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Sample records for janus tyrosinkinase 2-mutationen

  1. Ocean Drilling Program: Janus Web Database

    Science.gov (United States)

    JANUS Database Send questions/comments about the online database Request data not available online Janus database Search the ODP/TAMU web site ODP's main web site Janus Data Model Data Migration Overview in Janus Data Types and Examples Leg 199, sunrise. Janus Web Database ODP and IODP data are stored in

  2. Encapsulation by Janus spheroids

    OpenAIRE

    Li, Wei; Liu, Ya; Brett, Genevieve; Gunton, James D.

    2011-01-01

    The micro/nano encapsulation technology has acquired considerable attention in the fields of drug delivery, biomaterial engineering, and materials science. Based on recent advances in chemical particle synthesis, we propose a primitive model of an encapsulation system produced by the self-assembly of Janus oblate spheroids, particles with oblate spheroidal bodies and two hemi-surfaces coded with dissimilar chemical properties. Using Monte Carlo simulation, we investigate the encapsulation sys...

  3. JANUS characterization report

    International Nuclear Information System (INIS)

    1996-07-01

    The JANUS Reactor was operated from 1965 to 1992. All of the fuel was removed and shipped offsite in 1993. To provide information for use in finalizing the planning for the decommissioning of the reactor, the Health Physics Section of Argonne National Laboratory performed a characterization of the facility in January and February 1996. The characterization included measurements for radioactivity, hazardous materials, lead in wall paint, and asbestos. Measurements and smear samples for surface contamination were collected from every wall, ceiling and floor of the facility. Samples to determine activity concentrations were collected from vertical and horizontal corings into the reactor shield and foundation, and from coring into walls of the high dose and low dose rooms. Soil samples were collected outdoors from two drill holes, one south and one north of the JANUS exhaust stack. The predominant radionuclides detected were 60 Co, 152 Eu, and 154 Eu. The highest exposure rate was 175 mR/h at the center of the reactor core. No hazardous materials were found in pits or sumps. There are 20 identified areas with asbestos and 7 objects with lead based paint

  4. JANUS characterization report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-07-01

    The JANUS Reactor was operated from 1965 to 1992. All of the fuel was removed and shipped offsite in 1993. To provide information for use in finalizing the planning for the decommissioning of the reactor, the Health Physics Section of Argonne National Laboratory performed a characterization of the facility in January and February 1996. The characterization included measurements for radioactivity, hazardous materials, lead in wall paint, and asbestos. Measurements and smear samples for surface contamination were collected from every wall, ceiling and floor of the facility. Samples to determine activity concentrations were collected from vertical and horizontal corings into the reactor shield and foundation, and from coring into walls of the high dose and low dose rooms. Soil samples were collected outdoors from two drill holes, one south and one north of the JANUS exhaust stack. The predominant radionuclides detected were {sup 60}Co, {sup 152}Eu, and {sup 154}Eu. The highest exposure rate was 175 mR/h at the center of the reactor core. No hazardous materials were found in pits or sumps. There are 20 identified areas with asbestos and 7 objects with lead based paint.

  5. Scattering behaviour of Janus particles

    CERN Document Server

    Kaya, H

    2002-01-01

    Recent advances in polymer synthesis has produced so-called Janus micelles: tailor-made copolymer structures in which the blocks constitute separate moieties. We present expressions for the form factors, P(Q), and the radii of gyration, R sub g , of Janus particles with spherical and cylindrical morphology and check their validity by comparison to simulated scattering data, calculated from Monte Carlo generations of the pair-distance distribution function, p(r). The effect of block incompatibilities on the scattering is briefly discussed. (orig.)

  6. Thermocapillary reorientation of Janus drops

    Science.gov (United States)

    Rosales, Rodolfo; Saenz, Pedro

    2017-11-01

    Janus drops, named after the Ancient Roman two-faced god, are liquid drops formed from two immiscible fluids. Experimental observations indicate that a Janus drop may re-orientate in response to an applied external thermal gradient due to the Marangoni effect. Depending on the angle between the interior interface and the direction of the temperature gradient, disparities in the physical properties of the constituent liquids may lead to asymmetries in the thermocapillary flow. As a result, the drop will move along a curved path until a torque-free configuration is achieved, point after which it will continue on a straight trajectory. Here, we present the results of a theoretical investigation of this realignment phenomenon in the Stokes regime and in the limit of non-deformable interfaces. A 3D semi-analytical method in terms of polar spherical harmonics is developed to characterize and rationalize the hydrodynamic response (forces and torques), flow (velocity and temperature distribution) and trajectory of a Janus drop moving during the temperature-driven reorientation process. Furthermore, we discuss how this phenomenon may be exploited to develop dynamically reconfigurable micro-lenses. This work was partially supported by the US National Science Foundation through Grants DMS-1614043 and DMS-1719637.

  7. Selective encapsulation by Janus particles

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wei, E-mail: wel208@mrl.ucsb.edu [Materials Research Laboratory, University of California, Santa Barbara, California 93106 (United States); Ruth, Donovan; Gunton, James D. [Department of Physics, Lehigh University, Bethlehem, Pennsylvania 18015 (United States); Rickman, Jeffrey M. [Department of Physics, Lehigh University, Bethlehem, Pennsylvania 18015 (United States); Department of Materials Science and Engineering, Lehigh University, Bethlehem, Pennsylvania 18015 (United States)

    2015-06-28

    We employ Monte Carlo simulation to examine encapsulation in a system comprising Janus oblate spheroids and isotropic spheres. More specifically, the impact of variations in temperature, particle size, inter-particle interaction range, and strength is examined for a system in which the spheroids act as the encapsulating agents and the spheres as the encapsulated guests. In this picture, particle interactions are described by a quasi-square-well patch model. This study highlights the environmental adaptation and selectivity of the encapsulation system to changes in temperature and guest particle size, respectively. Moreover, we identify an important range in parameter space where encapsulation is favored, as summarized by an encapsulation map. Finally, we discuss the generalization of our results to systems having a wide range of particle geometries.

  8. Janus Monolayer Transition-Metal Dichalcogenides.

    Science.gov (United States)

    Zhang, Jing; Jia, Shuai; Kholmanov, Iskandar; Dong, Liang; Er, Dequan; Chen, Weibing; Guo, Hua; Jin, Zehua; Shenoy, Vivek B; Shi, Li; Lou, Jun

    2017-08-22

    The crystal configuration of sandwiched S-Mo-Se structure (Janus SMoSe) at the monolayer limit has been synthesized and carefully characterized in this work. By controlled sulfurization of monolayer MoSe 2 , the top layer of selenium atoms is substituted by sulfur atoms, while the bottom selenium layer remains intact. The structure of this material is systematically investigated by Raman, photoluminescence, transmission electron microscopy, and X-ray photoelectron spectroscopy and confirmed by time-of-flight secondary ion mass spectrometry. Density functional theory (DFT) calculations are performed to better understand the Raman vibration modes and electronic structures of the Janus SMoSe monolayer, which are found to correlate well with corresponding experimental results. Finally, high basal plane hydrogen evolution reaction activity is discovered for the Janus monolayer, and DFT calculation implies that the activity originates from the synergistic effect of the intrinsic defects and structural strain inherent in the Janus structure.

  9. Geometric asymmetry driven Janus micromotors

    Science.gov (United States)

    Zhao, Guanjia; Pumera, Martin

    2014-09-01

    The production and application of nano-/micromotors is of great importance. In order for the motors to work, asymmetry in their chemical composition or physical geometry must be present if no external asymmetric field is applied. In this paper, we present a ``coconut'' micromotor made of platinum through the partial or complete etching of the silica templates. It was shown that although both the inner and outer surfaces are made of the same material (Pt), motion of the structure can be observed as the convex surface is capable of generating oxygen bubbles. This finding shows that not only the chemical asymmetry of the micromotor, but also its geometric asymmetry can lead to fast propulsion of the motor. Moreover, a considerably higher velocity can be seen for partially etched coconut structures than the velocities of Janus or fully etched, shell-like motors. These findings will have great importance on the design of future micromotors.The production and application of nano-/micromotors is of great importance. In order for the motors to work, asymmetry in their chemical composition or physical geometry must be present if no external asymmetric field is applied. In this paper, we present a ``coconut'' micromotor made of platinum through the partial or complete etching of the silica templates. It was shown that although both the inner and outer surfaces are made of the same material (Pt), motion of the structure can be observed as the convex surface is capable of generating oxygen bubbles. This finding shows that not only the chemical asymmetry of the micromotor, but also its geometric asymmetry can lead to fast propulsion of the motor. Moreover, a considerably higher velocity can be seen for partially etched coconut structures than the velocities of Janus or fully etched, shell-like motors. These findings will have great importance on the design of future micromotors. Electronic supplementary information (ESI) available: Additional SEM images, data analysis, Videos S

  10. Janus kinase inhibitors: jackpot or potluck?

    Directory of Open Access Journals (Sweden)

    Pavithran Keechilat

    2012-06-01

    Full Text Available The reports of a unique mutation in the Janus kinase-2 gene (JAK2 in polycythemia vera by several independent groups in 2005 quickly spurred the development of the Janus kinase inhibitors. In one of the great victories of translational research in recent times, the first smallmolecule Janus kinase inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the management of a subset of myeloproliferative neoplasms (MPN: primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only covers high-risk and intermediate-2 risk myelofibrosis, inhibitors with greater potency are likely to offer better disease control and survival advantage in patients belonging to these categories, and possibly to the low-risk and intermediate-1 risk categories of MPN as well. But use of the Janus kinase inhibitors also probably has certain disadvantages, such as toxicity, resistance, withdrawal phenomenon, non-reversal of histology, and an implausible goal of disease clone eradication, some of which could offset the gains. In spite of this, Janus kinase inhibitors are here to stay, and for use in more than just myeloproliferative neoplasms.

  11. Self-assembly of hydrofluorinated Janus graphene monolayer

    DEFF Research Database (Denmark)

    Jin, Yakang; Xue, Qingzhong; Zhu, Lei

    2016-01-01

    With remarkably interesting surface activities, two-dimensional Janus materials arouse intensive interests recently in many fields. We demonstrate by molecular dynamic simulations that hydrofluorinated Janus graphene (J-GN) can self-assemble into Janus nanoscroll (J-NS) at room temperature. The van...

  12. Geometric Monte Carlo and black Janus geometries

    Energy Technology Data Exchange (ETDEWEB)

    Bak, Dongsu, E-mail: dsbak@uos.ac.kr [Physics Department, University of Seoul, Seoul 02504 (Korea, Republic of); B.W. Lee Center for Fields, Gravity & Strings, Institute for Basic Sciences, Daejeon 34047 (Korea, Republic of); Kim, Chanju, E-mail: cjkim@ewha.ac.kr [Department of Physics, Ewha Womans University, Seoul 03760 (Korea, Republic of); Kim, Kyung Kiu, E-mail: kimkyungkiu@gmail.com [Department of Physics, Sejong University, Seoul 05006 (Korea, Republic of); Department of Physics, College of Science, Yonsei University, Seoul 03722 (Korea, Republic of); Min, Hyunsoo, E-mail: hsmin@uos.ac.kr [Physics Department, University of Seoul, Seoul 02504 (Korea, Republic of); Song, Jeong-Pil, E-mail: jeong_pil_song@brown.edu [Department of Chemistry, Brown University, Providence, RI 02912 (United States)

    2017-04-10

    We describe an application of the Monte Carlo method to the Janus deformation of the black brane background. We present numerical results for three and five dimensional black Janus geometries with planar and spherical interfaces. In particular, we argue that the 5D geometry with a spherical interface has an application in understanding the finite temperature bag-like QCD model via the AdS/CFT correspondence. The accuracy and convergence of the algorithm are evaluated with respect to the grid spacing. The systematic errors of the method are determined using an exact solution of 3D black Janus. This numerical approach for solving linear problems is unaffected initial guess of a trial solution and can handle an arbitrary geometry under various boundary conditions in the presence of source fields.

  13. The Janus fluid a theoretical perspective

    CERN Document Server

    Fantoni, Riccardo

    2013-01-01

    The state-of-the-art in the theoretical statistical physics treatment of the Janus fluid is reported with a bridge between new research results published in journal articles and a contextual literature review. Recent Monte Carlo simulations on the Kern and Frenkel model of the Janus fluid have revealed that in the vapor phase, below the critical point, there is the formation of preferred inert clusters made up of a well-defined number of particles: the micelles and the vesicles. This is responsible for a re-entrant gas branch of the gas-liquid binodal. Detailed account of this findings are given in the first chapter where the Janus fluid is introduced as a product of new sophisticated synthesis laboratory techniques. In the second chapter a cluster theory is developed to approximate the exact clustering properties stemming from the simulations. It is shown that the theory is able to reproduce semi-quantitatively the micellization phenomenon.

  14. Janus droplet as a catalytic micromotor

    Science.gov (United States)

    Shklyaev, Sergey

    2015-06-01

    Self-propulsion of a Janus droplet in a solution of surfactant, which reacts on a half of a drop surface, is studied theoretically. The droplet acts as a catalytic motor creating a concentration gradient, which generates its surface-tension-driven motion; the self-propulsion speed is rather high, 60 μ \\text{m/s} and more. This catalytic motor has several advantages over other micromotors: simple manufacturing, easily attained neutral buoyancy. In contrast to a single-fluid droplet, which demonstrates a self-propulsion as a result of symmetry breaking instability, for the Janus one no stability threshold exists; hence, the droplet radius can be scaled down to micrometers.

  15. Janus neodymium glass laser operations manual

    International Nuclear Information System (INIS)

    Auerbach, J.M.; Holmes, N.C.; Trainor, R.J.

    1978-01-01

    A manual, prepared to guide personnel in operating and maintaining the Janus glass laser system, is presented. System components are described in detail. Step-by-step procedures are presented for firing the laser and for performing routine maintenance and calibration procedures

  16. CAMAC - the Janus face of digital equipment

    International Nuclear Information System (INIS)

    Johansson, R.

    1977-01-01

    A problem which arises when many instruments are found in major systems is that of communication between them. The CAMAC system is constructed on the principle of the addressable bus, obtained from data-technique. The system has adopted the well-known Janus faces as a symbol to denote: 'equality towards everyone'. (A.D.N.)

  17. Janus cyclic peptide-polymer nanotubes

    Science.gov (United States)

    Danial, Maarten; My-Nhi Tran, Carmen; Young, Philip G.; Perrier, Sébastien; Jolliffe, Katrina A.

    2013-11-01

    Self-assembled nanotubular structures have numerous potential applications but these are limited by a lack of control over size and functionality. Controlling these features at the molecular level may allow realization of the potential of such structures. Here we report a new generation of self-assembled cyclic peptide-polymer nanotubes with dual functionality in the form of either a Janus or mixed polymeric corona. A ‘relay’ synthetic strategy is used to prepare nanotubes with a demixing or mixing polymeric corona. Nanotube structure is assessed in solution using 1H-1H nuclear Overhauser effect spectroscopy NMR, and in bulk using differential scanning calorimetry. The Janus nanotubes form artificial pores in model phospholipid bilayers. These molecules provide a viable pathway for the development of intriguing nanotubular structures with dual functionality via a demixing or a mixing polymeric corona and may provide new avenues for the creation of synthetic transmembrane protein channel mimics.

  18. Microdosimetric spectra measurements of JANUS neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, I.R.; Williamson, F.S.

    1985-01-01

    Neutron radiation from the JANUS reactor at Argonne National Laboratory is being used with increasing frequency for major biological experiments. The fast neutron spectrum has a Kerma-weighted mean energy of 0.8 MeV and low gamma-ray contamination. In 1984 the JANUS fission converter plate of highly enriched uranium was replaced by one made of low-enriched uranium. We recorded microdosimetric spectra at several different positions in the high-flux irradiation room of JANUS before the change of the converter plate. Each set of measurements consisted of spectra taken at three different site diameters (0.5, 1.0, and 5.0 ..mu..m) and in both ''attenuator up'' and ''attenuator down'' configurations. At two conventional dosimetry reference positions, two sets of measurements were recorded. At three biological reference positions, measurements simulating several biological irradiation conditions, were taken. The dose rate at each position was estimated and compared with dose rates obtained previously by conventional dosimetry. Comparison of the different measurements showed no major change in spectra as a function of position or irradiation condition. First results from similar sets of measurements recorded after the installment of the new converter plate indicate no major change in the spectra. 11 refs., 4 figs., 5 tabs.

  19. Microdosimetric spectra measurements of JANUS neutrons

    International Nuclear Information System (INIS)

    Marshall, I.R.; Williamson, F.S.

    1985-01-01

    Neutron radiation from the JANUS reactor at Argonne National Laboratory is being used with increasing frequency for major biological experiments. The fast neutron spectrum has a Kerma-weighted mean energy of 0.8 MeV and low gamma-ray contamination. In 1984 the JANUS fission converter plate of highly enriched uranium was replaced by one made of low-enriched uranium. We recorded microdosimetric spectra at several different positions in the high-flux irradiation room of JANUS before the change of the converter plate. Each set of measurements consisted of spectra taken at three different site diameters (0.5, 1.0, and 5.0 μm) and in both ''attenuator up'' and ''attenuator down'' configurations. At two conventional dosimetry reference positions, two sets of measurements were recorded. At three biological reference positions, measurements simulating several biological irradiation conditions, were taken. The dose rate at each position was estimated and compared with dose rates obtained previously by conventional dosimetry. Comparison of the different measurements showed no major change in spectra as a function of position or irradiation condition. First results from similar sets of measurements recorded after the installment of the new converter plate indicate no major change in the spectra. 11 refs., 4 figs., 5 tabs

  20. An Optically Driven Bistable Janus Rotor with Patterned Metal Coatings.

    Science.gov (United States)

    Zong, Yiwu; Liu, Jing; Liu, Rui; Guo, Honglian; Yang, Mingcheng; Li, Zhiyuan; Chen, Ke

    2015-11-24

    Bistable rotation is realized for a gold-coated Janus colloidal particle in an infrared optical trap. The metal coating on the Janus particles are patterned by sputtering gold on a monolayer of closely packed polystyrene particles. The Janus particle is observed to stably rotate in an optical trap. Both the direction and the rate of rotation can be experimentally controlled. Numerical calculations reveal that the bistable rotation is the result of spontaneous symmetry breaking induced by the uneven curvature of the coating patterns on the Janus sphere. Our results thus provide a simple method to construct large quantities of fully functional rotary motors for nano- or microdevices.

  1. Double anisotropic electrically conductive flexible Janus-typed membranes.

    Science.gov (United States)

    Li, Xiaobing; Ma, Qianli; Tian, Jiao; Xi, Xue; Li, Dan; Dong, Xiangting; Yu, Wensheng; Wang, Xinlu; Wang, Jinxian; Liu, Guixia

    2017-12-07

    Novel type III anisotropic conductive films (ACFs), namely flexible Janus-typed membranes, were proposed, designed and fabricated for the first time. Flexible Janus-typed membranes composed of ordered Janus nanobelts were constructed by electrospinning, which simultaneously possess fluorescence and double electrically conductive anisotropy. For the fabrication of the Janus-typed membrane, Janus nanobelts comprising a conductive side and an insulative-fluorescent side were primarily fabricated, and then the Janus nanobelts are arranged into parallel arrays using an aluminum rotary drum as the collector to obtain a single anisotropically conductive film. Subsequently, a secondary electrospinning process was applied to the as-prepared single anisotropically conductive films to acquire the final Janus-typed membrane. For this Janus-typed membrane, namely its left-to-right structure, anisotropic electrical conduction synchronously exists on both sides, and furthermore, the two electrically conductive directions are perpendicular. By modulating the amount of Eu(BA) 3 phen complex and conducting polyaniline (PANI), the characteristics and intensity of the fluorescence-electricity dual-function in the membrane can be tuned. The high integration of this peculiar Janus-typed membrane with simultaneous double electrically conductive anisotropy-fluorescent dual-functionality is successfully realized in this study. This design philosophy and preparative technique will provide support for the design and construction of new types of special nanostructures with multi-functionality.

  2. Janus droplets: liquid marbles coated with dielectric/semiconductor particles.

    Science.gov (United States)

    Bormashenko, Edward; Bormashenko, Yelena; Pogreb, Roman; Gendelman, Oleg

    2011-01-04

    The manufacturing of water droplets wrapped with two different powders, carbon black (semiconductor) and polytetrafluoroethylene (dielectric), is presented. Droplets composed of two hemispheres (Janus droplets) characterized by various physical and chemical properties are reported first. Watermelon-like striped liquid marbles are reported. Janus droplets remained stable on solid and liquid supports and could be activated with an electric field.

  3. Janus monolayers of transition metal dichalcogenides

    KAUST Repository

    Lu, Ang-Yu

    2017-05-15

    Structural symmetry-breaking plays a crucial role in determining the electronic band structures of two-dimensional materials. Tremendous efforts have been devoted to breaking the in-plane symmetry of graphene with electric fields on AB-stacked bilayers or stacked van der Waals heterostructures. In contrast, transition metal dichalcogenide monolayers are semiconductors with intrinsic in-plane asymmetry, leading to direct electronic bandgaps, distinctive optical properties and great potential in optoelectronics. Apart from their in-plane inversion asymmetry, an additional degree of freedom allowing spin manipulation can be induced by breaking the out-of-plane mirror symmetry with external electric fields or, as theoretically proposed, with an asymmetric out-of-plane structural configuration. Here, we report a synthetic strategy to grow Janus monolayers of transition metal dichalcogenides breaking the out-of-plane structural symmetry. In particular, based on a MoS2 monolayer, we fully replace the top-layer S with Se atoms. We confirm the Janus structure of MoSSe directly by means of scanning transmission electron microscopy and energy-dependent X-ray photoelectron spectroscopy, and prove the existence of vertical dipoles by second harmonic generation and piezoresponse force microscopy measurements.

  4. A modified Janus cassette (Sweet Janus to improve allelic replacement efficiency by high-stringency negative selection in Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Yuan Li

    Full Text Available The Janus cassette permits marker-free allelic replacement or knockout in streptomycin-resistant Streptococcus pneumoniae (pneumococcus through sequential positive and negative selection. Spontaneous revertants of Janus can lead to high level of false-positives during negative selection, which necessitate a time-consuming post-selection screening process. We hypothesized that an additional counter-selectable marker in Janus would decrease the revertant frequency and reduce false-positives, since simultaneous reversion of both counter-selectable makers is much less likely. Here we report a modified cassette, Sweet Janus (SJ, in which the sacB gene from Bacillus subtilis conferring sucrose sensitivity is added to Janus. By using streptomycin and sucrose simultaneously as selective agents, the frequency of SJ double revertants was about 105-fold lower than the frequency of Janus revertants. Accordingly, the frequency of false-positives in the SJ-mediated negative selection was about 100-fold lower than what was seen for Janus. Thus, SJ enhances negative selection stringency and can accelerate allelic replacement in pneumococcus, especially when transformation frequency is low due to strain background or suboptimal transformation conditions. Results also suggested the sacB gene alone can function as a counter-selectable marker in the Gram-positive pneumococcus, which will have the advantage of not requiring a streptomycin-resistant strain for allelic replacement.

  5. JEOS. The JANUS earth observation satellite

    Science.gov (United States)

    Molette, P.; Jouan, J.

    The JANUS multimission platform has been designed to minimize the cost of the satellite (by a maximum reuse of equipment from other proprogrammes) and of its associated launch by Aŕiane (by a piggy-back configuration optimized for Ariane 4). The paper describes the application of the JANUS platform to an Earth observation mission with the objective to provide a given country with a permanent monitoring of its earth resources by exploitation of spaceborne imagery. According to this objective, and to minimize the overall system and operational cost, the JANUS Earth Observation Satellite (JEOS) will provide a limited coverage with real time transmission of image data, thus avoiding need for on-board storage and simplifying operations. The JEOS operates on a low earth, near polar sun synchronous orbit. Launched in a piggy-back configuration on Ariane 4, with a SPOT or ERS spacecraft, it reaches its operational orbit after a drift orbit of a few weeks maximum. In its operational mode, the JEOS is 3-axis stabilised, earth pointed. After presentation of the platform, the paper describes the solid state push-broom camera which is composed of four optical lenses mounted on a highly stable optical bench. Each lens includes an optics system, reused from an on-going development, and two CCD linear arrays of detectors. The camera provides four registered channels in visible and near IR bands. The whole optical bench is supported by a rotating mechanism which allows rotation of the optical axis in the across-track direction. The JEOS typical performance for a 700 km altitude is then summarized: spatial resolution 30 m, swath width 120 km, off-track capability 325 km,… The payload data handling and transmission electronics, derived from the French SPOT satellite, realizes the processing, formatting, and transmission to the ground; this allows reuse of the standard SPOT receiving stations. The camera is only operated when the spacecraft is within the visibility of the ground

  6. The Janus Head Article - On Quality in the Documentation Process

    Directory of Open Access Journals (Sweden)

    Henrik Andersen

    2006-03-01

    Full Text Available The god Janus in Greek mythology was a two-faced god; each face had its own view of the world. Our idea behind the Janus Head article is to give you two different and maybe even contradicting views on a certain topic. In this issue the topic is quality in the documentation process. In the first half of this issue’s Janus Head Article translators from the international company Grundfos give us their view of quality and how quality is managed in the documentation process at Grundfos. In the second half of the Janus Head Article scholars from the University of Southern Denmark describe and discuss quality in the documentation process at Grundfos from a researcher’s point of view.

  7. The Janus Head Article - On Quality in the Documentation Process

    Directory of Open Access Journals (Sweden)

    Henrik Andersen

    2012-08-01

    Full Text Available The god Janus in Greek mythology was a two-faced god; each face had its own view of the world. Our idea behind the Janus Head article is to give you two different and maybe even contradicting views on a certain topic. In this issue the topic is quality in the documentation process. In the first half of this issue’s Janus Head Article translators from the international company Grundfos give us their view of quality and how quality is managed in the documentation process at Grundfos. In the second half of the Janus Head Article scholars from the University of Southern Denmark describe and discuss quality in the documentation process at Grundfos from a researcher’s point of view.

  8. Fabrication of polymeric Janus particles by droplet microfluidics

    KAUST Repository

    Lone, Saifullah; Cheong, Inwoo

    2014-01-01

    Janus particles (JPs), with their fascinating property of asymmetry, have received considerable attention in recent years in the fields of colloidal and particulate chemistry. The particles offer a range of exciting potential applications

  9. Janus Associated Kinases Inhibitors in the Pharmacological Thera

    Directory of Open Access Journals (Sweden)

    Daniela Santos1

    2017-01-01

    Full Text Available Janus associated kinases inhibitors are a new strategy for the treatment of different clinical conditions like immunologic, inflammatory and oncology disorders. The aim of this study was to perform a review of all Janus associated kinases inhibitors available in national and international pharmaceutical market, their therapeutic indications and adverse effects, and the potential indications for investigation of those already available in the pharmaceutical market. It was also performed a review of the main new Janus associated kinases inhibitors that are still in clinical research. A literature review was conducted by consulting the summary of product characteristics of Janus associated kinases inhibitors available in the pharmaceutical market and a research in the bibliographic database PubMed using the terms «JAK inhibitors», «Janus associated kinases inhibitors» and «Janus kinases inhibitors». Ninety-five publications were included in the present review, published from January 2014 to January 2015. Drug databases of the European Medicines Agency and United States Food and Drug Administration were also consulted to search for Janus associated kinases inhibitors authorized in clinical practice. Currently, ruxolitinib and tofacitinib are available in the pharmaceutical market and oclatinib is approved as a veterinary medicinal product. Both drugs approved for human use have major adverse effects at hematological and immunological levels, which enhance the importance of the pharmacist’s role in the monitoring of patients involved in these treatments. However, several molecules are in pre-clinical and clinical studies trying to prove its potential in the treatment of several immunologic, inflammatory and oncology disorders. Thus, it is still necessary to deepen the knowledge in this area in order to overcome the risks of therapy with these agents. These risks weighed against the benefits of its clinical use have compromised the progress of

  10. Multi-fuel driven Janus micromotors.

    Science.gov (United States)

    Gao, Wei; D'Agostino, Mattia; Garcia-Gradilla, Victor; Orozco, Jahir; Wang, Joseph

    2013-02-11

    Here the first example of a chemically powered micromotor that harvests its energy from the reactions of three different fuels is presented. The new Al/Pd Janus microspheres-prepared by depositing a Pd layer on one side of Al microparticles-are propelled efficiently by the thrust of hydrogen bubbles generated from different reactions of Al in strong acidic and alkaline environments, and by an oxygen bubble thrust produced at their partial Pd coating in hydrogen peroxide media. High speeds and long lifetimes of 200 μm s(-1) and 8 min are achieved in strong alkaline media and acidic media, respectively. The ability to autonomously adapt to the presence of a new fuel (surrounding environment), without compromising the propulsion behavior is illustrated. These data also represent the first example of a chemically powered micromotor that propels autonomously and efficiently in alkaline environments (pH > 11) without additional fuels. The ability to use multiple fuel sources to power the same micromotor offers a broader scope of operation and considerable promise for diverse applications of micromotors in different chemical environments. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Design of Janus Nanoparticles with Atomic Precision

    Science.gov (United States)

    Sun, Qiang; Wang, Qian; Jena, Puru; Kawazoe, Yoshi

    2008-03-01

    Janus nanoparticles, characterized by their anisotropic structure and interactions have added a new dimension to nanoscience because of their potential applications in biomedicine, sensors, catalysis and assembled materials. The technological applications of these nanoparticles, however, have been limited as the current chemical, physical, and biosynthetic methods lack sufficient size and shape selectivity. We report a technique where gold clusters doped with tungsten can serve as a seed that facilitates the natural growth of anisotropic nanostructures whose size and shape can be controlled with atomic precision. Using ab initio simulated annealing and molecular dynamics calculations on AunW (n>12) clusters, we discovered that the W@Au12 cage cluster forms a very stable core with the remaining Au atoms forming patchy structures on its surface. The anisotropic geometry gives rise to anisotropies in vibrational spectra, charge distributions, electronic structures, and reactivity, thus making it useful to have dual functionalities. In particular, the core-patch structure is shown to possess a hydrophilic head and a hydrophobic tail. The W@Au12 clusters can also be used as building blocks of a nano-ring with novel properties.

  12. Directed Assembly of Janus Cylinders by Controlling the Solvent Polarity.

    Science.gov (United States)

    Kim, Jongmin; Choi, Chang-Hyung; Yeom, Su-Jin; Eom, Naye; Kang, Kyoung-Ku; Lee, Chang-Soo

    2017-08-01

    This study demonstrates the possibility of controlling the directed self-assembly of microsized Janus cylinders by changing the solvent polarity of the assembly media. Experimental results are analyzed and theoretical calculations of the free energy of adhesion (ΔG ad ) are performed to elucidate the underlying basic principles and investigate the effects of the solvent on the self-assembled structures. This approach will pave a predictive route for controlling the structures of assembly depending on the solvent polarity. In particular, we find that a binary solvent system with precisely controlled polarity induces directional assembly of the microsized Janus cylinders. Thus, the formation of two-dimensional (2D) and three-dimensional (3D) assembled clusters can be reliably tuned by controlling the numbers of constituent Janus cylinders in a binary solvent system. Finally, this approach is expanded to stepwise assembly, which forms unique microstructures via secondary growth of primary seed clusters formed by the Janus cylinders. We envision that this investigation is highly promising for the construction of desired superstructures using a wide variety of polymeric Janus microparticles with chemical and physical multicompartments.

  13. Neutron issues in the JANUS mouse program

    International Nuclear Information System (INIS)

    Carnes, B.A.; Grahn, D.

    1990-01-01

    Over the last 25 years, the JANUS program in the Biological and Medical Research Division at Argonne National Laboratory (ANL) has compiled a database on the response of both sexes of an F 1 hybrid mouse, the B6CF 1 (C57BL/6 x BALB/c), to external whole- body irradiation by 60 Co γ-rays and fission neutrons. Three basic patterns of exposure for both neutrons and γ-rays have been investigated: single exposures, 24 equal once-weekly exposures, and 60 equal once-weekly exposures. All irradiations were terminated at predetermined total doses, with dose calculated in centigrays at the midline of the mouse. Three endpoints will be discussed in this paper: (1) life shortening, (2) a point estimate for cumulative mortality, and (3) the hazard function. Life shortening is used as an analysis endpoint because it summarizes, in a single index, the integrated effect of all injuries accumulated by an organism. Histopathological analyses of the mice used in the ANL studies have indicated that 85% of the deaths were caused by neoplasms. Connective tissue tumors were the dominant tumor in the B6CF 1 mouse, with tumors of lymphoreticular origin accounting for approximately 80% of this class. The latter two endpoints will therefore be used to describe the life table experience of mice dying from the lymphoreticular class of tumors. Dose-response models will be applied to the three endpoints in order to describe the response function for neutron exposures, evaluate the effect of dose range and pattern of exposure on the response function for neutrons, and provide a set of neutron relative biological effectiveness (RBE) values of the ANL database. 25 refs

  14. JANUS reactor d and d project

    International Nuclear Information System (INIS)

    Fellhauer, C. R.

    1998-01-01

    Argonne National Laboratory (ANL-E) has recently completed the decontamination and decommissioning (D and D) of the JANUS Reactor Facility located in Building 202. The 200 KW reactor operated from August 1963 to March 1992. The facility was used to study the effects of both high and low doses of fission neutrons in animals. There were two exposure rooms on opposite sides of the reactor and the reactor was therefore named after the two-faced Roman god. The High Dose Room was capable of specimen exposure at a dose rate of 3,600 rads per hour. During calendar year 1996 a detailed characterization of the facility was performed by ANL-E Health Physics personnel. ANL-E Analytical Services performed the required sample analysis. An Auditable Safety Analysis and an Environmental Assessment were completed. D and D plans, procedures and procurement documents were prepared and approved. A D and D subcontractor was selected and a firm, fixed price contract awarded for the field work and final survey effort. The D and D subcontractor was mobilized to ANL-E in January 1997. Electrical isolation of all reactor equipment and control panels was accomplished and the equipment removed. A total of 207,230 pounds (94,082 Kg) of lead shielding was removed, surveyed and sampled, and free-released for recycle. All primary and secondary piping was removed, size reduced and packaged for disposal or recycled as appropriate. The reactor vessel was removed, sized reduced and packaged as radioactive waste in April. The activated graphite block reflector was removed next, followed by the bioshield concrete and steel. All of this material was packaged as low level waste. Total low level radioactive waste generation was 4002.1 cubic feet (113.3 cubic meters). Mixed waste generation was 538 cubic feet (15.2 cubic meters). The Final Release Survey was completed in September. The project field work was completed in 38 weeks without any lost-time accidents, personnel contaminations or unplanned

  15. Decontamination and dismantlement of the JANUS Reactor at Argonne National Laboratory-East. Project final report

    International Nuclear Information System (INIS)

    Fellhauer, C.R.; Clark, F.R.

    1997-10-01

    The decontamination and dismantlement of the JANUS Reactor at Argonne National Laboratory-East (ANL-E) was completed in October 1997. Descriptions and evaluations of the activities performed and analyses of the results obtained during the JANUS D and D Project are provided in this Final Report. The following information is included: objective of the JANUS D and D Project; history of the JANUS Reactor facility; description of the ANL-E site and the JANUS Reactor facility; overview of the D and D activities performed; description of the project planning and engineering; description of the D and D operations; summary of the final status of the JANUS Reactor facility based upon the final survey results; description of the health and safety aspects of the project, including personnel exposure and OSHA reporting; summary of the waste minimization techniques utilized and total waste generated by the project; and summary of the final cost and schedule for the JANUS D and D Project

  16. Erythrocyte membrane modified janus polymeric motors for thrombus therapy

    NARCIS (Netherlands)

    Shao, Jingxin; Abdelghani, Mona; Shen, Guizhi; Cao, Shoupeng; Williams, David S.; van Hest, Jan C.M.

    2018-01-01

    We report the construction of erythrocyte membrane-cloaked Janus polymeric motors (EM-JPMs) which are propelled by near-infrared (NIR) laser irradiation and are successfully applied in thrombus ablation. Chitosan (a natural polysaccharide with positive charge, CHI) and heparin (glycosaminoglycan

  17. Motion of a Janus particle very near a wall

    Science.gov (United States)

    Rashidi, Aidin; Wirth, Christopher L.

    2017-12-01

    This article describes the simulated Brownian motion of a sphere comprising hemispheres of unequal zeta potential (i.e., "Janus" particle) very near a wall. The simulation tool was developed and used to assist in the methodology development for applying Total Internal Reflection Microscopy (TIRM) to anisotropic particles. Simulations of the trajectory of a Janus sphere with cap density matching that of the base particle very near a boundary were used to construct 3D potential energy landscapes that were subsequently used to infer particle and solution properties, as would be done in a TIRM measurement. Results showed that the potential energy landscape of a Janus sphere has a transition region at the location of the boundary between the two Janus halves, which depended on the relative zeta potential magnitude. The potential energy landscape was fit to accurately obtain the zeta potential of each hemisphere, particle size, minimum potential energy position and electrolyte concentration, or Debye length. We also determined the appropriate orientation bin size and regimes over which the potential energy landscape should be fit to obtain system properties. Our simulations showed that an experiment may require more than 106 observations to obtain a suitable potential energy landscape as a consequence of the multivariable nature of observations for an anisotropic particle. These results illustrate important considerations for conducting TIRM for anisotropic particles.

