viruses in chickens were much higher than those of wild-bird viruses. Both domestic duck and wild-bird viruses replicated poorly in domestic ducks. None of the swine viruses replicated in chickens or domestic ducks; however, six viruses showed relatively high titres in mice, regardless of host origin, and induced clinical signs such as ruffled fur, squatting and weight loss. Thus, although the phylogenetic and antigenic analyses showed no evidence of interspecies transmission between birds and swine, the results suggest that Korean H1 viruses have the potential to cause disease in mammals. Therefore, we should intensify continuous monitoring of avian H1 viruses in mammals and seek to prevent interspecies transmission. © 2014 The Authors.

  5. Development of a diagnostic kit for Tamiflu-resistant influenza A (H1N1)

    International Nuclear Information System (INIS)

    Jung, I. L.; Hong, S. W.

    2012-01-01

    Swine influenza A, which has been pandemic worldwide since 2009, is a new type virus derived from A type influenza. Although some drugs against the contageous disease, such as relenza and tamiflu, have been commercialized, those drug resistant viruses could be also followed by the wide usage of drugs. For examples, Tamiflu-resistant viruses, the mutant type viruses, can not be cured by the treatment of tamiflu anymore. Thus, a quick diagnosis for the wild type (tamiflu-sensitive) and mutant (tamiflu-resistant) virus would be essential in order to prevent the wide spread of viruses. In spite of that, unfortunately, very few studies have been conducted until now. If we could tell the differences between tamiflu-resistant and -sensitive patients using by the proper diagnostic kit, not only patient specific treatment would be possible, but also the spread of viruses would be effectively prevented. Currently used detection methods for the swine influenza A H1N1, which were originated from CDC, USA, can not detect the tamiflu-resistant swine influenza A H1N1, but only can detect tamiflu-sensitive wine influenza A H1N1. In this study, all the primers for the detection of swInfA, swH1, MP and NA (neuraminidase) have been developed in order to detect both tamiflu-resistant and tamiflu-sensitive swine influenza A H1N1s simultaneously, and then, new multiplex RT-PCR methods has been established

  6. Binding of histone H1 to DNA is differentially modulated by redox state of HMGB1.

    Directory of Open Access Journals (Sweden)

    Eva Polanská

    Full Text Available HMGB1 is an architectural protein in chromatin, acting also as a signaling molecule outside the cell. Recent reports from several laboratories provided evidence that a number of both the intracellular and extracellular functions of HMGB1 may depend on redox-sensitive cysteine residues of the protein. In this study we demonstrate that redox state of HMGB1 can significantly modulate the ability of the protein to bind and bend DNA, as well as to promote DNA end-joining. We also report a high affinity binding of histone H1 to hemicatenated DNA loops and DNA minicircles. Finally, we show that reduced HMGB1 can readily displace histone H1 from DNA, while oxidized HMGB1 has limited capacity for H1 displacement. Our results suggested a novel mechanism for the HMGB1-mediated modulation of histone H1 binding to DNA. Possible biological consequences of linker histones H1 replacement by HMGB1 for the functioning of chromatin are discussed.

  7. Development of a diagnostic kit for Tamiflu-resistant influenza A (H1N1)

    Energy Technology Data Exchange (ETDEWEB)

    Jung, I. L.; Hong, S. W.

    2012-01-15

    Swine influenza A, which has been pandemic worldwide since 2009, is a new type virus derived from A type influenza. Although some drugs against the contageous disease, such as relenza and tamiflu, have been commercialized, those drug resistant viruses could be also followed by the wide usage of drugs. For examples, Tamiflu-resistant viruses, the mutant type viruses, can not be cured by the treatment of tamiflu anymore. Thus, a quick diagnosis for the wild type (tamiflu-sensitive) and mutant (tamiflu-resistant) virus would be essential in order to prevent the wide spread of viruses. In spite of that, unfortunately, very few studies have been conducted until now. If we could tell the differences between tamiflu-resistant and -sensitive patients using by the proper diagnostic kit, not only patient specific treatment would be possible, but also the spread of viruses would be effectively prevented. Currently used detection methods for the swine influenza A H1N1, which were originated from CDC, USA, can not detect the tamiflu-resistant swine influenza A H1N1, but only can detect tamiflu-sensitive wine influenza A H1N1. In this study, all the primers for the detection of swInfA, swH1, MP and NA (neuraminidase) have been developed in order to detect both tamiflu-resistant and tamiflu-sensitive swine influenza A H1N1s simultaneously, and then, new multiplex RT-PCR methods has been established.

  8. Production and characterization of a monoclonal antibody against recombinant cathepsin L1 of Fasciola gigantica.

    Science.gov (United States)

    Anuracpreeda, Panat; Srirakam, Thippawan; Pandonlan, Sudarat; Changklungmoa, Narin; Chotwiwatthanakun, Charoonroj; Tinikul, Yotsawan; Poljaroen, Jaruwan; Meemon, Krai; Sobhon, Prasert

    2014-08-01

    Monoclonal antibodies (MoAbs) against a recombinant cathepsin L1 of Fasciola gigantica (rFgCatL1) were produced in vitro by fusion of BALB/c mice spleen cells immunized with rFgCatL1 and mouse myeloma cells. Reactivity and specificity of these MoAbs were evaluated by indirect ELISA and immunoblotting techniques. Seven MoAb clones were selected from the stable hybridoma clones, namely 1E10, 1F5, 3D11, 4B10, 4D3, 4E3 and 5E7. Clones 1E10, 1F5 and 3D11 were IgM, whereas clones 4B10, 4D3, 4E3 and 5E7 were IgG1. All MoAbs had kappa light chain isotypes. All MoAbs reacted with rCatL1 at molecular weight (MW) 30kDa and with the native CatL1 at MW 27kDa in whole body (WB) extracts of metacercariae (Met), newly excysted juveniles (NEJ), 1, 3, 5-week-old juveniles (Ju), adult WB and adult excretory-secretory (ES) fractions, but not with adult tegumental antigens (TA). All of these MoAbs showed no cross-reactions with antigens of other parasites commonly found in ruminants and human, including Paramphistomum cervi, Eurytrema pancreaticum, Gigantocotyle explanatum, Schistosoma spindale, Schistosoma mansoni, Moniezia benedeni, Avitellina centripunctata, Trichuris sp., Haemonchus placei and Setaria labiato-papillosa. Localization of CatL1 in each developmental stages of F. gigantica by immunoperoxidase technique, using these MoAbs as probes, indicated that CatL1 was present at high concentration in the caecal epithelium and caecal lumen of metacercariae, NEJ, 1, 3, 5-week-old juveniles and adult fluke. This finding indicated that CatL1 is a copiously expressed parasite protein that is released into the ES, thus CatL1 and its MoAb could be a good candidate for immunodiagnosis of fasciolosis in ruminant and human. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Differential L1 regulation in pluripotent stem cells of humans and apes.

    Science.gov (United States)

    Marchetto, Maria C N; Narvaiza, Iñigo; Denli, Ahmet M; Benner, Christopher; Lazzarini, Thomas A; Nathanson, Jason L; Paquola, Apuã C M; Desai, Keval N; Herai, Roberto H; Weitzman, Matthew D; Yeo, Gene W; Muotri, Alysson R; Gage, Fred H

    2013-11-28

    Identifying cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic understanding of the evolution and diversity of our own species. Until now, preserved tissues have been the main source for most comparative studies between humans, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). However, these tissue samples do not fairly represent the distinctive traits of live cell behaviour and are not amenable to genetic manipulation. We propose that induced pluripotent stem (iPS) cells could be a unique biological resource to determine relevant phenotypical differences between human and NHPs, and that those differences could have potential adaptation and speciation value. Here we describe the generation and initial characterization of iPS cells from chimpanzees and bonobos as new tools to explore factors that may have contributed to great ape evolution. Comparative gene expression analysis of human and NHP iPS cells revealed differences in the regulation of long interspersed element-1 (L1, also known as LINE-1) transposons. A force of change in mammalian evolution, L1 elements are retrotransposons that have remained active during primate evolution. Decreased levels of L1-restricting factors APOBEC3B (also known as A3B) and PIWIL2 (ref. 7) in NHP iPS cells correlated with increased L1 mobility and endogenous L1 messenger RNA levels. Moreover, results from the manipulation of A3B and PIWIL2 levels in iPS cells supported a causal inverse relationship between levels of these proteins and L1 retrotransposition. Finally, we found increased copy numbers of species-specific L1 elements in the genome of chimpanzees compared to humans, supporting the idea that increased L1 mobility in NHPs is not limited to iPS cells in culture and may have also occurred in the germ line or embryonic cells developmentally upstream to germline specification during primate evolution. We propose that differences in L1 mobility may have

  10. The effect of myostatin on proliferation and lipid accumulation in 3T3-L1 preadipocytes.

    Science.gov (United States)

    Zhu, Hui Juan; Pan, Hui; Zhang, Xu Zhe; Li, Nai Shi; Wang, Lin Jie; Yang, Hong Bo; Gong, Feng Ying

    2015-06-01

    Myostatin is a critical negative regulator of skeletal muscle development, and has been reported to be involved in the progression of obesity and diabetes. In the present study, we explored the effects of myostatin on the proliferation and differentiation of 3T3-L1 preadipocytes by using 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide spectrophotometry, intracellular triglyceride (TG) assays, and real-time quantitative RT-PCR methods. The results indicated that recombinant myostatin significantly promoted the proliferation of 3T3-L1 preadipocytes and the expression of proliferation-related genes, including Cyclin B2, Cyclin D1, Cyclin E1, Pcna, and c-Myc, and IGF1 levels in the medium of 3T3-L1 were notably upregulated by 35.2, 30.5, 20.5, 33.4, 51.2, and 179% respectively (all Pmyostatin-treated 3T3-L1 cells. Meanwhile, the intracellular lipid content of myostatin-treated cells was notably reduced as compared with the non-treated cells. Additionally, the mRNA levels of Pparγ, Cebpα, Gpdh, Dgat, Acs1, Atgl, and Hsl were significantly downregulated by 22-76% in fully differentiated myostatin-treated adipocytes. Finally, myostatin regulated the mRNA levels and secretion of adipokines, including Adiponectin, Resistin, Visfatin, and plasminogen activator inhibitor-1 (PAI-1) in 3T3-L1 adipocytes (all Pmyostatin promoted 3T3-L1 proliferation by increasing the expression of cell-proliferation-related genes and by stimulating IGF1 secretion. Myostatin inhibited 3T3-L1 adipocyte differentiation by suppressing Pparγ and Cebpα expression, which consequently deceased lipid accumulation in 3T3-L1 cells by inhibiting the expression of critical lipogenic enzymes and by promoting the expression of lipolytic enzymes. Finally, myostatin modulated the expression and secretion of adipokines in fully differentiated 3T3-L1 adipocytes. © 2015 Society for Endocrinology.

  11. Mongrelised genetics of H1N1 virus: A bird′s eyeview

    Directory of Open Access Journals (Sweden)

    Nagarathna C

    2010-01-01

    Full Text Available H1N1 influenza, also known as "novel H1N1 virus" has led to a "global outcry." This virus is more virulent when compared with other seasonal flu viruses. Virulence may change as the adaptive mutation gene increases within the virus. A study at the US Centre for Disease Control and Prevention published in May 2009 found that children had no preexisting immunity to the new strain as they showed no cross-reactive antibody reaction when compared with adults aged 18-64 years, who showed a cross-reactive antibody reaction of 6-9% and older adults with 33% immunity. This review article depicts H1N1 virus, its virulence with genetic evolution potential and preventive protocol for the dental professionals. This would allow us to comprehend the changes in the disease process and contribute in its prevention as "prevention is better than cure."

  12. A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line

    KAUST Repository

    Benavente, Ernest Diez

    2017-12-16

    Plasmodium knowlesi, a common parasite of macaques, is recognized as a significant cause of human malaria in Malaysia. The P. knowlesi A1H1 line has been adapted to continuous culture in human erythrocytes, successfully providing an in vitro model to study the parasite. We have assembled a reference genome for the PkA1-H.1 line using PacBio long read combined with Illumina short read sequence data. Compared with the H-strain reference, the new reference has improved genome coverage and a novel description of methylation sites. The PkA1-H.1 reference will enhance the capabilities of the in vitro model to improve the understanding of P. knowlesi infection in humans.

  13. Examination of human brain tumors in situ with image-localized H-1 MR spectroscopy

    International Nuclear Information System (INIS)

    Luyten, P.R.; Segebarth, C.; Baleriaux, D.; Den Hollander, J.A.

    1987-01-01

    Human brain tumors were examined in situ by combined imaging and H-1 MR spectroscopy at 1.5 T. Water-suppressed localized H-1 MR spectra obtained from the brains of normal volunteers show resonances from lactate, N-acetyl aspartate (NAA), creatine, and choline. Several patients suffering from different brain tumors were examined, showing spectral changes in the region of 0.5-1.5 ppm; spectral editing showed that these changes were not due to lactic acid, but to lipid signals. The NAA signal was decreased in the tumors as compared with normal brain. This study shows that H-1 MR spectroscopy can monitor submillimolar changes in chemical composition of human brain tumors in situ

  14. Measurement and QCD Interpretation of the Inclusive Deep-Inelastic Scattering Cross Section by H1

    CERN Multimedia

    CERN. Geneva

    2001-01-01

    Deep inelastic electron proton collisions are a straightforward tool to study the QCD dynamics between quarks and gluons in the proton. A recent measurement and QCD analysis of the deep inelastic scattering cross section by the H1 experiment at HERA are presented. In a NLO QCD analysis of H1 structure function data, the gluon distribution in the proton is extracted to typically 3% experimental accuracy at low Bjorken x.. In a combined analysis of H1 and high precision µp data by the CERN muon experiment BCDMS, the gluon distribution at low x and the strong coupling constant as were for the first time extracted simultaneously.The strong coupling constant is determined with about 1% experimental accuracy, and QCD at NLO is confirmed over 5 orders of magnitude of Bjorken x at a new level of precision.

  15. Geophysical investigation of the 116-H-1 liquid waste disposal trench, 100-HR-1 operable unit

    International Nuclear Information System (INIS)

    Bergstrom, K.A.; Mitchell, T.H.

    1996-04-01

    A geophysical investigation and data integration were conducted for the 116-H-1 Liquid Waste Disposal Trench, which is located in the 100-HR-1 Operable Unit. The 116-H-1 Liquid Waste Disposal Trench is also known as the 107-H Liquid Waste Disposal Trench, the 107-H Rupture Effluent Trench, and the 107-H Trench (Deford and Einan 1995). The trench was primarily used to hold effluent from the 107-H Retention Basin that had become radioactive from contact with ruptured fuel elements. The effluent may include debris from the ruptured fuel elements (Koop 1964). The 116-H-1 Liquid Waste Disposal Trench was also used to hold water and sludge from the 107-H Retention Basin during the basin's deactivation in 1965

  16. Susceptibility of turkeys to pandemic-H1N1 virus by reproductive tract insemination

    Directory of Open Access Journals (Sweden)

    Suarez David L

    2010-02-01

    Full Text Available Abstract The current pandemic influenza A H1N1 2009 (pH1N1 was first recognized in humans with acute respiratory diseases in April 2009 in Mexico, in swine in Canada in June, 2009 with respiratory disease, and in turkeys in Chile in June 2009 with a severe drop in egg production. Several experimental studies attempted to reproduce the disease in turkeys, but failed to produce respiratory infection in turkeys using standard inoculation routes. We demonstrated that pH1N1 virus can infect the reproductive tract of turkey hens after experimental intrauterine inoculation, causing decreased egg production. This route of exposure is realistic in modern turkey production because turkey hens are handled once a week for intrauterine insemination in order to produce fertile eggs. This understanding of virus exposure provides an improved understanding of the pathogenesis of the disease and can improve poultry husbandry to prevent disease outbreaks.

  17. Caring from Afar: Asian H1B Migrant Workers and Aging Parents.

    Science.gov (United States)

    Lee, Yeon-Shim; Chaudhuri, Anoshua; Yoo, Grace J

    2015-09-01

    With the growth in engineering/technology industries, the United States has seen an increase in the arrival of highly skilled temporary migrant workers on H1B visas from various Asian countries. Limited research exists on how these groups maintain family ties from afar including caring for aging parents. This study explores the experiences and challenges that Asian H1B workers face when providing care from a distance. A total of 21 Chinese/Taiwanese, Korean, and Indian H1B workers participated in in-depth qualitative interviews. Key findings indicate that despite distance, caring relationships still continue through regular communications, financial remittances, and return visits, at the same time creating emotional, psychological, and financial challenges for the workers. Findings highlight the need for further research in understanding how the decline of aging parent's health impacts the migrants' adjustment and health in the United States.

  18. A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line

    KAUST Repository

    Benavente, Ernest Diez; de Sessions, Paola Florez; Moon, Robert W.; Grainger, Munira; Holder, Anthony A; Blackman, Michael J.; Roper, Cally; Drakeley, Christopher J.; Pain, Arnab; Sutherland, Colin J.; Hibberd, Martin L.; Campino, Susana; Clark, Taane G

    2017-01-01

    Plasmodium knowlesi, a common parasite of macaques, is recognized as a significant cause of human malaria in Malaysia. The P. knowlesi A1H1 line has been adapted to continuous culture in human erythrocytes, successfully providing an in vitro model to study the parasite. We have assembled a reference genome for the PkA1-H.1 line using PacBio long read combined with Illumina short read sequence data. Compared with the H-strain reference, the new reference has improved genome coverage and a novel description of methylation sites. The PkA1-H.1 reference will enhance the capabilities of the in vitro model to improve the understanding of P. knowlesi infection in humans.