  18. Fabrication of polymeric Janus particles by droplet microfluidics

    KAUST Repository

    Lone, Saifullah

    2014-01-01

    Janus particles (JPs), with their fascinating property of asymmetry, have received considerable attention in recent years in the fields of colloidal and particulate chemistry. The particles offer a range of exciting potential applications as they possess two distinctive parts with different chemistry, colors, polarities, and/or surfaces. Currently, a number of methodologies are available for the synthesis of JPs. This review presents a short description of polymeric JPs synthesized by droplet microfluidics. This journal is © the Partner Organisations 2014.

  19. Mechanical and electronic properties of Janus monolayer transition metal dichalcogenides

    Science.gov (United States)

    Shi, Wenwu; Wang, Zhiguo

    2018-05-01

    The mechanical and electronic properties of Janus monolayer transition metal dichalcogenides MXY (M  =  Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W; X/Y  =  S, Se, Te) were investigated using density functional theory. Results show that breaking the out-of-plane structural symmetry can be used to tune the electronic and mechanical behavior of monolayer transition metal dichalcogenides. The band gaps of monolayer WXY and MoXY are in the ranges of 0.16–1.91 and 0.94–1.69 eV, respectively. A semiconductor to metallic phase transition occurred in Janus monolayer MXY (M  =  Ti, Zr and Hf). The monolayers MXY (M  =  V, Nb, Ta and Cr) show metallic characteristics, which show no dependence on the structural symmetry breaking. The mechanical properties of MXY depended on the composition. Monolayer MXY (M  =  Mo, Ti, Zr, Hf and W) showed brittle characteristic, whereas monolayer CrXY and VXY are with ductile characteristic. The in-plane stiffness of pristine and Janus monolayer MXY are in the range between 22 and 158 N m‑1. The tunable electronic and mechanical properties of these 2D materials would advance the development of ultra-sensitive detectors, nanogenerators, low-power electronics, and energy harvesting and electromechanical systems.

  20. Precise Localization and Control of Catalytic Janus Micromotors using Weak Magnetic Fields

    NARCIS (Netherlands)

    Khalil, Islam S. M.; Magdanz, Veronika; Sanchez, Samuel; Schmidt, Oliver G.; Misra, Sarthak

    2015-01-01

    We experimentally demonstrate the precise localization of spherical Pt-Silica Janus micromotors (diameter 5 mu m) under the influence of controlled magnetic fields. First, we control the motion of the Janus micromotors in two-dimensional (2D) space. The control system achieves precise localization

  1. A protecting group approach toward synthesis of Au–silica Janus nanostars

    OpenAIRE

    D. Rodríguez-Fernández; T. Altantzis; H. Heidari; S. Bals; L.M. Liz-Marzán

    2013-01-01

    Abstract: The concept of protecting groups, widely used in organic chemistry, has been applied for the synthesis of Au-silica Janus stars, in which gold branches protrude from one half of Au-silica Janus spheres. This configuration opens up new possibilities to apply the plasmonic properties of gold nanostars, as well as a variety of chemical functionalizations on the silica component.

  2. A protecting group approach toward synthesis of Au-silica Janus nanostars.

    Science.gov (United States)

    Rodríguez-Fernández, Denis; Altantzis, Thomas; Heidari, Hamed; Bals, Sara; Liz-Marzán, Luis M

    2014-01-04

    The concept of protecting groups, widely used in organic chemistry, has been applied for the synthesis of Au-silica Janus stars, in which gold branches protrude from one half of Au-silica Janus spheres. This configuration opens up new possibilities to apply the plasmonic properties of gold nanostars, as well as a variety of chemical functionalizations on the silica component.

  3. Supersymmetric Janus solutions of dyonic ISO(7)-gauged N = 8 supergravity

    Science.gov (United States)

    Suh, Minwoo

    2018-04-01

    We study supersymmetric Janus solutions of dyonic ISO(7)-gauged N = 8 supergravity. We mostly find Janus solutions flowing to 3d N = 8 SYM phase which is the worldvolume theory on D2-branes and non-conformal. There are also solutions flowing from the critical points which are dual to 3d SCFTs from deformations of the D2-brane theory.

  4. The Janus serum bank and biomarkers of cancer

    Directory of Open Access Journals (Sweden)

    Randi Gislefoss

    2009-10-01

    Full Text Available The Janus serum bank, established in 1973, contains sera stored at –25 degrees collected from 330,000 originally healthy individuals. The number of cancer cases have increased from zero in 1973 to more than 50,000 in 2005, including invasive and non-invasive cancers. Information on cases have been obtained by coupling the Janus file against the Norwegian Cancer Registry. The sera have been used in over 70 different cancers research projects, usually in case-control studies and in collaboration with national and international research groups. The type of biomarker analysed include antibodies against Chlamydia, CMV, Epstein Barr virus, HPV and Helicobacter pylori. Leptin, long chain fatty acids, androgens and other hormones, vitamins as well as environmental toxins such as organochlorines are other types of cancer biomarkers investigated. Mutation analyses (BRCA-1 etc have been possible using PCR and the trace amounts of DNA remaining in the sera.Janus serum bank ble etablert i 1973 og inneholder sera lagret ved –25 grader, innsamlet fra 330.000 opprinnelig friske personer. Antall krefttilfeller har steget fra null i 1973 til over 50.000 i år 2005, inkludert både invasiv og ikke-invasiv kreft. Informasjon om kasus er tilgjengelig ved å koble Janus-filene mot Kreftregisterets databaser. Serumprøvene er blitt benyttet i over 70 forskjellige kreftforskningsprosjekter, som oftest i kasus-kontroll studier og i samarbeide med en rekke nasjonale og internasjonale forskningsgrupper. Mange ulike biomarkører på kreft er blitt analysert, bl.a. antistoffer mot Chlamydia, CMV, Epstein Barr virus, HPV og Helicobacter pylori. Leptin, lange fettsyrer, androgener og andre hormoner, vitaminer såvel som miljøgifter av typen organiske klorforbindelser er eksempler på andre kreftbiomarkører som er undersøkt. Det har også vært mulig å gjøre mutasjonsanalyser (BRCA-1 etc ved å bruke PCR til å amplifisere opp den spormengden DNA som finnes i serum.

  5. Self-assembly of active amphiphilic Janus particles

    Science.gov (United States)

    Mallory, S. A.; Alarcon, F.; Cacciuto, A.; Valeriani, C.

    2017-12-01

    In this article, we study the phenomenology of a two dimensional dilute suspension of active amphiphilic Janus particles. We analyze how the morphology of the aggregates emerging from their self-assembly depends on the strength and the direction of the active forces. We systematically explore and contrast the phenomenologies resulting from particles with a range of attractive patch coverages. Finally, we illustrate how the geometry of the colloids and the directionality of their interactions can be used to control the physical properties of the assembled active aggregates and suggest possible strategies to exploit self-propulsion as a tunable driving force for self-assembly.

  6. Janus effect of antifreeze proteins on ice nucleation.

    Science.gov (United States)

    Liu, Kai; Wang, Chunlei; Ma, Ji; Shi, Guosheng; Yao, Xi; Fang, Haiping; Song, Yanlin; Wang, Jianjun

    2016-12-20

    The mechanism of ice nucleation at the molecular level remains largely unknown. Nature endows antifreeze proteins (AFPs) with the unique capability of controlling ice formation. However, the effect of AFPs on ice nucleation has been under debate. Here we report the observation of both depression and promotion effects of AFPs on ice nucleation via selectively binding the ice-binding face (IBF) and the non-ice-binding face (NIBF) of AFPs to solid substrates. Freezing temperature and delay time assays show that ice nucleation is depressed with the NIBF exposed to liquid water, whereas ice nucleation is facilitated with the IBF exposed to liquid water. The generality of this Janus effect is verified by investigating three representative AFPs. Molecular dynamics simulation analysis shows that the Janus effect can be established by the distinct structures of the hydration layer around IBF and NIBF. Our work greatly enhances the understanding of the mechanism of AFPs at the molecular level and brings insights to the fundamentals of heterogeneous ice nucleation.

  7. Dynamic Colloidal Molecules Maneuvered by Light-Controlled Janus Micromotors.

    Science.gov (United States)

    Gao, Yirong; Mou, Fangzhi; Feng, Yizheng; Che, Shengping; Li, Wei; Xu, Leilei; Guan, Jianguo

    2017-07-12

    In this work, we propose and demonstrate a dynamic colloidal molecule that is capable of moving autonomously and performing swift, reversible, and in-place assembly dissociation in a high accuracy by manipulating a TiO 2 /Pt Janus micromotor with light irradiation. Due to the efficient motion of the TiO 2 /Pt Janus motor and the light-switchable electrostatic interactions between the micromotor and colloidal particles, the colloidal particles can be captured and assembled one by one on the fly, subsequently forming into swimming colloidal molecules by mimicking space-filling models of simple molecules with central atoms. The as-demonstrated dynamic colloidal molecules have a configuration accurately controlled and stabilized by regulating the time-dependent intensity of UV light, which controls the stop-and-go motion of the colloidal molecules. The dynamic colloidal molecules are dissociated when the light irradiation is turned off due to the disappearance of light-switchable electrostatic interaction between the motor and the colloidal particles. The strategy for the assembly of dynamic colloidal molecules is applicable to various charged colloidal particles. The simulated optical properties of a dynamic colloidal molecule imply that the results here may provide a novel approach for in-place building functional microdevices, such as microlens arrays, in a swift and reversible manner.

  8. The Janus Head Article - How Much Terminology Theory Can Practical Terminology Management Use?

    Directory of Open Access Journals (Sweden)

    Petra Drewer

    2007-03-01

    Full Text Available The god Janus in Greek mythology was a two-faced god; each face had its own view of the world. Our idea behind the Janus Head article is to give you two different and maybe even contradicting views on a certain topic. This issue’s Janus Head Article, however, features not two but three different views on terminology work, as researchers, professionals and students (the professionals of tomorrow discuss “How Much Terminology Theory Can Practical Terminology Management Use?” at DaimlerChrysler AG.

  9. The Janus Head Article - How Much Terminology Theory Can Practical Terminology Management Use?

    Directory of Open Access Journals (Sweden)

    Petra Drewer

    2012-08-01

    Full Text Available The god Janus in Greek mythology was a two-faced god; each face had its own view of the world. Our idea behind the Janus Head article is to give you two different and maybe even contradicting views on a certain topic. This issue’s Janus Head Article, however, features not two but three different views on terminology work, as researchers, professionals and students (the professionals of tomorrow discuss “How Much Terminology Theory Can Practical Terminology Management Use?” at DaimlerChrysler AG. 

  10. Synthesis and self-assembly of Janus and patchy colloidal particles

    Science.gov (United States)

    Jiang, Shan

    Colloidal particles are considered classically as spherical particles with homogeneous surface chemistry. When this is so, the interactions between particles are isotropic and governed only by their separations. One can take advantage of this to simulate atoms, visualizing them one-by-one in a microscope, albeit at a larger length scale and longer time scale than for true atoms. However if the particles are not homogeneous, but Janus or patchy instead, with different surface chemistry on different hemispheres or otherwise different surface sites that are addressably controlled, the interactions between these particles depend not only on their separation, but also on their orientation. Research on Janus and patchy colloidal particles has opened a new chapter in the colloid research field, allowing us to mimic the behavior of these colloidal analogues of molecules, and in this way to ask new and exciting questions of condensed matter physics. In this dissertation, I investigated the synthesis and self-assembly of Janus and patchy colloidal particles with emphasis on Janus amphiphilic particles, which are the colloidal counterpart of surfactant molecules. Improving the scale-up capability, and also the capacity to control the geometry of Janus particles, I developed a simple and versatile method to synthesize Janus particles using an approach based on Pickering emulsions with particles adsorbed at the liquid-liquid interface. I showed that this method can be scaled up to synthesize Janus particles in large quantity. Also, the Janus balance can be predictably controlled by adding surfactant molecules during emulsification. In addition, going beyond the Janus geometry, I developed another synthetic method to fabricate trivalent patchy colloidal particles using micro-contact printing. With these synthetic methods in hand, I explored the self-assembly of Janus amphiphilic particles in aqueous solutions, while controlling systematically the salt concentration, the particle

  11. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib.

    Science.gov (United States)

    Rothstein, Brooke; Joshipura, Deep; Saraiya, Ami; Abdat, Rana; Ashkar, Huda; Turkowski, Yana; Sheth, Vaneeta; Huang, Victor; Au, Shiu Chung; Kachuk, Courtney; Dumont, Nicole; Gottlieb, Alice B; Rosmarin, David

    2017-06-01

    Existing therapies for vitiligo are limited in efficacy and can be associated with undesirable side effects. Topical Janus kinase inhibitors may offer a new therapeutic option for vitiligo. We sought to assess the role of topical ruxolitinib 1.5% cream, a Janus kinase inhibitor, in vitiligo treatment. This 20-week, open-label, proof-of-concept trial of twice-daily topical ruxolitinib 1.5% cream was conducted in 12 patients with a minimum of 1% affected body surface area of vitiligo. The primary outcome was percent improvement in Vitiligo Area Scoring Index from baseline to week 20. Of 12 patients screened, 11 were enrolled and 9 completed the study (54.5% men; mean age, 52 years). Four patients with significant facial involvement at baseline had a 76% improvement in facial Vitiligo Area Scoring Index scores at week 20 (95% confidence interval, 53-99%; P = .001). A 23% improvement in overall Vitiligo Area Scoring Index scores was observed in all enrolled patients at week 20 (95% confidence interval, 4-43%; P = .02). Three of 8 patients responded on body surfaces and 1 of 8 patients responded on acral surfaces. Adverse events were minor, including erythema, hyperpigmentation, and transient acne. Limitations of the study include the small sample size and open-label study design. Topical ruxolitinib 1.5% cream provided significant repigmentation in facial vitiligo and may offer a valuable new treatment for vitiligo. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. An Optically Controlled Microscale Elevator Using Plasmonic Janus Particles.

    Science.gov (United States)

    Nedev, Spas; Carretero-Palacios, Sol; Kühler, Paul; Lohmüller, Theobald; Urban, Alexander S; Anderson, Lindsey J E; Feldmann, Jochen

    2015-04-15

    In this article, we report how Janus particles, composed of a silica sphere with a gold half-shell, can be not only stably trapped by optical tweezers but also displaced controllably along the axis of the laser beam through a complex interplay between optical and thermal forces. Scattering forces orient the asymmetric particle, while strong absorption on the metal side induces a thermal gradient, resulting in particle motion. An increase in the laser power leads to an upward motion of the particle, while a decrease leads to a downward motion. We study this reversible axial displacement, including a hysteretic jump in the particle position that is a result of the complex pattern of a tightly focused laser beam structure above the focal plane. As a first application we simultaneously trap a spherical gold nanoparticle and show that we can control the distance between the two particles inside the trap. This photonic micron-scale "elevator" is a promising tool for thermal force studies, remote sensing, and optical and thermal micromanipulation experiments.

  13. Sound Scattering and Its Reduction by a Janus Sphere Type

    Directory of Open Access Journals (Sweden)

    Deliya Kim

    2014-01-01

    Full Text Available Sound scattering by a Janus sphere type is considered. The sphere has two surface zones: a soft surface of zero acoustic impedance and a hard surface of infinite acoustic impedance. The zones are arranged such that axisymmetry of the sound field is preserved. The equivalent source method is used to compute the sound field. It is shown that, by varying the sizes of the soft and hard zones on the sphere, a significant reduction can be achieved in the scattered acoustic power and upstream directivity when the sphere is near a free surface and its soft zone faces the incoming wave and vice versa for a hard ground. In both cases the size of the sphere’s hard zone is much larger than that of its soft zone. The boundary location between the two zones coincides with the location of a zero pressure line of the incoming standing sound wave, thus masking the sphere within the sound field reflected by the free surface or the hard ground. The reduction in the scattered acoustic power diminishes when the sphere is placed in free space. Variations of the scattered acoustic power and directivity with the sound frequency are also given and discussed.

  14. Crystals of Janus colloids at various interaction ranges

    Energy Technology Data Exchange (ETDEWEB)

    Preisler, Z. [Dipartimento di Fisica, Università di Roma “Sapienza,” Piazzale Aldo Moro 5, 00185 Roma (Italy); Soft Condensed Matter, Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 5, 3584 CC Utrecht (Netherlands); Vissers, T. [Dipartimento di Fisica, Università di Roma “Sapienza,” Piazzale Aldo Moro 5, 00185 Roma (Italy); SUPA and School of Physics and Astronomy, The University of Edinburgh, James Clerk Maxwell Building, Peter Guthrie Tait Road, Edinburgh EH9 3FD (United Kingdom); Smallenburg, F. [Dipartimento di Fisica, Università di Roma “Sapienza,” Piazzale Aldo Moro 5, 00185 Roma (Italy); Institut für Theoretische Physik II: Weiche Materie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf (Germany); Sciortino, F. [Dipartimento di Fisica, Università di Roma “Sapienza,” Piazzale Aldo Moro 5, 00185 Roma (Italy)

    2016-08-14

    We investigate the effect of interaction range on the phase behaviour of Janus particles with a Kern-Frenkel potential. Specifically, we study interaction ranges Δ = 0.1σ, 0.3σ, 0.4σ, 0.5σ with σ the particle diameter, and use variable box shape simulations to predict crystal structures. We found that changing the interaction range beyond 0.2σ drastically increases the variety of possible crystal structures. In addition to close-packed structures, we find body-centered tetragonal and AA-stacked hexagonal crystals, as well as several lamellar crystals. For long interaction ranges and low temperatures, we also observe an extremely large number of metastable structures which compete with the thermodynamically stable ones. These competing structures hinder the detection of the lowest-energy crystal structures, and are also likely to interfere with the spontaneous formation of the ground-state structure. Finally, we determine the gas-liquid coexistence curves for several interaction ranges, and observe that these are metastable with respect to crystallization.

  15. Tofacitinib, an Oral Janus Kinase Inhibitor: Perspectives in Dermatology.

    Science.gov (United States)

    Kostovic, Kresimir; Gulin, Sandra J; Mokos, Zrinka B; Ceovic, Romana

    2017-05-31

    Tofacitinib (formerly known as CP-690,550, CP690550, tasocitinib), a novel selective immunosuppressant, is a small molecule classified as Janus kinase inhibitor. The aim of this review article is to present updated data summary on the tofacitinib in the field of dermatology. We undertook a structured search of bibliographic databases for peer-reviewed scientific articles, including review articles, original research articles as well as case report articles based on inclusion/exclusion criteria. Technical reports on tofacitinib from U.S. Food and Drug Administration and European Medical Agency were also included. Forty-three papers were included in this review. We report current data on tofacitinib chemical properties, pharmacology, non-clinical toxicity, as well as efficacy and safety in potential new indications in dermatology: psoriasis, alopecia areata, vitiligo, atopic dermatitis and nail dystrophy associated with alopecia areata. JAK/STAT pathway has an important role in the pathogenesis of psoriasis, alopecia areata, atopic dermatitis, and vitiligo. Despite encouraging efficacy, due to concerns about the overall safety profile of tofacitinib, additional studies will have to determine the adequate risk-to-benefit ratio. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Crystals of Janus colloids at various interaction ranges

    International Nuclear Information System (INIS)

    Preisler, Z.; Vissers, T.; Smallenburg, F.; Sciortino, F.

    2016-01-01

    We investigate the effect of interaction range on the phase behaviour of Janus particles with a Kern-Frenkel potential. Specifically, we study interaction ranges Δ = 0.1σ, 0.3σ, 0.4σ, 0.5σ with σ the particle diameter, and use variable box shape simulations to predict crystal structures. We found that changing the interaction range beyond 0.2σ drastically increases the variety of possible crystal structures. In addition to close-packed structures, we find body-centered tetragonal and AA-stacked hexagonal crystals, as well as several lamellar crystals. For long interaction ranges and low temperatures, we also observe an extremely large number of metastable structures which compete with the thermodynamically stable ones. These competing structures hinder the detection of the lowest-energy crystal structures, and are also likely to interfere with the spontaneous formation of the ground-state structure. Finally, we determine the gas-liquid coexistence curves for several interaction ranges, and observe that these are metastable with respect to crystallization.

  17. Supersymmetric RG flows and Janus from type II orbifold compactification

    Energy Technology Data Exchange (ETDEWEB)

    Karndumri, Parinya; Upathambhakul, Khem [Chulalongkorn University, String Theory and Supergravity Group, Department of Physics, Faculty of Science, Bangkok (Thailand)

    2017-07-15

    We study holographic RG flow solutions within four-dimensional N = 4 gauged supergravity obtained from type IIA and IIB string theories compactified on T{sup 6}/Z{sub 2} x Z{sub 2} orbifold with gauge, geometric and non-geometric fluxes. In type IIB non-geometric compactifications, the resulting gauged supergravity has ISO(3) x ISO(3) gauge group and admits an N = 4 AdS{sub 4} vacuum dual to an N = 4 superconformal field theory (SCFT) in three dimensions. We study various supersymmetric RG flows from this N = 4 SCFT to N = 4 and N = 1 non-conformal field theories in the IR. The flows preserving N = 4 supersymmetry are driven by relevant operators of dimensions Δ = 1, 2 or alternatively by one of these relevant operators, dual to the dilaton, and irrelevant operators of dimensions Δ = 4 while the N = 1 flows in addition involve marginal deformations. Most of the flows can be obtained analytically. We also give examples of supersymmetric Janus solutions preserving N = 4 and N = 1 supersymmetries. These solutions should describe two-dimensional conformal defects within the dual N = 4 SCFT. Geometric compactifications of type IIA theory give rise to N = 4 gauged supergravity with ISO(3) x U(1){sup 6} gauge group. In this case, the resulting gauged supergravity admits an N = 1 AdS{sub 4} vacuum. We also numerically study possible N = 1 RG flows to non-conformal field theories in this case. (orig.)

  18. Janus particle microshuttle: 1D directional self-propulsion modulated by AC electrical field

    Directory of Open Access Journals (Sweden)

    Jiliang Chen

    2014-03-01

    Full Text Available A catalytic Janus particle is capable of gaining energy from the surrounding fuel solution to drive itself to move continuously, which has an important impact in different fields, especially the field of micro-systems. However, the randomness of self-propulsion at the microscale restricts its use in practice. Achieving a directed self-propelled movement would greatly promote the application of the Janus particle. We proved experimentally that an AC electric field was an effective way to suppress Brownian motion and control the direction of self-propelled movement. The self-propulsion and dielectrophoretic response of a 2μm Janus particle were observed and the related basic data were collected. Interdigital electrodes, 20 μm in width, were energized in pulsed style to modulate the self-propulsion, which resulted in a shuttle-style motion in which a single Janus particle moved to and fro inside the strip electrode. The change of direction depends on its unique position: the catalyst side is always pointed outward and the orientation angle relative to the electrode is about 60°. Numerical simulation also proved that this position is reasonable. The present study could be beneficial with regard to self-propulsion and AC electrokinetics of the Janus particle.

  19. Highly Efficient Light-Driven TiO2-Au Janus Micromotors.

    Science.gov (United States)

    Dong, Renfeng; Zhang, Qilu; Gao, Wei; Pei, Allen; Ren, Biye

    2016-01-26

    A highly efficient light-driven photocatalytic TiO2-Au Janus micromotor with wireless steering and velocity control is described. Unlike chemically propelled micromotors which commonly require the addition of surfactants or toxic chemical fuels, the fuel-free Janus micromotor (diameter ∼1.0 μm) can be powered in pure water under an extremely low ultraviolet light intensity (2.5 × 10(-3) W/cm(2)), and with 40 × 10(-3) W/cm(2), they can reach a high speed of 25 body length/s, which is comparable to common Pt-based chemically induced self-electrophoretic Janus micromotors. The photocatalytic propulsion can be switched on and off by incident light modulation. In addition, the speed of the photocatalytic TiO2-Au Janus micromotor can be accelerated by increasing the light intensity or by adding low concentrations of chemical fuel H2O2 (i.e., 0.1%). The attractive fuel-free propulsion performance, fast movement triggering response, low light energy requirement, and precise motion control of the TiO2-Au Janus photocatalytic micromotor hold considerable promise for diverse practical applications.

  20. Induced-charge electroosmosis around conducting and Janus cylinder in microchip

    Directory of Open Access Journals (Sweden)

    Zhang Kai

    2012-01-01

    Full Text Available The induced-charge elecetroosmosis around conducting/Janus cylinder with arbitrary Debye thickness is studied numerically, when an direct current weak electric filed is suddenly applied in a confined microchannel. It’s found that there are four large circulations around the conducting cylinder, and the total flux in the microchannel is zero; there are two smaller circulations around the Janus cylinder, and they are compressed to wall. A bulk flux, which has a parabolic relation with the applied electric field, is also predicted.

  1. Voltage-controlled Enzymes: The new Janus Bifrons

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Villalba-Galea

    2012-09-01

    Full Text Available The Ciona intestinalis voltage sensitive phosphatase, Ci-VSP, was the first Voltage-controlled Enzyme (VEnz proven to be under direct command of the membrane potential. The discovery of Ci-VSP conjugated voltage sensitivity and enzymatic activity in a single protein. These two facets of Ci-VSP activity have provided a unique model for studying how membrane potential is sensed by proteins and a novel mechanism for control of enzymatic activity. These facets make Ci-VSP a fascinating and versatile enzyme.Ci-VSP has a voltage sensing domain (VSD that resembles those found in voltage-gated channels (VGC. The VSD resides in the N-terminus and is formed by four putative trans-membrane segments. The fourth segment contains charged residues which are likely involved in voltage sensing. Ci-VSP produces sensing currents in response to changes in potential, within a defined range of voltages. Sensing currents are analogous to gating currents in VGC. As known, these latter proteins contain four VSDs which are entangled in a complex interaction with the pore domain –the effector domain in VGC. This complexity makes studying the basis of voltage sensing in VGC a difficult enterprise. In contrast, Ci-VSP is thought to be monomeric and its catalytic domain –the VSP’s effector domain– can be cleaved off without disrupting the basic electrical functioning of the VSD. For these reasons, VSPs are considered a great model for studying the activity of a VSD in isolation. Finally, VSPs are also phosphoinositide phosphatases. Phosphoinositides are signaling lipids found in eukaryotes and are involved in many processes, including modulation of VGC activity and regulation of cell proliferation. Understanding VSPs as VEnz has been the center of attention in recent years and several reviews has been dedicated to this area. Thus, this review will be focused instead on the other face of this true Janus Bifrons and recapitulate what is known about VSPs as electrically

  2. Spiropyran-Decorated SiO₂-Pt Janus Micromotor: Preparation and Light-Induced Dynamic Self-Assembly and Disassembly.

    Science.gov (United States)

    Zhang, Qilu; Dong, Renfeng; Chang, Xueyi; Ren, Biye; Tong, Zhen

    2015-11-11

    The controlled self-assembly of self-propelled Janus micromotors may give the micromotors some potential applications in many fields. In this work, we design a kind of SiO2-Pt Janus catalytic micromotor functionalized by spiropyran (SP) moieties on the surface of the SiO2 hemisphere. The spiropyran-modified SiO2-Pt Janus micromotor exhibits autonomous self-propulsion in the presence of hydrogen peroxide fuel in N,N-dimethylformamide (DMF)/H2O (1:1 in volume) mixture. We demonstrate that the self-propelled Janus micromotors can dynamically assemble into multiple motors because of the electrostatic attractions and π-π stacking between MC molecules induced by UV light irradiation (λ = 365 nm) and also quickly disassemble into mono motors when the light is switched to green light (λ = 520 nm) for the first time. Furthermore, the assembled Janus motors can move together automatically with different motion patterns propelled by the hydrogen peroxide fuels upon UV irradiation. The work provides a new approach not only to the development of the potential application of Janus motors but also to the fundamental science of reversible self-assembly and disassembly of Janus micromotors.

  3. Structural design of liquid oxygen/liquid methane robotic lander JANUS

    Science.gov (United States)

    Chaidez, Mariana

    As the attempt to send humans to Mars has gained momentum in the last decade, the need to find alternative propellants that are safer, less toxic, and yields a better performance has become apparent [1]. Liquid methane and oxygen have emerged as a suitable alternative. In addition, the incorporation of liquid methane/liquid oxygen into the propulsion system has demonstrated an increase in engine performance, as well as a reduction in the volume, size and complexity of the propulsion system. In an attempt to further understand the technologies that are possible to develop using liquid oxygen (LO 2) and liquid methane (LCH4), a preliminary design of a robotic lander JANUS is being completed by the Center for Space Exploration and Technology Research (cSTER). The structural design of the vehicle is important because it acts as the skeleton of the vehicle and dictates the maneuverability of the robotic lander. To develop the structure of the robotic lander, six different design vehicle concepts with varying tank configurations were considered. Finite Element Analysis (FEA) was completed on each model to optimize each vehicle. Trade studies were completed to choose the best design for JANUS. Upon completion of the trade studies the design for the first prototype of JANUS was initiated in which the tank and thrust modules were designed. This thesis will describe the design process for the structural design of the JANUS.

  4. SERS-Fluorescence Dual-Mode pH-Sensing Method Based on Janus Microparticles.

    Science.gov (United States)

    Yue, Shuai; Sun, Xiaoting; Wang, Ning; Wang, Yaning; Wang, Yue; Xu, Zhangrun; Chen, Mingli; Wang, Jianhua

    2017-11-15

    A surface-enhanced Raman scattering (SERS)-fluorescence dual-mode pH-sensing method based on Janus microgels was developed, which combined the advantages of high specificity offered by SERS and fast imaging afforded by fluorescence. Dual-mode probes, pH-dependent 4-mercaptobenzoic acid, and carbon dots were individually encapsulated in the independent hemispheres of Janus microparticles fabricated via a centrifugal microfluidic chip. On the basis of the obvious volumetric change of hydrogels in different pHs, the Janus microparticles were successfully applied for sensitive and reliable pH measurement from 1.0 to 8.0, and the two hemispheres showed no obvious interference. The proposed method addressed the limitation that sole use of the SERS-based pH sensing usually failed in strong acidic media. The gastric juice pH and extracellular pH change were measured separately in vitro using the Janus microparticles, which confirmed the validity of microgels for pH sensing. The microparticles exhibited good stability, reversibility, biocompatibility, and ideal semipermeability for avoiding protein contamination, and they have the potential to be implantable sensors to continuously monitor pH in vivo.

  5. Visible-Light-Driven BiOI-Based Janus Micromotor in Pure Water.

    Science.gov (United States)

    Dong, Renfeng; Hu, Yan; Wu, Yefei; Gao, Wei; Ren, Biye; Wang, Qinglong; Cai, Yuepeng

    2017-02-08

    Light-driven synthetic micro-/nanomotors have attracted considerable attention due to their potential applications and unique performances such as remote motion control and adjustable velocity. Utilizing harmless and renewable visible light to supply energy for micro-/nanomotors in water represents a great challenge. In view of the outstanding photocatalytic performance of bismuth oxyiodide (BiOI), visible-light-driven BiOI-based Janus micromotors have been developed, which can be activated by a broad spectrum of light, including blue and green light. Such BiOI-based Janus micromotors can be propelled by photocatalytic reactions in pure water under environmentally friendly visible light without the addition of any other chemical fuels. The remote control of photocatalytic propulsion by modulating the power of visible light is characterized by velocity and mean-square displacement analysis of optical video recordings. In addition, the self-electrophoresis mechanism has been confirmed for such visible-light-driven BiOI-based Janus micromotors by demonstrating the effects of various coated layers (e.g., Al 2 O 3 , Pt, and Au) on the velocity of motors. The successful demonstration of visible-light-driven Janus micromotors holds a great promise for future biomedical and environmental applications.

  6. Design and Fabrication of Janus Nanoparticles for Interfacial Distribution in Block Copolymers

    NARCIS (Netherlands)

    Yang, Qiuyan; Loos, Katja

    Hybrid composites with highly ordered structures show promise for applications in various fields and thus there is great interest in their fabrication. In this context, Janus nanoparticles (JNPs) are synthesized with the aim of further incorporating them into polystyreneblock- poly(2-vinylpyridine)

  7. Janus: Graphical Software for Analyzing In-Situ Measurements of Solar-Wind Ions

    Science.gov (United States)

    Maruca, B.; Stevens, M. L.; Kasper, J. C.; Korreck, K. E.

    2016-12-01

    In-situ observations of solar-wind ions provide tremendous insights into the physics of space plasmas. Instrument on spacecraft measure distributions of ion energies, which can be processed into scientifically useful data (e.g., values for ion densities and temperatures). This analysis requires a strong, technical understanding of the instrument, so it has traditionally been carried out by the instrument teams using automated software that they had developed for that purpose. The automated routines are optimized for typical solar-wind conditions, so they can fail to capture the complex (and scientifically interesting) microphysics of transient solar-wind - such as coronal mass ejections (CME's) and co-rotating interaction regions (CIR's) - which are often better analyzed manually.This presentation reports on the ongoing development of Janus, a new software package for processing in-situ measurement of solar-wind ions. Janus will provide user with an easy-to-use graphical user interface (GUI) for carrying out highly customized analyses. Transparent to the user, Janus will automatically handle the most technical tasks (e.g., the retrieval and calibration of measurements). For the first time, users with only limited knowledge about the instruments (e.g., non-instrumentalists and students) will be able to easily process measurements of solar-wind ions. Version 1 of Janus focuses specifically on such measurements from the Wind spacecraft's Faraday Cups and is slated for public release in time for this presentation.

  8. Lagrangian derivation of the two coupled field equations in the Janus cosmological model

    Science.gov (United States)

    Petit, Jean-Pierre; D'Agostini, G.

    2015-05-01

    After a review citing the results obtained in previous articles introducing the Janus Cosmological Model, consisting of a set of two coupled field equations, where one metrics refers to the positive masses and the other to the negative masses, which explains the observed cosmic acceleration and the nature of dark energy, we present the Lagrangian derivation of the model.

  9. Decontamination and decommissioning of the JANUS reactor at the Argonne National Laboratory-East site

    International Nuclear Information System (INIS)

    Fellhauer, C.R.; Garlock, G.A.

    1997-05-01

    Argonne National Laboratory has begun the decontamination and decommissioning (D ampersand D) of the JANUS Reactor Facility. The project is managed by the Technology Development Division's D ampersand D Program personnel. D ampersand D procedures are performed by sub-contractor personnel. Specific activities involving the removal, size reduction, and packaging of radioactive components and facilities are discussed

  10. The magnetic interaction of Janus magnetic particles suspended in a viscous fluid

    NARCIS (Netherlands)

    Seong, Y.; Kang, T.G.; Hulsen, M.A.; den Toonder, J.M.J.; Anderson, P.D.

    2016-01-01

    We studied the magnetic interaction between circular Janus magnetic particles suspended in a Newtonian fluid under the influence of an externally applied uniform magnetic field. The particles are equally compartmentalized into paramagnetic and non-magnetic sides. A direct numerical scheme is

  11. Light-Driven Au-WO3@C Janus Micromotors for Rapid Photodegradation of Dye Pollutants.

    Science.gov (United States)

    Zhang, Qilu; Dong, Renfeng; Wu, Yefei; Gao, Wei; He, Zihan; Ren, Biye

    2017-02-08

    A novel light-driven Au-WO 3 @C Janus micromotor based on colloidal carbon WO 3 nanoparticle composite spheres (WO 3 @C) prepared by one-step hydrothermal treatment is described. The Janus micromotors can move in aqueous media at a speed of 16 μm/s under 40 mW/cm 2 UV light due to diffusiophoretic effects. The propulsion of such Au-WO 3 @C Janus micromotors (diameter ∼ 1.0 μm) can be generated by UV light in pure water without any external chemical fuels and readily modulated by light intensity. After depositing a paramagnetic Ni layer between the Au layer and WO 3 , the motion direction of the micromotor can be precisely controlled by an external magnetic field. Such magnetic micromotors not only facilitate recycling of motors but also promise more possibility of practical applications in the future. Moreover, the Au-WO 3 @C Janus micromotors show high sensitivity toward extremely low concentrations of sodium-2,6-dichloroindophenol (DCIP) and Rhodamine B (RhB). The moving speed of motors can be significantly accelerated to 26 and 29 μm/s in 5 × 10 -4 wt % DCIP and 5 × 10 -7 wt % RhB aqueous solutions, respectively, due to the enhanced diffusiophoretic effect, which results from the rapid photocatalytic degradation of DCIP and RhB by WO 3 . This photocatalytic acceleration of the Au-WO 3 @C Janus micromotors confirms the self-diffusiophoretic mechanism and opens an opportunity to tune the motility of the motors. This work also offers the light-driven micromotors a considerable potential for detection and rapid photodegradation of dye pollutants in water.

  12. Gold core@silver semishell Janus nanoparticles prepared by interfacial etching

    Science.gov (United States)

    Chen, Limei; Deming, Christopher P.; Peng, Yi; Hu, Peiguang; Stofan, Jake; Chen, Shaowei

    2016-07-01

    Gold core@silver semishell Janus nanoparticles were prepared by chemical etching of Au@Ag core-shell nanoparticles at the air/water interface. Au@Ag core-shell nanoparticles were synthesized by chemical deposition of a silver shell onto gold seed colloids followed by the self-assembly of 1-dodecanethiol onto the nanoparticle surface. The nanoparticles then formed a monolayer on the water surface of a Langmuir-Blodgett trough, and part of the silver shell was selectively etched away by the mixture of hydrogen peroxide and ammonia in the water subphase, where the etching was limited to the side of the nanoparticles that was in direct contact with water. The resulting Janus nanoparticles exhibited an asymmetrical distribution of silver on the surface of the gold cores, as manifested in transmission electron microscopy, UV-vis absorption, and X-ray photoelectron spectroscopy measurements. Interestingly, the Au@Ag semishell Janus nanoparticles exhibited enhanced electrocatalytic activity in oxygen reduction reactions, as compared to their Au@Ag and Ag@Au core-shell counterparts, likely due to a synergistic effect between the gold cores and silver semishells that optimized oxygen binding to the nanoparticle surface.Gold core@silver semishell Janus nanoparticles were prepared by chemical etching of Au@Ag core-shell nanoparticles at the air/water interface. Au@Ag core-shell nanoparticles were synthesized by chemical deposition of a silver shell onto gold seed colloids followed by the self-assembly of 1-dodecanethiol onto the nanoparticle surface. The nanoparticles then formed a monolayer on the water surface of a Langmuir-Blodgett trough, and part of the silver shell was selectively etched away by the mixture of hydrogen peroxide and ammonia in the water subphase, where the etching was limited to the side of the nanoparticles that was in direct contact with water. The resulting Janus nanoparticles exhibited an asymmetrical distribution of silver on the surface of the gold

  13. Control over Janus micromotors by the strength of a magnetic field

    Science.gov (United States)

    Baraban, Larysa; Makarov, Denys; Schmidt, Oliver G.; Cuniberti, Gianaurelio; Leiderer, Paul; Erbe, Artur

    2013-01-01

    For transportation of molecules or biological cells using artificial motors, the control over their motion, i.e. direction and speed of transfer, is important. Here, we demonstrate that modification of the velocity and orientation of a magnetic Janus particle can be efficiently controlled by tuning the strength of an applied homogeneous magnetic field. Interestingly, by keeping the same orientation of the magnetic field but changing its magnitude not only the velocity of capped particles can be altered but even their direction of motion can be reversed. We put forth a simple qualitative model, which allows us to explain this intriguing observation.For transportation of molecules or biological cells using artificial motors, the control over their motion, i.e. direction and speed of transfer, is important. Here, we demonstrate that modification of the velocity and orientation of a magnetic Janus particle can be efficiently controlled by tuning the strength of an applied homogeneous magnetic field. Interestingly, by keeping the same orientation of the magnetic field but changing its magnitude not only the velocity of capped particles can be altered but even their direction of motion can be reversed. We put forth a simple qualitative model, which allows us to explain this intriguing observation. Electronic supplementary information (ESI) available: Videos (1-3) describe the behavior of the magnetic Janus micromotors at different magnetic fields applied. The magnetic field is always applied along the positive direction of the y-axis. All the movies are recorded at the same frame rate of 21 images per second. Experiments were performed at 30 wt% of hydrogen peroxide in aqueous solution. Video 1 shows the motion of the Janus micromotors when a small magnetic field is applied (B = 0.2 mT). The particle is propelled in the direction ``opposite to the cap'' with a velocity of about 6 μm s-1. Video 2 displays the motion of the same Janus bead when an intermediately strong

  14. Strain-engineering of Janus SiC monolayer functionalized with H and F atoms

    Science.gov (United States)

    Drissi, L. B.; Sadki, K.; Kourra, M.-H.; Bousmina, M.

    2018-05-01

    Based on ab initio density functional theory calculations, the structural, electronic, mechanical, acoustic, thermodynamic, and piezoelectric properties of (F,H) Janus SiC monolayers are studied. The new set of derivatives shows buckled structures and different band gap values. Under strain, the buckling changes and the structures pass from semiconducting to metallic. The elastic limits and the metastable regions are determined. The Young's modulus and Poisson ratio reveal stronger behavior for the modified conformers with respect to graphene. The values of the Debye temperature make the new materials suitable for thermal application. Moreover, all the conformers show in-plane and out-of-plane piezoelectric responses comparable with known two-dimensional materials. If engineered, such piezoelectric Janus structures may be promising materials for various nanoelectromechanical applications.

  15. Janus and Huygens Dipoles: Near-Field Directionality Beyond Spin-Momentum Locking

    Science.gov (United States)

    Picardi, Michela F.; Zayats, Anatoly V.; Rodríguez-Fortuño, Francisco J.

    2018-03-01

    Unidirectional scattering from circularly polarized dipoles has been demonstrated in near-field optics, where the quantum spin-Hall effect of light translates into spin-momentum locking. By considering the whole electromagnetic field, instead of its spin component alone, near-field directionality can be achieved beyond spin-momentum locking. This unveils the existence of the Janus dipole, with side-dependent topologically protected coupling to waveguides, and reveals the near-field directionality of Huygens dipoles, generalizing Kerker's condition. Circular dipoles, together with Huygens and Janus sources, form the complete set of all possible directional dipolar sources in the far- and near-field. This allows the designing of directional emission, scattering, and waveguiding, fundamental for quantum optical technology, integrated nanophotonics, and new metasurface designs.

  16. Hybrid, silica-coated, Janus-like plasmonic-magnetic nanoparticles

    OpenAIRE

    Sotiriou, Georgios A.; Hirt, Ann M.; Lozach, Pierre-Yves; Teleki, Alexandra; Krumeich, Frank; Pratsinis, Sotiris E.

    2011-01-01

    Hybrid plasmonic-magnetic nanoparticles possess properties that are attractive in bioimaging, targeted drug delivery, in vivo diagnosis and therapy. The stability and toxicity, however, of such nanoparticles challenge their safe use today. Here, biocompatible, SiO2-coated, Janus-like Ag/Fe2O3 nanoparticles are prepared by one-step, scalable flame aerosol technology. A nanothin SiO2 shell around these multifunctional nanoparticles leaves intact their morphology, magnetic and plasmonic properti...

  17. Hydrophobic Janus Foam Motors: Self-Propulsion and On-The-Fly Oil Absorption

    Directory of Open Access Journals (Sweden)

    Xiaofeng Li

    2018-01-01

    Full Text Available In this work, we for the first time have proposed and fabricated a self-propelled Janus foam motor for on-the-fly oil absorption on water by simply loading camphor/stearic acid (SA mixture as fuels into one end of the SA-modified polyvinyl alcohol (PVA foam. The as-fabricated Janus foam motors show an efficient Marangoni effect-based self-propulsion on water for a long lifetime due to the effective inhibition of the rapid release of camphor by the hydrophobic SA in the fuel mixture. Furthermore, they can automatically search, capture, and absorb oil droplets on the fly, and then be spontaneously self-assembled after oil absorption due to the self-propulsion of the motors as well as the attractive capillary interactions between the motors and oil droplets. This facilitates the subsequent collection of the motors from water after the treatment. Since the as-developed Janus foam motors can effectively integrate intriguing behaviors of the self-propulsion, efficient oil capture, and spontaneous self-assembly, they hold great promise for practical applications in water treatment.

  18. Using commodity accelerometers and gyroscopes to improve speed and accuracy of JanusVF

    Science.gov (United States)

    Hutson, Malcolm; Reiners, Dirk

    2010-01-01

    Several critical limitations exist in the currently available commercial tracking technologies for fully-enclosed virtual reality (VR) systems. While several 6DOF solutions can be adapted to work in fully-enclosed spaces, they still include elements of hardware that can interfere with the user's visual experience. JanusVF introduced a tracking solution for fully-enclosed VR displays that achieves comparable performance to available commercial solutions but without artifacts that can obscure the user's view. JanusVF employs a small, high-resolution camera that is worn on the user's head, but faces backwards. The VR rendering software draws specific fiducial markers with known size and absolute position inside the VR scene behind the user but in view of the camera. These fiducials are tracked by ARToolkitPlus and integrated by a single-constraint-at-a-time (SCAAT) filter to update the head pose. In this paper we investigate the addition of low-cost accelerometers and gyroscopes such as those in Nintendo Wii remotes, the Wii Motion Plus, and the Sony Sixaxis controller to improve the precision and accuracy of JanusVF. Several enthusiast projects have implemented these units as basic trackers or for gesture recognition, but none so far have created true 6DOF trackers using only the accelerometers and gyroscopes. Our original experiments were repeated after adding the low-cost inertial sensors, showing considerable improvements and noise reduction.

  19. Precise Localization and Control of Catalytic Janus Micromotors Using Weak Magnetic Fields

    Directory of Open Access Journals (Sweden)

    Islam S. M. Khalil

    2015-01-01

    Full Text Available We experimentally demonstrate the precise localization of spherical Pt-Silica Janus micromotors (diameter 5 μm under the influence of controlled magnetic fields. First, we control the motion of the Janus micromotors in two-dimensional (2D space. The control system achieves precise localization within an average region-of-convergence of 7 μm. Second, we show that these micromotors provide sufficient propulsion force, allowing them to overcome drag and gravitational forces and move both downwards and upwards. This propulsion is studied by moving the micromotors in three-dimensional (3D space. The micromotors move downwards and upwards at average speeds of 19.1 μm/s and 9.8 μm/s, respectively. Moreover, our closed-loop control system achieves localization in 3D space within an average region-of-convergence of 6.3 μm in diameter. The precise motion control and localization of the Janus micromotors in 2D and 3D spaces provides broad possibilities for nanotechnology applications.

  20. Electrically and magnetically dual-driven Janus particles for handwriting-enabled electronic paper

    Energy Technology Data Exchange (ETDEWEB)

    Komazaki, Y., E-mail: komazaki@dt.k.u-tokyo.ac.jp; Hirama, H.; Torii, T. [Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8563 (Japan)

    2015-04-21

    In this work, we describe the synthesis of novel electrically and magnetically dual-driven Janus particles for a handwriting-enabled twisting ball display via the microfluidic technique. One hemisphere of the Janus particles contains a charge control agent, which allows the display color to be controlled by applying a voltage and superparamagnetic nanoparticles, allows handwriting by applying a magnetic field to the display. We fabricated a twisting ball display utilizing these Janus particles and tested the electric color control and handwriting using a magnet. As a result, the display was capable of permitting handwriting with a small magnet in addition to conventional color control using an applied voltage (80 V). Handwriting performance was improved by increasing the concentration of superparamagnetic nanoparticles and was determined to be possible even when 80 V was applied across the electrodes for 4 wt. % superparamagnetic nanoparticles in one hemisphere. This improvement was impossible when the concentration was reduced to 2 wt. % superparamagnetic nanoparticles. The technology presented in our work can be applied to low-cost, lightweight, highly visible, and energy-saving electronic message boards and large whiteboards because the large-size display can be fabricated easily due to its simple structure.

  1. Electrically and magnetically dual-driven Janus particles for handwriting-enabled electronic paper

    International Nuclear Information System (INIS)

    Komazaki, Y.; Hirama, H.; Torii, T.

    2015-01-01

    In this work, we describe the synthesis of novel electrically and magnetically dual-driven Janus particles for a handwriting-enabled twisting ball display via the microfluidic technique. One hemisphere of the Janus particles contains a charge control agent, which allows the display color to be controlled by applying a voltage and superparamagnetic nanoparticles, allows handwriting by applying a magnetic field to the display. We fabricated a twisting ball display utilizing these Janus particles and tested the electric color control and handwriting using a magnet. As a result, the display was capable of permitting handwriting with a small magnet in addition to conventional color control using an applied voltage (80 V). Handwriting performance was improved by increasing the concentration of superparamagnetic nanoparticles and was determined to be possible even when 80 V was applied across the electrodes for 4 wt. % superparamagnetic nanoparticles in one hemisphere. This improvement was impossible when the concentration was reduced to 2 wt. % superparamagnetic nanoparticles. The technology presented in our work can be applied to low-cost, lightweight, highly visible, and energy-saving electronic message boards and large whiteboards because the large-size display can be fabricated easily due to its simple structure

  2. Hydrophobic/Hydrophilic Cooperative Janus System for Enhancement of Fog Collection.

    Science.gov (United States)

    Cao, Moyuan; Xiao, Jiasheng; Yu, Cunming; Li, Kan; Jiang, Lei

    2015-09-09

    Harvesting micro-droplets from fog is a promising method for solving global freshwater crisis. Different types of fog collectors have been extensively reported during the last decade. The improvement of fog collection can be attributed to the immediate transportation of harvested water, the effective regeneration of the fog gathering surface, etc. Through learning from the nature's strategy for water preservation, the hydrophobic/hydrophilic cooperative Janus system that achieved reinforced fog collection ability is reported here. Directional delivery of the surface water, decreased re-evaporation rate of the harvested water, and thinner boundary layer of the collecting surface contribute to the enhancement of collection efficiency. Further designed cylinder Janus collector can facilely achieve a continuous process of efficient collection, directional transportation, and spontaneous preservation of fog water. This Janus fog harvesting system should improve the understanding of micro-droplet collection system and offer ideas to solve water resource crisis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Look at nuclear artillery yield options using JANUS, a wargame simulation code

    International Nuclear Information System (INIS)

    Andre, C.G.

    1982-01-01

    JANUS, a two-sided, interactive wargame simulation code, was used to explore how using each of several different yield options in a nuclear artillery shell might affect a tactical battlefield simulation. In a general sense, the results or outcomes of these simulations support the results or outcomes of previous studies. In these simulations the Red player knew of the anticipated nuclear capability of the Blue player. Neither side experienced a decisive win over the other, and both continued fighting and experienced losses that, under most historical circumstances, would have been termed unacceptable - that is, something else would have happened (the attack would have been called off). During play, each side had only fragmentary knowledge of the remaining resources on the other side - thus each side desired to continue fighting on the basis of known information. We found that the anticipated use of nuclear weapons by either side affects the character of a game significantly and that, if the employment of nuclear weapons is to have a decided effect on the progress and outcome of a battle, each side will have to have an adequate number of nuclear weapons. In almost all the simulations we ran using JANUS, enhanced radiation (ER) weapons were more effective than 1-kt fission weapons in imposing overall losses on Red. The typical visibility in the JANUS simulation limited each side's ability to acquire units deep into enemy territory and so the 10-kt fission weapon was not useful against enemy tanks that were not engaged in battle

  4. The Janus effect on superhydrophilic Cu mesh decorated with Ni-NiO/Ni(OH)2 core-shell nanoparticles for oil/water separation

    Science.gov (United States)

    Luo, Zhi-Yong; Lyu, Shu-Shen; Fu, Yuan-Xiang; Heng, Yi; Mo, Dong-Chuan

    2017-07-01

    Janus effect has been studied for emerging materials like Janus membranes, Janus nanoparticles, etc., and the applications including fog collection, oil/water separation, CO2 removal and stabilization of multiphasic mixtures. However, the Janus effect on oil/water separation is still unclear. Herein, Janus Cu mesh decorated with Ni-NiO/Ni(OH)2 core-shell nanoparticles is synthesized via selective electrodeposition, in which we keep one side of Cu mesh (Janus A) to be superhydrophilic, while manipulate the wettability of another side (Janus B) from hydrophobic to superhydrophilic. Experimental results indicate that Cu mesh with both-side superhydrophilic shows the superior oil/water separation performance (separation efficiency >99.5%), which is mainly due to its higher water capture percentage as well as larger oil intrusion pressure. Further, we demonstrate the orientation of Janus membranes for oil/water separation, and summarize that the wettability of the upper surface plays a more important role than the lower surface to achieve remarkable performance. Our work provides a clear insight of Janus effect on oil/water separation, it is significative to design high-performance membranes for oil/water separation and many other applications.

  5. MOF@MOF core–shell vs. Janus particles and the effect of strain: potential for guest sorption, separation and sequestration

    NARCIS (Netherlands)

    Szilagyi, P.A.; Lutz, M.; Gascon, J.; Juan-Alcañiz, J.; van Esch, J.; Kapteijn, F.; Geerlings, H.; Dam, B.; van der Krol, R.

    2013-01-01

    The effect of strain on core–shell MOFcore@MOFshell particles is discussed and compared with that observed for analogous Janus particles. Whereas Janus particles do not display any effect of strain, the core of fully coated core–shell particles collapsed upon the formation of the outer shell,

  6. Thermal annealing response following irradiation of a CMOS imager for the JUICE JANUS instrument

    Science.gov (United States)

    Lofthouse-Smith, D.-D.; Soman, M. R.; Allanwood, E. A. H.; Stefanov, K. D.; Holland, A. D.; Leese, M.; Turne, P.

    2018-03-01

    ESA's JUICE (JUpiter ICy moon Explorer) spacecraft is an L-class mission destined for the Jovian system in 2030. Its primary goals are to investigate the conditions for planetary formation and the emergence of life, and how does the solar system work. The JANUS camera, an instrument on JUICE, uses a 4T back illuminated CMOS image sensor, the CIS115 designed by Teledyne e2v. JANUS imager test campaigns are studying the CIS115 following exposure to gammas, protons, electrons and heavy ions, simulating the harsh radiation environment present in the Jovian system. The degradation of 4T CMOS device performance following proton fluences is being studied, as well as the effectiveness of thermal annealing to reverse radiation damage. One key parameter for the JANUS mission is the Dark current of the CIS115, which has been shown to degrade in previous radiation campaigns. A thermal anneal of the CIS115 has been used to accelerate any annealing following the irradiation as well as to study the evolution of any performance characteristics. CIS115s have been irradiated to double the expected End of Life (EOL) levels for displacement damage radiation (2×1010 protons, 10 MeV equivalent). Following this, devices have undergone a thermal anneal cycle at 100oC for 168 hours to reveal the extent to which CIS115 recovers pre-irradiation performance. Dark current activation energy analysis following proton fluence gives information on trap species present in the device and how effective anneal is at removing these trap species. Thermal anneal shows no quantifiable change in the activation energy of the dark current following irradiation.

  7. Janus graphene oxide nanosheet: A promising additive for enhancement of polymeric membranes performance prepared via phase inversion.

    Science.gov (United States)

    Akbari, Mahdi; Shariaty-Niassar, Mojtaba; Matsuura, Takeshi; Ismail, Ahmad Fauzi

    2018-10-01

    Although polymeric membranes find important role in water and waste water treatment in recent years, their fouling is still an important problem. Application of hydrophilic nanoparticles (NPs) is one of the proposed methods for reducing fouling of membranes but their dispersion and stability in hydrophobic polymer matrix is challenging. In this study Janus functionalization of the NPs was introduced as a promising technique toward achieving this goal. Polysulfone (PSf) membranes containing various concentrations of graphene oxide (GO) nanosheets and Janus graphene oxide (Janus GO) nanosheets (as additives) were fabricated via phase inversion. The synthesized nanosheets were characterized by field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy and dynamic light scattering (DLS). The prepared membranes also were then characterized by scanning electron microscopy (SEM), contact angle (CA), water uptake, porosity, mean pore size and casting solution viscosity. The membrane performance was also tested by determining pure water flux (PWF), bovine serum albumin (BSA) separation, flux reduction by fouling and flux recovery. CA reduced from 85° to 68° and PWF increased from 23.15 L/m 2  h to 230.61 L/m 2  h for PSF and Janus GO nanosheets containing membrane, respectively. Also investigation of antifouling performance of membranes revealed that membrane with the 1 wt.% of Janus GO nanosheets had higher water flux recovery ratio (FRR) and lower irreversible fouling (R ir ) of 84% and 16%, respectively. These improvements were attributed to the better dispersion and stability of Janus GO nanosheets in the prepared mixed matrix membranes. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Janus probe, a detection system for high energy reactor gamma-ray spectrometry

    International Nuclear Information System (INIS)

    Gold, R.; Kaiser, B.J.

    1980-03-01

    In reactor environments, gamma-ray spectra are continuous and the absolute magnitude as well as the general shape of the gamma continuum are of paramount importance. Consequently, conventional methods of gamma-ray detection are not suitable for in-core gamma-ray spectrometry. To meet these specific needs, a method of continuous gamma-ray spectrometry, namely Compton Recoil Gamma-Ray Spectrometry, was developed for in-situ observations of reactor environments. A new gamma-ray detection system has been developed which extends the applicability of Compton Recoil Gamma-Ray Spectrometry up to roughly 7 MeV. This detection system is comprised of two separate Si(Li) detectors placed face-to-face. Hence this new detection system is called the Janus probe. Also shown is the block diagram of pulse processing instrumentation for the Janus probe. This new gamma probe not only extends the upper energy limit of in-core gamma-ray spectrometry, but in addition possesses other fundamental advantages

  9. Self-assembly of Janus particles into helices with tunable pitch

    Science.gov (United States)

    Fernández, M. Sobrino; Misko, V. R.; Peeters, F. M.

    2015-10-01

    Janus particles present an important class of building blocks for directional assembly. These are compartmentalized colloids with two different hemispheres. In this work we consider a three-dimensional model of Janus spheres that contain one hydrophobic and one charged hemisphere. Using molecular dynamics simulations, we study the morphology of these particles when confined in a channel-like environment. The interplay between the attractive and repulsive forces on each particle gives rise to a rich phase space where the relative orientation of each particle plays a dominant role in the formation of large-scale clusters. The interest in this system is primarily due to the fact that it could give a better understanding of the mechanisms of the formation of polar membranes. A variety of ordered membranelike morphologies is found consisting of single and multiple connected chain configurations. The helicity of these chains can be chosen by simply changing the salt concentration of the solution. Special attention is given to the formation of Bernal spirals. These helices are composed of regular tetrahedra and are known to exhibit nontrivial translational and rotational symmetry.

  10. Highly controllable near-surface swimming of magnetic Janus nanorods: application to payload capture and manipulation

    International Nuclear Information System (INIS)

    Mair, Lamar O; Carpenter, Jerome; Evans, Benjamin; Hall, Adam R; Shields, Adam; Superfine, Richard; Ford, Kris; Millard, Michael

    2011-01-01

    Directed manipulation of nanomaterials has significant implications in the field of nanorobotics, nanobiotechnology, microfluidics and directed assembly. With the goal of highly controllable nanomaterial manipulation in mind, we present a technique for the near-surface manoeuvering of magnetic nanorod swimmers and its application to controlled micromanipulation. We fabricate magnetic Janus nanorods and show that the magnetic rotation of these nanorods near a floor results in predictable translational motion. The nanorod plane of rotation is nearly parallel to the floor, the angle between rod tilt and floor being expressed by θ, where 0 0 0 . Orthogonal magnetic fields control in-plane motion arbitrarily. Our model for translation incorporates symmetry breaking through increased drag at the no-slip surface boundary. Using this method we demonstrate considerable rod steerability. Additionally, we approach, capture, and manipulate a polystyrene microbead as proof of principle. We attach Janus nanorods to the surfaces of cells and utilize these rods to manipulate individual cells, proving the ability to manoeuver payloads with a wide range of sizes.

  11. JANUS - A setup for low-energy Coulomb excitation at ReA3

    Science.gov (United States)

    Lunderberg, E.; Belarge, J.; Bender, P. C.; Bucher, B.; Cline, D.; Elman, B.; Gade, A.; Liddick, S. N.; Longfellow, B.; Prokop, C.; Weisshaar, D.; Wu, C. Y.

    2018-03-01

    A new experimental setup for low-energy Coulomb excitation experiments was constructed in a collaboration between the National Superconducting Cyclotron Laboratory (NSCL), Lawrence Livermore National Laboratory (LLNL), and the University of Rochester and was commissioned at the general purpose beam line of NSCL's ReA3 reaccelerator facility. The so-called JANUS setup combines γ-ray detection with the Segmented Ge Array (SeGA) and scattered particle detection using a pair of segmented double-sided Si detectors (Bambino 2). The low-energy Coulomb excitation program that JANUS enables will complement intermediate-energy Coulomb excitation studies that have long been performed at NSCL by providing access to observables that quantify collectivity beyond the first excited state, including the sign and magnitude of excited-state quadrupole moments. In this work, the setup and its performance will be described based on the commissioning run that used stable 78Kr impinging onto a 1.09 mg/cm2208Pb target at a beam energy of 3.9 MeV/u.

  12. Arrays of Au-TiO{sub 2} Janus-like nanoparticles fabricated by block copolymer templates and their photocatalytic activity in the degradation of methylene blue

    Energy Technology Data Exchange (ETDEWEB)

    Fu Xiaoning; Liu Jun; Yang Hui; Sun Jiuchuan [Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials, School of Chemistry and Chemical Engineering, University of Jinan, 106 Jiwei Road, Jinan 250022 (China); Li Xue, E-mail: lixue0312@yahoo.com [Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials, School of Chemistry and Chemical Engineering, University of Jinan, 106 Jiwei Road, Jinan 250022 (China); Zhang Xiaokai [College of Physics and Electronics, Shandong Normal University, 88 Wenhuadong Road, Jinan 250014 (China); Jia Yuxi, E-mail: jia_yuxi@sdu.edu.cn [School of Materials Science and Engineering, Shandong University, Jinan 250061 (China)

    2011-10-17

    Highlights: {center_dot} Fabrication of an array of Au-titania Janus nanoparticles on silicon substrate. {center_dot} PS-b-PEO block copolymer is used as templates. {center_dot} Au-TiO{sub 2} Janus-like nanoparticles exhibit higher photocatalytic activity. - Abstract: A simple approach towards the fabrication of an array of Au-titania Janus-like nanoparticles is presented. Monolayer organic-inorganic hybrid films are produced by spin coating the mixture of polystyrene-block-poly (ethylene oxide) (PS-b-PEO)/HAuCl{sub 4} solution and titania sol-gel precursor solution. HAuCl{sub 4} and titania are incorporated in the PEO domains. After removing the organic matrix by deep UV irradiation, arrays of Au-TiO{sub 2} Janus-like nanoparticles on the substrate surface are obtained. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) measurements are employed to characterize the Janus-like nanoparticles. The photocatalytic degradation of methylene blue (MB) chosen as the test reaction to examine the photocatalytic activity of the Au-TiO{sub 2} Janus-like nanoparticles is shown to be more effective as compared to that of TiO{sub 2} nanoparticles or Au-TiO{sub 2} composite nanoparticles. The increased photocatalytic activity of Au-TiO{sub 2} Janus-like nanoparticles is attributed to the Au-TiO{sub 2} heterointerfaces.

  13. Charting thermal emission variability at Pele, Janus Patera and Kanehekili Fluctus with the Galileo NIMS Io Thermal Emission Database (NITED)

    Science.gov (United States)

    Davies, Ashley Gerard; Veeder, Glenn J.; Matson, Dennis L.; Johnson, Torrence V.

    2012-09-01

    Using the NIMS Io Thermal Emission Database (NITED), a collection of over 1000 measurements of radiant flux from Io’s volcanoes (Davies, A.G. et al. [2012]. Geophys. Res. Lett. 39, L01201. doi:10.1029/2011GL049999), we have examined the variability of thermal emission from three of Io’s volcanoes: Pele, Janus Patera and Kanehekili Fluctus. At Pele, the 5-μm thermal emission as derived from 28 night time observations is remarkably steady at 37 ± 10 GW μm-1, re-affirming previous analyses that suggested that Pele an active, rapidly overturning silicate lava lake. Janus Patera also exhibits relatively steady 5-μm thermal emission (≈20 ± 3 GW μm-1) in the four observations where Janus is resolved from nearby Kanehekili Fluctus. Janus Patera might contain a Pele-like lava lake with an effusion rate (QF) of ≈40-70 m3 s-1. It should be a prime target for a future mission to Io in order to obtain data to determine lava eruption temperature. Kanehekili Fluctus has a thermal emission spectrum that is indicative of the emplacement of lava flows with insulated crusts. Effusion rate at Kanehekili Fluctus dropped by an order of magnitude from ≈95 m3 s-1 in mid-1997 to ≈4 m3 s-1 in late 2001.

  14. Activation of the interleukin-6/Janus kinase/STAT3 pathway in pleomorphic adenoma of the parotid gland

    DEFF Research Database (Denmark)

    Andreasen, Simon; Therkildsen, Marianne Hamilton; Grauslund, Morten

    2015-01-01

    The interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway is of crucial importance in promoting tumorigenesis in several malignant tumors but may also be active in benign tumors, e.g., of pleomorphic adenoma (PA). In this study we characterize ...

  15. Cryptic elevational zonation in trapdoor spiders (Araneae, Antrodiaetidae, Aliatypus janus complex) from the California southern Sierra Nevada.

    Science.gov (United States)

    Starrett, James; Hayashi, Cheryl Y; Derkarabetian, Shahan; Hedin, Marshal

    2018-01-01

    The relative roles of ecological niche conservatism versus niche divergence in promoting montane speciation remains an important topic in biogeography. Here, our aim was to test whether lineage diversification in a species complex of trapdoor spiders corresponds with riverine barriers or with an ecological gradient associated with elevational tiering. Aliatypus janus was sampled from throughout its range, with emphasis on populations in the southern Sierra Nevada Mountains of California. We collected multi-locus genetic data to generate a species tree for A. janus and its close relatives. Coalescent based hypothesis tests were conducted to determine if genetic breaks within A. janus conform to riverine barriers. Ecological niche models (ENM) under current and Last Glacial Maximum (LGM) conditions were generated and hypothesis tests of niche conservatism and divergence were performed. Coalescent analyses reveal deeply divergent genetic lineages within A. janus, likely corresponding to cryptic species. Two primary lineages meet along an elevational gradient on the western slopes of the southern Sierra Nevada Mountains. ENMs under both current and LGM conditions indicate that these groups occupy largely non-overlapping niches. ENM hypothesis testing rejected niche identity between the two groups, and supported a sharp ecological gradient occurring where the groups meet. However, the niche similarity test indicated that the two groups may not inhabit different background niches. The Sierra Nevada Mountains provide a natural laboratory for simultaneously testing ecological niche divergence and conservatism and their role in speciation across a diverse range of taxa. Aliatypus janus represents a species complex with cryptic lineages that may have diverged due to parapatric speciation along an ecological gradient, or been maintained by the evolution of ecological niche differences following allopatric speciation. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Foe or friend? Janus-faces of the neurovascular unit in the formation of brain metastases.

    Science.gov (United States)

    Wilhelm, Imola; Fazakas, Csilla; Molnár, Kinga; Végh, Attila G; Haskó, János; Krizbai, István A

    2018-04-01

    Despite the potential obstacle represented by the blood-brain barrier for extravasating malignant cells, metastases are more frequent than primary tumors in the central nervous system. Not only tightly interconnected endothelial cells can hinder metastasis formation, other cells of the brain microenvironment (like astrocytes and microglia) can also be very hostile, destroying the large majority of metastatic cells. However, malignant cells that are able to overcome these harmful mechanisms may benefit from the shielding and even support provided by cerebral endothelial cells, astrocytes and microglia, rendering the brain a sanctuary site against anti-tumor strategies. Thus, cells of the neurovascular unit have a Janus-faced attitude towards brain metastatic cells, being both destructive and protective. In this review, we present the main mechanisms of brain metastasis formation, including those involved in extravasation through the brain vasculature and survival in the cerebral environment.

  17. Holographic two-point functions for Janus interfaces in the D1/D5 CFT

    Energy Technology Data Exchange (ETDEWEB)

    Chiodaroli, Marco [Department of Physics and Astronomy, Uppsala University, SE-75108 Uppsala (Sweden); Estes, John [Department of Physics, Long Island University,1 University Plaza, Brooklyn, NY 11201 (United States); Korovin, Yegor [Max-Planck-Institut für Gravitationsphysik, Albert-Einstein-Institut, Am Mühlenberg 1, 14476 Golm (Germany)

    2017-04-26

    This paper investigates scalar perturbations in the top-down supersymmetric Janus solutions dual to conformal interfaces in the D1/D5 CFT, finding analytic closed-form solutions. We obtain an explicit representation of the bulk-to-bulk propagator and extract the two-point correlation function of the dual operator with itself, whose form is not fixed by symmetry alone. We give an expression involving the sum of conformal blocks associated with the bulk-defect operator product expansion and briefly discuss finite-temperature extensions. To our knowledge, this is the first computation of a two-point function which is not completely determined by symmetry for a fully-backreacted, top-down holographic defect.

  18. The design of Janus, the visible camera for the ESA JUICE mission

    Science.gov (United States)

    Della Corte, Vincenzo; Schmitz, Nicole; Castro, José Maria; Leese, Mark; Debei, Stefano; Magrin, Demetrio; Michalik, Harald

    2014-05-01

    The JUICE (JUpiter ICy moons Explorer) mission was selected in May 2012 as the first Large mission in the frame of the ESA Cosmic Vision 2015-2025 program. The mission is aimed at an in-depth characterization of the Jovian system, with an operational phase of about 3.5 years. During the whole operational phase, JANUS (Jovis, Amorum ac Natorum Undique Scrutator) will acquire panchromatic and narrow-band images in the visible - NIR range of many targets within the Jovian system: the Galilean satellites surfaces and exospheres, Jupiter atmosphere, minor and irregular satellites, the ring system. After a long trade-off between different design solutions, based on performance requirements, mission design and constraints, the present JANUS design has been based on the following architectural choices detailed below. A catoptric telescope with excellent optical quality is coupled with a framing CMOS detector, avoiding any scan-ning mechanism or operational requirement on the S/C. The three mirror anastigmatic (TMA) off-axis design with F#=4.67 allows an MTF between 62% and 72% at Nyquist, with good straylight rejection. The detector is the CIS115 from e2v; it is a CMOS with a squared 7 micron pixel pitch and image format of 2000x1504. It performs a high readout rate of up to 40 Mpixel/s, high quantum efficiency and low readout noise and dark signal. Fine tuning of instrument parameters allows to perform both high resolution targeted observations and lower resolution global coverage of targets, as required to meet science objectives. The IFoV (Fieldo of View per pixel) is 15 microrad, al-lowing sampling of 7.5 m/pixel from 500 km and 15 km/pixel from 10E6 km, while the FoV is 1.72x1.29 deg. The acquisition parameters allow to cope with the many different observation requirements and conditions that JANUS will face. Design of the two electronics units (a proximity electronics controlling the detector and a main electronics controlling the instrument and the interfaces with

  19. Test and evaluation procedures for Sandia's Teraflops Operating System (TOS) on Janus.

    Energy Technology Data Exchange (ETDEWEB)

    Barnette, Daniel Wayne

    2005-10-01

    This report describes the test and evaluation methods by which the Teraflops Operating System, or TOS, that resides on Sandia's massively-parallel computer Janus is verified for production release. Also discussed are methods used to build TOS before testing and evaluating, miscellaneous utility scripts, a sample test plan, and a proposed post-test method for quickly examining the large number of test results. The purpose of the report is threefold: (1) to provide a guide to T&E procedures, (2) to aid and guide others who will run T&E procedures on the new ASCI Red Storm machine, and (3) to document some of the history of evaluation and testing of TOS. This report is not intended to serve as an exhaustive manual for testers to conduct T&E procedures.

  20. Janus field theories from non-linear BF theories for multiple M2-branes

    International Nuclear Information System (INIS)

    Ryang, Shijong

    2009-01-01

    We integrate the nonpropagating B μ gauge field for the non-linear BF Lagrangian describing N M2-branes which includes terms with even number of the totally antisymmetric tensor M IJK in arXiv:0808.2473 and for the two-types of non-linear BF Lagrangians which include terms with odd number of M IJK as well in arXiv:0809:0985. For the former Lagrangian we derive directly the DBI-type Lagrangian expressed by the SU(N) dynamical A μ gauge field with a spacetime dependent coupling constant, while for the low-energy expansions of the latter Lagrangians the B μ integration is iteratively performed. The derived Janus field theory Lagrangians are compared.

  1. JANUS neutron irradiation of a mouse cell line containing a shuttle vector plasmid

    International Nuclear Information System (INIS)

    Nagy, B.; Grdina, D.J.; Ashman, C.R.