  19. Robust Non-Local TV-L1 Optical Flow Estimation with Occlusion Detection.

    Science.gov (United States)

    Zhang, Congxuan; Chen, Zhen; Wang, Mingrun; Li, Ming; Jiang, Shaofeng

    2017-06-05

    In this paper, we propose a robust non-local TV-L1 optical flow method with occlusion detection to address the problem of weak robustness of optical flow estimation with motion occlusion. Firstly, a TV-L1 form for flow estimation is defined using a combination of the brightness constancy and gradient constancy assumptions in the data term and by varying the weight under the Charbonnier function in the smoothing term. Secondly, to handle the potential risk of the outlier in the flow field, a general non-local term is added in the TV-L1 optical flow model to engender the typical non-local TV-L1 form. Thirdly, an occlusion detection method based on triangulation is presented to detect the occlusion regions of the sequence. The proposed non-local TV-L1 optical flow model is performed in a linearizing iterative scheme using improved median filtering and a coarse-to-fine computing strategy. The results of the complex experiment indicate that the proposed method can overcome the significant influence of non-rigid motion, motion occlusion, and large displacement motion. Results of experiments comparing the proposed method and existing state-of-the-art methods by respectively using Middlebury and MPI Sintel database test sequences show that the proposed method has higher accuracy and better robustness.

  20. Generation and Nuclear Translocation of Sumoylated Transmembrane Fragment of Cell Adhesion Molecule L1

    Science.gov (United States)

    Lutz, David; Wolters-Eisfeld, Gerrit; Joshi, Gunjan; Djogo, Nevena; Jakovcevski, Igor; Schachner, Melitta; Kleene, Ralf

    2012-01-01

    The functions of the cell adhesion molecule L1 in the developing and adult nervous system are triggered by homophilic and heterophilic interactions that stimulate signal transductions that activate cellular responses. Here, we show that stimulation of signaling by function-triggering L1 antibodies or L1-Fc leads to serine protease-dependent cleavage of full-length L1 at the plasma membrane and generation of a sumoylated transmembrane 70-kDa fragment comprising the intracellular and transmembrane domains and part of the extracellular domain. The 70-kDa transmembrane fragment is transported from the plasma membrane to a late endosomal compartment, released from endosomal membranes into the cytoplasm, and transferred from there into the nucleus by a pathway that depends on importin and chromatin-modifying protein 1. Mutation of the sumoylation site at Lys1172 or of the nuclear localization signal at Lys1147 abolished L1-stimulated generation or nuclear import of the 70-kDa fragment, respectively. Nuclear import of the 70-kDa fragment may activate cellular responses in parallel or in association with phosphorylation-dependent signaling pathways. Alterations in the levels of the 70-kDa fragment during development and in the adult after spinal cord injury or in a mouse model of Alzheimer disease suggest that this fragment is functionally implicated in development, regeneration, neurodegeneration, tumorigenesis, and possibly synaptic plasticity in the mature nervous system. PMID:22431726

  1. RAC1 P29S regulates PD-L1 expression in melanoma

    Science.gov (United States)

    Vu, Ha Linh; Rosenbaum, Sheera; Purwin, Timothy J.; Davies, Michael A.; Aplin, Andrew E.

    2015-01-01

    Summary Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC1 in 5–9% of samples, but the role of RAC1 P29 mutations in melanoma biology remains unclear. Using reverse phase protein array analysis to examine the changes in protein/phospho-protein expression, we identified cyclin B1, PD-L1, Ets-1, and Syk as being selectively upregulated with RAC1 P29S expression and downregulated with RAC1 P29S depletion. Using the melanoma patient samples in TCGA, we found PD-L1 expression to be significantly increased in RAC1 P29S patients compared to RAC1 WT as well as other RAC1 mutants. The finding that PD-L1 is upregulated suggests that oncogenic RAC1 P29S may promote suppression of the antitumor immune response. This is a new insight into the biological function of RAC1 P29S mutations with potential clinical implications as PD-L1 is a candidate biomarker for increased benefit from treatment with anti-PD1 or anti-PD-L1 antibodies. PMID:26176707

  2. Progress of PD-1/PD-L1 Inhibitors in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Zhansheng JIANG

    2017-02-01

    Full Text Available Pembrolizumab, an inhibitor target programmed death 1 (PD-1, was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC. It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1 inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS with single pembrolizumab in first line was nearly 1 year (10.3 months, the hazard ratio for death fell by 40%. Overall survival (OS was more or less 1 year with single drug pembrolizumab, nivolumab and atezolizumab for second line therapy. PD-L1 expression was a predictor of PD-1/PD-L1 inhibitors. The positive rate of PD-L1 (more than 1% in advanced NSCLC was about 60% with little difference between the tissue types. However, there was no gold standard test of PD-L1 expression.

  3. [Mode of action of plantaricin L-1, an antilisteria bacteriocin produced by Lactobacillus plantarum].

    Science.gov (United States)

    Zhou, Wei; Liu, Guo-rong; Li, Ping-lan; Dai, Yun-qing; Zhou, Kang

    2007-04-01

    Plantaricin L-1, an anti-Listeria bacteriocin, was produced by Lactobacillus plantarum and successfully purified by SP-Sepharose FF cation exchange chromatography. The mechanism on energized cells of Listeria monocytogenes was studied with purified plantaricin L-1. After adding plantaricin L-1 to Listeria monocytogenes at 64 AU/mL, leakage of intercellular K+ ions, inorganic phosphate, lactic dehydrogenase, UV-absorbing materials and the intracellular ATP was observed, and the action resulted in the dissipation of the membrane potential (delta psi) and pH gradient (delta psi), two components of the proton motive force (PMF). All the data suggested that the primary site of action of plantaricin L-1 was the cytoplasmic membrane of sensitive cells. By forming the nonselective pores which leak ions and small organic compounds plantaricin L-1 induced the cells death, this action was similar to membrane corruption caused by peptide effect. Penetrability increased due to the enlarged pore and dysfuction of membrane transporters, which ensured efficient killing of target bacteria.

  4. Wind Turbine Pitch Control and Load Mitigation Using an L1 Adaptive Approach

    Directory of Open Access Journals (Sweden)

    Danyong Li

    2014-01-01

    Full Text Available We present an application of L1 adaptive output feedback control design to wind turbine collective pitch control and load mitigation. Our main objective is the design of an L1 output feedback controller without wind speed estimation, ensuring that the generator speed tracks the reference trajectory with robustness to uncertain parameters and time-varying disturbances (mainly the uniform wind disturbance across the wind turbine rotor. The wind turbine model CART (controls advanced research turbine developed by the national renewable energy laboratory (NREL is used to validate the performance of the proposed L1 adaptive controller using the FAST (fatigue, aerodynamics, structures, and turbulence code. A comparative study is also conducted between the proposed controller and the most popular methods in practice: gain scheduling PI (GSPI controls and disturbance accommodating control (DAC methods. The results show better performance of L1 output feedback controller over the other two methods. Moreover, based on the FAST software and LQR analysis in the reference model selection of L1 adaptive controller, tradeoff can be achieved between control performance and loads mitigation.

  5. Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1

    Science.gov (United States)

    Ye, Shoudong; Li, Ping; Tong, Chang; Ying, Qi-Long

    2013-01-01

    Mouse embryonic stem cell (mESC) self-renewal can be maintained by activation of the leukaemia inhibitory factor (LIF)/signal transducer and activator of transcription 3 (Stat3) signalling pathway or dual inhibition (2i) of glycogen synthase kinase 3 (Gsk3) and mitogen-activated protein kinase kinase (MEK). Several downstream targets of the pathways involved have been identified that when individually overexpressed can partially support self-renewal. However, none of these targets is shared among the involved pathways. Here, we show that the CP2 family transcription factor Tfcp2l1 is a common target in LIF/Stat3- and 2i-mediated self-renewal, and forced expression of Tfcp2l1 can recapitulate the self-renewal-promoting effect of LIF or either of the 2i components. In addition, Tfcp2l1 can reprogram post-implantation epiblast stem cells to naïve pluripotent ESCs. Tfcp2l1 upregulates Nanog expression and promotes self-renewal in a Nanog-dependent manner. We conclude that Tfcp2l1 is at the intersection of LIF- and 2i-mediated self-renewal pathways and plays a critical role in maintaining ESC identity. Our study provides an expanded understanding of the current model of ground-state pluripotency. PMID:23942238

  6. Effect of the novel influenza A (H1N1 virus in the human immune system.

    Directory of Open Access Journals (Sweden)

    Evangelos J Giamarellos-Bourboulis

    Full Text Available BACKGROUND: The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host. METHODOLOGY/PRINCIPAL FINDINGS: Blood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL-1beta, IL-6, IL-18, interferon (FN-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs. CONCLUSIONS/SIGNIFICANCE: Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza.

  7. Effect of the novel influenza A (H1N1) virus in the human immune system.

    Science.gov (United States)

    Giamarellos-Bourboulis, Evangelos J; Raftogiannis, Maria; Antonopoulou, Anastasia; Baziaka, Fotini; Koutoukas, Pantelis; Savva, Athina; Kanni, Theodora; Georgitsi, Marianna; Pistiki, Aikaterini; Tsaganos, Thomas; Pelekanos, Nikolaos; Athanassia, Sofia; Galani, Labrini; Giannitsioti, Efthymia; Kavatha, Dimitra; Kontopidou, Flora; Mouktaroudi, Maria; Poulakou, Garyfallia; Sakka, Vissaria; Panagopoulos, Periklis; Papadopoulos, Antonios; Kanellakopoulou, Kyriaki; Giamarellou, Helen

    2009-12-23

    The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host. Blood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-18, interferon (FN)-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs). Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza.