    1989-01-01

    The study presented here represents the initial steps of our attempt to characterize JANUS neutron induced mutagenesis in mammalian cells. The approach which we are taking is to use a mammalian cell system which allows one to determine the actual changes in DNA base sequence which occur when a gene mutates. Recently, several systems have been described which make possible the rapid and unambiguous determination of DNA base sequence changes in genes of eukaryotic cells. In some of these systems, a target gene is introduced into the mammalian cells as part of a shuttle vector which is capable of replication in both mammalian cells and bacteria. In this study we have used such a system for the analysis of neutron-induced mutations in the presence and absence of the radioprotector N-(2-mercaptoethyl)-1,3-diaminopropane, WR1065. 20 refs., 5 figs., 1 tab

  2. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme.

    Science.gov (United States)

    Curtis, Jeffrey R; Lee, Eun Bong; Kaplan, Irina V; Kwok, Kenneth; Geier, Jamie; Benda, Birgitta; Soma, Koshika; Wang, Lisy; Riese, Richard

    2016-05-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To further assess the potential role of Janus kinase inhibition in the development of malignancies, we performed an integrated analysis of data from the tofacitinib RA clinical development programme. Malignancy data (up to 10 April 2013) were pooled from six phase II, six Phase III and two long-term extension (LTE) studies involving tofacitinib. In the phase II and III studies, patients with moderate-to-severe RA were randomised to various tofacitinib doses as monotherapy or with background non-biological disease-modifying antirheumatic drugs (DMARDs), mainly methotrexate. The LTE studies (tofacitinib 5 or 10 mg twice daily) enrolled patients from qualifying prior phase I, II and III index studies. Of 5671 tofacitinib-treated patients, 107 developed malignancies (excluding non-melanoma skin cancer (NMSC)). The most common malignancy was lung cancer (n=24) followed by breast cancer (n=19), lymphoma (n=10) and gastric cancer (n=6). The rate of malignancies by 6-month intervals of tofacitinib exposure indicates rates remained stable over time. Standardised incidence ratios (comparison with Surveillance, Epidemiology and End Results) for all malignancies (excluding NMSC) and selected malignancies (lung, breast, lymphoma, NMSC) were within the expected range of patients with moderate-to-severe RA. The overall rates and types of malignancies observed in the tofacitinib clinical programme remained stable over time with increasing tofacitinib exposure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Implementation and Testing of the JANUS Standard with SSC Pacific’s Software-Defined Acoustic Modem

    Science.gov (United States)

    2017-10-01

    JANUS limit) was typed from the keyboard by the user. Next, the transmitter bash script was run and the user typed the ASCII text of choice, or the...FDECO Forward Deployed Energy and Communications Outpost CONOPS concept of operation DSP digital signal processor FPGA field programmable gate array...deployed by U.S. and international military and civilian organizations have for decades operated without any type of widely adopted standards or

  4. Preparation of Janus Particles and Alternating Current Electrokinetic Measurements with a Rapidly Fabricated Indium Tin Oxide Electrode Array.

    Science.gov (United States)

    Chen, Yu-Liang; Jiang, Hong-Ren

    2017-06-23

    This article provides a simple method to prepare partially or fully coated metallic particles and to perform the rapid fabrication of electrode arrays, which can facilitate electrical experiments in microfluidic devices. Janus particles are asymmetric particles that contain two different surface properties on their two sides. To prepare Janus particles, a monolayer of silica particles is prepared by a drying process. Gold (Au) is deposited on one side of each particle using a sputtering device. The fully coated metallic particles are completed after the second coating process. To analyze the electrical surface properties of Janus particles, alternating current (AC) electrokinetic measurements, such as dielectrophoresis (DEP) and electrorotation (EROT)- which require specifically designed electrode arrays in the experimental device- are performed. However, traditional methods to fabricate electrode arrays, such as the photolithographic technique, require a series of complicated procedures. Here, we introduce a flexible method to fabricate a designed electrode array. An indium tin oxide (ITO) glass is patterned by a fiber laser marking machine (1,064 nm, 20 W, 90 to 120 ns pulse-width, and 20 to 80 kHz pulse repetition frequency) to create a four-phase electrode array. To generate the four-phase electric field, the electrodes are connected to a 2-channel function generator and to two invertors. The phase shift between the adjacent electrodes is set at either 90° (for EROT) or 180° (for DEP). Representative results of AC electrokinetic measurements with a four-phase ITO electrode array are presented.

  5. Relative biological effectiveness measurements using murine lethality and survival of intestinal and hematopoietic stem cells after Fermilab neutrons compared to JANUS reactor neutrons and 60Co gamma rays

    International Nuclear Information System (INIS)

    Hanson, W.R.; Crouse, D.A.; Fry, R.J.M.; Ainsworth, E.J.

    1984-01-01

    The relative biological effectiveness (RBE) of the 25-MeV (average energy) neutron beam at the Fermi National Accelerator Laboratory was measured using murine bone marrow (LD/sub 50/30/) and gut (LD/sub 50/6/) lethality and killing of hematopoietic colony forming units (CFU-S) or intestinal clonogenic cells (ICC). The LD/sub 50/30/ and LD/sub 50/6/ for mice exposed to the Fermilab neutron beam were 6.6 and 8.7 Gy, respectively, intermediate between those of JANUS neutrons and 60 Co γ rays. The D 0 values for CFU-S and ICC were 47 cGy and 1.05 Gy, respectively, also intermediate between the lowest values found for JANUS neutrons and the highest values found after 60 Co γ rays. The split-dose survival ratios for CFU-S at intervals of 1-6 hr between doses were essentially 1.0 for both neutron sources. The 3-hr split-dose survival ratios for ICC were 1.0 for JANUS neutrons, 1.85 for Fermilab neutrons, and 6.5 for 60 Co γ rays. The RBE estimates for LD/sub 50/30/ were 1.5 and 2.3 for Fermilab and JANUS neutrons, respectively. Based on LD/sub 50/6/, the RBEs were 1.9 (Fermilab) and 3.0 (JANUS). The RBEs for CFU-S D 0 were 1.4 (Fermilab) and 1.9 (JANUS) and for jejunal microcolony D 0 1.4 (Fermilab) and 2.8 (JANUS)

  6. Ultrathin and Ion-Selective Janus Membranes for High-Performance Osmotic Energy Conversion.

    Science.gov (United States)

    Zhang, Zhen; Sui, Xin; Li, Pei; Xie, Ganhua; Kong, Xiang-Yu; Xiao, Kai; Gao, Longcheng; Wen, Liping; Jiang, Lei

    2017-07-05

    The osmotic energy existing in fluids is recognized as a promising "blue" energy source that can help solve the global issues of energy shortage and environmental pollution. Recently, nanofluidic channels have shown great potential for capturing this worldwide energy because of their novel transport properties contributed by nanoconfinement. However, with respect to membrane-scale porous systems, high resistance and undesirable ion selectivity remain bottlenecks, impeding their applications. The development of thinner, low-resistance membranes, meanwhile promoting their ion selectivity, is a necessity. Here, we engineered ultrathin and ion-selective Janus membranes prepared via the phase separation of two block copolymers, which enable osmotic energy conversion with power densities of approximately 2.04 W/m 2 by mixing natural seawater and river water. Both experiments and continuum simulation help us to understand the mechanism for how membrane thickness and channel structure dominate the ion transport process and overall device performance, which can serve as a general guiding principle for the future design of nanochannel membranes for high-energy concentration cells.

  7. Large In-Plane and Vertical Piezoelectricity in Janus Transition Metal Dichalchogenides.

    Science.gov (United States)

    Dong, Liang; Lou, Jun; Shenoy, Vivek B

    2017-08-22

    Piezoelectricity in 2D van der Waals materials has received considerable interest because of potential applications in nanoscale energy harvesting, sensors, and actuators. However, in all the systems studied to date, strain and electric polarization are confined to the basal plane, limiting the operation of piezoelectric devices. In this paper, based on ab initio calculations, we report a 2D materials system, namely, the recently synthesized Janus MXY (M = Mo or W, X/Y = S, Se, or Te) monolayer and multilayer structures, with large out-of-plane piezoelectric polarization. For MXY monolayers, both strong in-plane and much weaker out-of-plane piezoelectric polarizations can be induced by a uniaxial strain in the basal plane. For multilayer MXY, we obtain a very strong out-of-plane piezoelectric polarization when strained transverse to the basal plane, regardless of the stacking sequence. The out-of-plane piezoelectric coefficient d 33 is found to be strongest in multilayer MoSTe (5.7-13.5 pm/V depending on the stacking sequence), which is larger than that of the commonly used 3D piezoelectric material AlN (d 33 = 5.6 pm/V); d 33 in other multilayer MXY structures are a bit smaller, but still comparable. Our study reveals the potential for utilizing piezoelectric 2D materials and their van der Waals multilayers in device applications.

  8. Sensitive Monitoring of Enterobacterial Contamination of Food Using Self-Propelled Janus Microsensors.

    Science.gov (United States)

    Pacheco, M; Jurado-Sánchez, B; Escarpa, A

    2018-02-20

    Food poisoning caused by bacteria is a major cause of disease and death worldwide. Herein we describe the use of Janus micromotors as mobile sensors for the detection of toxins released by enterobacteria as indicators of food contamination. The micromotors are prepared by a Pickering emulsion approach and rely on the simultaneous encapsulation of platinum nanoparticles for enhanced bubble-propulsion and receptor-functionalized quantum dots (QDs) for selective binding with the 3-deoxy-d-manno-oct-2-ulosonic acid target in the endotoxin molecule. Lipopolysaccharides (LPS) from Salmonella enterica were used as target endotoxins, which upon interaction with the QDs induce a rapid quenching of the native fluorescence of the micromotors in a concentration-dependent manner. The micromotor assay can readily detect concentrations as low as 0.07 ng mL -1 of endotoxin, which is far below the level considered toxic to humans (275 μg mL -1 ). Micromotors have been successfully applied for the detection of Salmonella toxin in food samples in 15 min compared with several hours required by the existing Gold Standard method. Such ultrafast and reliable approach holds considerable promise for food contamination screening while awaiting the results of bacterial cultures in a myriad of food safety and security defense applications.

  9. Causality and correlations between BSE and NYSE indexes: A Janus faced relationship

    Science.gov (United States)

    Neeraj; Panigrahi, Prasanta K.

    2017-09-01

    We study the multi-scale temporal correlations and causality connections between the New York Stock Exchange (NYSE) and Bombay Stock Exchange (BSE) monthly average closing price indexes for a period of 300 months, encompassing the time period of the liberalisation of the Indian economy and its gradual global exposure. In multi-scale analysis; clearly identifiable 1, 2 and 3 year non-stationary periodic modulations in NYSE and BSE have been observed, with NYSE commensurating changes in BSE at 3 years scale. Interestingly, at one year time scale, the two exchanges are phase locked only during the turbulent times, while at the scale of three year, in-phase nature is observed for a much longer time frame. The two year time period, having characteristics of both one and three year variations, acts as the transition regime. The normalised NYSE's stock value is found to Granger cause those of BSE, with a time lag of 9 months. Surprisingly, observed Granger causality of high frequency variations reveals BSE behaviour getting reflected in the NYSE index fluctuations, after a smaller time lag. This Janus faced relationship, shows that smaller stock exchanges may provide a natural setting for simulating market fluctuations of much bigger exchanges. This possibly arises due to the fact that high frequency fluctuations form an universal part of the financial time series, and are expected to exhibit similar characteristics in open market economies.

  10. Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

    Directory of Open Access Journals (Sweden)

    Maes Michael

    2012-06-01

    Full Text Available Abstract It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia, physio-somatic (fatigue, hyperalgesia, malaise, anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuroinflammation and (neurodegenerative processes following less well defined triggers.

  11. A new trend in pathogenetic treatment of rheumatoid arthritis: tofacitinib, the first inhibitor of Janus kinase

    Directory of Open Access Journals (Sweden)

    Dmitry Evgenyevich Karateev

    2014-01-01

    Full Text Available The Problem of effective treatment of rheumatoid arthritis (RA has not been solved yet. In patients with an inadequate response to the synthetic disease-modifying antirheumatic drugs (DMARDs, TNF inhibitors and other genetically engineered (GE drugs may give an incomplete effect or be totally ineffective in 20–40% of cases. The search for new therapeutic options is very active in many directions, including modulation of intracellular signaling pathways. The most impressive clinical results in RA patients have been achieved for Janus kinase (JAK inhibitor, tofacitinib, – Tofa (CP-690,550, a low molecular weight drug for oral administration. Unlike the conventional synthetic DMARD, Tofa belongs to targeted therapy drugs; its pharmacological effects largely resemble those of GE drugs (blockade of the biological effects of cytokines. In particular, some features of its mechanism of action (e.g., interleukin 6 inhibition make it similar to tocilizumab. In all trials, Tofa proved to exhibit high clinical efficacy and satisfactory safety. Tofa was shown to be significantly more effective than methotrexate and placebo (in monotherapy, as well as in combination with DMARDs in RA patients with an inadequate response to standard DMARDs and TNFa inhibitors (regarding response to treatment, individual parameters of disease activity, achievement of low disease activity and remission, functional impairment. Furthermore, Tofa can inhibit joint damage progression.

  12. Are Janus Kinase Inhibitors Superior over Classic Biologic Agents in RA Patients?

    Directory of Open Access Journals (Sweden)

    Przemyslaw J. Kotyla

    2018-01-01

    Full Text Available The Janus Kinases (JAKs are a family of intracellular tyrosine kinases that provide transmission signals from cytokine, interferons, and many hormones receptors to the nucleus resulting in synthesis of many biologically active compounds and changing cell metabolism and function. That was theoretical background to synthetize the JAK inhibitors (Jakinibs. In recent years a substantial battery of evidence has been collected indicating the potential role of Jakinibs to interact with the specific elements of the immune system, therefore changing the inflammatory response. JAK kinase blockade offers a unique opportunity to block most of the key cytokines enabling the deep interaction into immune system functioning. Following discovery first Jakinibs were intensively studied in various forms of autoimmune diseases, including rheumatoid arthritis, and finally two Jakinibs tofacitinib and Baricitinib have been approved for the treatment of rheumatoid arthritis. Some clinical data indicated that under special circumstances Jakinibs may be even superior to biologics in the treatment of RA; however this suggestion should be verified in large clinical and observational studies.

  13. Tofacitinib Represses the Janus Kinase-Signal Transducer and Activators of Transcription Signalling Pathway in Keratinocytes.

    Science.gov (United States)

    Srivastava, Ankit; Ståhle, Mona; Pivarcsi, Andor; Sonkoly, Enikö

    2018-05-08

    Tofacitinib is a Janus kinase (JAK) inhibitor, which has shown efficacy in treating psoriasis. The mode of action of tofacitinib is not completely understood but it has been thought to be mediated by the inhibition of CD4+ T-cell activation. Here, we investigated whether the molecular targets of tofacitinib are expressed in keratinocytes, and whether tofacitinib can modulate the activity of the JAK/Signal Transducer and Activators of Transcription (STAT)-pathway in keratinocytes. Transcriptomic profiling of human keratinocytes treated with IL-22 in combination with tofacitinib revealed that tofacitinib could prevent the majority of IL-22-mediated gene expression changes. Pathway analysis of tofacitinib-regulated genes in keratinocytes revealed enrichment of genes involved in the JAK/STAT signalling pathway. Quantitative real-time-PCR confirmed the upregulation of S100A7 and downregulation of EGR1 expression by IL-22, which was prevented by tofacitinib pre-treatment. These results indicate a direct effect of tofacinitib on keratinocytes, which can have relevance for systemic as well as for topical treatment of psoriasis with tofacitinib.

  14. Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure.

    Science.gov (United States)

    Liu, Lucy Y; Strassner, James P; Refat, Maggi A; Harris, John E; King, Brett A

    2017-10-01

    Vitiligo is an autoimmune disease in which cutaneous depigmentation occurs. Existing therapies are often inadequate. Prior reports have shown benefit of the Janus kinase (JAK) inhibitors. To evaluate the efficacy of the JAK 1/3 inhibitor tofacitinib in the treatment of vitiligo. This is a retrospective case series of 10 consecutive patients with vitiligo treated with tofacitinib. Severity of disease was assessed by body surface area of depigmentation. Ten consecutive patients were treated with tofacitinib. Five patients achieved some repigmentation at sites of either sunlight exposure or low-dose narrowband ultraviolet B phototherapy. Suction blister sampling revealed that the autoimmune response was inhibited during treatment in both responding and nonresponding lesions, suggesting that light rather than immunosuppression was primarily required for melanocyte regeneration. Limitations include the small size of the study population, retrospective nature of the study, and lack of a control group. Treatment of vitiligo with JAK inhibitors appears to require light exposure. In contrast to treatment with phototherapy alone, repigmentation during treatment with JAK inhibitors may require only low-level light. Maintenance of repigmentation may be achieved with JAK inhibitor monotherapy. These results support a model wherein JAK inhibitors suppress T cell mediators of vitiligo and light exposure is necessary for stimulation of melanocyte regeneration. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. Self-Standing Nanocellulose Janus-Type Films with Aldehyde and Carboxyl Functionalities.

    Science.gov (United States)

    Nypelö, Tiina; Amer, Hassan; Konnerth, Johannes; Potthast, Antje; Rosenau, Thomas

    2018-03-12

    Nanocellulose-based self-standing films are becoming a substrate for flexible electronics, diagnostics, and sensors. Strength and surface chemistry are vital variables for these film-based endeavors, the former is one of the assets of nanocellulose. To contribute to the latter, nanocellulose films are tuned with a side-specific functionalization, having an aldehyde and a carboxyl side. The functionalities were obtained combining premodification of the film components by periodate oxidation with ozone post-treatment. Periodate oxidation of cellulose nanocrystals results in film components that interact through intra- and intermolecular hemiacetals and lead to films with an elastic modulus of 11 GPa. The ozone treatment of one film side induces conversion of the aldehyde into carboxyl functionalities. The ozone treatment on individual crystals was largely destructive. Remarkably, such degradation is not observed for the self-standing film, and the film strength at break is preserved. Preserving a physically intact film despite ozone treatment is a credit to using the dry film structure held together by interparticle covalent linkages. Additionally, gas-phase post-treatment avoids disintegration that could result from immersion into solvents. The crystalline cellulose "Janus" film is suggested as an interfacial component in biomaterial engineering, separation technology, or in layered composite materials for tunable affinity between the layers.

  16. Design of Janus nanoparticles with atomic precision: tungsten-doped gold nanostructures.

    Science.gov (United States)

    Sun, Qiang; Wang, Qian; Jena, Puru; Kawazoe, Yoshiyuki

    2008-02-01

    Janus nanoparticles, characterized by their anisotropic structure and interactions, have added a new dimension to nanoscience because of their potential applications in biomedicine, sensors, catalysis, and assembled materials. The technological applications of these nanoparticles, however, have been limited as the current chemical, physical, and biosynthetic methods lack sufficient size and shape selectivity. We report a technique where gold clusters doped with tungsten can serve as a seed that facilitates the natural growth of anisotropic nanostructures whose size and shape can be controlled with atomic precision. Using ab initio simulated annealing and molecular dynamics calculations on AunW (n > 12) clusters, we discovered that the W@Au12 cage cluster forms a very stable core with the remaining Au atoms forming patchy structures on its surface. The anisotropic geometry gives rise to anisotropies in vibrational spectra, charge distributions, electronic structures, and reactivity, thus making it useful to have dual functionalities. In particular, the core-patch structure is shown to possess a hydrophilic head and a hydrophobic tail. The W@Au12 clusters can also be used as building blocks of a nanoring with novel properties.

  17. The Janus Kinase (JAK) FERM and SH2 Domains: Bringing Specificity to JAK-Receptor Interactions.

    Science.gov (United States)

    Ferrao, Ryan; Lupardus, Patrick J

    2017-01-01

    The Janus kinases (JAKs) are non-receptor tyrosine kinases essential for signaling in response to cytokines and interferons and thereby control many essential functions in growth, development, and immune regulation. JAKs are unique among tyrosine kinases for their constitutive yet non-covalent association with class I and II cytokine receptors, which upon cytokine binding bring together two JAKs to create an active signaling complex. JAK association with cytokine receptors is facilitated by N-terminal FERM and SH2 domains, both of which are classical mediators of peptide interactions. Together, the JAK FERM and SH2 domains mediate a bipartite interaction with two distinct receptor peptide motifs, the proline-rich "Box1" and hydrophobic "Box2," which are present in the intracellular domain of cytokine receptors. While the general sidechain chemistry of Box1 and Box2 peptides is conserved between receptors, they share very weak primary sequence homology, making it impossible to posit why certain JAKs preferentially interact with and signal through specific subsets of cytokine receptors. Here, we review the structure and function of the JAK FERM and SH2 domains in light of several recent studies that reveal their atomic structure and elucidate interaction mechanisms with both the Box1 and Box2 receptor motifs. These crystal structures demonstrate how evolution has repurposed the JAK FERM and SH2 domains into a receptor-binding module that facilitates interactions with multiple receptors possessing diverse primary sequences.

  18. The Janus-Faced Role of Gambling Flow in Addiction Issues.

    Science.gov (United States)

    Trivedi, Rohit H; Teichert, Thorsten

    2017-03-01

    Flow experience has been widely investigated in experiential activities such as sports, the performing arts, gaming, and Internet usage. Most studies focus on the positive aspects of flow experience and its effect on performance. In stark contrast, gambling research focusing on the negative side of addiction lacks an in-depth investigation of gamblers' (positive) flow encounters. This separation of research lines seems out of place given that recent research indicates connections between flow and addiction. Joining both constructs in a causal-effects model helps one gain a better understanding of their relationship and its contingencies. This article empirically investigates whether and how it is possible to observe a "Janus face" of flow with its various sub-dimensions in online gambling. Empirical data were collected from 500 online gamblers by applying a structured questionnaire with established scales. The data were analyzed with a confirmatory factor analysis and a double-hurdle model to separate casual gamblers who are unsusceptible to any addiction issues from gamblers affected by initiatory addiction issues. The findings indicate that online gambling addiction is negatively influenced by two sub-dimensions of flow experience, namely a sense of control and concentration on the task at hand, whereas it is enhanced by a transformation of time and autotelic experience.

  19. Janus Kinase 2 (JAK2) Dissociates Hepatosteatosis from Hepatocellular Carcinoma in Mice.

    Science.gov (United States)

    Shi, Sally Yu; Luk, Cynthia T; Schroer, Stephanie A; Kim, Min Jeong; Dodington, David W; Sivasubramaniyam, Tharini; Lin, Lauren; Cai, Erica P; Lu, Shun-Yan; Wagner, Kay-Uwe; Bazinet, Richard P; Woo, Minna

    2017-03-03

    Hepatocellular carcinoma is an end-stage complication of non-alcoholic fatty liver disease (NAFLD). Inflammation plays a critical role in the progression of non-alcoholic fatty liver disease and the development of hepatocellular carcinoma. However, whether steatosis per se promotes liver cancer, and the molecular mechanisms that control the progression in this disease spectrum remain largely elusive. The Janus kinase signal transducers and activators of transcription (JAK-STAT) pathway mediates signal transduction by numerous cytokines that regulate inflammation and may contribute to hepatocarcinogenesis. Mice with hepatocyte-specific deletion of JAK2 (L-JAK2 KO) develop extensive fatty liver spontaneously. We show here that this simple steatosis was insufficient to drive carcinogenesis. In fact, L-JAK2 KO mice were markedly protected from chemically induced tumor formation. Using the methionine choline-deficient dietary model to induce steatohepatitis, we found that steatohepatitis development was completely arrested in L-JAK2 KO mice despite the presence of steatosis, suggesting that JAK2 is the critical factor required for inflammatory progression in the liver. In line with this, L-JAK2 KO mice exhibited attenuated inflammation after chemical carcinogen challenge. This was associated with increased hepatocyte apoptosis without elevated compensatory proliferation, thus thwarting expansion of transformed hepatocytes. Taken together, our findings identify an indispensable role of JAK2 in hepatocarcinogenesis through regulating critical inflammatory pathways. Targeting the JAK-STAT pathway may provide a novel therapeutic option for the treatment of hepatocellular carcinoma. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Thromboembolism with Janus Kinase (JAK) Inhibitors for Rheumatoid Arthritis: How Real is the Risk?

    Science.gov (United States)

    Scott, Ian C; Hider, Samantha L; Scott, David L

    2018-03-02

    Two different Janus kinase (JAK) inhibitors-baricitinib and tofacitinib-are effective and licensed in active rheumatoid arthritis (RA). There have been recent concerns about potential thromboembolic risks with these drugs. Concerns about baricitinib focus on clinical trial findings. Using all publically available data, we estimate thromboembolic risks are approximately five events per 1000 patient years with 4 mg baricitinib daily. Concerns about tofacitinib have been raised by analyses of the Federal Drug Administration Adverse Event Reporting System (FAERs). These show some evidence of increased risks of pulmonary thrombosis, though not pulmonary embolism or venous thrombosis. Observational studies suggest in the general population and non-RA controls there are one to four thromboembolic events per 1000 patient years. In RA, thromboembolic risks increase to three to seven per 1000 patient years. The impact of biologics and disease-modifying anti-rheumatic drugs (DMARDs) on disease risk appears minimal, and the number of thromboembolic events is between four and eight per 1000 patient years. In the short term, full details of thromboembolic events in trials of JAK inhibitors need to be published. As the numbers of thromboembolic events will be small and patients enrolled in trials are not representative of all RA patients who may receive JAK inhibitors, this information is unlikely to provide definitive answers. Consequently, in the longer term, large observational studies are needed to accurately quantify thromboembolic risks attributable to JAK inhibitors and other drugs used to treat RA, and differentiate these from risks attributable to RA itself and its comorbidities.

  1. The Janus-faced role of ezrin in "linking" cells to either normal or metastatic phenotype.

    Science.gov (United States)

    Brambilla, Daria; Fais, Stefano

    2009-11-15

    In the majority of eukaryotic cells, the ezrin, radixin and moesin (ERM) proteins are involved in many physiologic functions including regulation of actin cytoskeleton, control of cell shape, adhesion, motility and modulation of signal transduction pathways. In a previous study, we used a dominant negative ezrin-mutant to address ezrin involvement in remodeling of actin cytoskeleton and subsequently we depicted ezrin key role in melanoma cell migration and progression. Herein, we highlight recent advances on ezrin involvement in the metastatic phenomenon, including also some more neglected ezrin-related functions. Novel molecular processes driven by ezrin activation include: phagocytosis, acquisition of resistance to chemotherapeutics and triggering of programmed cell death signals. Recent data support an integrated role of ezrin also in development of tumor malignancy. On one hand, ezrin may be responsible of deranged execution of specific known functions such as adhesion and motility and on the other, it may also participate to unique metastatic determinants, through the establishment of aberrant linkages with tumor-related proteins. For instance, ezrin misslocalization, absence or deranged activity has started to be correlated with tumor progression in many tumors of different species, including humans. Concomitantly, ezrin may act simultaneously as a regulatory or deregulatory chaperon in both normal and tumor cells. It is still to be established whether this Janus-faced feature of ezrin is due to some unknown transforming Zelig-like property or to the fact that a tumor-associated molecule preferentially links to ezrin thus distracting it from its normal connections. However, the contribution of ezrin functional deregulation to the acquisition of the metastatic phenotype appears clear and ezrin or ezrin aberrant associations may represent good candidates for future anti-tumor therapies.

  2. Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor.

    Science.gov (United States)

    Charles-Schoeman, Christina; Wicker, Pierre; Gonzalez-Gay, Miguel A; Boy, Mary; Zuckerman, Andrea; Soma, Koshika; Geier, Jamie; Kwok, Kenneth; Riese, Richard

    2016-12-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The implications of treatment with tofacitinib on cardiovascular (CV) risk in RA are unknown. Therefore, CV adverse events (AEs), and blood pressure and lipid level changes, in tofacitinib-treated patients with RA were evaluated. Data were pooled from six Phase (P)3 studies (24 months) and two open-label long-term extension (LTE) studies (60 months) of tofacitinib in patients with RA and inadequate response to DMARDs. Tofacitinib was administered alone or with non-biologic DMARDs. CV events, including major adverse CV events (MACE: CV death and non-fatal CV events) and congestive heart failure (CHF), were assessed by a blinded adjudication committee. Overall, 4271 patients from P3 studies and 4827 enrolled from P2/P3 studies into LTE studies were evaluated, representing 3942 and 8699 patient-years of exposure to tofacitinib, respectively. Blood pressure remained stable over time across studies. The number of investigator-reported hypertension-related AEs in tofacitinib-treated patients was low in P3 studies (Months 0-3: 2.8%; Months 3-6: 1.4%; >6 months: 2.8%). Across studies, lipid level increases were generally observed within 1-3 months of treatment and stabilized thereafter. Patients with events (incidence rate [IR]/100 patient-years) for MACE and CHF, respectively, were: 23 (0.58) and 9 (0.23) in P3 studies, and 32 (0.37) and 8 (0.09) in LTE studies; IRs were comparable with placebo (P3) and did not increase over time (LTE). Tofacitinib was associated with a low incidence of CV events in a large Phase 3 program, including LTE studies. Further long-term studies are underway. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. La imagen numismática de Jano = Numismatic image of Janus

    Directory of Open Access Journals (Sweden)

    María Teresa Pradas Blasco

    2014-12-01

    Full Text Available El análisis iconográfico de la muestra numismática permite distinguir dos periodos distintos, en extensión y contenido: entre el 225 a. C. y el 31 a. C. aparece, se repite y, finalmente, se contamina el tipo «cabeza de Jano», y entre el 119 d. C. y el 260 d. C. se recupera al dios mediante el tipo «cuerpo de Jano». Al contrastar este resultado, aunque las fuentes literarias no coinciden con exactitud en la descripción sin embargo muestran concomitancias relevantes en cuanto a la cronología y a la interpretación. En la República, la imagen reiterada y simple se vincula con el poder militar de Roma pero, insólitamente, el rescate antonino marca el uso y el cambio de significado ya que Jano se integra en un programa que requiere del dios su competencia temporal.Iconographic analysis of the numismatic sample allows us to distinguish two different periods, both in length as well as in content: between 225 BC and 31 BC, the «Janus’ head» type appears, is repeated and, in the end, is contaminated; between 119 AD and 260 AD, the god´s image is recovered by means of the «Janus’ body» type. Contrasting this result, although the literary sources do not agree accurately on the description, they show important similarities in terms of chronology and interpretation. In the Republic, the repeated and simple image is linked to the military power of Rome but, unusually, the Antonine rescue changes the use and meaning because Janus is included in a program that needs the god’s functions concerning time.

  4. Shape-dependent guidance of active Janus particles by chemically patterned surfaces

    Science.gov (United States)

    Uspal, W. E.; Popescu, M. N.; Tasinkevych, M.; Dietrich, S.

    2018-01-01

    Self-phoretic chemically active Janus particles move by inducing—via non-equilibrium chemical reactions occurring on their surfaces—changes in the chemical composition of the solution in which they are immersed. This process leads to gradients in chemical composition along the surface of the particle, as well as along any nearby boundaries, including solid walls. Chemical gradients along a wall can give rise to chemi-osmosis, i.e., the gradients drive surface flows which, in turn, drive flow in the volume of the solution. This bulk flow couples back to the particle, and thus contributes to its self-motility. Since chemi-osmosis strongly depends on the molecular interactions between the diffusing molecular species and the wall, the response flow induced and experienced by a particle encodes information about any chemical patterning of the wall. Here, we extend previous studies on self-phoresis of a sphere near a chemically patterned wall to the case of particles with rod-like, elongated shape. We focus our analysis on the new phenomenology potentially emerging from the coupling—which is inoperative for a spherical shape—of the elongated particle to the strain rate tensor of the chemi-osmotic flow. Via detailed numerical calculations, we show that the dynamics of a rod-like particle exhibits a novel ‘edge-following’ steady state: the particle translates along the edge of a chemical step at a steady distance from the step and with a steady orientation. Moreover, within a certain range of system parameters, the edge-following state co-exists with a ‘docking’ state (the particle stops at the step, oriented perpendicular to the step edge), i.e., a bistable dynamics occurs. These findings are rationalized as a consequence of the competition between the fluid vorticity and the rate of strain by using analytical theory based on the point-particle approximation which captures quasi-quantitatively the dynamics of the system.

  5. Reversible Photoinduced Reductive Elimination of H2 from the Nitrogenase Dihydride State, the E4(4H) Janus Intermediate

    OpenAIRE

    Lukoyanov, Dmitriy; Khadka, Nimesh; Yang, Zhi-Yong; Dean, Dennis R.; Seefeldt, Lance C.; Hoffman, Brian M.

    2016-01-01

    We recently demonstrated that N2 reduction by nitrogenase involves the obligatory release of one H2 per N2 reduced. These studies focused on the E4(4H) ‘Janus intermediate’, which has accumulated four reducing equivalents as two [Fe-H-Fe] bridging hydrides. E4(4H) is poised to bind and reduce N2 through reductive elimination (re) of the two hydrides as H2, coupled to the binding/reduction of N2. To obtain atomic-level details of the re activation process, we carried out in situ 450 nm photoly...

  6. Photomedicine and Stem Cells; The Janus face of photodynamic therapy (PDT) to kill cancer stem cells, and photobiomodulation (PBM) to stimulate normal stem cells

    Science.gov (United States)

    Abrahamse, Heidi; Hamblin, Michael R.

    2017-12-01

    Janus, the ancient Roman god depicted with two faces is an appropriate metaphor for light therapy. In the right photodynamic therapy conditions, light is able to kill nearly anything that is living such as cancers, microorganisms, parasites, and more. On the opposite face, light of the correct wavelength and proper dose (photobiomodulation) can heal, regenerate, protect, revitalize and restore any kind of dead, damaged, stressed, dying, degenerating cells, tissue, or organ system. This book discusses both sides of Janus' face in regards to light therapy.

  7. Simultaneous Detection and Removal of Formaldehyde at Room Temperature: Janus Au@ZnO@ZIF-8 Nanoparticles

    Science.gov (United States)

    Wang, Dawei; Li, Zhiwei; Zhou, Jian; Fang, Hong; He, Xiang; Jena, Puru; Zeng, Jing-Bin; Wang, Wei-Ning

    2018-03-01

    The detection and removal of volatile organic compounds (VOCs) are of great importance to reduce the risk of indoor air quality concerns. This study reports the rational synthesis of a dual-functional Janus nanostructure and its feasibility for simultaneous detection and removal of VOCs. The Janus nanostructure was synthesized via an anisotropic growth method, composed of plasmonic nanoparticles, semiconductors, and metal organic frameworks (e.g., Au@ZnO@ZIF-8). It exhibits excellent selective detection to formaldehyde (HCHO, as a representative VOC) at room temperature over a wide range of concentrations (from 0.25 to 100 ppm), even in the presence of water and toluene molecules as interferences. In addition, HCHO was also found to be partially oxidized into non-toxic formic acid simultaneously with detection. The mechanism underlying this technology was unraveled by both experimental measurements and theoretical calculations: ZnO maintains the conductivity, while ZIF-8 improves the selective gas adsorption; the plasmonic effect of Au nanorods enhances the visible-light-driven photocatalysis of ZnO at room temperature. [Figure not available: see fulltext.

  8. Modulation of expression of genes encoding nuclear proteins following exposure to JANUS neutrons or γ-rays

    International Nuclear Information System (INIS)

    Woloschak, G.E.; Chang-Liu, Chin-Mei

    1994-01-01

    Previous work has shown that exposure of cells to ionizing radiations causes modulation of a variety of genes, including those encoding c-fos, interleukin-1, tumor necrosis factor, cytoskeletal elements, and many more. The experiments reported herein were designed to examine the effects of either JANUS neutron or γ-ray exposure on expression of genes encoding nucleus-associated proteins (H4-histone, c-jun, c-myc, Rb, and p53). Cycling Syrian hamster embryo cells were irradiated with varying doses and dose rates of either JANUS fission-spectrum neutrons or γ-rays; after incubation of the cell cultures for 1 h following radiation exposure, mRNA was harvested and analyzed by Northern blot. Results revealed induction of transcripts for c-jun, H4-histone, and Rb following γ-ray but not following neutron exposure. Interestingly, expression of c-myc was repressed following γ-ray but not following neutron exposure. Radiations at different doses and dose rates were compared for each of the genes studied

  9. PEAR SHOOT SAWFLY (JANUS COMPRESSUS FABRICIUS – LIFE CYCLE AND BIOLOGICAL AND MORPHOLOGICAL CHARACTERISTIC

    Directory of Open Access Journals (Sweden)

    Tihomir Validžić

    2014-06-01

    Full Text Available The aim of the thesis was to investigate life cycle, biological and morphological characteristics of pear shoot sawfly (Janus compressus Fabricius, Hymenoptera Cephidae, furthermore to identify natural enemies in order to protect pear from this pest. The trial was conducted in the period of three years: 2010, 2011 and 2012 in pear orchards at five localities. Monitoring of adult sawfly was done by yellow sticky traps. Laboratory research was done at the Faculty of Agriculture, Department of Plant Protection, Section of Entomology and Nematology. In this study, pear shoot sawfly in Eastern Slavonia occurred in the period of four weeks, starting from the third decade of April with the peak population at the beginning of the May. Adults flight is the most intensive during warm and sunny days, when temperatures are above 14°C. Adult sawflies are characterized by elongated body and antennae, usually 7-12 mm long and sexual dimorphism is present. Pest is univoltine. Basic colour of adult sawfly is black. Antennae are moniliform and consist of 20 (male - 22 (female segments. Females have red or dark red colored abdomen, while males have yellow or orange one. Eggs are cylindrically shaped, 0.8-1.0 mm long. Female lays approximately 30 eggs. Embryonic development of pear shoot sawfly eggs lasts from 11 to 14 days. Larvae are 8-10 mm long, white or pale yellow. Larvae molt three times. Pear shoot sawfly larvae were parasitized by insects from Hymenoptera order, from five identified and one unidentified genera. Level of parasitism by genera is as follows: Eurytoma sp. (Hymenoptera: Eurytomidae – 9.83%, Tetrastichus sp. (Hymenoptera: Eulophidae – 2.01%, Eupelmus sp. (Hymenoptera: Eupelmidae – 1.66%, Pteromalus sp. (Hymenoptera: Pteromalidae – 0.55%, Ichneumonida sp. (Hymenoptera: Pimplinae – 0.35% and unidentified genera – 0.62%. Plant parasitic species Metopoplax origani (Hemiptera: Lygaeidae was found in 1.80% of analyzed shoots. Larvae were

  10. Hydrodynamic interaction of a self-propelling particle with a wall : Comparison between an active Janus particle and a squirmer model.

    Science.gov (United States)

    Shen, Zaiyi; Würger, Alois; Lintuvuori, Juho S

    2018-03-27

    Using lattice Boltzmann simulations we study the hydrodynamics of an active spherical particle near a no-slip wall. We develop a computational model for an active Janus particle, by considering different and independent mobilities on the two hemispheres and compare the behaviour to a standard squirmer model. We show that the topology of the far-field hydrodynamic nature of the active Janus particle is similar to the standard squirmer model, but in the near-field the hydrodynamics differ. In order to study how the near-field effects affect the interaction between the particle and a flat wall, we compare the behaviour of a Janus swimmer and a squirmer near a no-slip surface via extensive numerical simulations. Our results show generally a good agreement between these two models, but they reveal some key differences especially with low magnitudes of the squirming parameter [Formula: see text]. Notably the affinity of the particles to be trapped at a surface is increased for the active Janus particles when compared to standard squirmers. Finally, we find that when the particle is trapped on the surface, the velocity parallel to the surface exceeds the bulk swimming speed and scales linearly with [Formula: see text].

  11. Development and Integration of the Janus Robotic Lander: A Liquid Oxygen-Liquid Methane Propulsion System Testbed

    Science.gov (United States)

    Ponce, Raul

    Initiatives have emerged with the goal of sending humans to other places in our solar system. New technologies are being developed that will allow for more efficient space systems to transport future astronauts. One of those technologies is the implementation of propulsion systems that use liquid oxygen and liquid methane (LO2-LCH4) as propellants. The benefits of a LO2-LCH4 propulsion system are plenty. One of the main advantages is the possibility of manufacturing the propellants at the destination body. A space vehicle which relies solely on liquid oxygen and liquid methane for its main propulsion and reaction control engines is necessary to exploit this advantage. At the University of Texas at El Paso (UTEP) MIRO Center for Space Exploration Technology Research (cSETR) such a vehicle is being developed. Janus is a robotic lander vehicle with the capability of vertical take-off and landing (VTOL) which integrates several LO2-LCH 4 systems that are being devised in-house. The vehicle will serve as a testbed for the parallel operation of these propulsion systems while being fed from common propellant tanks. The following work describes the efforts done at the cSETR to develop the first prototype of the vehicle as well as the plan to move forward in the design of the subsequent prototypes that will lead to a flight vehicle. In order to ensure an eventual smooth integration of the different subsystems that will form part of Janus, requirements were defined for each individual subsystem as well as the vehicle as a whole. Preliminary testing procedures and layouts have also been developed and will be discussed to detail in this text. Furthermore, the current endeavors in the design of each subsystem and the way that they interact with one another within the lander will be explained.

  12. Reversible Photoinduced Reductive Elimination of H2 from the Nitrogenase Dihydride State, the E(4)(4H) Janus Intermediate.

    Science.gov (United States)

    Lukoyanov, Dmitriy; Khadka, Nimesh; Yang, Zhi-Yong; Dean, Dennis R; Seefeldt, Lance C; Hoffman, Brian M

    2016-02-03

    We recently demonstrated that N2 reduction by nitrogenase involves the obligatory release of one H2 per N2 reduced. These studies focus on the E4(4H) "Janus intermediate", which has accumulated four reducing equivalents as two [Fe-H-Fe] bridging hydrides. E4(4H) is poised to bind and reduce N2 through reductive elimination (re) of the two hydrides as H2, coupled to the binding/reduction of N2. To obtain atomic-level details of the re activation process, we carried out in situ 450 nm photolysis of E4(4H) in an EPR cavity at temperatures below 20 K. ENDOR and EPR measurements show that photolysis generates a new FeMo-co state, denoted E4(2H)*, through the photoinduced re of the two bridging hydrides of E4(4H) as H2. During cryoannealing at temperatures above 175 K, E4(2H)* reverts to E4(4H) through the oxidative addition (oa) of the H2. The photolysis quantum yield is temperature invariant at liquid helium temperatures and shows a rather large kinetic isotope effect, KIE = 10. These observations imply that photoinduced release of H2 involves a barrier to the combination of the two nascent H atoms, in contrast to a barrierless process for monometallic inorganic complexes, and further suggest that H2 formation involves nuclear tunneling through that barrier. The oa recombination of E4(2H)* with the liberated H2 offers compelling evidence for the Janus intermediate as the point at which H2 is necessarily lost during N2 reduction; this mechanistically coupled loss must be gated by N2 addition that drives the re/oa equilibrium toward reductive elimination of H2 with N2 binding/reduction.

  13. Synthesis, Characterization, and Mechanism of Formation of Janus-Like Nanoparticles of Tantalum Silicide-Silicon (TaSi2/Si

    Directory of Open Access Journals (Sweden)

    Andrey V. Nomoev

    2014-12-01

    Full Text Available Metal-semiconductor Janus-like nanoparticles with the composition tantalum silicide-silicon (TaSi2/Si were synthesized for the first time by means of an evaporation method utilizing a high-power electron beam. The composition of the synthesized particles were characterized using high-resolution transmission electron microscopy (HRTEM, X-ray diffraction (XRD, selective area electron diffraction (SAED, and energy dispersive X-ray fluorescence (EDX analysis. The system is compared to previously synthesized core-shell type particles in order to show possible differences responsible for the Janus-like structure forming instead of a core-shell architecture. It is proposed that the production of Janus-like as opposed to core-shell or monophase particles occurs due to the ability of Ta and Si to form compounds and the relative content of Ta and Si atoms in the produced vapour. Based on the results, a potential mechanism of formation for the TaSi2/Si nanoparticles is discussed.

  14. Adrenal incidentaloma and the Janus Kinase 2 V617F mutation: A case-based review of the literature

    Directory of Open Access Journals (Sweden)

    Mustafa Unubol

    2013-01-01

    Full Text Available Adrenal incidentaloma was detected in an 81-year-old male patient and a 37-year-old female patient who had been diagnosed with essential thrombocytosis. Each patient′s Janus Kinase 2 (JAK2 V617F mutation was positive, and they were evaluated as having non-functional adrenal incidentaloma. The JAK2 activates the signal transducers and activators of transcription (STAT proteins which then activate the phosphoinositol-3 kinases, Ras, mitogen-activated protein (MAP kinases, and transcription. Constitutive activation causes cell proliferation and dysregulation of apoptosis. It is thought that STAT3 activation-mediated JAK family kinases have a central role in the solid tumor cell series. Permanent activation of STAT3 and STAT5 causes tumor cell proliferation, survival, metastasis, and an increase in tumor-mediated inflammation in solid and hematologic tumors. According to our literature screening, irregular JAK signaling, seen at the pathogenesis of many solid and hematologic tumors, has not been previously evaluated with regard to adrenal tumors. As a result, our cases are the first coexistence of JAK V617F mutation with adrenal incidentaloma in the literature. Because of this, we think that JAK2 mutation must be evaluated to clarify the etiology of adrenal incidentalomas.

  15. Similarities and differences in signal transduction by interleukin 4 and interleukin 13: analysis of Janus kinase activation.

    Science.gov (United States)

    Keegan, A D; Johnston, J A; Tortolani, P J; McReynolds, L J; Kinzer, C; O'Shea, J J; Paul, W E

    1995-08-15

    The cytokines interleukin (IL) 4 and IL-13 induce many of the same biological responses, including class switching to IgE and induction of major histocompatibility complex class II antigens and CD23 on human B cells. It has recently been shown that IL-4 induces the tyrosine phosphorylation of a 170-kDa protein, a substrate called 4PS, and of the Janus kinase (JAK) family members JAK1 and JAK3. Because IL-13 has many functional effects similar to those of IL-4, we compared the ability of IL-4 and IL-13 to activate these signaling molecules in the human multifactor-dependent cell line TF-1. In this report we demonstrate that both IL-4 and IL-13 induced the tyrosine phosphorylation of 4PS and JAK1. Interestingly, although IL-4 induced the tyrosine phosphorylation of JAK3, we did not detect JAK3 phosphorylation in response to IL-13. These data suggest that IL-4 and IL-13 signal in similar ways via the activation of JAK1 and 4PS. However, our data further indicate that there are significant differences because IL-13 does not activate JAK3.

  16. Magneto-Plasmonic Janus Vesicles for Magnetic Field-Enhanced Photoacoustic and Magnetic Resonance Imaging of Tumors

    KAUST Repository

    Liu, Yijing; Yang, Xiangyu; Huang, Zhiqi; Huang, Peng; Zhang, Yang; Deng, Lin; Wang, Zhantong; Zhou, Zijian; Liu, Yi; Kalish, Heather; Khachab, Niveen M.; Chen, Xiaoyuan; Nie, Zhihong

    2016-01-01

    Magneto-plasmonic Janus vesicles (JVs) integrated with gold nanoparticles (AuNPs) and magnetic NPs (MNPs) were prepared asymmetrically in the membrane for in vivo cancer imaging. The hybrid JVs were produced by coassembling a mixture of hydrophobic MNPs, free amphiphilic block copolymers (BCPs), and AuNPs tethered with amphiphilic BCPs. Depending on the size and content of NPs, the JVs acquired spherical or hemispherical shapes. Among them, hemispherical JVs containing 50 nm AuNPs and 15 nm MNPs showed a strong absorption in the near-infrared (NIR) window and enhanced the transverse relaxation (T2) contrast effect, as a result of the ordering and dense packing of AuNPs and MNPs in the membrane. The magneto-plasmonic JVs were used as drug delivery vehicles, from which the release of a payload can be triggered by NIR light and the release rate can be modulated by a magnetic field. Moreover, the JVs were applied as imaging agents for in vivo bimodal photoacoustic (PA) and magnetic resonance (MR) imaging of tumors by intravenous injection. With an external magnetic field, the accumulation of the JVs in tumors was significantly increased, leading to a signal enhancement of approximately 2–3 times in the PA and MR imaging, compared with control groups without a magnetic field.

  17. Photochemically Powered AgCl Janus Micromotors as a Model System to Understand Ionic Self-Diffusiophoresis.

    Science.gov (United States)

    Zhou, Chao; Zhang, H P; Tang, Jinyao; Wang, Wei

    2018-03-13

    Micromotors are an emerging class of micromachines that could find potential applications in biomedicine, environmental remediation, and microscale self-assembly. Understanding their propulsion mechanisms holds the key to their future development. This is especially true for a popular category of micromotors that are driven by asymmetric surface photochemical reactions. Many of these micromotors release ionic species and are propelled via a mechanism termed "ionic self-diffusiophoresis". However, exactly how it operates remains vague. To address this fundamental yet important issue, we have developed a dielectric-AgCl Janus micromotor that clearly moves away from the AgCl side when exposed to UV or strong visible light. Taking advantage of numerical simulations and acoustic levitation techniques, we have provided tentative explanations for its speed decay over time as well as its directionality. In addition, photoactive AgCl micromotors demonstrate interesting gravitactic behaviors that hint at three-dimensional transport or sensing applications. The current work presents a well-controlled and easily fabricated model system to understand chemically powered micromotors, highlighting the usefulness of acoustic levitation for studying active matter free from the effect of boundaries.

  18. Dye-Enhanced Self-Electrophoretic Propulsion of Light-Driven TiO2-Au Janus Micromotors

    Science.gov (United States)

    Wu, Yefei; Dong, Renfeng; Zhang, Qilu; Ren, Biye

    2017-07-01

    Light-driven synthetic micro-/nanomotors have attracted considerable attention in recent years due to their unique performances and potential applications. We herein demonstrate the dye-enhanced self-electrophoretic propulsion of light-driven TiO2-Au Janus micromotors in aqueous dye solutions. Compared to the velocities of these micromotors in pure water, 1.7, 1.5, and 1.4 times accelerated motions were observed for them in aqueous solutions of methyl blue (10-5 g L-1), cresol red (10-4 g L-1), and methyl orange (10-4 g L-1), respectively. We determined that the micromotor speed changes depending on the type of dyes, due to variations in their photodegradation rates. In addition, following the deposition of a paramagnetic Ni layer between the Au and TiO2 layers, the micromotor can be precisely navigated under an external magnetic field. Such magnetic micromotors not only facilitate the recycling of micromotors, but also allow reusability in the context of dye detection and degradation. In general, such photocatalytic micro-/nanomotors provide considerable potential for the rapid detection and "on-the-fly" degradation of dye pollutants in aqueous environments.

  19. Carbonate-based Janus micromotors moving in ultra-light acidic environment generated by HeLa cells in situ

    Science.gov (United States)

    Guix, Maria; Meyer, Anne K.; Koch, Britta; Schmidt, Oliver G.

    2016-02-01

    Novel approaches to develop naturally-induced drug delivery in tumor environments in a deterministic and controlled manner have become of growing interest in recent years. Different polymeric-based microstructures and other biocompatible substances have been studied taking advantage of lactic acidosis phenomena in tumor cells, which decrease the tumor extracellular pH down to 6.8. Micromotors have recently demonstrated a high performance in living systems, revealing autonomous movement in the acidic environment of the stomach or moving inside living cells by using acoustic waves, opening the doors for implementation of such smart microengines into living entities. The need to develop biocompatible motors which are driven by natural fuel sources inherently created in biological systems has thus become of crucial importance. As a proof of principle, we here demonstrate calcium carbonate Janus particles moving in extremely light acidic environments (pH 6.5), whose motion is induced in conditioned acidic medium generated by HeLa cells in situ. Our system not only obviates the need for an external fuel, but also presents a selective activation of the micromotors which promotes their motion and consequent dissolution in presence of a quickly propagating cell source (i.e. tumor cells), therefore inspiring new micromotor configurations for potential drug delivery systems.

  20. Theoretical study of the self-assembly of Janus Bottlebrush Polymers from A-Branch-B Diblock Macromonomers

    Science.gov (United States)

    Gadelrab, Karim; Alexander-Katz, Alfredo; LaboratoryTheoretical Soft Materials Team

    The self-assembly of block copolymers BCP has provided an impressive control over the nanoscale structure of soft matter. While the main focus of the research in the field has been directed towards simple linear diblocks, the development of advanced polymer architecture provided improved performance and access to new structures. In particular, bottlebrush BCPs (BBCPs) have interesting characteristics due to their dense functionality, high molecular weight, low levels of entanglement, and tendency to efficiently undergo rapid bulk phase separation. In this work, we are interested in theoretically studying the self-assembly of Janus-type ``A-branch-B'' BBCPs where A and B blocks can phase separate with the bottlebrush polymer backbone serving as the interface between the two blocks. Hence, the polymer backbone adds an extra constraint on the equilibrium spacing between neighboring linear diblock chains. In this regard, the segment length of the backbone separating the AB junctions has a direct effect of the observed domain spacing and effective segregation strength of the AB blocks. We employ self-consistent field theoretic SCFT simulations to capture the effect of volume fraction of different constituents and construct a phase diagram of the accessible morphologies of these BBCPs.

  1. Magneto-Plasmonic Janus Vesicles for Magnetic Field-Enhanced Photoacoustic and Magnetic Resonance Imaging of Tumors

    KAUST Repository

    Liu, Yijing

    2016-11-10

    Magneto-plasmonic Janus vesicles (JVs) integrated with gold nanoparticles (AuNPs) and magnetic NPs (MNPs) were prepared asymmetrically in the membrane for in vivo cancer imaging. The hybrid JVs were produced by coassembling a mixture of hydrophobic MNPs, free amphiphilic block copolymers (BCPs), and AuNPs tethered with amphiphilic BCPs. Depending on the size and content of NPs, the JVs acquired spherical or hemispherical shapes. Among them, hemispherical JVs containing 50 nm AuNPs and 15 nm MNPs showed a strong absorption in the near-infrared (NIR) window and enhanced the transverse relaxation (T2) contrast effect, as a result of the ordering and dense packing of AuNPs and MNPs in the membrane. The magneto-plasmonic JVs were used as drug delivery vehicles, from which the release of a payload can be triggered by NIR light and the release rate can be modulated by a magnetic field. Moreover, the JVs were applied as imaging agents for in vivo bimodal photoacoustic (PA) and magnetic resonance (MR) imaging of tumors by intravenous injection. With an external magnetic field, the accumulation of the JVs in tumors was significantly increased, leading to a signal enhancement of approximately 2–3 times in the PA and MR imaging, compared with control groups without a magnetic field.

  2. The Janus-faced roles of Krüppel-like factor 4 in oral squamous cell carcinoma cells.

    Science.gov (United States)

    Li, Wenwen; Liu, Man; Su, Ying; Zhou, Xinying; Liu, Yao; Zhang, Xinyan

    2015-12-29

    Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor that regulates many essential processes, including development and cell differentiation, proliferation, and apoptosis. Along with these roles in normal cells and tissues, KLF4 has important tumor suppressive and oncogenic functions in some malignancies. However, the roles of KLF4 in oral squamous cell carcinoma remain unclear. This study investigated the epigenetic alterations and possible roles of KLF4 in oral cancer carcinogenesis. Notably, KLF4 expression was significantly decreased in human oral cancer tissues compared with healthy controls, and KLF4 promoter hypermethylation contributed to the suppression of KLF4 expression. KLF4 expression was associated with tumor grade. Its expression was much lower in poorly differentiated oral cancers than in well-differentiated cancer cells. KLF4 exerted its antitumor activity in vitro and/or in vivo by inhibiting cell proliferation, cell cycle progression, cell colony formation and by inducing apoptosis. In addition, KLF4 over-expression promoted oral cancer cell migration and invasion in vitro. Knockdown of KLF4 promoted oral cancer cells growth and colony formation, and simultaneously inhibited cell migration and invasion. Mechanistic studies revealed that MMP-9 might contribute to KLF4-mediated cell migration and invasion. These results provide evidence that KLF4 might play Janus-faced roles in oral cancer carcinogenesis, acting both as a tumor suppressor and as an oncogene.

  3. Micro - Focused Phototherapy Associated To Janus Kinase Inhibitor: A Promising Valid Therapeutic Option for Patients with Localized Vitiligo

    Directory of Open Access Journals (Sweden)

    Serena Gianfaldoni

    2018-01-01

    Full Text Available BACKGROUND: Vitiligo is an acquired pigmentary cutaneous disease, characterised by the progressive loss of melanocytes, resulting in hypopigmented skin areas which progressively become amelanotic. Classically, vitiligo treatments are unsatisfactory and challenging. Despite the continuous introduction of new therapies, phototherapy is still the mainstay for vitiligo repigmentation. AIM: The aim of this multicenter observational retrospective study was to evaluate the efficacy and safety of the nb - UVB micro - phototherapy (BIOSKIN EVOLUTION®, used alone or in associations with an oral Janus kinase inhibitor (Tofacitinib citrate, in the treatment of stable or active forms of localised vitiligo. MATERIAL AND METHODS: Fifty eight patients had been treated with n-UVB micro-photootherapy (Group A; 9 patients had been treated with phototherapy plus Tofacitinb citrate (Group B. RESULTS: Among Group A, 42 patients (72% obtained a re-pigmentation rate higher than 75%, with a medium value of 77%. 11 patients (19% achieved a marked improvement of the clinical findings with a repigmentation rate between 50-75%; 4 patients (8% showed a moderate response with a lesional repigmentation of 25-50%. Only one patient (1% had a poor response to the phototherapeutic treatment CONCLUSION: Nb - UVB micro-focused phototherapy is one of the most effective therapeutic options for vitiligo treatment. The association of micro-focused phototherapy to Tofacitinib citrate seems to provide better clinical results in term of repigmentation rate.

  4. Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

    Science.gov (United States)

    Krishnaswami, Sriram; Boy, Mary; Chow, Vincent; Chan, Gary

    2015-03-01

    Tofacitinib is an oral Janus kinase inhibitor. This randomized, double-blind, parallel-group, placebo-controlled study was the first evaluation of tofacitinib in humans. The objectives were to characterize the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics of escalating single tofacitinib doses in healthy subjects. Tofacitinib (0.1, 0.3, 1, 3, 10, 30, 60, and 100 mg) or placebo was administered as oral powder for constitution. For each dose, 7-9 subjects were randomized to tofacitinib and 3-5 subjects to placebo. Ninety-five males and females (age range 19-45) completed the study. Forty-nine treatment-emergent all-causality adverse events (AEs) were observed; nausea and headache were the most frequently reported. Tofacitinib PK was characterized by rapid absorption (time to peak serum concentration [Tmax ] 0.5-1 hour), rapid elimination (mean terminal half-lives 2.3-3.1 hours), and dose-proportional systemic exposures (peak serum concentration [Cmax ] and area under the serum concentration-time curve from time zero to infinity [AUC0-∞ ]). No appreciable correlation was observed between tofacitinib dose and lymphocyte subset counts. Single-dose tofacitinib up to 100 mg in healthy subjects had a safety profile of mostly mild AEs, and no deaths, serious AEs, severe AEs or discontinuations due to AEs. © 2014, The American College of Clinical Pharmacology.

  5. Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and interleukin-6 during treatment for rheumatoid arthritis

    Science.gov (United States)

    Migita, K; Izumi, Y; Jiuchi, Y; Kozuru, H; Kawahara, C; Izumi, M; Sakai, T; Nakamura, M; Motokawa, S; Nakamura, T; Kawakami, A

    2014-01-01

    The Janus kinase inhibitor tofacitinib is currently being investigated as a disease-modifying agent in rheumatoid arthritis (RA). We investigated the in-vivo effects of tofacitinib treatment for 4 weeks on elevated circulating acute-phase serum amyloid (SAA) levels in 14 Japanese patients with RA. SAA levels fell from 110·5 ± 118·5 μg/ml (mean ± standard deviation) at treatment initiation to 15·3 ± 13·3 μg/ml after 4 weeks treatment with tofacitinib. The reduction in SAA levels was greater in patients receiving tofacitinib plus methotrexate compared with those receiving tofacitinib monotherapy. Tofacitinib was also associated with reduced serum interleukin (IL)-6, but had no effect on serum levels of soluble IL-6 receptor. Patients were divided into groups with adequate (normalization) and inadequate SAA responses (without normalization). Serum IL-6 levels were reduced more in the group with adequate SAA response compared with those with inadequate SAA response. These results suggest that tofacitinib down-regulates the proinflammatory cytokine, IL-6, accompanied by reduced serum SAA levels in patients with active RA. The ability to regulate elevated serum IL-6 and SAA levels may explain the anti-inflammatory activity of tofacitinib. PMID:24665995

  6. Splenomegaly in myelofibrosis—new options for therapy and the therapeutic potential of Janus kinase 2 inhibitors

    Directory of Open Access Journals (Sweden)

    Randhawa Jasleen

    2012-08-01

    Full Text Available Abstract Splenomegaly is a common sign of primary myelofibrosis (PMF, post-polycythemia vera myelofibrosis (post-PV MF, and post-essential thrombocythemia myelofibrosis (post-ET MF that is associated with bothersome symptoms, which have a significant negative impact on patients’ quality of life. It may also be present in patients with advanced polycythemia vera (PV or essential thrombocythemia (ET. Until recently, none of the therapies used to treat MF were particularly effective in reducing splenomegaly. The discovery of an activating Janus kinase 2 (JAK2 activating mutation (JAK2V617F that is present in almost all patients with PV and in about 50-60 % of patients with ET and PMF led to the initiation of several trials investigating the clinical effectiveness of various JAK2 (or JAK1/JAK2 inhibitors for the treatment of patients with ET, PV, and MF. Some of these trials have documented significant clinical benefit of JAK inhibitors, particularly in terms of regression of splenomegaly. In November 2011, the US Food and Drug Administration approved the use of the JAK1- and JAK2-selective inhibitor ruxolitinib for the treatment of patients with intermediate or high-risk myelofibrosis, including PMF, post-PV MF, and post-ET MF. This review discusses current therapeutic options for splenomegaly associated with primary or secondary MF and the treatment potential of the JAK inhibitors in this setting.

  7. Frequency of janus associated kinase 2 (jak2) mutation in patients of bcr-abl negative myeloproliferative neoplasms

    International Nuclear Information System (INIS)

    Sadiq, M.A.; Ahmed, S.; Ali, N.

    2013-01-01

    To determine the frequency of Janus associated kinase 2 mutation in the patients of BCR-ABL negative classical myeloproliferative neoplasms. Study Design: Cross-sectional descriptive study Place and Duration of Study: Molecular Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi from Jul 2011 to Jul 2012. Patients and Methods: Ninety three consecutive patients of Polycythaemia vera (PV), Essential thrombocythaemia (ET) and Idiopathic myelofibrosis (IMF) diagnosed by the conventional haematological criteria were included in the study. All patients were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific PCR. Results: Out of the 93 myeloproliferative neoplasm (MPN) patients, 33(35%) had polycythaemia vera, 36(39%) had essential thrombocythaemia and 24(26%) had idiopathic myelofibrosis. JAK2 mutation was seen in 64/93 (69%) patients including 33/33(100%) in PV, 19/36(52.6%) in ET and 12/24(50%) in IMF. Conclusion: Classical myeloproliferative neoplasms are an important group of heamatological disorder in our country. JAK2 gene mutation is seen in significant proportion of these disorders (69%). JAK2 mutation analysis can be used to differentiate between polycythemia vera and secondary polycythemia in most cases with near certainty, where it was found in 100% of the cases. (author)

  8. Performance and fuel cycle cost analysis of one Janus 30 conceptual design for several fuel element design options

    Energy Technology Data Exchange (ETDEWEB)

    Nurdin, Martias [Research Centre for Nuclear Techniques, National Atomic Energy Agency (Indonesia); Matos, J E; Freese, K E [RERTR Program, Argonne National Laboratory (United States)

    1983-09-01

    The performance and fuel cycle costs for a 25 MW, JANUS 30 reactor conceptual design by INTERATOM, Federal Republic of Germany, for BATAN, Republic of Indonesia have been studied using 19.75% enriched uranium in four fuel element design options. All of these fuel element designs have either been proposed by INTERATOM for various reactors or are currently in use with 93% enriched uranium in reactors in the Federal Republic of Germany. Aluminide, oxide, and silicide fuels were studied for selected designs using the range of uranium densities that are either currently qualified or are being developed and demonstrated internationally. These uranium densities include 1.7-2.3 g/cm{sup 3} in aluminide fuel, 1.7-3.2 g/cm{sup 3} in oxide fuel, and 2.9-6.8 g/cm{sup 3} in silicide fuel. As of November 1982) both the aluminide and the oxide fuels with about 1.7 g U/cm{sup 3} are considered to be fully-proven for licensing purposes. Irradiation screening and proof testing of fuels with uranium densities greater than 1.7 g/cm{sup 3} are currently in progress, and these tests need to be completed in order to obtain licensing authorization for routine reactor use. To assess the long-term fuel adaptation strategy as well as the present fuel acceptance, reactor performance and annual fuel cycle costs were computed for seventeen cases based on a representative end-of-cycle excess reactivity and duty factor. In addition, a study was made to provide data for evaluating the trade-off between the increased safety associated with thicker cladding and the economic penalty due to increased fuel consumption. (author)

  9. Aggression behaviour induced by oral administration of the Janus-kinase inhibitor tofacitinib, but not oclacitinib, under stressful conditions.

    Science.gov (United States)

    Fukuyama, Tomoki; Tschernig, Thomas; Qi, Yulin; Volmer, Dietrich A; Bäumer, Wolfgang

    2015-10-05

    Janus kinase (JAK) inhibitors have recently been developed for allergic diseases. We focused on the 2 different JAK inhibitors, tofacitinib (selective for JAK3) and oclacitinib (selective for JAK1 and 2), to clarify the mechanism of anti-inflammatory and anti-itching potency of these drugs. In the process of detecting anti-itching potency, we observed that tofacitinib treated mice showed aggression behaviour. The objective of the study reported here was to investigate the aggressive behaviour induced by tofacitinib by using a mouse model of allergic dermatitis and the resident-intruder test. For the allergic dermatitis model, female BALB/c mice were sensitised and challenged topically with toluene-2,4-diisocyanate (TDI). Vehicle, tofacitinib or oclacitinib, was administered orally 30 min before TDI challenge. Scratching, aggression and standing behaviours were monitored in the 60 min period immediately following challenge of TDI. Another group of male BALB/c mice treated with vehicle, tofacitinib or oclacitinib was evaluated in the resident-intruder test and brains were obtained to determine blood brain barrier penetration. In the allergic dermatitis model, a significant increase in aggression and standing behaviour was only obvious in the tofacitinib treatment group. There was no effect in non-sensitised mice, but similar aggression was also induced by tofacitinib in male resident-intruder test. Penetration of blood-brain barrier was observed both in tofacitinib and oclacitinib treated mice. These results suggest that aggression was induced by tofacitinib under some kind of stressful environment. This study indicates a possible role of the JAK-STAT pathway in modulation of aggression behaviour. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. The Janus kinase inhibitor tofacitinib inhibits TNF-α-induced gliostatin expression in rheumatoid fibroblast-like synoviocytes.

    Science.gov (United States)

    Kawaguchi, Yohei; Waguri-Nagaya, Yuko; Tatematsu, Naoe; Oguri, Yusuke; Kobayashi, Masaaki; Nozaki, Masahiro; Asai, Kiyofumi; Aoyama, Mineyoshi; Otsuka, Takanobu

    2018-01-15

    Gliostatin (GLS) is known to have angiogenic and arthritogenic activity, and GLS expression levels in serum from patients with rheumatoid arthritis (RA) are significantly correlated with the disease activity. Tofacitinib is a novel oral Janus kinase (JAK) inhibitor and is effective in treating RA. However, the mechanism of action of tofacitinib in fibroblast-like synoviocytes (FLSs) has not been elucidated. The purpose of this study was to investigate the modulatory effects of tofacitinib on serum GLS levels in patients with RA and GLS production in FLSs derived from patients with RA. Six patients with RA who had failed therapy with at least one TNF inhibitor and were receiving tofacitinib therapy were included in the study. Serum samples were collected to measure CRP, MMP-3 and GLS expression. FLSs derived from patients with RA were cultured and stimulated by TNFα with or without tofacitinib. GLS expression levels were determined using reverse transcription-polymerase chain reaction (RT-PCR), EIA and immunocytochemistry, and signal transducer and activator of transcription (STAT) protein phosphorylation levels were determined by western blotting. Treatment with tofacitinib decreased serum GLS levels in all patients. GLS mRNA and protein expression levels were significantly increased by treatment with TNF-α alone, and these increases were suppressed by treatment with tofacitinib, which also inhibited TNF-α-induced STAT1 phosphorylation. JAK/STAT activation plays a pivotal role in TNF-α-mediated GLS up-regulation in RA. Suppression of GLS expression in FLSs has been suggested to be one of the mechanisms through which tofacitinib exerts its anti-inflammatory effects.

  11. Development of a novel pH sensor based upon Janus Green B immobilized on triacetyl cellulose membrane: Experimental design and optimization

    Science.gov (United States)

    Chamkouri, Narges; Niazi, Ali; Zare-Shahabadi, Vali

    2016-03-01

    A novel pH optical sensor was prepared by immobilizing an azo dye called Janus Green B on the triacetylcellulose membrane. Condition of the dye solution used in the immobilization step, including concentration of the dye, pH, and duration were considered and optimized using the Box-Behnken design. The proposed sensor showed good behavior and precision (RSD < 5%) in the pH range of 2.0-10.0. Advantages of this optical sensor include on-line applicability, no leakage, long-term stability (more than 6 months), fast response time (less than 1 min), high selectivity and sensitivity as well as good reversibility and reproducibility.

  12. Chemical Adsorption and Physical Confinement of Polysulfides with the Janus-faced Interlayer for High-performance Lithium-Sulfur Batteries.

    Science.gov (United States)

    Chiochan, Poramane; Kaewruang, Siriroong; Phattharasupakun, Nutthaphon; Wutthiprom, Juthaporn; Maihom, Thana; Limtrakul, Jumras; Nagarkar, Sanjog; Horike, Satoshi; Sawangphruk, Montree

    2017-12-18

    We design the Janus-like interlayer with two different functional faces for suppressing the shuttle of soluble lithium polysulfides (LPSs) in lithium-sulfur batteries (LSBs). At the front face, the conductive functionalized carbon fiber paper (f-CFP) having oxygen-containing groups i.e., -OH and -COOH on its surface was placed face to face with the sulfur cathode serving as the first barrier accommodating the volume expansion during cycling process and the oxygen-containing groups can also adsorb the soluble LPSs via lithium bonds. At the back face, a crystalline coordination network of [Zn(H 2 PO 4 ) 2 (TzH) 2 ] n (ZnPTz) was coated on the back side of f-CFP serving as the second barrier retarding the left LPSs passing through the front face via both physical confinement and chemical adsorption (i.e. Li bonding). The LSB using the Janus-like interlayer exhibits a high reversible discharge capacity of 1,416 mAh g -1 at 0.1C with a low capacity fading of 0.05% per cycle, 92% capacity retention after 200 cycles and ca. 100% coulombic efficiency. The fully charged LSB cell can practically supply electricity to a spinning motor with a nominal voltage of 3.0 V for 28 min demonstrating many potential applications.

  13. Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis.