  8. Sensitive and selective magnetoimmunosensing platform for determination of the food allergen Ara h 1

    International Nuclear Information System (INIS)

    Montiel, V. Ruiz-Valdepeñas; Campuzano, S.; Pellicanò, A.; Torrente-Rodríguez, R.M.; Reviejo, A.J.; Cosio, M.S.; Pingarrón, J.M.

    2015-01-01

    Highlights: • First amperometric magnetoimmunosensor for Ara h 1 determination. • Sensitive and selective detection of Ara h 1 in 2 h. • LOD of 6.3 ng mL −1 . • Determinations in food extracts and saliva. • Potential applicability in food safety and consumer protection. - Abstract: A highly sensitive disposable amperometric immunosensor based on the use of magnetic beads (MBs) is described for determination of Ara h 1, the major peanut allergen, in only 2 h. The approach uses a sandwich configuration involving selective capture and biotinylated detector antibodies and carboxylic acid-modified MBs (HOOC-MBs). The MBs bearing the immunoconjugates are captured by a magnet placed under the surface of a disposable screen-printed carbon electrode (SPCE) and the affinity reactions are monitored amperometrically at −0.20 V (vs a Ag pseudo-reference electrode) in the presence of hydroquinone (HQ) as electron transfer mediator and upon addition of H 2 O 2 as the enzyme substrate. The developed immunosensor exhibits a wide range of linearity between 20.8 and 1000.0 ng mL −1 Ara h 1, a detection limit of 6.3 ng mL −1 , a great selectivity, a good reproducibility with a RSD of 6.3% for six different immunosensors and a useful lifetime of 25 days. The usefulness of the immunosensor was demonstrated by determining Ara h 1 in different matrices (food extracts and saliva). The results correlated properly with those provided by a commercial ELISA method offering a reliable and promising analytical screening tool in the development of user-friendly devices for on-site determination of Ara h 1

  9. Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination.

    Directory of Open Access Journals (Sweden)

    Simon Thebault

    Full Text Available Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03 vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR and contactin-associated protein 2 (CASPR2, both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054 in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6. In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.

  10. Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination.

    Science.gov (United States)

    Thebault, Simon; Waters, Patrick; Snape, Matthew D; Cottrell, Dominic; Darin, Niklas; Hallböök, Tove; Huutoniemi, Anne; Partinen, Markku; Pollard, Andrew J; Vincent, Angela

    2015-01-01

    Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03) vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult) with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein 2 (CASPR2), both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH) were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054) in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6). In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.

  11. Household transmission of 2009 H1N1 influenza virus in Yazd, Iran

    Directory of Open Access Journals (Sweden)

    F. Behnaz

    2012-08-01

    Full Text Available Summary: Objectives: The 2009 pandemic influenza A (H1N1 virus is a public health challenge. Notably, laboratory-confirmed cases do not represent the age group most susceptible to infection. To characterize the age distribution of all cases of H1N1 influenza, we studied the personal contacts of confirmed cases to identify the age group at the highest risk. Methods: We investigated the family members of 162 laboratory-confirmed cases of 2009 H1N1 in Yazd, Iran. Family members were retrospectively asked whether they had ≥2 respiratory symptoms within 7 days of the last contact with the associated index cases. The ages and symptoms of the patients as well as the interval between diagnosis and the onset of symptoms among household contacts were determined using a questionnaire. Results: We identified 596 family members of index cases, 83 (13.9% of whom developed acute respiratory illness. No acute respiratory illness was found in 104 families (64%; however, there were 2 cases in 15 families (9.3% and ≥3 cases in 4 families (24%. Household contacts from 5 to 18 years old were more susceptible to acute respiratory illness than those who were ≥51 years old (RR = 3.174, 95% CI 1.313–7.675 P-value = 0.01. Conclusion: Individuals ≤18 years old were most susceptible to infection by the H1N1 virus. Therefore, in low-income populations, prevention of the spread of H1N1 to this age group should be emphasized. Keywords: Household transmission, 2009 Influenza A (H1N1 virus

  12. [Study on genetic instability of nm23H1 gene in Chinese with original gallbladder tumor].

    Science.gov (United States)

    Lu, Hai Ying; Zhang, Guo Qiang; Li, Ji Cheng

    2006-06-01

    The aim of this study was to examine the microsatellite instability (MSI) and loss of heterozygosity (LOH) of locus D17S396 on chromosome 17 and their influence on the expression of nm23H1 in gallbladder tumors, which may provide experimental basis for the tumor occurrence and metastasis. Techniques such as DNA extraction from formalin-fixed paraffin-embedded tissues, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), ordinary silver stain were used to study MSI and LOH of locus D17S396. Envision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of gene nm23H1. In our experiment, the frequency of genetic instability of malignant gallbladder tumors was 42.55%, which was higher than that of gallbladder adenomas, while there were no genetic instability occurred in chronic cholecystitis tissue. The frequency of LOH seemed higher with the deteriorism of gallbladder tumor. Among 47 gallbladder carcinomas, the frequency of LOH and MSI were different between different differentiation cases (P gallbladder carcinoma, gallbladder adenoma and chronic cholecystitis tissue were different (P gallbladder carcinomas, the positive frequency of nm23H1 protein in LOH positive group was lower than that of LOH negative group (P gallbladder tumor. Both MSI and LOH of nm23H1 gene controlled the development of gallbladder tumor independently in different paths. MSI may be an early stage molecule marker of gallbladder carcinoma. LOH may be molecule marker for the deteriorism of gallbladder tissue, which could inhibit the expression of nm23H1 in local tissue of gallbladder carcinoma and endow it with high aggressive and poor prognosis. Increasing the amount of nm23H1 protein expression could effectively restrain gallbladder carcinoma metastasis and improve prognosis of patients.

  13. Sensitive and selective magnetoimmunosensing platform for determination of the food allergen Ara h 1

    Energy Technology Data Exchange (ETDEWEB)

    Montiel, V. Ruiz-Valdepeñas, E-mail: victor_lega90@hotmail.com [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, E-28040 Madrid (Spain); Campuzano, S., E-mail: susanacr@quim.ucm.es [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, E-28040 Madrid (Spain); Pellicanò, A., E-mail: alessandro.pellicano@unimi.it [Department of Food, Environmental and Nutritional Sciences (DEFENS), University of Milan, Via Celoria 2, 20133 Milan (Italy); Torrente-Rodríguez, R.M., E-mail: rebeca.magnolia@gmail.com [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, E-28040 Madrid (Spain); Reviejo, A.J., E-mail: reviejo@quim.ucm.es [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, E-28040 Madrid (Spain); Cosio, M.S., E-mail: stella.cosio@unimi.it [Department of Food, Environmental and Nutritional Sciences (DEFENS), University of Milan, Via Celoria 2, 20133 Milan (Italy); Pingarrón, J.M., E-mail: pingarro@quim.ucm.es [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, E-28040 Madrid (Spain)

    2015-06-23

    Highlights: • First amperometric magnetoimmunosensor for Ara h 1 determination. • Sensitive and selective detection of Ara h 1 in 2 h. • LOD of 6.3 ng mL{sup −1}. • Determinations in food extracts and saliva. • Potential applicability in food safety and consumer protection. - Abstract: A highly sensitive disposable amperometric immunosensor based on the use of magnetic beads (MBs) is described for determination of Ara h 1, the major peanut allergen, in only 2 h. The approach uses a sandwich configuration involving selective capture and biotinylated detector antibodies and carboxylic acid-modified MBs (HOOC-MBs). The MBs bearing the immunoconjugates are captured by a magnet placed under the surface of a disposable screen-printed carbon electrode (SPCE) and the affinity reactions are monitored amperometrically at −0.20 V (vs a Ag pseudo-reference electrode) in the presence of hydroquinone (HQ) as electron transfer mediator and upon addition of H{sub 2}O{sub 2} as the enzyme substrate. The developed immunosensor exhibits a wide range of linearity between 20.8 and 1000.0 ng mL{sup −1} Ara h 1, a detection limit of 6.3 ng mL{sup −1}, a great selectivity, a good reproducibility with a RSD of 6.3% for six different immunosensors and a useful lifetime of 25 days. The usefulness of the immunosensor was demonstrated by determining Ara h 1 in different matrices (food extracts and saliva). The results correlated properly with those provided by a commercial ELISA method offering a reliable and promising analytical screening tool in the development of user-friendly devices for on-site determination of Ara h 1.

  14. Pandemic (H1N1) 2009 virus infection during pregnancy in South India.

    Science.gov (United States)

    Pramanick, Angsumita; Rathore, Swati; Peter, John V; Moorthy, Mahesh; Lionel, Jessie

    2011-04-01

    To assess the clinical profile of pregnant/puerperal women from a semi-urban Indian population who were infected with pandemic (H1N1) 2009 virus (P[H1N1]2009v) and to evaluate their outcome. In a cross-sectional study, 566 women (79 pregnant/puerperal, 487 nonpregnant) who presented to a tertiary care hospital with influenza-like illness were tested for P(H1N1)2009v by real-time reverse transcriptase polymerase chain reaction. Outcomes measures were the maternal mortality and the perinatal mortality rate (PMR). Twenty (25%) pregnant/puerperal and 144 (30%) nonpregnant women tested positive for P(H1N1)2009v, with 5 pregnant and 3 postpartum women requiring admission to the intensive care unit (ICU). P(H1N1)2009v-related mortality was higher in pregnant than nonpregnant women (25% versus 8%; P=0.04). In the pregnant/puerperal cohort, factors associated with death included delayed presentation (median 6days versus 1.5days in survivors; P=0.007), need for ICU admission (P=0.004), need for ventilation (P=0.001), and renal failure (P=0.001). The PMR was 55.5/1000 births compared with 33.5/1000 births in the hospital overall during the study period. In a low-income country, P(H1N1)2009v infection in pregnancy is associated with considerable mortality. Delayed presentation to a tertiary care center, lack of awareness, and restricted access to treatment might have contributed to the high mortality. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Passive dosing of triclosan in multi-generation tests with copepods - Stable exposure concentrations and effects at the low µg l-1 range

    DEFF Research Database (Denmark)

    Ribbenstedt, Anton; Mustajärvi, Lukas; Breitholtz, Magnus

    2017-01-01

    to test the applicability of passive dosing to maintain stable concentrations of the organochlorine bacteriocide triclosan in the water phase during a 6-week multi-generation population development test with the harpacticoid copepod Nitocra spinipes. Triclosan was loaded into silicone (1000 mg), which...... was used as passive dosing phase in the exposure vials. The distribution ratio for triclosan between silicone and water (Dsilicone-water ) was 10466 ± 1927. A population development test was conducted at three concentration levels of triclosan that were measured to be 3-5 µg L(-1) , 7-11 µg L(-1) and 16...... exerted on juvenile development. Progressively lower development index values in the populations exposed to increasing triclosan concentrations suggest developmental retardation. Our results further stress the need for chronic exposure during ecotoxicity testing in chemical risk assessment as even...

  16. How Does Influenza A (H1N1 Infection Proceed in Allogeneic Stem Cell Transplantation Recipients?

    Directory of Open Access Journals (Sweden)

    Sinem Civriz Bozdağ

    2012-03-01

    Full Text Available Clinical course of H1N1 infection in Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT patients is contraversial. We report three AHSCT patients who were infected with Influenza A/H1N1 infection. All of the patients were diagnosed with different hematological diagnosis and were at different stages of transplantation.All of them were treated with oseltamivir,zanamivir was switched with oseltamivir in one patient. All of the three patients were survived without any complication. Swine flu, can display with different courses and progress with bacterial or other viral infections in immunsupressed patients.

  17. Beam tests and calibration of the H1 liquid argon calorimeter with electrons

    International Nuclear Information System (INIS)

    Andrieu, B.; Ban, J.; Barrelet, E.

    1994-03-01

    Results are presented on the energy calibration of the H1 liquid argon calorimeter modules with electrons from a test beam in the energy range of 3.7 GeV to 80 GeV. The method to determine the calibration for the H1 experiment from these measurements by the use of detailed simulations is described. Various systematic checks of this calibration are given. The calorimeter response is uniform in space within ±1% and linear with energy within ±1%. An average energy resolution of about 11.5%/√(E[GeV]) is achieved. (orig.)

  18. Histamine H1 receptors are expressed in mouse and frog semicircular canal sensory epithelia.

    Science.gov (United States)

    Botta, Laura; Tritto, Simona; Perin, Paola; Laforenza, Umberto; Gastaldi, Giulia; Zampini, Valeria; Zucca, Gianpiero; Valli, Stefano; Masetto, Sergio; Valli, Paolo

    2008-03-05

    Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. Their site and mechanism of action, however, are still poorly understood. To increase our knowledge of the histaminergic system in the vestibular organs, we have investigated the expression of H1 and H3 histamine receptors in the frog and mouse semicircular canal sensory epithelia. Analysis was performed by mRNA reverse transcriptase-PCR, immunoblotting and immunocytochemistry experiments. Our data show that both frog and mouse vestibular epithelia express H1 receptors. Conversely no clear evidence for H3 receptors expression was found.

  19. Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil

    OpenAIRE

    Feifel, David; Pappas, Katherine

    2016-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuron...

  20. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

    Directory of Open Access Journals (Sweden)

    Paola Faverio

    2014-01-01

    Full Text Available We present the results of bronchoalveolar lavage (BAL performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS. Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage.

  1. Clinical characteristics of acute encephalopathies associated with influenza H1N1-2009 in children

    International Nuclear Information System (INIS)

    Watanabe, Yashihiro; Tsuji, Megumi; Sameshima, Kiyoko; Wada, Takahito; Iai, Mizue; Yamashita, Sumimasa; Hayashi, Takuya; Aida, Noriko; Osaka, Hiroshi

    2012-01-01

    We report 12 cases of acute encephalopathy associated with influenza H1N1-2009 treated according to Japanese guideline (2009). In all 12 cases, electroencephalogram presented diffuse or localized high-amplitude slow waves. Brain CT and MRI showed abnormalities in 4 and 6 cases, respectively. We used hypothermia therapy for 5 patients. One patient showed impairment in short term memory, while the rest of the patients showed no sequelae. These 12 cases presented here suggest the early recognition and therapy according to the newly proposed guideline may reduce severe sequelae and mortality by acute encephalopathy associated with influenza H1N1-2009. (author)

  2. The Influenza Virus and the 2009 H1N1 Outbreak

    Science.gov (United States)

    2016-04-08

    MDW/SGVU SUBJECT: Professional Presentation Approval 8 APR 2016 1. Your paper, entitled The Influenza Virus and the 2009 HlNl Outbreak presented at...L TO BE PUBLISHED OR PRESENTED The Influenza Virus and the 2009 H1N1 Outbreak 2. FUNDING RECEIVED FOR THIS STUDY? DYES [g] NO FUNDING SOURCE: I I...336:!. ~~ 2 C-; MARKE. COON. :vtajor. USAF Acting Chic!’. Civil I.aw The Influenza Virus and the 2009 H 1 N 1 Outbreak Thomas. F. Gibbons, Ph.D

  3. Cell Volume Regulation and Signaling in 3T3-L1 Pre-adipocytes and Adipocytes

    DEFF Research Database (Denmark)

    Eduardsen, Kathrine; Larsen, Susanne; Novak, Ivana

    2011-01-01

    Caveolae have been implicated in sensing of cell volume perturbations, yet evidence is still limited and findings contradictory. Here, we investigated the possible role of caveolae in cell volume regulation and volume sensitive signaling in an adipocyte system with high (3T3-L1 adipocytes......); intermediate (3T3-L1 pre-adipocytes); and low (cholesterol-depleted 3T3-L1 pre-adipocytes) caveolae levels. Using large-angle light scattering, we show that compared to pre-adipocytes, differentiated adipocytes exhibit several-fold increased rates of volume restoration following osmotic cell swelling (RVD......) and osmotic cell shrinkage (RVI), accompanied by increased swelling-activated taurine efflux. However, caveolin-1 distribution was not detectably altered after osmotic swelling or shrinkage, and caveolae integrity, as studied by cholesterol depletion or expression of dominant negative Cav-1, was not required...

  4. Time Series Imputation via L1 Norm-Based Singular Spectrum Analysis

    Science.gov (United States)

    Kalantari, Mahdi; Yarmohammadi, Masoud; Hassani, Hossein; Silva, Emmanuel Sirimal

    Missing values in time series data is a well-known and important problem which many researchers have studied extensively in various fields. In this paper, a new nonparametric approach for missing value imputation in time series is proposed. The main novelty of this research is applying the L1 norm-based version of Singular Spectrum Analysis (SSA), namely L1-SSA which is robust against outliers. The performance of the new imputation method has been compared with many other established methods. The comparison is done by applying them to various real and simulated time series. The obtained results confirm that the SSA-based methods, especially L1-SSA can provide better imputation in comparison to other methods.

  5. Critical contrastive rhetoric: The influence of L2 letter writing instruction on L1letter writing

    Directory of Open Access Journals (Sweden)

    Mehrnoosh Fakharzadeh

    2014-08-01

    Full Text Available The present study employed critical contrastive rhetoric to investigate the L2 to L1 transfer of organizational pattern and directness level of speech acts in business complaint letters. By examining the L1 complaint letters of 30 tourism university students in two phases of study, pre and post instruction of English complaint letter, the study revealed that the rhetorical organization of Persian letters are in a state of hybridity. The post instruction comparison of letters, however, showed a tendency towards applying English conventions both in organization and directness level of complaint speech act in the L1 complaint letters. The results also revealed that after instruction the expert in the field of tourism viewed some letters as inappropriate in terms of politeness which is reflected through some lexical items.