    Science.gov (United States)

    Klein, Sabine; Rick, Johanna; Lehmann, Jennifer; Schierwagen, Robert; Schierwagen, Irela Gretchen; Verbeke, Len; Hittatiya, Kanishka; Uschner, Frank Erhard; Manekeller, Steffen; Strassburg, Christian P; Wagner, Kay-Uwe; Sayeski, Peter P; Wolf, Dominik; Laleman, Wim; Sauerbruch, Tilman; Trebicka, Jonel

    2017-01-01

    Angiotensin II (AngII) activates via angiotensin-II-type-I receptor (AT1R) Janus-kinase-2 (JAK2)/Arhgef1 pathway and subsequently RHOA/Rho-kinase (ROCK), which induces experimental and probably human liver fibrosis. This study investigated the relationship of JAK2 to experimental and human portal hypertension. The mRNA and protein levels of JAK2/ARHGEF1 signalling components were analysed in 49 human liver samples and correlated with clinical parameters of portal hypertension in these patients. Correspondingly, liver fibrosis (bile duct ligation (BDL), carbon tetrachloride (CCl 4 )) was induced in floxed-Jak2 knock-out mice with SM22-promotor (SM22 Cre+ -Jak2 f/f ). Transcription and contraction of primary myofibroblasts from healthy and fibrotic mice and rats were analysed. In two different cirrhosis models (BDL, CCl 4 ) in rats, the acute haemodynamic effect of the JAK2 inhibitor AG490 was assessed using microsphere technique and isolated liver perfusion experiments. Hepatic transcription of JAK2/ARHGEF1 pathway components was upregulated in liver cirrhosis dependent on aetiology, severity and complications of human liver cirrhosis (Model for End-stage Liver disease (MELD) score, Child score as well as ascites, high-risk varices, spontaneous bacterial peritonitis). SM22 Cre+ - Jak2 f/f mice lacking Jak2 developed less fibrosis and lower portal pressure (PP) than SM22 Cre- -Jak2 f/f upon fibrosis induction. Myofibroblasts from SM22 Cre+ -Jak2 f/f mice expressed less collagen and profibrotic markers upon activation. AG490 relaxed activated hepatic stellate cells in vitro. In cirrhotic rats, AG490 decreased hepatic vascular resistance and consequently the PP in vivo and in situ. Hepatic JAK2/ARHGEF1/ROCK expression is associated with portal hypertension and decompensation in human cirrhosis. The deletion of Jak2 in myofibroblasts attenuated experimental fibrosis and acute inhibition of JAK2 decreased PP. Thus, JAK2 inhibitors, already in clinical use for other

  14. The Role of Janus Kinase 3 in the Regulation of Na+/K+ ATPase under Energy Depletion

    Directory of Open Access Journals (Sweden)

    Zohreh Hosseinzadeh

    2015-05-01

    Full Text Available Background/Aims: Janus kinase-3 (JAK3 is activated during energy depletion. Energy-consuming pumps include the Na+/K+-ATPase. The present study explored whether JAK3 regulates Na+/K+-ATPase in dendritic cells (DCs. Methods: Ouabain (100 µM-sensitive (Iouabain and K+-induced (Ipump outward currents were determined by utilizing whole cell patch-clamp, Na+/K+-ATPase α1-subunit mRNA levels by RT-PCR, Na+/K+-ATPase protein abundance by flow cytometry or immunofluorescence, and cellular ATP by luciferase-assay in DCs from bone marrow of JAK3-knockout (jak3-/- or wild-type mice (jak3+/+. Ipump was further determined by voltage clamp in Xenopus oocytes expressing JAK3, active A568VJAK3 or inactive K851AJAK3. Results: Na+/K+-ATPase α1-subunit mRNA and protein levels, as well as Ipump and Iouabain were significantly higher in jak3-/-DCs than in jak3+/+DCs. Energy depletion by 4h pre-treatment with 2,4-dinitro-phenol significantly decreased Ipump in jak3+/+ DCs but not in jak3-/-DCs. Cellular ATP was significantly lower in jak3-/-DCs than in jak3+/+DCs and decreased in both genotypes by 2,4-dinitro-phenol, an effect significantly more pronounced in jak3-/-DCs than in jak3+/+DCs and strongly blunted by ouabain in both jak3+/+ and jak3-/-DCs. Ipump and Iouabain in oocytes were decreased by expression of JAK3 and of A568VJAK3 but not of K851AJAK3. JAK3 inhibitor WHI-P154 (4-[(3'-bromo-4'-hydroxyphenylamino]-6,7-dimethoxyquinazoline, 22 μM enhanced Ipump and Iouabain in JAK3 expressing oocytes. The difference between A568VJAK3 and K851AJAK3 expressing oocytes was virtually abrogated by actinomycin D (50 nM. Conclusions: JAK3 down-regulates Na+/K+-ATPase activity, an effect involving gene expression and profoundly curtailing ATP consumption.

  15. Synthesis of polystyrene-polyphenylsiloxane Janus particles through colloidal assembly with unexpected high selectivity: Mechanistic insights and their application in the design of polystyrene particles with multiple polyphenylsiloxane patches

    NARCIS (Netherlands)

    Mann, D.; Voogt, S.; Keul, H.; Möller, M.; Verheijen, M.; Buskens, P.

    2017-01-01

    Janus particles are of great research interest because of their reduced symmetry, which provides them with unique physical and chemical properties. Such particles can be prepared from spherical structures through colloidal assembly. Whilst colloidal assembly has the potential to be a low cost and

  16. Janus-faced probability

    CERN Document Server

    Rocchi, Paolo

    2014-01-01

    The problem of probability interpretation was long overlooked before exploding in the 20th century, when the frequentist and subjectivist schools formalized two conflicting conceptions of probability. Beyond the radical followers of the two schools, a circle of pluralist thinkers tends to reconcile the opposing concepts. The author uses two theorems in order to prove that the various interpretations of probability do not come into opposition and can be used in different contexts. The goal here is to clarify the multifold nature of probability by means of a purely mathematical approach and to show how philosophical arguments can only serve to deepen actual intellectual contrasts. The book can be considered as one of the most important contributions in the analysis of probability interpretation in the last 10-15 years.

  17. A versatile strategy towards non-covalent functionalization of graphene by surface-confined supramolecular self-assembly of Janus tectons

    Directory of Open Access Journals (Sweden)

    Ping Du

    2015-03-01

    Full Text Available Two-dimensional (2D, supramolecular self-assembly at surfaces is now well-mastered with several existing examples. However, one remaining challenge to enable future applications in nanoscience is to provide potential functionalities to the physisorbed adlayer. This work reviews a recently developed strategy that addresses this key issue by taking advantage of a new concept, Janus tecton materials. This is a versatile, molecular platform based on the design of three-dimensional (3D building blocks consisting of two faces linked by a cyclophane-type pillar. One face is designed to steer 2D self-assembly onto C(sp2-carbon-based flat surfaces, the other allowing for the desired functionality above the substrate with a well-controlled lateral order. In this way, it is possible to simultaneously obtain a regular, non-covalent paving as well as supramolecular functionalization of graphene, thus opening interesting perspectives for nanoscience applications.

  18. Development of a novel pH sensor based upon Janus Green B immobilized on triacetyl cellulose membrane: Experimental design and optimization.

    Science.gov (United States)

    Chamkouri, Narges; Niazi, Ali; Zare-Shahabadi, Vali

    2016-03-05

    A novel pH optical sensor was prepared by immobilizing an azo dye called Janus Green B on the triacetylcellulose membrane. Condition of the dye solution used in the immobilization step, including concentration of the dye, pH, and duration were considered and optimized using the Box-Behnken design. The proposed sensor showed good behavior and precision (RSDpH range of 2.0-10.0. Advantages of this optical sensor include on-line applicability, no leakage, long-term stability (more than 6 months), fast response time (less than 1 min), high selectivity and sensitivity as well as good reversibility and reproducibility. Copyright © 2015. Published by Elsevier B.V.

  19. Properties of Electrospun Nanofibers of Multi-Block Copolymers of [Poly-ε-caprolactone-b-poly(tetrahydrofuran-co-ε-caprolactone]m Synthesized by Janus Polymerization

    Directory of Open Access Journals (Sweden)

    Muhammad Ijaz Shah

    2017-10-01

    Full Text Available Novel biodegradable multiblock copolymers of [PCL-b-P(THF-co-CL]m with PCL fractions of 53.3 and 88.4 wt % were prepared by Janus polymerization of ε-caprolactone (CL and tetrahydrofuran (THF. Their electrospun mats were obtained with optimized parameters containing bead-free nanofibers whose diameters were between 290 and 520 nm. The mechanical properties of the nanofiber scaffolds were measured showing the tensile strength and strain at break of 8–10 MPa and 123–161%, respectively. Annealing improved their mechanical properties and their tensile strength and strain at break of the samples increased to 10–13 MPa and 267–338%, respectively. Due to the porous structure and crystallization in nanoscale confinement, the mechanical properties of the nanofiber scaffolds appeared as plastics, rather than as the elastomers observed in bulk thermal-molded film.

  20. Studies of acute and chronic radiation injury at the Biological and Medical Research Division, Argonne National Laboratory, 1970-1992: The JANUS Program Survival and Pathology Data

    International Nuclear Information System (INIS)

    Grahn, D.; Wright, B.J.; Carnes, B.A.; Williamson, F.S.; Fox, C.

    1995-02-01

    A research reactor for exclusive use in experimental radiobiology was designed and built at Argonne National Laboratory in the 1960's. It was located in a special addition to Building 202, which housed the Division of Biological and Medical Research. Its location assured easy access for all users to the animal facilities, and it was also near the existing gamma-irradiation facilities. The water-cooled, heterogeneous 200-kW(th) reactor, named JANUS, became the focal point for a range of radiobiological studies gathered under the rubic of open-quotes the JANUS programclose quotes. The program ran from about 1969 to 1992 and included research at all levels of biological organization, from subcellular to organism. More than a dozen moderate- to large-scale studies with the B6CF 1 mouse were carried out; these focused on the late effects of whole-body exposure to gamma rays or fission neutrons, in matching exposure regimes. In broad terms, these studies collected data on survival and on the pathology observed at death. A deliberate effort was made to establish the cause of death. This archieve describes these late-effects studies and their general findings. The database includes exposure parameters, time of death, and the gross pathology and histopathology in codified form. A series of appendices describes all pathology procedures and codes, treatment or irradiation codes, and the manner in which the data can be accessed in the ORACLE database management system. A series of tables also presents summaries of the individual experiments in terms of radiation quality, sample sizes at entry, mean survival times by sex, and number of gross pathology and histopathology records

  1. Molecular modeling-driven approach for identification of Janus kinase 1 inhibitors through 3D-QSAR, docking and molecular dynamics simulations.

    Science.gov (United States)

    Itteboina, Ramesh; Ballu, Srilata; Sivan, Sree Kanth; Manga, Vijjulatha

    2017-10-01

    Janus kinase 1 (JAK 1) belongs to the JAK family of intracellular nonreceptor tyrosine kinase. JAK-signal transducer and activator of transcription (JAK-STAT) pathway mediate signaling by cytokines, which control survival, proliferation and differentiation of a variety of cells. Three-dimensional quantitative structure activity relationship (3 D-QSAR), molecular docking and molecular dynamics (MD) methods was carried out on a dataset of Janus kinase 1(JAK 1) inhibitors. Ligands were constructed and docked into the active site of protein using GLIDE 5.6. Best docked poses were selected after analysis for further 3 D-QSAR analysis using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodology. Employing 60 molecules in the training set, 3 D-QSAR models were generate that showed good statistical reliability, which is clearly observed in terms of r 2 ncv and q 2 loo values. The predictive ability of these models was determined using a test set of 25 molecules that gave acceptable predictive correlation (r 2 Pred ) values. The key amino acid residues were identified by means of molecular docking, and the stability and rationality of the derived molecular conformations were also validated by MD simulation. The good consonance between the docking results and CoMFA/CoMSIA contour maps provides helpful clues about the reasonable modification of molecules in order to design more efficient JAK 1 inhibitors. The developed models are expected to provide some directives for further synthesis of highly effective JAK 1 inhibitors.

  2. Studies of acute and chronic radiation injury at the Biological and Medical Research Division, Argonne National Laboratory, 1970-1992: The JANUS Program Survival and Pathology Data

    Energy Technology Data Exchange (ETDEWEB)

    Grahn, D.; Wright, B.J.; Carnes, B.A.; Williamson, F.S.; Fox, C.

    1995-02-01

    A research reactor for exclusive use in experimental radiobiology was designed and built at Argonne National Laboratory in the 1960`s. It was located in a special addition to Building 202, which housed the Division of Biological and Medical Research. Its location assured easy access for all users to the animal facilities, and it was also near the existing gamma-irradiation facilities. The water-cooled, heterogeneous 200-kW(th) reactor, named JANUS, became the focal point for a range of radiobiological studies gathered under the rubic of {open_quotes}the JANUS program{close_quotes}. The program ran from about 1969 to 1992 and included research at all levels of biological organization, from subcellular to organism. More than a dozen moderate- to large-scale studies with the B6CF{sub 1} mouse were carried out; these focused on the late effects of whole-body exposure to gamma rays or fission neutrons, in matching exposure regimes. In broad terms, these studies collected data on survival and on the pathology observed at death. A deliberate effort was made to establish the cause of death. This archieve describes these late-effects studies and their general findings. The database includes exposure parameters, time of death, and the gross pathology and histopathology in codified form. A series of appendices describes all pathology procedures and codes, treatment or irradiation codes, and the manner in which the data can be accessed in the ORACLE database management system. A series of tables also presents summaries of the individual experiments in terms of radiation quality, sample sizes at entry, mean survival times by sex, and number of gross pathology and histopathology records.

  3. Dependence of the Internal Structure on Water/Particle Volume Ratio in an Amphiphilic Janus Particle-Water-Oil Ternary System: From Micelle-like Clusters to Emulsions of Spherical Droplets.

    Science.gov (United States)

    Noguchi, Tomohiro G; Iwashita, Yasutaka; Kimura, Yasuyuki

    2017-01-31

    Amphiphilic Janus particles (AJP), composed of hydrophilic and hydrophobic hemispheres, are one of the simplest anisotropic colloids, and they exhibit higher surface activities than particles with homogeneous surface properties. Consequently, a ternary system of AJP, water, and oil can form extremely stable Pickering emulsions, with internal structures that depend on the Janus structure of the particles and the system composition. However, the detail of these structures has not been fully explored, especially for the composition range where the amount of the minority liquid phase and AJP are comparable, where one would expect the Janus characteristics to be directly reflected. In this study, we varied the volume ratio of the particles and the minority liquid phase, water, by 2 orders of magnitude around the comparable composition range, and observed the resultant structures at the resolution of the individual particle dimensions by optical microscopy. When the volume ratio of water is smaller than that of the Janus particles, capillary interactions between the hydrophilic hemispheres of the particles induce micelle-like clusters in which the hydrophilic sides of the particles face inward. With increasing water content, these clusters grow into a rodlike morphology. When the water volume exceeds that of the particles, the structure transforms into an emulsion state composed of spherical droplets, colloidosomes, because of the surface activity of particles at the liquid-liquid interface. Thus, we found that a change in volume fraction alters the mechanism of structure formation in the ternary system, and large resulting morphological changes in the self-assembled structures reflect the anisotropy of the particles. The self-assembly shows essential commonalities with that in microemulsions of surfactant molecules, however the AJP system is stabilized only kinetically. Analysis of the dependence of the emulsion droplet size on composition shows that almost all the

  4. Identification and characterization of metabolites of ASP015K, a novel oral Janus kinase inhibitor, in rats, chimeric mice with humanized liver, and humans.

    Science.gov (United States)

    Nakada, Naoyuki; Oda, Kazuo

    2015-01-01

    1. Here, we elucidated the structure of metabolites of novel oral Janus kinase inhibitor ASP015K in rats and humans and evaluated the predictability of human metabolites using chimeric mice with humanized liver (PXB mice). 2. Rat biological samples collected after oral dosing of (14)C-labelled ASP015K were examined using a liquid chromatography-radiometric detector and mass spectrometer (LC-RAD/MS). The molecular weight of metabolites in human and the liver chimeric mouse biological samples collected after oral dosing of non-labelled ASP015K was also investigated via LC-MS. Metabolites were also isolated from rat bile samples and analyzed using nuclear magnetic resonance. 3. Metabolic pathways of ASP015K in rats and humans were found to be glucuronide conjugation, methyl conjugation, sulfate conjugation, glutathione conjugation, hydroxylation of the adamantane ring and N-oxidation of the 1H-pyrrolo[2,3-b]pyridine ring. The main metabolite of ASP015K in rats was the glucuronide conjugate, while the main metabolite in humans was the sulfate conjugate. Given that human metabolites were produced by human hepatocytes in chimeric mice with humanized liver, this human model mouse was believed to be useful in predicting the human metabolic profile of various drug candidates.

  5. Nitrogen-Doped Nanoporous Carbon Membranes with Co/CoP Janus-Type Nanocrystals as Hydrogen Evolution Electrode in Both Acidic and Alkaline Environments

    KAUST Repository

    Wang, Hong

    2017-03-31

    Self-supported electrocatalysts being generated and employed directly as electrodes for energy conversion has been intensively pursued in the fields of materials chemistry and energy. Herein, we report a synthetic strategy to prepare freestanding hierarchically structured, nitrogen-doped nanoporous graphitic carbon membranes functionalized with Janus-type Co/CoP nanocrystals (termed as HNDCM-Co/CoP), which were successfully applied as a highly efficient, binder-free electrode in the hydrogen evolution reaction (HER). Benefited from multiple structural merits, such as a high degree of graphitization, three-dimensionally interconnected micro/meso/macropores, uniform nitrogen doping, well-dispersed Co/CoP nanocrystals, as well as the confinement effect of the thin carbon layer on the nanocrystals, HNDCM-Co/CoP exhibited superior electrocatalytic activity and long-term operation stability for HER under both acidic and alkaline conditions. As a proof-of-concept of practical usage, a 5.6 cm × 4 cm × 60 μm macroscopic piece of HNDCM-Co/CoP was prepared in our laboratory. Driven by a solar cell, electroreduction of water in alkaline conditions (pH 14) was performed, and H was produced at a rate of 16 mL/min, demonstrating its potential as real-life energy conversion systems.

  6. Putin's and Russian-led Eurasian Economic Union: A hybrid half-economics and half-political “Janus Bifrons”

    Directory of Open Access Journals (Sweden)

    Bruno S. Sergi

    2018-01-01

    Full Text Available The Eurasian Economic Union is an institution formalized in January 2015 for the purpose of regional economic integration; it includes five countries: Russia, Kazakhstan, Belarus, Armenia, and Kyrgyzstan, and may include Mongolia and Tajikistan in the future. With a GDP of $1.59 trillion in 2015, an industrial production of $1.3 trillion in 2014, and population of almost 200 million as of 2016, the EEAU could represent a geopolitical success that supports both Putin's ambitious political agenda and the Union's economic prospects. Although the efforts of this Union are ongoing and long-term success is not certain, the Russia-led Eurasian Economic Union can be considered a hybrid half-economics and half-political “Janus Bifrons” that serves as a powerful illustration of what Putin envisions for the post-Soviet space. Despite promising steps so far, more should be done toward the achievement of economic development and balanced opportunity for all Eurasian countries. Russia's longstanding role within the Union, as well as its power and political motivations, are all considerations that must be accounted for.

  7. Molecular tilt-dependent and tyrosine-enhanced electron transfer across ITO/SAM/[DPPC–Au NP–Tyrosine] Janus nanoparticle junction

    Energy Technology Data Exchange (ETDEWEB)

    Sarangi, Nirod Kumar; Patnaik, Archita, E-mail: archita59@yahoo.com [Indian Institute of Technology Madras, Department of Chemistry (India)

    2016-09-15

    Enhanced interfacial electron transfer (ET) across the otherwise insulating indium tin oxide/alkanethiol self-assembled monolayer (SAM)/redox molecule junction was accomplished when a Janus gold nanoparticle (JNP) protected by bioinspired phosphatidylcholine (DPPC) lipid and tyrosine amino acid ligands was anchored on it. In addition to the most theoretical and experimental investigations on the distance-dependent ET across Metal–Organic SAM–Nanoparticle (NP) architectures, the current results succinctly illustrate molecular tilt angle of the SAM and the characteristic of JNP as key factors in expediting the ET rate via electron tunneling. In the absence of JNP, electron tunneling with a tunneling factor β = 1.1 Å{sup −1} across the SAM was the rate-limiting step, evidenced from electrochemical impedance spectroscopy (EIS). The apparent electron transfer rate constant (k{sub app}{sup 0}) for anchored SAM was enhanced by at least one order of magnitude than the DPPC-only protected nanoparticle, suggesting the potential role of tyrosine towards the enhanced ET. The asymmetric and biogenic nature of the construct sheds light on a potential bioelectronic device for novel electronic attributes.Graphical abstractEntry of TOC .

  8. Tofacitinib, an oral Janus kinase inhibitor, in patients from Mexico with rheumatoid arthritis: Pooled efficacy and safety analyses from Phase 3 and LTE studies.

    Science.gov (United States)

    Burgos-Vargas, Ruben; Cardiel, Mario; Xibillé, Daniel; Pacheco-Tena, César; Pascual-Ramos, Virginia; Abud-Mendoza, Carlos; Mahgoub, Ehab; Rahman, Mahboob; Fan, Haiyun; Rojo, Ricardo; García, Erika; Santana, Karina

    2017-05-25

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized efficacy and safety of tofacitinib in Mexican patients from RA Phase 3 and long-term extension (LTE) studies. Data from Mexican patients with RA and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) were taken from four Phase 3 studies (pooled across studies) and one open-label LTE study of tofacitinib. Patients received tofacitinib 5 or 10mg twice daily, adalimumab (one Phase 3 study) or placebo (four Phase 3 studies) as monotherapy or in combination with conventional synthetic DMARDs. Efficacy up to Month 12 (Phase 3) and Month 36 (LTE) was assessed by American College of Rheumatology 20/50/70 response rates, Disease Activity Score (erythrocyte sedimentation rate), and Health Assessment Questionnaire-Disability Index. Safety, including incidence rates (IRs; patients with events/100 patient-years) for adverse events (AEs) of special interest, was assessed throughout the studies. 119 and 212 Mexican patients were included in the Phase 3 and LTE analyses, respectively. Tofacitinib-treated patients in Phase 3 had numerically greater improvements in efficacy responses versus placebo at Month 3. Efficacy was sustained in Phase 3 and LTE studies. IRs for AEs of special interest were similar to those with tofacitinib in the global and Latin American RA populations. In Mexican patients from the tofacitinib global RA program, tofacitinib efficacy was demonstrated up to Month 12 in Phase 3 studies and Month 36 in the LTE study, with a safety profile consistent with tofacitinib global population. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  9. Effects of the oral Janus kinase inhibitor tofacitinib on patient-reported outcomes in patients with active rheumatoid arthritis: results of two Phase 2 randomised controlled trials.

    Science.gov (United States)

    Wallenstein, Gene V; Kanik, Keith S; Wilkinson, Bethanie; Cohen, Stanley; Cutolo, Maurizio; Fleischmann, Roy; Genovese, Mark C; Gomez Reino, Juan; Gruben, David; Kremer, Joel; Krishnaswami, Sriram; Lee, Eun Bong; Pascual-Ramos, Virginia; Strand, Vibeke; Zwillich, Samuel H

    2016-01-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we investigated the effects of tofacitinib on patient-reported outcomes (PRO) in patients with active RA. Two, 6-month, double-blind, placebo-controlled Phase 2b studies were performed. The combination study evaluated patients with inadequate response to methotrexate who received tofacitinib 1-15 mg twice daily (BID), 20 mg once daily or placebo, on background methotrexate. In the monotherapy study, patients with inadequate response to disease-modifying anti-rheumatic drugs received tofacitinib 1-15 mg BID, adalimumab 40 mg once every other week or placebo. PROs measured were: Patient's Assessment of Arthritis Pain (PAAP), Patient's Assessment of Disease Activity, HAQ-DI, FACIT-F and SF-36. In the combination study (n=507), significant improvements (ptofacitinib groups. In the monotherapy study (n=384), significant improvements in PAAP were observed at Week 12 for tofacitinib 5, 10 and 15 mg BID, and in HAQ-DI for tofacitinib 3, 5, 10 and 15 mg BID. Significant improvements versus placebo were seen at Week 2 in PAAP (both studies) and HAQ‑DI (monotherapy study) with tofacitinib, and were maintained throughout each study. In both studies, improvements in several domains of the SF-36 in the tofacitinib groups were observed at Weeks 12 and 24. In patients with active RA, tofacitinib, either in combination with methotrexate or as monotherapy, demonstrated rapid and sustained improvement in pain, physical functioning and health-related quality of life.

  10. Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study.

    Science.gov (United States)

    Yamanaka, Hisashi; Tanaka, Yoshiya; Takeuchi, Tsutomu; Sugiyama, Naonobu; Yuasa, Hirotoshi; Toyoizumi, Shigeyuki; Morishima, Yosuke; Hirose, Tomohiro; Zwillich, Samuel

    2016-01-28

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented. Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate. Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treatment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate (ESR))tofacitinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding non-melanoma skin cancer). Mean changes from baseline (start of the index study) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib. ACR20/50/70 response rates, DAS-defined remission rates and HAQ-DI scores were sustained through to study completion. Tofacitinib (with or without background methotrexate) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis. The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population. Clinicaltrials.gov NCT00661661 . Registered 7 February 2008.

  11. Electrochemical behaviors of Janus Green B in through-hole copper electroplating: An insight by experiment and density functional theory calculation using Safranine T as a comparison

    International Nuclear Information System (INIS)

    Wang, Chong; Zhang, Jinqiu; Yang, Peixia; An, Maozhong

    2013-01-01

    Highlights: ► Using Safranine T as a comparison to study the mechanism of JGB in the through-hole electroplating. ► Quantum chemical calculation is employed to analysis electronic properties and orbital information of levelers in the present paper. ► Finding out the probable reactive site for the adsorption of JGB on the copper surface. ► Offering some theoretical information to design and synthesize new additives for electroplating. -- Abstract: Janus Green B (JGB) and Safranine T (ST) were used as levelers in the through-hole (TH) copper electroplating experiments. Although JGB and ST have a similar part in the structure, the results indicate that JGB is an effective leveler used for TH electroplating whereas ST is not. A uniform plating is obtained using 1 ppm JGB as a leveler. In contrast, ST could not increase the value of uniformity power (UP). Electrochemical behaviors of JGB and ST were evaluated by potentiodynamic polarization and galvanostatic measurements using rotating disk electrode (RDE). JGB could effectively affect the cathodic polarization. However, the addition of ST changed the cathodic polarization weakly. Quantum chemical calculations based on density functional theory (DFT) were used to obtain some electronic properties and orbital information. The calculations on frontier molecular orbital suggested that the electron donating ability of JGB was higher than that of ST, which gave rise to stronger adsorption of JGB on the cathodic surface and stronger inhibition of copper electrodeposition on the cathode. Furthermore, the results of frontier molecular orbital and Fukui function distributions showed that the N=N region or aminoazobenzene region of JGB was the probable reactive site for the adsorption of JGB on the copper surface

  12. Identification of SH2B2β as an Inhibitor for SH2B1- and SH2B2α-Promoted Janus Kinase-2 Activation and Insulin Signaling

    OpenAIRE

    Li, Minghua; Li, Zhiqin; Morris, David L.; Rui, Liangyou

    2007-01-01

    The SH2B family has three members (SH2B1, SH2B2, and SH2B3) that contain conserved dimerization (DD), pleckstrin homology, and SH2 domains. The DD domain mediates the formation of homo- and heterodimers between members of the SH2B family. The SH2 domain of SH2B1 (previously named SH2-B) or SH2B2 (previously named APS) binds to phosphorylated tyrosines in a variety of tyrosine kinases, including Janus kinase-2 (JAK2) and the insulin receptor, thereby promoting the activation of JAK2 or the ins...

  13. Treatment of plaque psoriasis with an ointment formulation of the Janus kinase inhibitor, tofacitinib: a Phase 2b randomized clinical trial.

    Science.gov (United States)

    Papp, Kim A; Bissonnette, Robert; Gooderham, Melinda; Feldman, Steven R; Iversen, Lars; Soung, Jennifer; Draelos, Zoe; Mamolo, Carla; Purohit, Vivek; Wang, Cunshan; Ports, William C

    2016-10-03

    Most psoriasis patients have mild to moderate disease, commonly treated topically. Current topical agents have limited efficacy and undesirable side effects associated with long-term use. Tofacitinib is a small molecule Janus kinase inhibitor investigated for the topical treatment of psoriasis. This was a 12-week, randomized, double-blind, parallel-group, vehicle-controlled Phase 2b study of tofacitinib ointment (2 % and 1 %) applied once (QD) or twice (BID) daily in adults with mild to moderate plaque psoriasis. Primary endpoint: proportion of patients with Calculated Physician's Global Assessment (PGA-C) clear or almost clear and ≥2 grade improvement from baseline at Weeks 8 and 12. Secondary endpoints: proportion of patients with PGA-C clear or almost clear; proportion achieving Psoriasis Area and Severity Index 75 (PASI75) response; percent change from baseline in PASI and body surface area; change from baseline in Itch Severity Item (ISI). Adverse events (AEs) were monitored and clinical laboratory parameters measured. Overall, 435 patients were randomized and 430 patients received treatment. The proportion of patients with PGA-C clear or almost clear and ≥2 grade improvement from baseline at Week 8 was 18.6 % for 2 % tofacitinib QD (80 % confidence interval [CI] for difference from vehicle: 3.8, 18.2 %) and 22.5 % for 2 % tofacitinib BID (80 % CI: 3.1, 18.5 %); this was significantly higher vs vehicle for both dosage regimens. No significant difference vs vehicle was seen at Week 12. Significantly more patients achieved PGA-C clear or almost clear with 2 % tofacitinib QD and BID and 1 % tofacitinib QD (not BID) at Week 8, and with 2 % tofacitinib BID at Week 12. Pruritus was significantly reduced vs vehicle with 2 % and 1 % tofacitinib BID (starting Day 2), and 2 % tofacitinib QD (starting Day 3). Overall, 44.2 % of patients experienced AEs, 8.1 % experienced application site AEs, and 2.3 % experienced serious AEs. The highest incidence

  14. Janus faces of Jeans instabilities

    International Nuclear Information System (INIS)

    Verheest, Frank; Jacobs, Gerald; Cadez, Vladimir M.

    2000-01-01

    Self-gravitating clouds have been shown by Jeans to be unstable to harmonic perturbations whose wavelength exceeds some critical value involving the mass density and some thermal velocity or equivalent information. Based upon the assumption that the unperturbed cloud is initially uniform, the Jeans instability is non-oscillatory and purely growing. However, Newtonian gravitation precludes strictly homogeneous equilibria, but a way out is offered, in theory, by considering local perturbations, small compared to the inhomogeneity scale lengths. While in itself plausible, this procedure can in most cases not be tested for internal consistency, because real knowledge about the equilibrium is lacking, and is therefore called the Jeans swindle. The severe limitations of such an approach lead to an unavoidable dichotomy, and an example of a plasma will be discussed where the computations can be done explicitly, both for the stationary as well as for the perturbed state, showing that the system is stable at all wavelengths compatible with the equilibrium inhomogeneity. Nevertheless, the present state of affairs does not allow self-consistent equilibria to be worked out in more complicated configurations, like in dusty plasmas with external magnetic fields. This typically leads to the Jeans swindle being used a little longer than desirable

  15. The Janus Facet of Nanomaterials

    Directory of Open Access Journals (Sweden)

    Julianna Kardos

    2015-01-01

    Full Text Available Application of nanoscale materials (NMs displays a rapidly increasing trend in electronics, optics, chemical catalysis, biotechnology, and medicine due to versatile nature of NMs and easily adjustable physical, physicochemical, and chemical properties. However, the increasing abundance of NMs also poses significant new and emerging health and environmental risks. Despite growing efforts, understanding toxicity of NMs does not seem to cope with the demand, because NMs usually act entirely different from those of conventional small molecule drugs. Currently, large-scale application of available safety assessment protocols, as well as their furthering through case-by-case practice, is advisable. We define a standard work-scheme for nanotoxicity evaluation of NMs, comprising thorough characterization of structural, physical, physicochemical, and chemical traits, followed by measuring biodistribution in live tissue and blood combined with investigation of organ-specific effects especially regarding the function of the brain and the liver. We propose a range of biochemical, cellular, and immunological processes to be explored in order to provide information on the early effects of NMs on some basic physiological functions and chemical defense mechanisms. Together, these contributions give an overview with important implications for the understanding of many aspects of nanotoxicity.

  16. The Janus Facet of Nanomaterials

    Science.gov (United States)

    Kardos, Julianna; Jablonkai, István; Bóta, Attila; Visy, Júlia

    2015-01-01

    Application of nanoscale materials (NMs) displays a rapidly increasing trend in electronics, optics, chemical catalysis, biotechnology, and medicine due to versatile nature of NMs and easily adjustable physical, physicochemical, and chemical properties. However, the increasing abundance of NMs also poses significant new and emerging health and environmental risks. Despite growing efforts, understanding toxicity of NMs does not seem to cope with the demand, because NMs usually act entirely different from those of conventional small molecule drugs. Currently, large-scale application of available safety assessment protocols, as well as their furthering through case-by-case practice, is advisable. We define a standard work-scheme for nanotoxicity evaluation of NMs, comprising thorough characterization of structural, physical, physicochemical, and chemical traits, followed by measuring biodistribution in live tissue and blood combined with investigation of organ-specific effects especially regarding the function of the brain and the liver. We propose a range of biochemical, cellular, and immunological processes to be explored in order to provide information on the early effects of NMs on some basic physiological functions and chemical defense mechanisms. Together, these contributions give an overview with important implications for the understanding of many aspects of nanotoxicity. PMID:26075225

  17. AMBIGUOUS JANUS OF MODERN DEMOCRACY

    Directory of Open Access Journals (Sweden)

    Volodymyr V. Khmil

    2016-06-01

    Full Text Available Purpose. The purpose of the research is to analyze ambiguous concept of  democracy as a phenomenon of political and social formation based on political and instrumental approach. As a result, some deep fundamentals of  human social existence and values as social life basis are blurred. Task. The task of  this investigation is to reveal the concept of democracy in its invariative philosophical  meaning and find the consequences of global social transformations towards social entropy. Methods of investigation. To implement the task an activity approach has been used with further possibility to single out two approaches - politological and philosophical. The focus on democracy from philosophic point of view makes possible to anticipate negative entropic processes that lead  to future ambiguity. Subject matter. Chaotic social processes can result in  ruined family, spiritual, legal and moral formations. Regulatory and legal paradigms are becoming less effective and entail disintegration of spiritual and value constituents of worldview causing necessary conditions for social entropy. Originality and Findings. Possible threats for human freedom that hinder the way to targeted  prospects of mankind have been considered in the paper. Thus, taking into account all positive aspects of democracy, it is simultaneously becoming the tool of continuous differentiation of society into tiny autonomous communities similar to nomadic atomization of society. The concept based on moral substantial existence basis as in “axis time” by K. Jaspers that can prevent social entropy resulting in world anthropologic catastrophes has been grounded in the present research.

  18. A janus-faced manipulation

    OpenAIRE

    Etges, Christine Bareño

    2000-01-01

    Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-Graduação em Letras/Inglês e Literatura Correspondente. Narrativas de viagem são especialmente interessantes em tradução uma vez que seus autores já 'traduziram' a realidade do país que visitaram, tanto literalmente quanto figurativamente. O tradutor tem, então, a desafiadora tarefa de traduzir o traduzido. Quando acontece de o tradutor ser um nativo do país visitado, a ta...

  19. The Janus face of caffeine.

    Science.gov (United States)

    Porciúncula, Lisiane O; Sallaberry, Cássia; Mioranzza, Sabrina; Botton, Paulo Henrique S; Rosemberg, Denis B

    2013-11-01

    Caffeine is certainly the psychostimulant substance most consumed worldwide. Over the past years, chronic consumption of caffeine has been associated with prevention of cognitive decline associated to aging and mnemonic deficits of brain disorders. While its preventive effects have been reported extensively, the cognitive enhancer properties of caffeine are relatively under debate. Surprisingly, there are scarce detailed ontogenetic studies focusing on neurochemical parameters related to the effects of caffeine during prenatal and earlier postnatal periods. Furthermore, despite the large number of epidemiological studies, it remains unclear how safe is caffeine consumption during pregnancy and brain development. Thus, the purpose of this article is to review what is currently known about the actions of caffeine intake on neurobehavioral and adenosinergic system during brain development. We also reviewed other neurochemical systems affected by caffeine, but not only during brain development. Besides, some recent epidemiological studies were also outlined with the control of "pregnancy signal" as confounding variable. The idea is to tease out how studies on the impact of caffeine consumption during brain development deserve more attention and further investigation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Response surface methodology approach for optimization of adsorption of Janus Green B from aqueous solution onto ZnO/Zn(OH)2-NP-AC: Kinetic and isotherm study

    Science.gov (United States)

    Ghaedi, M.; Khafri, H. Zare; Asfaram, A.; Goudarzi, A.

    2016-01-01

    The Janus Green B (JGB) adsorption onto homemade ZnO/Zn(OH)2 nanoparticles loaded on activated carbon (AC) which characterized by FESEM and XRD analysis has been reported. Combination of response surface methodology (RSM) and central composite design (CCD) has been employed to model and optimize variables using STATISTICA 10.0 software. The influence of parameters over pH (2.0-8.0), adsorbent (0.004-0.012 g), sonication time (4-8 min) and JGB concentration (3-21 mg L-1) on JGB removal percentage was investigated and their main and interaction contribution was examined. It was revealed that 21 mg L-1 JGB, 0.012 g ZnO/Zn(OH)2-NP-AC at pH 7.0 and 7 min sonication time permit to achieve removal percentage more than 99%. Finally, a good agreement between experimental and predicted values after 7 min was achieved using pseudo-second-order rate equation. The Langmuir adsorption is appropriate for correlation of equilibrium data. The small amount of adsorbent (0.008-0.015 g) is applicable for successful removal of JGB (RE > 99%) in short time (7 min) with high adsorption capacity (81.3-98.03 mg g-1).

  1. Mangiferin ameliorates Porphyromonas gingivalis-induced experimental periodontitis by inhibiting phosphorylation of nuclear factor-κB and Janus kinase 1-signal transducer and activator of transcription signaling pathways.

    Science.gov (United States)

    Li, H; Wang, Q; Ding, Y; Bao, C; Li, W

    2017-02-01

    Mangiferin is a natural polyphenol compound with anti-inflammatory properties. However, there have been few reports on the effect of mangiferin on periodontitis. Here, we investigated the anti-inflammatory effects of this compound on experimental periodontitis and the underlying mechanisms. Mice were inoculated with Porphyromonas gingivalis to induce periodontitis, and treated with mangiferin orally (50 mg/kg bodyweight, once a day) for 8 wk. Then, the alveolar bone loss was examined using a scanning electronic microscope. Expression of tumor necrosis factor-α (TNF-α) and the phosphorylation levels of nuclear factor-κB (NF-κB) and Janus kinase 1-signal transducer and activator of adhesion (JAK1-STAT) pathways in the gingival epithelium were detected using western blot analysis and immunohistochemical staining. The results showed that mice with periodontitis exhibited greater alveolar bone loss, stronger expression of TNF-α and higher phosphorylation levels of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia, compared with control mice with no periodontitis. Moreover, treatment with mangiferin could significantly inhibit alveolar bone loss, TNF-α production and phosphorylation of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia. Mangiferin has anti-inflammatory effects on periodontitis, which is associated with its ability to down-regulate the phosphorylation of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Overexpression of microRNA-375 impedes platelet-derived growth factor-induced proliferation and migration of human fetal airway smooth muscle cells by targeting Janus kinase 2.

    Science.gov (United States)

    Ji, Yamei; Yang, Xin; Su, Huixia

    2018-02-01

    The abnormal proliferation and migration of airway smooth muscle (ASM) cells play a critical role in airway remodeling during the development of asthma. MicroRNAs (miRNAs) have emerged as critical regulators of ASM cell proliferation and migration in airway remodeling. In this study, we aimed to investigate the potential role of miR-375 in the regulation of platelet-derived growth factor (PDGF)-induced fetal ASM cell proliferation and migration. Our results showed that miR-375 expression was significantly decreased in fetal ASM cells that were treated with PDGF. Functional data showed that overexpression of miR-375 inhibited the proliferation and migration of fetal ASM cells, whereas inhibition of miR-375 enhanced the proliferation and migration of fetal ASM cells. The results of bioinformatics analysis and a dual-luciferase reporter assay showed that miR-375 binds directly to the 3'-untranslated region of Janus kinase 2 (JAK2). Further data confirmed that miR-375 negatively regulates the expression of JAK2 in fetal ASM cells. Moreover, miR-375 also impeded the PDGF-induced activation of signal transducer and activator of transcription 3 (STAT3) in fetal ASM cells. However, restoration of JAK2 expression partially reversed the inhibitory effect of miR-375 on fetal ASM cell proliferation and migration. Overall, our results demonstrate that miR-375 inhibits fetal ASM cell proliferation and migration by targeting JAK2/STAT3 signaling. Our study provides a potential therapeutic target for the development of novel treatment strategies for pediatric asthma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study.

    Science.gov (United States)

    Papp, Kim A; Krueger, James G; Feldman, Steven R; Langley, Richard G; Thaci, Diamant; Torii, Hideshi; Tyring, Stephen; Wolk, Robert; Gardner, Annie; Mebus, Charles; Tan, Huaming; Luo, Yingchun; Gupta, Pankaj; Mallbris, Lotus; Tatulych, Svitlana

    2016-05-01

    Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. There was no dose comparison beyond week 52. Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  4. Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study

    Science.gov (United States)

    Takeuchi, Tsutomu; Tanaka, Yoshiya; Iwasaki, Manabu; Ishikura, Hiroaki; Saeki, Satoshi; Kaneko, Yuichiro

    2016-01-01

    Objective To evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA). Methods In a 12-week, double-blind study, 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were randomised equally to once-daily placebo or peficitinib 25, 50, 100 and 150 mg. The primary endpoint was American College of Rheumatology (ACR) 20 response in the peficitinib treatment groups versus placebo at week 12. Results Mean age was 53.0 years, 81.1% were female and 25.3% had previously used antitumour necrosis factor therapy. Peficitinib 50, 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo, and response rates increased up to 150 mg with a statistically significant dose response. The total incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo (64.3%) and peficitinib 25, 50, 100 and 150 mg groups (70.9%, 64.9%, 52.7% and 67.2%, respectively). TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis, increased blood creatine phosphokinase and diarrhoea. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in peficitinib 25 and 100 mg). Conclusions Treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile. These findings support further developments of peficitinib for RA treatment. Trial registration number NCT01649999; Results. PMID:26672064

  5. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of Latin American patients with rheumatoid arthritis: Pooled efficacy and safety analyses of Phase 3 and long-term extension studies.

    Science.gov (United States)

    Radominski, Sebastião Cezar; Cardiel, Mario Humberto; Citera, Gustavo; Goecke, Annelise; Jaller, Juan Jose; Lomonte, Andrea Barranjard Vannucci; Miranda, Pedro; Velez, Patricia; Xibillé, Daniel; Kwok, Kenneth; Rojo, Ricardo; García, Erika Gabriela

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assessed tofacitinib efficacy and safety in the Latin American (LA) subpopulation of global Phase 3 and long-term extension (LTE) studies. Data from LA patients with RA and inadequate response to disease-modifying antirheumatic drugs (DMARDs) were pooled across five Phase 3 studies. Phase 3 patients received tofacitinib 5 or 10mg twice daily (BID), adalimumab or placebo; patients in the single LTE study received tofacitinib 5 or 10mg BID; treatments were administered alone or with conventional synthetic DMARDs. Efficacy was reported up to 12 months (Phase 3) and 36 months (LTE) by American College of Rheumatology (ACR) 20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate [ESR]) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Incidence rates (IRs; patients with event/100 patient-years) of adverse events (AEs) of special interest were reported. The Phase 3 studies randomized 496 LA patients; the LTE study enrolled 756 LA patients from Phase 2 and Phase 3. In the Phase 3 studies, patients who received tofacitinib 5 and 10mg BID showed improvements vs placebo at Month 3 in ACR20 (68.9% and 75.7% vs 35.6%), ACR50 (45.8% and 49.7% vs 20.7%) and ACR70 (17.5% and 23.1% vs 6.9%) responses, mean change from baseline in HAQ-DI (-0.6 and -0.8 vs -0.3) and DAS28-4(ESR) score (-2.3 and -2.4 vs -1.4). The improvements were sustained up to Month 36 in the LTE study. In the Phase 3 studies, IRs with tofacitinib 5 and 10mg BID and placebo were 7.99, 6.57 and 9.84, respectively, for SAEs, and 3.87, 5.28 and 3.26 for discontinuation due to AEs. IRs of AEs of special interest in tofacitinib-treated LA patients were similar to the global population. In Phase 3 and LTE studies in LA patients with RA, tofacitinib demonstrated efficacy up to 36 months with a manageable safety profile up to 60 months, consistent with the overall tofacitinib

  6. The Janus Face of Governance Theory

    DEFF Research Database (Denmark)

    Sørensen, Eva; Torfing, Jacob

    2017-01-01

    While the main current in the growing research on governance has praised its virtues, a critical undertow has insisted that governance carries the danger of depoliticization and democratic decline. Chapter 2 aims to complicate things by arguing that interactive forms of governance intending...... science perspective has a sharper eye for the political choices, conflicts, and power struggles. If the political science perspective has a blind spot, it concerns the role of elected politicians in the exercise of political meta-governance. That role is further developed towards the end of the chapter...

  7. Supersymmetric Janus solutions in four dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Bobev, Nikolay [Perimeter Institute for Theoretical Physics,31 Caroline Street North, ON N2L 2Y5 (Canada); Pilch, Krzysztof [Department of Physics and Astronomy, University of Southern California,Los Angeles, CA 90089 (United States); Warner, Nicholas P. [Department of Physics and Astronomy, University of Southern California,Los Angeles, CA 90089 (United States); Institut de Physique Théorique, CEA Saclay,CNRS-URA 2306, 91191 Gif sur Yvette (France); Institut des Hautes Etudes Scientifiques,Le Bois-Marie, 35 route de Chartres, Bures-sur-Yvette, 91440 (France)

    2014-06-10

    We use maximal gauged supergravity in four dimensions to construct the gravity dual of a class of supersymmetric conformal interfaces in the theory on the world-volume of multiple M2-branes. We study three classes of examples in which the (1+1)-dimensional defects preserve (4,4), (0,2) or (0,1) supersymmetry. Many of the solutions have the maximally supersymmetric AdS{sub 4} vacuum dual to the N=8 ABJM theory on both sides of the interface. We also find new special classes of solutions including one that interpolates between the maximally supersymmetric vacuum and a conformal fixed point with N=1 supersymmetry and G{sub 2} global symmetry. We find another solution that interpolates between two distinct conformal fixed points with N=1 supersymmetry and G{sub 2} global symmetry. In eleven dimensions, this G{sub 2} to G{sub 2} solution corresponds to a domain wall across which a magnetic flux reverses orientation.

  8. Supersymmetric Janus solutions in four dimensions

    International Nuclear Information System (INIS)

    Bobev, Nikolay; Pilch, Krzysztof; Warner, Nicholas P.

    2014-01-01

    We use maximal gauged supergravity in four dimensions to construct the gravity dual of a class of supersymmetric conformal interfaces in the theory on the world-volume of multiple M2-branes. We study three classes of examples in which the (1+1)-dimensional defects preserve (4,4), (0,2) or (0,1) supersymmetry. Many of the solutions have the maximally supersymmetric AdS 4 vacuum dual to the N=8 ABJM theory on both sides of the interface. We also find new special classes of solutions including one that interpolates between the maximally supersymmetric vacuum and a conformal fixed point with N=1 supersymmetry and G 2 global symmetry. We find another solution that interpolates between two distinct conformal fixed points with N=1 supersymmetry and G 2 global symmetry. In eleven dimensions, this G 2 to G 2 solution corresponds to a domain wall across which a magnetic flux reverses orientation

  9. The Janus Face of urban policy

    DEFF Research Database (Denmark)

    Andersen, John

    be characterised by a duality between 1. Participatory empowering welfare oriented inclusion strategies, which targets deprived districts and neighbourhoods (politics of positive selectivism recognising increasing spatial inequality as a political issue) - based on notions of the Multicultural and Solidaristic...... City. 2. Neoelitist/corporatist market driven strategic growth strategies, which are based on notions of the Entrepreneurial City. The tension between the two orientations represents the most important challenge for urban democracy and inclusive governance concerned with problems of overcoming social...

  10. Analýza sortimentu firmy Janus

    OpenAIRE

    Kudrnová, Gabriela

    2009-01-01

    The thesis describes a company that distributes laser printers and copy machines. Using the portfolio analysis, I seek for products that should be on offer further and those that should be excluded from the sortiment. The thesis also describes services that serve as a support of the product. At the end the portfolio of this company is compared to portfolios of competing companies.

  11. Co-assembly towards Janus micelles

    NARCIS (Netherlands)

    Voets, I.K.; Leermakers, F.A.M.; Keizer, de A.; Charlaganov, M.; Cohen Stuart, M.A.

    2011-01-01

    In this paper, we report on our recent findings concerning the structure of complex coacervate core micelles composed of two types of (complementary) block copolymers. Both copolymers have a polyelectrolyte (one cationic and the other anionic) block combined with a neutral one. The opposite charges

  12. The Janus Faces of IHRM in Russian MNEs

    DEFF Research Database (Denmark)

    Andreeva, Tatiana; Festing, Marion; Minbaeva, Dana

    2014-01-01

    MNEs actively promote a mix of global best practices and local HRM practices. We do not find any instances of the reverse transfer of management practices from subsidiaries in developed countries to the MNEs' headquarters or any examples of cross-pollination among subsidiaries.......This article analyzes variations in the international human resource management ( IHRM) approaches of Russian multinational enterprises ( MNEs) in the contexts of developed and developing countries. The data were gathered through interviews conducted at the headquarters of Russian MNEs...... and at their subsidiaries in developed and developing countries. The results indicate that Russian MNEs adopt HRM practices of Western origin. However, these MNEs differ radically in their choices of IHRM approaches. Many of these differences depend on the countries these MNEs target in their international expansion...

  13. George W. Bush in Political Time: The Janus Presidency

    NARCIS (Netherlands)

    Magliocca, G.N.

    2009-01-01

    This essay places George W. Bush's presidency and the Bush administration in some historical context by applying the model of “political time” developed in recent books by Stephen Skowronek (2008) and Keith Whittington (2007). My thesis is that Bush's political failure during his second term was

  14. Politesse, impolitesse, auto-politesse: Janus revisité

    Directory of Open Access Journals (Sweden)

    Carmen Alberdi Urquizu

    2009-04-01

    Full Text Available The interactional analysis has highlighted that one of the main targets of the communication is the one to establish personalrelationships. This goal is primarily subjected to the respect of Politeness Principle, in regard of which «self-politeness» andimpoliteness appear to be inappropriate. Nevertheless, a brief analysis of these behaviors shows that we cannot reduce the human reactions to mere dichotomies.

  15. A Guide to Lexical Acquisition in the JANUS System.

    Science.gov (United States)

    1986-02-01

    meaning " cut with a saw". or the past tense form of the verb see. In this case. there are three lexical items corresponding to the word saw. ""P 1.2. How...her petunias No one knows where the captain is buried Today we will learn who invented electricity I can never remember when William invaded England

  16. Unifying and Dividing Processes in National Media: The Janus Face ...

    African Journals Online (AJOL)

    The article aims to open up a theoretical space where the nation building project's inherent contradictions can thrive, making it possible to see the construction of a new South Africa as a dialectical area of both converging and diverging processes. Using the national broadcaster South African Broadcasting Corporation ...

  17. The Janus face of death receptor signalling during tumour immunoediting.

    Directory of Open Access Journals (Sweden)

    Eimear O' Reilly

    2016-10-01

    Full Text Available Cancer immune-surveillance is essential for the inhibition of carcinogenesis. Malignantly transformed cells can be recognised by both the innate and adaptive immune systems through different mechanisms. Immune effector cells induce extrinsic cell death in the identified tumour cells by expressing death ligand cytokines of the tumour necrosis factor ligand family. However, some tumour cells can escape immune elimination and progress. Acquisition of resistance to the death-ligand induced apoptotic pathway can be obtained through cleavage of effector-cell expressed death-ligands into a poorly active form, mutations or silencing of the death receptors or overexpression of decoy receptors and pro-survival proteins. Although the immune system is highly effective in the elimination of malignantly transformed cells, abnormal/ dysfunctional death-ligand signalling curbs its cytotoxicity. Moreover, death receptors can also transmit pro-survival and pro-migratory signals. Consequently, dysfunctional death receptor-mediated apoptosis/necroptosis signalling does not only give a passive resistance against cell death, but actively drives tumour cell motility, invasion and contributes to consequent metastasis. This dual contribution of the death ligand-death receptor signalling in both the early, elimination phase and then in the late, escape phase of the tumour immunoediting process is discussed in this review. Death receptor agonists still hold potential for cancer therapy since they can execute the tumour-eliminating immune-effector function even in the absence of activation of the immune system against the tumour. The opportunities and challenges of developing death receptor agonists into effective cancer therapeutics are also discussed.

  18. Solenoid for Laser Induced Plasma Experiments at Janus

    Science.gov (United States)

    Klein, Sallee; Leferve, Heath; Kemp, Gregory; Mariscal, Derek; Rasmus, Alex; Williams, Jackson; Gillespie, Robb; Manuel, Mario; Kuranz, Carolyn; Keiter, Paul; Drake, R.

    2017-10-01

    Creating invariant magnetic fields for experiments involving laser induced plasmas is particularly challenging due to the high voltages at which the solenoid must be pulsed. Creating a solenoid resilient enough to survive through large numbers of voltage discharges, enabling it to endure a campaign lasting several weeks, is exceptionally difficult. Here we present a solenoid that is robust through 40 μs pulses at a 13 kV potential. This solenoid is a vast improvement over our previously fielded designs in peak magnetic field capabilities and robustness. Designed to be operated at small-scale laser facilities, the solenoid housing allows for versatility of experimental set-ups among diagnostic and target positions. Within the perpendicular field axis at the center there is 300 degrees of clearance which can be easily modified to meet the needs of a specific experiment, as well as an f/3 cone for transmitted or backscattered light. After initial design efforts, these solenoids are relatively inexpensive to manufacture.

  19. The cosmological Janus model: comparison with observational data

    Science.gov (United States)

    Petit, Jean-Pierre; Dagostini, Gilles

    2017-01-01

    In 2014 we presented a model based on a system of two coupled field equations to describe two populations of particles, one positive and the other mass of negative mass. The analysis of this system by Newtonian approximation show that the masses of the same signs attract according to Newton's law while the masses of opposite signs repel according to an anti-Newton law. This eliminates the runaway phenomenon. It uses the time-dependent exact solution of this system to build the bolometric magnitude distribution of the red-shift. Comparing the prediction of our model -which requires adjustment with a single parameter- with the data from 740 supernovae highlighting the acceleration of the universe gives an excellent agreement. The comparison is then made with the multi-parametric Λ CDM model.

  20. Ühe näoga Janus / Mart Raukas

    Index Scriptorium Estoniae

    Raukas, Mart

    2008-01-01

    Tänapäeva lääne poliitikud, lähtudes oma avaldustes aina enam tüüpilistest moraalihinnangutest, unustavad, et ükski moraalne reageering ei ole pelgalt reageering faktidele, vaid selle teeb moraalselt relevantseks olukorrale langetatud hinnang ja sellest lähtuv reageering. Õigluseta ühiskond ei erine suurest röövlijõugust ning see, kes mõistab hukka ühe suurriigi tegevuse, olgu kriitiline ka teise suurjõu osas

  1. Neutrophils and Granulocytic MDSC: The Janus God of Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Serena Zilio

    2016-09-01

    Full Text Available Neutrophils are the most abundant circulating blood cell type in humans, and are the first white blood cells recruited at the inflammation site where they orchestrate the initial immune response. Although their presence at the tumor site was recognized in the 1970s, until recently these cells have been neglected and considered to play just a neutral role in tumor progression. Indeed, in recent years neutrophils have been recognized to play a dual role in tumor development by either assisting the growth, angiogenesis, invasion, and metastasis or by exerting tumoricidal action directly via the secretion of antitumoral compounds, or indirectly via the orchestration of antitumor immunity. Understanding the biology of these cells and influencing their polarization in the tumor micro- and macro-environment may be the key for the development of new therapeutic strategies, which may finally hold the promise of an effective immunotherapy for cancer.

  2. Direct Assembly of Magnetic Janus Particles at a Droplet Interface

    NARCIS (Netherlands)

    Xie, Qingguang; Davies, Gary B.; Harting, Jens

    2017-01-01

    Self-assembly of nanoparticles at fluid-fluid interfaces is a promising route to fabricate functional materials from the bottom-up. However, directing and controlling particles into highly tunable and predictable structures, while essential, is a challenge. We present a liquid interface assisted

  3. The Janus face of 'New Ways of Work': rise, risks and regulation of nomadic work

    NARCIS (Netherlands)

    Popma, J.

    2013-01-01

    The Internet and the use of portable computers, mobile phones and tablets have increased the importance of ‘new ways of work’. This work, which is place- and time-independent, can lead to more autonomy and greater flexibility for workers, but it also carries serious physical as well as psychosocial

  4. Iodine (I 2 ) as a Janus-Faced Ligand in Organometallics

    KAUST Repository

    Rogachev, Andrey Yu.

    2013-02-27

    The four known diiodine complexes have distinct geometries. These turn out, as we demonstrate by a bonding analysis, to be a direct consequence of diiodine acting as an acceptor in one set, the van Koten complexes, and as a donor in the Cotton, Dikarev, and Petrukhina extended structure. The primary analytical tool utilized is perturbation theory within the natural bond orbital (NBO) framework, supported by an energy decomposition analysis. The study begins by delineating the difference between canonical molecular orbitals (MOs) and NBOs. When iodine acts as an acceptor, bonding collinearly in the axial position of a square-planar d8 Pt(II) complex, the dominant contributor to the bonding is a σ*(I-I) orbital as the acceptor orbital, while a mainly dz 2 orbital centered on the metal center is the corresponding donor. That this kind of bonding is characteristic of axial bonding in d8 complexes was supported by model calculations with incoming donors and acceptors, NH3 and BH3. In contrast, the distinct "bent" coordination of the I2 bound at the axial position of the [Rh2(O2CCF3)4] paddle-wheel complex is associated with a dominant donation from a p-type lone pair localized on one of two iodine atoms, the σ*(Rh-Rh) antibonding orbital of the metal complex acting as an acceptor orbital. We check the donor capabilities of I2 in some hypothetical complexes with Lewis acids, H+, AlCl3, B(CF3)3. Also, we look at the weakly bound donor-acceptor couple [(I2)·(I2)]. We explore the reasons for the paucity of I2 complexes and propose candidates for synthesis. © 2013 American Chemical Society.

  5. Radial arrangement of Janus-like setae permits friction control in spiders.

    Science.gov (United States)

    Wolff, Jonas O; Gorb, Stanislav N

    2013-01-01

    Dynamic attachment is the key to move on steep surfaces, with mechanisms being still not well understood. The hunting spider Cupiennius salei (Arachnida, Ctenidae) possesses hairy attachment pads (claw tufts) at its distal legs, consisting of directional branched setae. The morphological investigation revealed that adhesive setae are arranged in a radial manner within the distal tarsus. Friction of claw tufts on smooth glass was measured to reveal the functional effect of seta arrangement within the pad. Measurements revealed frictional anisotropy in both longitudinal and transversal directions. Contact behaviour of adhesive setae was investigated in a reflection interference contrast microscope (RICM). Observations on living spiders showed, that only a small part of the hairy pads is in contact at the same time. Thus the direction of frictional forces is depending on leg placement and rotation. This may aid controlling the attachment to the substrate.

  6. Probing altered hematopoietic progenitors of preleukemic dogs with JANUS fission neutrons

    International Nuclear Information System (INIS)

    Seed, T.M.; Kaspar, L.V.

    1990-01-01

    Toward the goal of developing basic insights to mechanisms of radiation leukemogenesis, the authors have developed a canine model that responds to protracted courses of low-daily-dose gamma irradiation with high incidences of myeloproliferative disease (MPD), principally myeloid leukemia. Using this model system, the authors have identified and partially characterized a four-phase preclinical sequence in the induction of MPD, including (1) suppression, (2) recovery, (3) accommodation, and (4) preleukemic transition. Further, they have identified within this sequence, a critical early hematopoietic target cell event that appears to promote progression of the initial preclinical phase to the second preclinical phase. This key target cell event is characterized by the acquisition of increased radioresistance to low-LET gamma rays by granulocyte/monocyte-committed progenitors (CFU-GM). In order to gain further insight into the basis of this critical event, the acquired survival responses of preleukemic progenitors have been probed in vitro with high-LET fission neutrons. 23 refs., 4 figs., 1 tab

  7. The Janus-Faced Role of Antioxidants in Cancer Cachexia: New Insights on the Established Concepts

    Directory of Open Access Journals (Sweden)

    Mohamad Assi

    2016-01-01

    Full Text Available Chronic inflammation and excessive loss of skeletal muscle usually occur during cancer cachexia, leading to functional impairment and delaying the cure of cancer. The release of cytokines by tumor promotes the formation of reactive oxygen species (ROS, which in turn regulate catabolic pathways involved in muscle atrophy. ROS also exert a dual role within tumor itself, as they can either promote proliferation and vascularization or induce senescence and apoptosis. Accordingly, previous studies that used antioxidants to modulate these ROS-dependent mechanisms, in cancer and cancer cachexia, have obtained contradictory results, hence the need to gather the main findings of these studies and draw global conclusions in order to stimulate more oriented research in this field. Based on the literature reviewed in this paper, it appears that antioxidant supplementation is (1 beneficial in cancer cachectic patients with antioxidant deficiencies, (2 most likely harmful in cancer patients with adequate antioxidant status (i.e., lung, gastrointestinal, head and neck, and esophageal, and (3 not recommended when undergoing radiotherapy. At the moment, measuring the blood levels of antioxidants may help to identify patients with systemic deficiencies. This approach is simple to realize but could not be a gold standard method for cachexia, as it does not necessarily reflect the redox state in other organs, like muscle.

  8. The Janus-Faced Role of Antioxidants in Cancer Cachexia: New Insights on the Established Concepts

    Science.gov (United States)

    Rébillard, Amélie

    2016-01-01

    Chronic inflammation and excessive loss of skeletal muscle usually occur during cancer cachexia, leading to functional impairment and delaying the cure of cancer. The release of cytokines by tumor promotes the formation of reactive oxygen species (ROS), which in turn regulate catabolic pathways involved in muscle atrophy. ROS also exert a dual role within tumor itself, as they can either promote proliferation and vascularization or induce senescence and apoptosis. Accordingly, previous studies that used antioxidants to modulate these ROS-dependent mechanisms, in cancer and cancer cachexia, have obtained contradictory results, hence the need to gather the main findings of these studies and draw global conclusions in order to stimulate more oriented research in this field. Based on the literature reviewed in this paper, it appears that antioxidant supplementation is (1) beneficial in cancer cachectic patients with antioxidant deficiencies, (2) most likely harmful in cancer patients with adequate antioxidant status (i.e., lung, gastrointestinal, head and neck, and esophageal), and (3) not recommended when undergoing radiotherapy. At the moment, measuring the blood levels of antioxidants may help to identify patients with systemic deficiencies. This approach is simple to realize but could not be a gold standard method for cachexia, as it does not necessarily reflect the redox state in other organs, like muscle. PMID:27642498

  9. The Janus Face of NKT Cell Function in Autoimmunity and Infectious Diseases.

    Science.gov (United States)

    Torina, Alessandra; Guggino, Giuliana; La Manna, Marco Pio; Sireci, Guido

    2018-02-01

    Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II, and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defense against infections but, on the other hand, their effector functions can be involved in the pathogenesis of several inflammatory disorders due to their exposure to different microbial or self-antigens, respectively. A deep understanding of the biology and functions of type I, II, and NKT-like cells as well as their interplay with cell types acting in innate (neuthrophils, innate lymphoid cells, machrophages, and dendritic cells) and adaptive immunity (CD4⁺,CD8⁺, and double negative T cells) should be important to design potential immunotherapies for infectious and autoimmune diseases.

  10. A Janus-Faced Approach to Learning. A Critical Discussion of Habermas' Pragmatic Approach

    Science.gov (United States)

    Italia, Salvatore

    2017-01-01

    A realist approach to learning is what I propose here. This is based on a non-epistemic dimension whose presence is a necessary assumption for a concept of learning of a life-world as complementary to learning within a life-world. I develop my approach in opposition to Jürgen Habermas' pragmatic approach, which seems to lack of something from a…

  11. Improvement of Janus Using Pegasus 1-Meter Resolution Database With a Transputer Network

    Science.gov (United States)

    1994-03-01

    Figure 4.9 shows the six jacks on the end of the HSI-card. Facing the back of the SPARC Station LINKO LINKI LINK2 LINK3 DOWN UP Figure 4.9: HSI-Card Link...shown in Figure 4.22. Facing the back of the Sun SPARC Station LINK0 LINKI LINK2 LINK3 DOWN UP "b Telephone Cable Facing the front of the Remote Tram...Holder LINKO LINKI LINK2 LINK3 DOWN UPI Figure 4.20: The Connection Between Sun SPARC Station and Remote Tram Holder 58 (3) Se.inu Up t• Link Speed

  12. Introduction « Les visages de Janus »

    OpenAIRE

    Mellet, Paul-Alexis; Soussen, Claire

    2013-01-01

    This workshop dedicated to relations between people of different faiths is focused on the links between majority and minorities in Europe between the 12th and 17th centuries. From the Iberic Peninsula to Byzantium, from Sicily to northern France, the artistic influences, commercial exchanges and theological debates that occurred, whether those involved were willing or reluctant participants in them, are examined here by historians both medieval and modern. Janus’s face seems to symbolize perf...

  13. Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone.

    Science.gov (United States)

    Detremmerie, Charlotte; Vanhoutte, Paul M; Leung, Susan

    2017-07-01

    The natural compound thymoquinone, extracted from Nigella sativa (black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC) producing inosine 3',5'-cyclic monophosphate (cyclic IMP) rather than guanosine 3',5'-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.

  14. Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone

    Directory of Open Access Journals (Sweden)

    Charlotte Detremmerie

    2017-07-01

    Full Text Available The natural compound thymoquinone, extracted from Nigella sativa (black cumin, is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC producing inosine 3ʹ,5ʹ-cyclic monophosphate (cyclic IMP rather than guanosine 3ʹ,5ʹ-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.

  15. Note: On-chip multifunctional fluorescent-magnetic Janus helical microswimmers

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, G., E-mail: gilgueng.hwang@lpn.cnrs.fr; Decanini, D.; Leroy, L.; Haghiri-Gosnet, A. M. [Laboratoire de Photonique et de Nanostructures, CNRS, Route de Nozay, Marcoussis 91460 (France)

    2016-03-15

    Microswimmers integrated into microfluidic devices that are capable of self-illumination through fluorescence could revolutionize many aspects of technology, especially for biological applications. Few illumination and propulsion techniques of helical microswimmers inside microfluidic channels have been demonstrated. This paper presents the fabrication, detachment, and magnetic propulsions of multifunctional fluorescent-magnetic helical microswimmers integrated inside microfluidics. The fabrication process is based on two-photon laser lithography to pattern 3-D nanostructures from fluorescent photoresist coupled with conventional microfabrication techniques for magnetic thin film deposition by shadowing. After direct integration inside a microfluidic device, injected gas bubble allows gentle detachment of the integrated helical microswimmers whose magnetic propulsion can then be directly applied inside the microfluidic channel using external electromagnetic coil setup. With their small scale, fluorescence, excellent resistance to liquid/gas surface tension, and robust propulsion capability inside the microfluidic channel, the microswimmers can be used as high-resolution and large-range mobile micromanipulators inside microfluidic channels.

  16. Dazzles, decoys, and deities : the Janus face of anti-facial recognition masks

    NARCIS (Netherlands)

    de Vries, P.B.

    2017-01-01

    Over the past few years a growing number of artists have critiqued the ubiquity of identity recognition technologies. Specifically, the use of these technologies by state security programs, tech-giants and multinational corporations has met with opposition and controversy. A popular form of

  17. Type two innate lymphoid cells; the Janus cells in health and disease

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-01-01

    Summary Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2 and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by costimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. PMID:28658553

  18. Type two innate lymphoid cells: the Janus cells in health and disease.

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-07-01

    Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Improving the engine power of a catalytic Janus-sphere micromotor by roughening its surface.

    Science.gov (United States)

    Longbottom, Brooke W; Bon, Stefan A F

    2018-03-15

    Microspheres with catalytic caps have become a popular model system for studying self-propelled colloids. Existing experimental studies involve predominantly "smooth" particle surfaces. In this study we determine the effect of irregular surface deformations on the propulsive mechanism with a particular focus on speed. The particle surfaces of polymer microspheres were deformed prior to depositing a layer of platinum which resulted in the formation of nanoscopic pillars of catalyst. Self-propulsion was induced upon exposure of the micromotors to hydrogen peroxide, whilst they were dispersed in water. The topological surface features were shown to boost speed (~2×) when the underlying deformations are small (nanoscale), whilst large deformations afforded little difference despite a substantial apparent catalytic surface area. Colloids with deformed surfaces were more likely to display a mixture of rotational and translational propulsion than their "smooth" counterparts.

  20. Aquaporins in Spinal Cord Injury: The Janus Face of AQP4

    Science.gov (United States)

    Nesic, Olivera; Guest, James D.; Zivadinovic, Dragoslava; Narayana, Ponnada A.; Herrera, Juan J.; Grill, Raymond J.; Mokkapati, Venkata U.L.; Gelman, Benjamin B.; Lee, Julieann

    2010-01-01

    Although malfunction of spinal cord water channels (aquaporins, AQP) likely contributes to severe disturbances in ion/water homeostasis after spinal cord injury (SCI), their roles are still poorly understood. Here we report and discuss the potential significance of changes in the AQP4 expression in human SCI that generates GFAP-labeled astrocytes devoid of AQP4, and GFAP-labeled astroglia that overexpress AQP4. We used a rat model of contusion SCI to study observed changes in human SCI. AQP4-negative astrocytes are likely generated during the process of SCI-induced replacement of lost astrocytes, but their origin and role in SCI remains to be investigated. We found that AQP4-overexpression is likely triggered by hypoxia. Our transcriptional profiling of injured rat cords suggests that elevated AQP4-mediated water influx accompanies increased uptake of chloride and potassium ions which represents a protective astrocytic reaction to hypoxia. However, unbalanced water intake also results in astrocytic swelling that can contribute to motor impairment, but likely only in milder injuries. In severe rat SCI, a low abundance of AQP4-overexpressing astrocytes was found during the motor recovery phase. Our results suggest that severe rat contusion SCI is a better model to analyze AQP4 functions after SCI. We found that AQP4 increases in the chronic post-injury phase are associated with the development of pain-like behavior in SCI rats, while possible mechanisms underlying pain development may involve astrocytic swelling-induced glutamate release. In contrast, the formation and size of fluid-filled cavities occurring later after SCI does not appear to be affected by the extent of increased AQP4 levels. Therefore, the effect of therapeutic interventions targeting AQP4 will depend not only on the time interval after SCI or animal models, but also on the balance between protective role of increased AQP4 in hypoxia and deleterious effects of ongoing astrocytic swelling. PMID:20109536

  1. Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications

    Science.gov (United States)

    Rahmani, Sahar; Villa, Carlos H.; Dishman, Acacia F.; Grabowski, Marika E.; Pan, Daniel C.; Durmaz, Hakan; Misra, Asish C; Colón-Meléndez, Laura; Solomon, Michael J.; Muzykantov, Vladimir R.; Lahann, Joerg

    2016-01-01

    Background Nanoparticles with controlled physical properties have been widely used for controlled release applications. In addition to shape, the anisotropic nature of the particles can be an important design criterion to ensure selective surface modification or independent release of combinations of drugs. Purpose Electrohydrodynamic (EHD) co-jetting is used for the fabrication of uniform anisotropic nanoparticles with individual compartments and initial physicochemical and biological characterization is reported. Methods EHD co-jetting is used to create nanoparticles, which are characterized at each stage with scanning electron microscopy (SEM), structured illumination microscopy (SIM), dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Surface immobilization techniques are used to incorporate polyethylene glycol (PEG) and I125 radiolabels into the nanoparticles. Particles are injected in mice and the particle distribution after 1, 4 and 24 hours is assessed. Results and discussion Nanoparticles with an average diameter of 105.7 nm are prepared by EHD co-jetting. The particles contain functional chemical groups for further surface modification and radiolabeling. The density of PEG molecules attached to the surface of nanoparticles is determined to range between 0.02 and 6.04 ligands per square nanometer. A significant fraction of the nanoparticles (1.2% injected dose per mass of organ) circulates in the blood after 24 h. Conclusion EHD co-jetting is a versatile method for the fabrication of nanoparticles for drug delivery. Circulation of the nanoparticles for 24 h is a pre-requisite for subsequent studies to explore defined targeting of the nanoparticles to a specific anatomic site. PMID:26453170

  2. Prevalence of Janus kinase 2 mutations in patients with unusual site venous thrombosis

    Directory of Open Access Journals (Sweden)

    Ana Lisa Basquiera

    2011-08-01

    Full Text Available We aimed to study patients with splanchnic vein thrombosis (SVT and cerebral vein thrombosis (CVT searching for JAK2 mutations. We evaluated 14 patients (median age: 41.5 years with portal vein thrombosis (PVT = 7; mesenteric vein thrombosis (MVT = 3; and CVT = 4. JAK2 V617F was assessed by allele specific PCR of peripheral blood DNA. In addition, DNA was sequenced for other JAK2 mutations. Other inherited and acquired thrombophilia risk factors were evaluated. JAK2 V617F was positive in four out of seven patients with PVT and in one CVT patient. These five patients had a diagnosis of myeloproliferative disorder (MPD at the moment of the occurrence of thrombosis (n = 2 or later (n = 2. Patients with MVT and CVT were negative for JAK2 V617F, except one patient with CVT and a diagnosis of essential thrombocythemia. No other JAK2 mutations were found in this cohort. Besides MPD, other thrombophilia risk factors were identified in five patients. One patient had MPD as well as thrombophilia risk factor. In this group, 4 out of 7 of the patients with PVT carried the JAK2 V617F mutation with or without overt MPD. However, the investigation of other JAK2 mutations may not be necessary in patients with thrombosis at unusual sites.

  3. Theory-Based Evaluation Meets Ambiguity: The Role of Janus Variables

    Science.gov (United States)

    Dahler-Larsen, Peter

    2018-01-01

    As theory-based evaluation (TBE) engages in situations where multiple stakeholders help develop complex program theory about dynamic phenomena in politically contested settings, it becomes difficult to develop and use program theory without ambiguity. The purpose of this article is to explore ambiguity as a fruitful perspective that helps TBE face…

  4. JANUS: A Compilation System for Balancing Parallelism and Performance in OpenVX

    Science.gov (United States)

    Omidian, Hossein; Lemieux, Guy G. F.