  6. Asymmetric light transmission based on coupling between photonic crystal waveguides and L1/L3 cavity

    Science.gov (United States)

    Zhang, Jinqiannan; Chai, Hongyu; Yu, Zhongyuan; Cheng, Xiang; Ye, Han; Liu, Yumin

    2017-09-01

    A compact design of all-optical diode with mode conversion function based on a two-dimensional photonic crystal waveguide and an L1 or L3 cavity is theoretically investigated. The proposed photonic crystal structures comprise a triangular arrangement of air holes embedded in a silicon substrate. Asymmetric light propagation is achieved via the spatial mode match/mismatch in the coupling region. The simulations show that at each cavity's resonance frequency, the transmission efficiency of the structure with the L1 and L3 cavities reach 79% and 73%, while the corresponding unidirectionalities are 46 and 37 dB, respectively. The functional frequency can be controlled by simply adjusting the radii of specific air holes in the L1 and L3 cavities. The proposed structure can be used as a frequency filter, a beam splitter and has potential applications in all-optical integrated circuits.

  7. A Prototype of Tropospheric Delay Correction in L1-SAIF Augmentation

    Science.gov (United States)

    Takeichi, Noboru; Sakai, Takeyasu; Fukushima, Sounosuke; Ito, Ken

    L1-SAIF signal is one of the navigation signals of Quasi-Zenith Satellite System, which provides an augmentation function for mobile users in Japan. This paper presents the detail of the tropospheric delay correction in L1-SAIF augmentation. The tropospheric delay correction information is generated at the ground station using the data collected at GEONET (GPS Earth Observation NETwork) stations. The correction message contains the information of the zenith tropospheric delay (ZTD) values at 105 Tropospheric Grid Points (TGP) in the experiment area. From this message a mobile user can acquire the ZTD value at some neighboring TGPs, and estimate the local ZTD value accurately by using a suitable ZTD model function. Only 3 L1-SAIF messages are necessary to provide all of the tropospheric correction information. Several investigations using the actual data observed at many GEONET stations overall Japan have proved that it is possible to achieve the correction accuracy of 13.2mm (rms).

  8. Development of Real-Time Precise Positioning Algorithm Using GPS L1 Carrier Phase Data

    Directory of Open Access Journals (Sweden)

    Jeong-Ho Joh

    2002-12-01

    Full Text Available We have developed Real-time Phase DAta Processor(RPDAP for GPS L1 carrier. And also, we tested the RPDAP's positioning accuracy compared with results of real time kinematic(RTK positioning. While quality of the conventional L1 RTK positioning highly depend on receiving condition, the RPDAP can gives more stable positioning result because of different set of common GPS satellites, which searched by elevation mask angle and signal strength. In this paper, we demonstrated characteristics of the RPDAP compared with the L1 RTK technique. And we discussed several improvement ways to apply the RPDAP to precise real-time positioning using low-cost GPS receiver. With correcting the discussed weak points in near future, the RPDAP will be used in the field of precise real-time application, such as precise car navigation and precise personal location services.

  9. L1 track triggering with associative memory for the CMS HL-LHC tracker

    International Nuclear Information System (INIS)

    Sabes, D.

    2014-01-01

    One of the proposed solutions currently under study in Compact Muon Solenoid (CMS) collaboration [1] to reconstruct tracks at the first level trigger (L1) for the High Luminosity - Large Hadron Collider (HL-LHC) is based on the usage of Associative Memory [2] (AM) chips. The tracker information is first reduced to suppress low p T tracks and sent to boards equipped with AM chips. Each AM compares the tracker information with pre-calculated expectations (pattern matching) in a very short time (order of a μs), therefore providing a solution to the challenging computational problem of pattern recognition in a very busy environment. Associated to fast track fit methods, like the Hough transform, the AM approach should be able to fulfil the very demanding requirements of L1 tracking. The proposed architecture for the AM-based L1 track reconstruction system will be presented, together with the latest results obtained using a complete software emulation of this system

  10. Efficient L1 regularization-based reconstruction for fluorescent molecular tomography using restarted nonlinear conjugate gradient.

    Science.gov (United States)

    Shi, Junwei; Zhang, Bin; Liu, Fei; Luo, Jianwen; Bai, Jing

    2013-09-15

    For the ill-posed fluorescent molecular tomography (FMT) inverse problem, the L1 regularization can protect the high-frequency information like edges while effectively reduce the image noise. However, the state-of-the-art L1 regularization-based algorithms for FMT reconstruction are expensive in memory, especially for large-scale problems. An efficient L1 regularization-based reconstruction algorithm based on nonlinear conjugate gradient with restarted strategy is proposed to increase the computational speed with low memory consumption. The reconstruction results from phantom experiments demonstrate that the proposed algorithm can obtain high spatial resolution and high signal-to-noise ratio, as well as high localization accuracy for fluorescence targets.

  11. Kinetic imaging of NPC1L1 and sterol trafficking between plasma membrane and recycling endosomes in hepatoma cells

    DEFF Research Database (Denmark)

    Hartwig Petersen, Nicole; Færgeman, Nils J; Yu, Liqing

    2008-01-01

    fluorescent protein (NPC1L1-EGFP) and cholesterol analogues in hepatoma cells. At steady state about 42% of NPC1L1 resided in the transferrin (Tf) positive, sterol enriched endocytic recycling compartment (ERC), while time-lapse microscopy demonstrated NPC1L1 traffic between plasma membrane and ERC...... the ERC to the plasma membrane. NPC1L1-EGFP facilitated transport of fluorescent sterols from the plasma membrane to the ERC. Insulin induced translocation of vesicles containing NPC1L1 and fluorescent sterol from the ERC to the cell membrane. Upon polarization of hepatoma cells NPC1L1 resided almost...... exclusively in the canalicular membrane, where the protein is highly mobile. Our study demonstrates dynamic trafficking of NPC1L1 between cell surface and intracellular compartments and suggests that this transport is involved in NPC1L1 mediated cellular sterol uptake....

  12. A Small Spacecraft Swarm Deployment and Stationkeeping Strategy for Sun-Earth L1 Halo Orbits

    Science.gov (United States)

    Renea Conn, Tracie; Bookbinder, Jay

    2018-01-01

    Spacecraft orbits about the Sun-Earth librarian point L1 have been of interest since the 1950s. An L1 halo orbit was first achieved with the International Sun-Earth Explorer-3 (ISEE-3) mission, and similar orbits around Sun-Earth L1 were achieved in the Solar and Heliospheric Observatory (SOHO), Advanced Composition Explorer (ACE), Genesis, and Deep Space Climate Observatory (DSCOVR) missions. With recent advancements in CubeSat technology, we envision that it will soon be feasible to deploy CubeSats at L1. As opposed to these prior missions where one large satellite orbited alone, a swarm of CubeSats at L1 would enable novel science data return, providing a topology for intersatellite measurements of heliophysics phenomena both spatially and temporally, at varying spatial scales.The purpose of this iPoster is to present a flight dynamics strategy for a swarm of numerous CubeSats orbiting Sun-Earth L1. The presented method is a coupled, two-part solution. First, we present a deployment strategy for the CubeSats that is optimized to produce prescribed, time-varying intersatellite baselines for the purposes of collecting magnetometer data as well as radiometric measurements from cross-links. Second, we employ a loose control strategy that was successfully applied to SOHO and ACE for minimized stationkeeping propellant expenditure. We emphasize that the presented solution is practical within the current state-of-the-art and heritage CubeSat technology, citing capabilities of CubeSat designs that will launch on the upcoming Exploration Mission 1 (EM-1) to lunar orbits and beyond. Within this iPoster, we present animations of the simulated deployment strategy and resulting spacecraft trajectories. Mission design parameters such as total Δv required for long-term station keeping and minimum/maximum/mean spacecraft separation distances are also presented.

  13. A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3

    Science.gov (United States)

    Murthy, Aditya; Li, Yun; Peng, Ivan; Reichelt, Mike; Katakam, Anand Kumar; Noubade, Rajkumar; Roose-Girma, Merone; Devoss, Jason; Diehl, Lauri; Graham, Robert R.; van Lookeren Campagne, Menno

    2014-02-01

    Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.

  14. The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule

    Energy Technology Data Exchange (ETDEWEB)

    Fransen, E.; Vits, L.; Van Camp, G.; Willems, P.J. [Univ. of Antwerp (Belgium)

    1996-07-12

    Mutations in the gene encoding the neuronal cell adhesion molecule L1 are responsible for several syndromes with clinical overlap, including X-linked hydrocephalus (XLH, HSAS), MASA (mental retardation, aphasia, shuffling gait, adducted thumbs) syndrome, complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum (ACC). We review 34 L1 mutations in patients with these phenotypes. 22 refs., 3 figs., 4 tabs.

  15. Genetic variants in CHI3L1 influencing YKL-40 levels

    DEFF Research Database (Denmark)

    Kjaergaard, Alisa D; Johansen, Julia S; Nordestgaard, Børge G

    2013-01-01

    Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population.......Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population....

  16. L1{sub 0} phase formation in ternary FePdNi alloys

    Energy Technology Data Exchange (ETDEWEB)

    Montes-Arango, A.M. [Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA 02115 (United States); Bordeaux, N.C. [Department of Chemical Engineering, Northeastern University, Boston, MA 02115 (United States); Liu, J.; Barmak, K. [Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY 10027 (United States); Lewis, L.H., E-mail: lhlewis@neu.edu [Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA 02115 (United States); Department of Chemical Engineering, Northeastern University, Boston, MA 02115 (United States)

    2015-11-05

    Metallurgical routes to highly metastable phases are required to access new materials with new functionalities. To this end, the stability of the tetragonal chemically ordered L1{sub 0} phase in the ternary Fe–Pd–Ni system is quantified to provide enabling information concerning synthesis of L1{sub 0}-type FeNi, a highly attractive yet highly elusive advanced permanent magnet candidate. Fe{sub 50}Pd{sub 50−x}Ni{sub x} (x = 0–7 at%) samples were arc-melted and annealed at 773 K (500 °C) for 100 h to induce formation of the chemically ordered L1{sub 0} phase. Coupled calorimetry, structural and magnetic investigations allow determination of an isothermal section of the ternary Fe–Pd–Ni phase diagram featuring a single phase L1{sub 0} region near the FePd boundary for x < 6 at%. It is demonstrated that increased Ni content in Fe{sub 50}Pd{sub 50−x}Ni{sub x} alloys systematically decreases the order-disorder transition temperature, resulting in a lower thermodynamic driving force for the ordering phase transformation. The Fe{sub 50}Pd{sub 50−x}Ni{sub x} L1{sub 0} → fcc disordering transformation is determined to occur via a two-step process, with compositionally-dependent enthalpies and transition temperatures. These results highlight the need to investigate ternary alloys with higher Ni content to determine the stability range of the L1{sub 0} phase near the FeNi boundary, thereby facilitating kinetic access to the important L1{sub 0} FeNi ferromagnetic phase. - Highlights: • Chemical ordering in FePdNi enhances intrinsic and extrinsic magnetic properties. • 773 K annealed FePdNi alloys studied show a stable L1{sub 0} phase for Ni ≤ 5.2 at%. • Chemical disordering in FePdNi occurs by a previously unreported two-step process. • Ni additions to FePd dramatically decrease the chemical order-disorder temperature. • The chemical-ordering transformation kinetics are greatly affected by Ni content.

  17. Copolyimide mixed matrix membranes with oriented microporous titanosilicate JDF-L1sheet particles

    OpenAIRE

    Galve, Alejandro; Vispe, Eugenio; Téllez, Carlos; Coronas, Joaquín

    2011-01-01

    JDF-L1 is a microporous titanosilicate exhibiting a layer structure with pore size of about 3 Å. It is consequently an attractive material to separate H2-containing mixtures. This is the reason why JDF-L1, after disaggregation by means of hexadecyltrimethylammonium surfactant, has been combined with a carboxyl group containing copolyimide (6FDA-4MPD/6FDA-DABA 4:1) to produce mixed matrix membranes, which were applied to the separation of H2/CH4 and O2/N2 mixtures. Additionally, due to the she...

  18. Direct synthesis of L1 type Fe-Pt nanoparticles using microwave-polyol method

    International Nuclear Information System (INIS)

    Minami, Rumiko; Kitamoto, Yoshitaka; Chikata, Tsukasa; Kato, Shunsaku

    2005-01-01

    We report the synthesis of Fe-Pt nanoparticles with microwave irradiation during polyol-reduction reaction. Chemically ordered Fe-Pt nanoparticles with L1 structure are fabricated at 250 deg. C using a microwave-polyol method without any post-synthesis treatments. Moessbauer analyses reveal the nanoparticles have partially ordered L1 structure. The partially ordered Fe-Pt nanoparticles exhibit coercivity of 3.4 kOe, saturation magnetization of 49 emu/g, and anisotropy field of 83 kOe at room temperature

  19. Design of L1 -Adaptive Controller for Single Axis Positioning Table

    Directory of Open Access Journals (Sweden)

    Amjad Jalil Humaidi

    2017-11-01

    Full Text Available L1 adaptive controller has proven to provide fast adaptation with guaranteed transients in a large variety of systems. It is commonly used for controlling systems with uncertain time-varying unknown parameters. The effectiveness of L1 adaptive controller for position control of single axis has been examined and compared with Model Reference Adaptive Controller (MRAC. The Linear servo motor is one of the main constituting elements of the x-y table which is mostly used in automation application. It is characterized by time-varying friction and disturbance

  20. Experimental study on L-[1-13C] phenylalanine breath test for quantitative assessment of liver function with animal

    International Nuclear Information System (INIS)

    Yan Weili; Fudan Univ., Shanghai; Lin Xiangtong; Sun Dayu; Jiang Yibin; Sun Xu; Rong Lan; Liang Qi

    2006-01-01

    Objective: Using a small animal breath test model we designed and L-[1- 13 C] phenylalanine breath test ( 13 C-PheBT) of rats, the authors investigated its feasibility and validity and determined effective parameter of the test. Methods: Twenty male Sprague-Dawley (SD) weighting 280-290 g rats randomized into two groups acute hepatitis rats (n=10) and control rats (n=10). Hepatitis was induced by carbon tetrachloride (CCl 4 ) olive oil administration through intragastric gavage. PheBT was assisted by small mechanical ventilator improved and air samples were collected discontinuously, 20 mg/kg body weight L-[1- 13 C] phenylalanine ( 13 C-Phe) was administered intravenously. Twenty-nine breath samples were taken before and different intervals within sixty minutes after administration. 13 Cenrichment was measured by isotope ratio mass spectrometer. Results: All time phase curves of 13 C enrichment in rat breath reached a peak almost at 2 min after the intravenous administration of 13 C-Phe. The PheBT parameters, 13 C excretion rate constant (PheBT-K), of CCl 4 hepatitis rats were significantly lower than that of normal control rats [(2.45 ± 0.25) x 10 -2 min -1 vs (2.98 ± 0.19) x 10 -2 min -1 , t = 5.40, P 13 C fast phase disposition constant did not statistically differ between the two groups (t=0.58, P>0.05). PheBT-K had significant negative cor-relation with serum ALT, AKP, TBA and total bilirum TBIL (the correlation coefficient r is -0.74, -0.73, -0.82 and -0.67 respectively, P 0.05). Conclusions: It was indicated that the small animal breath test model we designed was a virtual tool to use in experimental study on breath test and PheBT-K was a sensitive index. (authors)

  1. Trichosanthes cucumerina extracts enhance glucose uptake and regulate adiponectin and leptin concentrations in 3T3-L1 adipocytes model

    Directory of Open Access Journals (Sweden)

    Sassi, A.,

    2017-10-01

    Full Text Available Trichosanthes cucumerina (Cucurbitaceae commonly known as Snake gourd or Labu Ular is considered the largest genre in the Cucurbitaceae family and is mainly found in the southeast areas of Asia. It has been used in Ayurvedic medicine as a treatment for certain diseases such as Diabetes mellitus, but these acclaims lack scientific-based evidence. In this study, water and ethanol extracts of three parts of Trichosanthes cucumerina namely; whole vegetable, peels, and seeds, were assessed for toxicity through a cell viability assay using 3T3-L1 pre-adipocytes model which revealed a maximum toleration concentration of 0.063 mg/mL. The extracts were further tested on adipocytes’ differentiation and positively showed a stimulation of lipid droplets formation during adipogenesis and significantly (p<0.001 increased glycerol release levels (75.34±3.69 μg/ml during adipolysis. The extracts also significantly (p<0.001 promoted the uptake of glucose into the cells (2636.22±91.33 Bq in an action similar to that of insulin. Similar results were observed during ELISA assay with a significant increase (p<0.001 in adiponectin concentrations (3593.1±225.25 ng/mL and a decrease in leptin concentrations (23870±5066.07 pg/mL. The present study results indicate a beneficial effect of Trichosanthes cucumerina extracts on adipogenesis, adipolysis and glucose uptake, in addition to a regulation of adiponectin and leptin concentrations in 3T3-L1 adipocytes which can be of clinical importance in energy regulation which is a key factor in treating diabetes, obesity, and metabolic syndrome.

  2. The Effects of Giving and Receiving Marginal L1 Glosses on L2 Vocabulary Learning by Upper Secondary Learners

    Science.gov (United States)

    Samian, Hosein Vafadar; Foo, Thomas Chow Voon; Mohebbi, Hassan

    2016-01-01

    This paper reports the findings of a study that investigated the effect of giving and receiving marginal L1 glosses on L2 vocabulary learning. To that end, forty nine Iranian learners of English were assigned to three different experimental conditions including marginal L1 glosses Giver (n = 17), marginal L1 glosses Receiver (n = 17), and no…

  3. L2 Acquisition of Prosodic Properties of Speech Rhythm: Evidence from L1 Mandarin and German Learners of English

    Science.gov (United States)

    Li, Aike; Post, Brechtje

    2014-01-01

    This study examines the development of speech rhythm in second language (L2) learners of typologically different first languages (L1s) at different levels of proficiency. An empirical investigation of durational variation in L2 English productions by L1 Mandarin learners and L1 German learners compared to native control values in English and the…

  4. 2-[1-(1-Naphthyl-1H-1,2,3-triazol-4-yl]pyridine

    Directory of Open Access Journals (Sweden)

    Ulrich S. Schubert

    2009-05-01

    Full Text Available In the crystal structure of the title compound, C17H12N4, the angle between the naphthalene and 1H-1,2,3-triazole ring systems is 71.02 (4° and that between the pyridine and triazole rings is 8.30 (9°.

  5. A diagnostic for 2D density profiles in Heliac H-1

    International Nuclear Information System (INIS)

    Howard, J.; Sharp, L.E.

    1989-01-01

    A novel multi-view scanning interferometer is described. An air turbine driven scanning rotating grating wheel is used to produce ∼ 30 distinct spatial channels in four equi-spaced views of the H-1 plasma. The interferometer signals, derived from just three detectors, are multiplexed in time with a resolution of ∼ 1 ms. 7 refs., 3 figs

  6. Factores genéticos en casos graves de gripe (H1N1 2009

    Directory of Open Access Journals (Sweden)

    Francesc Calafell i Majó

    2011-01-01

    Full Text Available La pandemia de gripe (H1N1 2009 generó una serie de cuestiones, entre las cuales estuvo que entre un 25 y un 30% de los casos graves de gripe no presentaron ningún factor de riesgo obvio. Hipotetizamos que un elemento que puede contribuir a la respuesta son factores de riesgo gené ticos del huésped involucrados en la mala progresió n de la enfermedad. Varios indicios nos llevaron a esta hipótesis: estudios de agregación familiar en islandeses y mormones de Utah muestran una cierta heredabilidad de la mortalidad por gripe; se conocen casi 300 genes humanos necesarios para la replicació n del virus de la gripe; y los pacientes más graves de gripe (H1N12009 mostraron una desregulació n del sistema inmune adaptativo. Estamos abordando este problema mediante un diseñ o caso-control (casos hospitalizados de gripe (H1N12009 confirmados contra casos ambulatorios, tambié n confirmados para (H1N12009, en el que se genotiparán más de un milló n de polimorfismos de cambios de nucleó tido (SNPs y de variació n de número de copia (CNVs en casos y controles.

  7. Pandemic influenza A/H1N1 virus incursion into Africa: countries ...

    African Journals Online (AJOL)

    Pandemic influenza A/H1N1 virus incursion into Africa: countries, hosts and ... features are important for planning control measures between countries and to ... in humans, infections in pigs earlier reported in America, Europe and Asia were ...

  8. Transmission of Hemagglutinin D222G Mutant Strain of Pandemic (H1N1) 2009 Virus

    Science.gov (United States)

    Facchini, Marzia; Spagnolo, Domenico; De Marco, Maria A.; Calzoletti, Laura; Zanetti, Alessandro; Fumagalli, Roberto; Tanzi, Maria L.; Cassone, Antonio; Rezza, Giovanni; Donatelli, Isabella

    2010-01-01

    A pandemic (H1N1) 2009 virus strain carrying the D222G mutation was identified in a severely ill man and was transmitted to a household contact. Only mild illness developed in the contact, despite his obesity and diabetes. The isolated virus reacted fully with an antiserum against the pandemic vaccine strain. PMID:20409386

  9. IgE epitopes of intact and digested Ara h 1

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Nielsen, H.; Madsen, Charlotte Bernhard

    2012-01-01

    epitopes have been suggested to be of great importance. ObjectiveThe aim of this study was to identify IgE specific epitopes of intact and digested Ara h 1, and to compare epitope patterns between humans and rats. MethodsSera from five peanut allergic patients and five Brown Norway rats were used...... to identify intact and digested Ara h 1-specific IgE epitopes by competitive immunoscreening of a phage-displayed random hepta-mer peptide library using polyclonal IgE from the individual sera. The resulting peptide sequences were mapped on the surface of a three-dimensional structure of the Ara h 1 molecule...... to mimic epitopes using a computer-based algorithm. ResultsPatients as well as rats were shown to have individual IgE epitope patterns. All epitope mimics were conformational and found to cluster into three different areas of the Ara h 1 molecule. Five epitope motifs were identified by patient IgE, which...

  10. Outcomes of influenza A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E

    2014-01-01

    BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were...

  11. The Influenza A(H1N1)v Pandemic : An Exploratory System Dynamics Approach

    NARCIS (Netherlands)

    Pruyt, E.; Hamarat, C.

    2010-01-01

    This paper presents a small exploratory System Dynamics model related to the dynamics of the 2009 flu pandemic, also known as the Mexican flu, swine flu, or A(H1N1)v. The model was developed in May 2009 in order to quickly foster understanding about the possible dynamics of this new flu variant and

  12. Chalcones as novel influenza A (H1N1) neuraminidase inhibitors from Glycyrrhiza inflata

    DEFF Research Database (Denmark)

    Dao, Trong Tuan; Nguyen, Phi Hung; Lee, Hong Sik

    2011-01-01

    The emergence of highly pathogenic influenza A virus strains, such as the new H1N1 swine influenza (novel influenza), represents a serious threat to global human health. During our course of an anti-influenza screening program on natural products, one new licochalcone G (1) and seven known (2-8) ...

  13. Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.

    Science.gov (United States)

    Gohil, Devanshi; Kothari, Sweta; Shinde, Pramod; Meharunkar, Rhuta; Warke, Rajas; Chowdhary, Abhay; Deshmukh, Ranjana

    2017-08-01

    Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country. Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period. Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains. Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites. Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion. Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually. The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.

  14. Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program

    NARCIS (Netherlands)

    Salmon, Daniel A.; Akhtar, Aysha; Mergler, Michelle J.; Vannice, Kirsten S.; Izurieta, Hector; Ball, Robert; Lee, Grace M.; Vellozzi, Claudia; Garman, Patrick; Cunningham, Francesca; Gellin, Bruce; Koh, Howard; Lurie, Nicole

    The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by

  15. Track finding and fitting in the H1 Forward Track Detector

    International Nuclear Information System (INIS)

    Burke, S.; Henderson, R.C.W.; Maxfield, S.J.; Patel, G.D.; Morris, J.V.; Sankey, D.P.C.; Skillicorn, I.O.

    1995-07-01

    The tracking environment in the H1 Forward Tracker Detector, where the hit multiplicity from proton fragments is high, is parituclarly hostile. The techniques and software which have been developed for pattern recognition and Kalman fitting of charged particle tracks in this region are described in detail. (orig.)

  16. Learning from Successful School-based Vaccination Clinics during 2009 pH1N1

    Science.gov (United States)

    Klaiman, Tamar; O'Connell, Katherine; Stoto, Michael A.

    2014-01-01

    Background: The 2009 H1N1 vaccination campaign was the largest in US history. State health departments received vaccines from the federal government and sent them to local health departments (LHDs) who were responsible for getting vaccines to the public. Many LHD's used school-based clinics to ensure children were the first to receive limited…

  17. Antivirals Use During the Pandemic H1N1 2009 Outbreak

    Centers for Disease Control (CDC) Podcasts

    2012-01-23

    Charisma Atkins, CDC public health analyst, discusses antiviral use during the 2009 H1N1 pandemic flu outbreak.  Created: 1/23/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/23/2012.

  18. 75 FR 10395 - Attestation Applications by Facilities Temporarily Employing H-1C Nonimmigrant Foreign Workers as...

    Science.gov (United States)

    2010-03-05

    ... collectively bargained wage rates, the IFR stipulated that the State Workforce Agency (SWA) shall determine the... accorded flexibility to address prevailing wage rates across diverse professional occupations that are not... workforce through the H-1C program would protect U.S. workers from any negative effect on wages or terms and...

  19. Influenza Virus A (H1N1) in Giant Anteaters (Myrmecophaga tridactyla)

    OpenAIRE

    Nofs, Sally; Abd-Eldaim, Mohamed; Thomas, Kathy V.; Toplon, David; Rouse, Dawn; Kennedy, Melissa

    2009-01-01

    In February 2007, an outbreak of respiratory disease occurred in a group of giant anteaters (Myrmecophaga tridactyla) at the Nashville Zoo. Isolates from 2 affected animals were identified in March 2007 as a type A influenza virus related to human influenza subtype H1N1.

  20. Influenza virus A (H1N1) in giant anteaters (Myrmecophaga tridactyla).

    Science.gov (United States)

    Nofs, Sally; Abd-Eldaim, Mohamed; Thomas, Kathy V; Toplon, David; Rouse, Dawn; Kennedy, Melissa

    2009-07-01

    In February 2007, an outbreak of respiratory disease occurred in a group of giant anteaters (Myrmecophaga tridactyla) at the Nashville Zoo. Isolates from 2 affected animals were identified in March 2007 as a type A influenza virus related to human influenza subtype H1N1.