    2018-04-01

    Embedded systems typically do not have enough on-chip memory for entire an image buffer. Programming systems like OpenCV operate on entire image frames at each step, making them use excessive memory bandwidth and power. In contrast, the paradigm used by OpenVX is much more efficient; it uses image tiling, and the compilation system is allowed to analyze and optimize the operation sequence, specified as a compute graph, before doing any pixel processing. In this work, we are building a compilation system for OpenVX that can analyze and optimize the compute graph to take advantage of parallel resources in many-core systems or FPGAs. Using a database of prewritten OpenVX kernels, it automatically adjusts the image tile size as well as using kernel duplication and coalescing to meet a defined area (resource) target, or to meet a specified throughput target. This allows a single compute graph to target implementations with a wide range of performance needs or capabilities, e.g. from handheld to datacenter, that use minimal resources and power to reach the performance target.

  5. The Janus Cosmological Model (JCM) : An answer to the missing cosmological antimatter

    Science.gov (United States)

    D'Agostini, Gilles; Petit, Jean-Pierre

    2017-01-01

    Cosmological antimatter absence remains unexplained. Twin universes 1967 Sakarov's model suggests an answer: excess of matter and anti-quarks production in our universe is balanced by equivalent excess of antimatter and quark in twin universe. JCM provides geometrical framework, with a single manifold , two metrics solutions of two coupled field equations, to describe two populations of particles, one with positive energy-mass and the other with negative energy-mass : the `twin matter'. In a quantum point of view, it's a copy of the standard matter but with negative mass and energy. The matter-antimatter duality holds in both sectors. The standard and twin matters do not interact except through the gravitational coupling expressed in field equations. The twin matter is unobservable from matter-made apparatus. Field equations shows that matter and twin matter repel each other. Twin matter surrounding galaxies explains their confinement (dark matter role) and, in the dust universe era, mainly drives the process of expansion of the positive sector, responsible of the observed acceleration (dark energy role).

  6. Putting impact into context: the Janus face of the public value of arts and humanities research

    NARCIS (Netherlands)

    Benneworth, Paul Stephen

    2014-01-01

    This article provides an overview to the Forum on the Public Value of Arts and Humanities Research which follows it. The author argues that the current gloom in the arts and humanities as a result of the increasing pressure for societal utility does not recognise the complete picture. A growing

  7. Ares, Janus, Globalization: A Primer For The Military Leader in NATO

    National Research Council Canada - National Science Library

    Clemons, Dean

    2002-01-01

    ...: international military and commercial investment; dual-use technologies; and export control. As a primer on these stakes for the rising military leader within the North Atlantic Treaty, the study elucidates the issue of cooperation vs...

  8. Insulin induces suppressor of cytokine signaling-3 tyrosine phosphorylation through janus-activated kinase

    NARCIS (Netherlands)

    Peraldi, P; Filloux, C; Emanuelli, B; Hilton, DJ; Van Obberghen, E

    2001-01-01

    Suppressor of cytokine signaling (SOCS) proteins were originally described as cytokine-induced molecules involved in negative feedback loops. We have shown that SOCS-3 is also a component of the insulin signaling network (1), Indeed, insulin leads to SOCS-3 expression in 3T3-L1 adipocytes. Once

  9. Controlled capillary assembly of magnetic Janus Particles at fluid-fluid interfaces

    NARCIS (Netherlands)

    Xie, Q.; Davies, G.B.; Harting, J.D.R.

    2016-01-01

    Capillary interactions can be used to direct assembly of particles adsorbed at fluid-fluid interfaces. Precisely controlling the magnitude and direction of capillary interactions to assemble particles into favoured structures for materials science purposes is desirable but challenging. In this

  10. The Janus Face of NKT Cell Function in Autoimmunity and Infectious Diseases

    Directory of Open Access Journals (Sweden)

    Alessandra Torina

    2018-02-01

    Full Text Available Natural killer T cells (NKT are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II, and NKT-like expressing different antigen receptors (TCR were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defense against infections but, on the other hand, their effector functions can be involved in the pathogenesis of several inflammatory disorders due to their exposure to different microbial or self-antigens, respectively. A deep understanding of the biology and functions of type I, II, and NKT-like cells as well as their interplay with cell types acting in innate (neuthrophils, innate lymphoid cells, machrophages, and dendritic cells and adaptive immunity (CD4+,CD8+, and double negative T cells should be important to design potential immunotherapies for infectious and autoimmune diseases.

  11. Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions

    Directory of Open Access Journals (Sweden)

    Elisa Wirthgen

    2018-01-01

    Full Text Available Tryptophan metabolites are known to participate in the regulation of many cells of the immune system and are involved in various immune-mediated diseases and disorders. Kynurenic acid (KYNA is a product of one branch of the kynurenine pathway of tryptophan metabolism. The influence of KYNA on important neurophysiological and neuropathological processes has been comprehensively documented. In recent years, the link of KYNA to the immune system, inflammation, and cancer has become more apparent. Given this connection, the anti-inflammatory and immunosuppressive functions of KYNA are of particular interest. These characteristics might allow KYNA to act as a “double-edged sword.” The metabolite contributes to both the resolution of inflammation and the establishment of an immunosuppressive environment, which, for instance, allows for tumor immune escape. Our review provides a comprehensive update of the significant biological functions of KYNA and focuses on its immunomodulatory properties by signaling via G-protein-coupled receptor 35 (GPR35- and aryl hydrocarbon receptor-mediated pathways. Furthermore, we discuss the role of KYNA–GPR35 interaction and microbiota associated KYNA metabolism for gut homeostasis.

  12. Stability of selected serum hormones and lipids after long-term storage in the Janus Serum Bank.

    Science.gov (United States)

    Gislefoss, Randi E; Grimsrud, Tom K; Mørkrid, Lars

    2015-04-01

    The potential value of a biobank depends on the quality of the samples, i.e. how well they reflect the biological or biochemical state of the donors at the time of sampling. Documentation of sample quality has become a particularly important issue for researchers and users of biobank studies. The aim of this study was to investigate the long-term stability of selected components: cholesterol, high density cholesterol (HDLC), low density cholesterol (LDLC), apolipoprotein A1 (apo-A1), apolipoprotein B (apo B), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH) and free thyroxin (FT4). Samples, stored at -25°C, from 520 men aged 40-49 years at blood sampling distributed in equally sized groups (n=130) according to length of storage, 0, 4, 17 and 29 years, respectively, were used in a cross sectional design. The freshly collected serum samples were used as a reference group to calculate storage related changes. The differences between fresh samples and samples stored for 29 years were substantial for apo-A1 (+12%), apo-B (+22.3%), HDLC (-69.2%), LDLC (+31.3%), and PRL (-33.5%), while total cholesterol, FSH, LH, TSH and FT4 did not show any significant difference. The study showed large differences in serum level of the selected components. The lipids and apolipoproteins were all changed except for total cholesterol. Most hormones investigated (FSH, LH, TSH and FT4) proved to be stable after 29 years of storage while PRL showed sign of degradation. The observed differences are probably due to long-term storage effects and/or external factors (i.e. diet and smoking). Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  13. The "Janus face" of the thrombin binding aptamer: Investigating the anticoagulant and antiproliferative properties through straightforward chemical modifications.

    Science.gov (United States)

    Esposito, Veronica; Russo, Annapina; Amato, Teresa; Vellecco, Valentina; Bucci, Mariarosaria; Mayol, Luciano; Russo, Giulia; Virgilio, Antonella; Galeone, Aldo

    2018-02-01

    The thrombin binding aptamer (TBA) is endowed with both anticoagulant and antiproliferative activities. Its chemico-physical and/or biological properties can be tuned by the site-specific replacement of selected residues. Four oligodeoxynucleotides (ODNs) based on the TBA sequence (5'-GGTTGGTGTGGTTGG-3') and containing 2'-deoxyuridine (U) or 5-bromo-2'-deoxyuridine (B) residues at positions 4 or 13 have been investigated by NMR and CD techniques. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay) have been tested and compared with two further ODNs containing 5-hydroxymethyl-2'-deoxyuridine (H) residues in the same positions, previously investigated. The CD and NMR data suggest that all the investigated ODNs are able to form G-quadruplexes strictly resembling that of TBA. The introduction of B residues in positions 4 or 13 increases the melting temperature of the modified aptamers by 7 °C. The replacement of thymidines with U in the same positions results in an enhanced anticoagulant activity compared to TBA, also at low ODN concentration. Although all ODNs show antiproliferative properties, only TBA derivatives containing H in the positions 4 and 13 lose the anticoagulant activity and remarkably preserve the antiproliferative one. All ODNs have shown antiproliferative activities against two cancer cell lines but only those with U and B are endowed with anticoagulant activities similar or improved compared to TBA. The appropriate site-specific replacement of the residues in the TT loops of TBA with commercially available thymine analogues is a useful strategy either to improve the anticoagulant activity or to preserve the antiproliferative properties by quenching the anticoagulant ones. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. [War and medicine in a culture of peace. 1. When the doors of the Janus temple open].

    Science.gov (United States)

    Piérard, G E

    2001-11-01

    More than 40 major wars took place during the past decade. The origins and the warlike means that were engaged were very different from those of older conflicts. Wars between nations are less numerous. They have been replaced by civilian wars that are more rooted on cultural and religious grounds than on economic interests alone. During this short period of time, warfare was responsible for about 2 millions of direct deaths and 20 millions displaced people and refugees. The injured and victims of starvation and epidemics were innumerable and awaited for civilian medical help.

  15. Implementation and Testing of the JANUS Standard with SSC Pacific’s Software-Defined Acoustic Modem

    Science.gov (United States)

    2017-12-01

    Communications Outpost (FDECO) Innovative Naval Prototype (INP) Program by the Advanced Photonic Technologies Branch (Code 55360), Space and Naval Warfare...Systems Center Pacific (SSC Pacific), San Diego, CA. Further support was provided by the 55340 Enterprise Communications and Networks Branch (Code 55340...names of names of manufacturers is not to be construed as official government endorsement or approval of commercial products or services referenced in

  16. Janus-Faced Myeloid-Derived Suppressor Cell Exosomes for the Good and the Bad in Cancer and Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Margot Zöller

    2018-02-01

    Full Text Available Myeloid-derived suppressor cells (MDSCs are a heterogeneous population of immature myeloid cells originally described to hamper immune responses in chronic infections. Meanwhile, they are known to be a major obstacle in cancer immunotherapy. On the other hand, MDSC can interfere with allogeneic transplant rejection and may dampen autoreactive T cell activity. Whether MDSC-Exosomes (Exo can cope with the dangerous and potentially therapeutic activities of MDSC is not yet fully explored. After introducing MDSC and Exo, it will be discussed, whether a blockade of MDSC-Exo could foster the efficacy of immunotherapy in cancer and mitigate tumor progression supporting activities of MDSC. It also will be outlined, whether application of native or tailored MDSC-Exo might prohibit autoimmune disease progression. These considerations are based on the steadily increasing knowledge on Exo composition, their capacity to distribute throughout the organism combined with selectivity of targeting, and the ease to tailor Exo and includes open questions that answers will facilitate optimizing protocols for a MDSC-Exo blockade in cancer as well as for strengthening their therapeutic efficacy in autoimmune disease.

  17. Archive of Historic Core Data from the Ocean Drilling Program (ODP) Legs 101-129 (Pre-JANUS)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Ocean Drilling Program (ODP) operated the drilling vessel JOIDES Resolution from 1984-2003 for over 100 cruises worldwide. The ODP was funded by the U.S....

  18. DFT study of structure, IR and Raman spectra of the fluorescent "Janus" dendron built from cyclotriphosphazene core

    Science.gov (United States)

    Furer, V. L.; Vandyukova, I. I.; Vandyukov, A. E.; Fuchs, S.; Majoral, J. P.; Caminade, A. M.; Kovalenko, V. I.

    2011-11-01

    The FTIR and FT-Raman spectra of the zero generation dendron, possessing five fluorescent dansyl terminal groups, cyclotriphosphazene core, and one carbamate function G0v were studied. The structural optimization and normal mode analysis were performed for G0v dendron on the basis of the density functional theory (DFT). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that dendron molecule G0v has a concave lens structure with slightly non-planar cyclotriphosphazene core. The experimental IR and Raman spectra of G0v dendron were interpreted by means of potential energy distributions. Relying on DFT calculations a complete vibrational assignment is proposed. The frequency of ν(N-H) band in the IR spectrum reveal the presence of H-bonds in the G0v dendron.

  19. Influence of Enzyme Quantity and Distribution on the Self-Propulsion of Non-Janus Urease-Powered Micromotors.

    Science.gov (United States)

    Patiño, Tania; Feiner-Gracia, Natalia; Arqué, Xavier; Miguel-López, Albert; Jannasch, Anita; Stumpp, Tom; Schäffer, Erik; Albertazzi, Lorenzo; Sánchez, Samuel

    2018-05-29

    The use of enzyme catalysis to power micro- and nanomachines offers unique features such as biocompatibility, versatility, and fuel bioavailability. Yet, the key parameters underlying the motion behavior of enzyme-powered motors are not completely understood. Here, we investigate the role of enzyme distribution and quantity on the generation of active motion. Two different micromotor architectures based on either polystyrene (PS) or polystyrene coated with a rough silicon dioxide shell (PS@SiO 2 ) were explored. A directional propulsion with higher speed was observed for PS@SiO 2 motors when compared to their PS counterparts. We made use of stochastically optical reconstruction microscopy (STORM) to precisely detect single urease molecules conjugated to the micromotors surface with a high spatial resolution. An asymmetric distribution of enzymes around the micromotor surface was observed for both PS and PS@SiO 2 architectures, indicating that the enzyme distribution was not the only parameter affecting the motion behavior. We quantified the number of enzymes present on the micromotor surface and observed a 10-fold increase in the number of urease molecules for PS@SiO 2 motors compared to PS-based micromotors. To further investigate the number of enzymes required to generate a self-propulsion, PS@SiO 2 particles were functionalized with varying amounts of urease molecules and the resulting speed and propulsive force were measured by optical tracking and optical tweezers, respectively. Surprisingly, both speed and force depended in a nonlinear fashion on the enzyme coverage. To break symmetry for active propulsion, we found that a certain threshold number of enzymes molecules per micromotor was necessary, indicating that activity may be due to a critical phenomenon. Taken together, these results provide new insights into the design features of micro/nanomotors to ensure an efficient development.

  20. Nanofluid of graphene-based amphiphilic Janus nanosheets for tertiary or enhanced oil recovery: High performance at low concentration.

    Science.gov (United States)

    Luo, Dan; Wang, Feng; Zhu, Jingyi; Cao, Feng; Liu, Yuan; Li, Xiaogang; Willson, Richard C; Yang, Zhaozhong; Chu, Ching-Wu; Ren, Zhifeng

    2016-07-12

    The current simple nanofluid flooding method for tertiary or enhanced oil recovery is inefficient, especially when used with low nanoparticle concentration. We have designed and produced a nanofluid of graphene-based amphiphilic nanosheets that is very effective at low concentration. Our nanosheets spontaneously approached the oil-water interface and reduced the interfacial tension in a saline environment (4 wt % NaCl and 1 wt % CaCl2), regardless of the solid surface wettability. A climbing film appeared and grew at moderate hydrodynamic condition to encapsulate the oil phase. With strong hydrodynamic power input, a solid-like interfacial film formed and was able to return to its original form even after being seriously disturbed. The film rapidly separated oil and water phases for slug-like oil displacement. The unique behavior of our nanosheet nanofluid tripled the best performance of conventional nanofluid flooding methods under similar conditions.

  1. In the eyes of Janus : The intellectual structure of HRM-performance debate and its future prospects

    NARCIS (Netherlands)

    Kaše, R.; Paauwe, J.; Batistič, S.

    2014-01-01

    Purpose The purpose of this paper is to offer a perspective on the future of the human resource management (HRM)-performance debate and its prospects for interaction with practice by evaluating the debate's intellectual structure. Design/methodology/approach With co-citation analysis the paper

  2. Improving the spectral analysis of Fluorescence Resonance Energy Transfer in live cells: application to interferon receptors and Janus kinases.

    Science.gov (United States)

    Krause, Christopher D; Digioia, Gina; Izotova, Lara S; Pestka, Sidney

    2013-10-01

    The observed Fluorescence Resonance Energy Transfer (FRET) between fluorescently labeled proteins varies in cells. To understand how this variation affects our interpretation of how proteins interact in cells, we developed a protocol that mathematically separates donor-independent and donor-dependent excitations of acceptor, determines the electromagnetic interaction of donors and acceptors, and quantifies the efficiency of the interaction of donors and acceptors. By analyzing large populations of cells, we found that misbalanced or insufficient expression of acceptor or donor as well as their inefficient or reversible interaction influenced FRET efficiency in vivo. Use of red-shifted donors and acceptors gave spectra with less endogenous fluorescence but produced lower FRET efficiency, possibly caused by reduced quenching of red-shifted fluorophores in cells. Additionally, cryptic interactions between jellyfish FPs artefactually increased the apparent FRET efficiency. Our protocol can distinguish specific and nonspecific protein interactions even within highly constrained environments as plasma membranes. Overall, accurate FRET estimations in cells or within complex environments can be obtained by a combination of proper data analysis, study of sufficient numbers of cells, and use of properly empirically developed fluorescent proteins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Microglial Janus kinase/signal transduction and activator of transcription 3 pathway activity directly impacts astrocyte and spinal neuron characteristics

    Czech Academy of Sciences Publication Activity Database

    Molet, J.; Mauborgne, A.; Diallo, Michael; Armand, V.; Geny, D.; Villanueva, L.; Boucher, Y.; Pohl, M.

    2016-01-01

    Roč. 136, č. 1 (2016), s. 133-147 ISSN 0022-3042 R&D Projects: GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : astrocytes * cell plasticity * JAK/STAT3 pathway * microglia conditioned media * spinal cord neurons Subject RIV: FH - Neurology Impact factor: 4.083, year: 2016

  4. Immunomodulatory effect of the topical ophthalmic Janus kinase inhibitor tofacitinib (CP-690,550) in patients with dry eye disease.

    Science.gov (United States)

    Huang, Jing-Feng; Yafawi, Rolla; Zhang, Min; McDowell, Michael; Rittenhouse, Kay D; Sace, Frederick; Liew, Shiao Hui Melissa; Cooper, Scott R; Pickering, Eve H

    2012-07-01

    To evaluate the immunomodulatory effect of topical ophthalmic tofacitinib (CP-690,550) after an 8-week treatment period in patients with dry eye disease (DED). Biomarker substudy of a phase 1/2 prospective, randomized, vehicle- and comparator-controlled clinical trial (NCT00784719). A total of 82 patients with moderate to severe DED enrolled. Patients received 1 of 5 doses of tofacitinib (0.0003%, 0.001%, 0.003%, or 0.005% twice daily [BID] or 0.005% once daily [QD]), active comparator (cyclosporine ophthalmic emulsion, 0.05% [Restasis, Allergan Inc., Irvine, CA]), or vehicle control BID for 8 weeks. Conjunctival impression cytology and tear fluid samples were collected at baseline and after an 8-week treatment period. Conjunctival cells were analyzed by flow cytometry for human leukocyte antigen DR-1 (HLA-DR). Tear fluids were analyzed by microsphere-based immunoassays for tear levels of cytokines and inflammation markers. Reduction in inflammation assessed by change from baseline in conjunctival cell surface level of HLA-DR and tear level of cytokines and inflammation markers. At week 8, a decrease in conjunctival cell surface expression of HLA-DR was observed in patients treated with tofacitinib 0.005% QD and 0.003% BID: 71% and 67% of baseline, respectively, compared with 133% of baseline in patients treated with vehicle (P=0.023 and P=0.006, compared with vehicle, respectively). Matrix metalloproteinase (MMP)-3 in tears was reduced from baseline at week 8 (40% of baseline, P=0.035) in the tofacitinib 0.005% QD group, whereas the vehicle group showed 77% of baseline (P>0.20). Interleukin (IL)-1β in tears was 36% of baseline (P=0.053) in the tofacitinib 0.005% QD group and 95% of baseline (P > 0.20) in the vehicle group. Several other cytokines and inflammation markers in tears, including MMP-9, IL-15, IL-17A, and IL-12p70, were markedly reduced in the tofacitinib 0.005% QD group but not the vehicle group. There was an association between the changes in HLA-DR and the tear inflammation markers (P<0.05): HLA-DR with IL-12p70 (r=0.49) and IL-1β (r=0.46), IL-12p70 with IL-1β (r=0.90), and IL-17A with MMP-9 (r=0.82). Topical ophthalmic tofacitinib may act as an immunomodulator in patients with DED. Treatment for 8 weeks showed a promising reduction of conjunctival cell surface HLA-DR expression and tear levels of proinflammatory cytokines and inflammation markers. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  5. Hidden Transcripts from “Below” in Rural Politics of the Philippines: Interpreting the Janus-facedness of Patron-Client Ties and Tulong (Help)

    OpenAIRE

    Soon Chuan Yean

    2012-01-01

    This paper argues that ordinary people often contest rather than submit to the powerful elites to gain material interests and political favoritism. Ordinary people are both shrewd and critical in making judgments and evaluations on politicians as well as the (unequal) relation of powers. Based on fieldwork interviews in the Philippines, this paper identifies the perception of (local) politics from ordinary people’s point of view in a seemingly mundane political environment. If the political e...

  6. Correlation Analysis Between Expression Levels of Hepatic Growth Hormone Receptor, Janus Kinase 2, Insulin-Like Growth Factor-I Genes and Dwarfism Phenotype in Bama Minipig.

    Science.gov (United States)

    Yang, Haowen; Jiang, Qinyang; Wu, Dan; Lan, Ganqiu; Fan, Jing; Guo, Yafen; Chen, Baojian; Yang, Xiurong; Jiang, Hesheng

    2015-02-01

    Animal growth and development are complex and sophisticated biological metabolic processes, in which genes plays an important role. In this paper, we employed real-time quantitative PCR (RT-qPCR) to analyze the expression levels of hepatic GHR, JAK2 and IGF-I genes in 1, 30, 180 day of Bama minipig and Landrace with attempt to verify the correlation between the expression of these growth-associated genes and the dwarfism phenotype of Bama minipig. The results showed that the expression levels of these 3 genes in Bama minipigs were down-regulated expressed from 1 day to 30 day, and which was up-regulated expressed in Landrace. The expression levels of the 3 genes on 1, 30, 180 day were prominently higher in Landrace than in Bama minipigs. The significant differences of the 3 genes expression levels on 1 day between this two breeds indicate that different expressions of these genes might occur before birth. It is speculated that the down-regulated expression of the 3 genes may have a close correlation with the dwarfism phenotype of Bama minipig. More investigations in depth of this study is under progress with the help of biochip nanotechnology.

  7. Na1.25Ni1.25Fe1.75(PO4)3 nanoparticles as a janus electrode material for Li-ion batteries

    Science.gov (United States)

    Karegeya, Claude; Mahmoud, Abdelfattah; Hatert, Frédéric; Vertruyen, Bénédicte; Cloots, Rudi; Lippens, Pierre-Emmanuel; Boschini, Frédéric

    2018-06-01

    A solvothermal method was used to prepare Na1.25Ni1.25Fe1.75(PO4)3 nanoparticles, a new promising electrode material for lithium-ion batteries. The composition and the crystal structure were determined by 57Fe Mössbauer spectroscopy and powder X-ray diffraction Rietveld refinements and confirmed by magnetic measurements. The structural formula □0.75Na1.25Ni1.25Fe1.75(PO4)3 was obtained showing a significant amount of Na vacancies, which enhances Li diffusion. Na1.25Ni1.25Fe1.75(PO4)3 was used as negative and positive electrode material and shows excellent electrochemical performances. As negative electrode in the voltage range 0.03-3.5 V vs. Li+/Li, the first discharge at current density of 40 mA g-1 delivers a specific capacity of 1186 mAh g-1, which is almost three times its theoretical capacity (428 mAh g-1). Then, reversible capacity of 550 mAh g-1 was obtained at 50 mA g-1 with high rate capability (150 mAh g-1 at 500 mA g-1) and capacity retention of 350 cycles. As positive electrode material, specific capacities of about 145 and 99 mAh g-1 were delivered at current densities of 5 and 50 mA g-1, respectively, in the voltage range of 1.5-4.5 V vs. Li+/Li. In addition, we show that the use of solvothermal synthesis contributes to the synthesis of small sized particles leading to good electrochemical performances.

  8. The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons

    Directory of Open Access Journals (Sweden)

    Cezary Watala

    2013-11-01

    Full Text Available Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diabetes-associated sequelae, numerous diabetic complications are still commonly encountered in diabetic patients. Therefore, there is a strong need for safe and effective antihyperglycaemic agents that provide an alternative or compounding option for the treatment of diabetes. In recent years, amino-terminated poly(amidoamine (PAMAM dendrimers (G2, G3 and G4 have attracted attention due to their protective value as anti-glycation and anti-carbonylation agents that can be used to limit the nonenzymatic modifications of biomacromolecules. The focus of this review is to present a detailed survey of our own data, as well as of the available literature regarding the toxicity, pharmacological properties and overall usefulness of PAMAM dendrimers. This presentation pays particular and primary attention to their therapeutic use in poorly controlled diabetes and its complications, but also in other conditions, such as Alzheimer’s disease, in which such nonenzymatic modifications may underlie the pathophysiological mechanisms. The impact of dendrimer administration on the overall survival of diabetic animals and on glycosylation, glycoxidation, the brain-blood barrier and cellular bioenergetics are demonstrated. Finally, we critically discuss the potential advantages and disadvantages accompanying the use of PAMAM dendrimers in the treatment of metabolic impairments that occur under conditions of chronic hyperglycaemia.

  9. Nitrogen-Doped Nanoporous Carbon Membranes with Co/CoP Janus-Type Nanocrystals as Hydrogen Evolution Electrode in Both Acidic and Alkaline Environments

    KAUST Repository

    Wang, Hong; Min, Shixiong; Wang, Qiang; Li, Debao; Casillas, Gilberto; Ma, Chun; Li, Yangyang; Liu, Zhixiong; Li, Lain-Jong; Yuan, Jiayin; Antonietti, Markus; Wu, Tao

    2017-01-01

    reaction (HER). Benefited from multiple structural merits, such as a high degree of graphitization, three-dimensionally interconnected micro/meso/macropores, uniform nitrogen doping, well-dispersed Co/CoP nanocrystals, as well as the confinement effect

  10. Prediagnostic serum calcium and albumin and ovarian cancer: A nested case-control study in the Norwegian Janus Serum Bank Cohort.

    Science.gov (United States)

    Schwartz, Gary G; Tretli, Steinar; Vos, Linda; Robsahm, Trude E

    2017-08-01

    Women with higher serum calcium may be more likely to be diagnosed and die of ovarian cancer. We evaluated that finding in a large, prospective cohort. We conducted a nested case-control study using a population-based biobank from Norway. We compared 202 ovarian cancer cases and 202 controls, matched for age, date at blood draw, and county of residence, with respect to serum calcium and albumin, adjusted for anthropometric variables. We evaluated risks using the entire follow-up period as well as 2-15 years and 16-25 years ("early" and "late", respectively). For the entire follow-up, risk was significantly increased in the highest tertile of albumin and for high albumin and calcium jointly. Risks for ovarian cancer differed markedly by follow-up time. In early follow-up, women in the highest tertile of serum calcium had a 2.5-fold increased risk, adjusted for height and body mass index (OR=2.47, 95% C.I. 1.12-5.45) with a significant dose-response (p=0.024). Risk was not elevated in late follow-up (OR=0.62, 95% C.I. 0.27-1.36). Similarly, in early follow-up, women in the highest tertile of serum albumin had an increased risk (OR=2.55, 95% C.I.1.22-5.49) with a significant dose-response (p=0.009). Conversely, risk was not increased in late follow-up (OR=1.36, 95% C.I. 0.65-2.83). These data confirm a prospective association between higher serum calcium and ovarian cancer. An association in early, but not late, follow-up suggests that the higher calcium reflects the presence of existing cancer. A positive association with serum albumin is novel and should be interpreted cautiously. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  11. Calreticulin mutation analysis in non-mutated Janus kinase 2 essential thrombocythemia patients in Chiang Mai University: analysis of three methods and clinical correlations.

    Science.gov (United States)

    Rattarittamrong, Ekarat; Tantiworawit, Adisak; Kumpunya, Noppamas; Wongtagan, Ornkamon; Tongphung, Ratchanoo; Phusua, Arunee; Chai-Adisaksopha, Chatree; Hantrakool, Sasinee; Rattanathammethee, Thanawat; Norasetthada, Lalita; Charoenkwan, Pimlak; Lekawanvijit, Suree

    2018-03-09

    The primary objective was to determine the prevalence of calreticulin (CALR) mutation in patients with non-JAK2V617F mutated essential thrombocythemia (ET). The secondary objectives were to evaluate the accuracy of CALR mutation analysis by high-resolution melting (HRM) analysis and real-time polymerase chain reaction (PCR) compared with DNA sequencing and to compare clinical characteristics of CALR mutated and JAK2V617F mutated ET. This was a prospective cohort study involving ET patients registered at Chiang Mai University in the period September 2015-September 2017 who were aged more than 2 years, and did not harbor JAK2V617F mutation. The presence of CALR mutation was established by DNA sequencing, HRM, and real-time PCR for type 1 and type 2 mutation. Clinical data were compared with that from ET patients with mutated JAK2V617F. Twenty-eight patients were enrolled onto the study. CALR mutations were found in 10 patients (35.7%). Three patients had type 1 mutation, 5 patients had type 2 mutation, 1 patient had type 18 mutation, and 1 patients had novel mutations (c.1093 C-G, c.1098_1131 del, c.1135 G-A). HRM could differentiate between the types of mutation in complete agreement with DNA sequencing. Patients with a CALR mutation showed a significantly greater male predominance and had a higher platelet count when compared with 42 JAK2V617F patients. The prevalence of CALR mutation in JAK2V617F-negative ET in this study is 35.7%. HRM is an effective method of detecting CALR mutation and is a more advantageous method of screening for CALR mutation.

  12. Reversibility of peripheral blood leukocyte phenotypic and functional changes after exposure to and withdrawal from tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

    Science.gov (United States)

    Weinhold, Kent J; Bukowski, Jack F; Brennan, Todd V; Noveck, Robert J; Staats, Janet S; Lin, Liwen; Stempora, Linda; Hammond, Constance; Wouters, Ann; Mojcik, Christopher F; Cheng, John; Collinge, Mark; Jesson, Michael I; Hazra, Anasuya; Biswas, Pinaki; Lan, Shuping; Clark, James D; Hodge, Jennifer A

    2018-06-01

    This study evaluated the short-term effects of tofacitinib treatment on peripheral blood leukocyte phenotype and function, and the reversibility of any such effects following treatment withdrawal in healthy volunteers. Cytomegalovirus (CMV)-seropositive subjects received oral tofacitinib 10 mg twice daily for 4 weeks and were followed for 4 weeks after drug withdrawal. There were slight increases in total lymphocyte and total T-cell counts during tofacitinib treatment, and B-cell counts increased by up to 26%. There were no significant changes in granulocyte or monocyte counts, or granulocyte function. Naïve and central memory T-cell counts increased during treatment, while all subsets of activated T cells were decreased by up to 69%. T-cell subsets other than effector memory cluster of differentiation (CD)4+, activated naïve CD4+ and effector CD8+ T-cell counts and B-cell counts, normalized 4 weeks after withdrawal. Following ex vivo activation, measures of CMV-specific T-cell responses, and antigen non-specific T-cell-mediated cytotoxicity and interferon (IFN)-γ production, decreased slightly. These T-cell functional changes were most pronounced at Day 15, partially normalized while still on tofacitinib and returned to baseline after drug withdrawal. Total natural killer (NK)-cell counts decreased by 33%, returning towards baseline after drug withdrawal. NK-cell function decreased during tofacitinib treatment, but without a consistent time course across measured parameters. However, markers of NK-cell-mediated cytotoxicity, antibody-dependent cellular cytotoxicity and IFN-γ production were decreased up to 42% 1 month after drug withdrawal. CMV DNA was not detectable in whole blood, and there were no cases of herpes zoster reactivation. No new safety concerns arose. In conclusion, the effect of short-term tofacitinib treatment on leukocyte composition and function in healthy CMV+ volunteers is modest and largely reversible 4 weeks after withdrawal. Copyright © 2018 Pfizer Inc. Published by Elsevier Inc. All rights reserved.

  13. The Janus face of iron on anoxic worlds: iron oxides are both protective and destructive to life on the early Earth and present-day Mars.

    Science.gov (United States)

    Wadsworth, Jennifer; Cockell, Charles S

    2017-05-01

    The surface of the early Earth was probably subjected to a higher flux of ultraviolet (UV) radiation than today. UV radiation is known to severely damage DNA and other key molecules of life. Using a liquid culture and a rock analogue system, we investigated the interplay of protective and deleterious effects of iron oxides under UV radiation on the viability of the model organism, Bacillus subtilis. In the presence of hydrogen peroxide, there exists a fine balance between iron oxide's protective effects against this radiation and its deleterious effects caused by Photo-Fenton reactions. The maximum damage was caused by a concentration of hematite of ∼1 mg/mL. Concentrations above this confer increasing protection by physical blockage of the UV radiation, concentrations below this cause less effective UV radiation blockage, but also a correspondingly less effective Photo-Fenton reaction, providing an overall advantage. These results show that on anoxic worlds, surface habitability under a high UV flux leaves life precariously poised between the beneficial and deleterious effects of iron oxides. These results have relevance to the Archean Earth, but also the habitability of the Martian surface, where high levels of UV radiation in combination with iron oxides and hydrogen peroxide can be found. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. How to use ibrutinib

    Directory of Open Access Journals (Sweden)

    Е. А. Nikitin

    2017-01-01

    Full Text Available The emergence of new targeted drugs, affecting B-cell receptor signaling pathway opens a new page in the treatment of chronic lymphocytic leukemia (CLL. It is not simply expanding choice, it will likely to change total strategy of CLL management. Clinical trials have shown improvement of overall survival in CLL patients in both first line and relapsed disease settings. Targeted drugs lack typical complications of chemotherapy, such as myelosupression. However, they have their specific side effects that require particular attention to avoid unjustified dose reduction and treatment cessation. The present review focuses on practical use of ibrutinib, the first inhibitor of Bruton’s tyrosinkinase.

  15. Machine Translation

    Indian Academy of Sciences (India)

    Research Mt System Example: The 'Janus' Translating Phone Project. The Janus ... based on laptops, and simultaneous translation of two speakers in a dialogue. For more ..... The current focus in MT research is on using machine learning.

  16. Object-Oriented Modular Architecture for Ground Combat Simulation

    National Research Council Canada - National Science Library

    Luqi; Berzins, V; Shing, M; Saluto, M; Williams, J

    2000-01-01

    .... It describes the effective use of computer-aided prototyping techniques for re-engineering the legacy software to develop an object-oriented modular architecture for the Janus combat simulation system. Janus...

  17. Supplementary methods in breast cancer screening: ultrasonography and magnetic resonance tomography of the breast; Mammasonographie und Magnetresonanz-Mammographie als ergaenzende Methoden im Mammographiescreening

    Energy Technology Data Exchange (ETDEWEB)

    Delorme, S. [Deutsches Krebsforschungszentrum Heidelberg (Germany). Abt. fuer Onkologische Diagnostik und Therapie

    2001-04-01

    Ultrasonography and magnetic resonance (MR) tomography are helpful tools to evaluate unclear lesions found at screening mammography. Ultrasound is particularly useful to prove the presence of a cyst or to further examine unclear, asymmetrical densities. With MR mammography, carcinomas can be found even when X-ray mammography or ultrasonography are limited due to diffuse, benign, proliferative changes. Ultrasound guidance has greatly facilitated core needle biopsy for suspicious lesions. Additionally, approved devices for MR-guided biopsy are commercially available. As a primary screening tool, ultrasound or MR mammography may be used only in women who are positive for BRCA-1 or BRCA-2 mutations or who are otherwise at high risk for breast cancer. (orig.) [German] Sonographie und Magnetresonanz-Mammographie koennen zur Abklaerung unklarer Befunde eingesetzt werden, die im Rahmen des Mammographiescreenings auffallen. Die Mammosonographie eignet sich besonders zum Nachweis von Zysten und zur Abklaerung unklarer Dichte-Asymmetrien. Mit der Magnetresonanz-Mammographie koennen Karzinome auch dann nachgewiesen werden, wenn die Untersuchungsbedingungen fuer die Roentgenmammographie oder die Sonographie aufgrund einer Mastopathie unguenstig sind. Bei der differenzialdiagnostischen Abklaerung von Herdbefunden hat die Moeglichkeit der sonographischen Fuehrung einer Stanz- oder Vakuumbiopsie das Verfahren wesentlich vereinfacht. Fuer die MR-gesteuerte Biopsie sind inzwischen zugelassene Fuehrungshilfen kommerziell erhaeltlich. Als primaere Screeningmethode kommen sowohl die Sonographie als auch die Magnetresonanz-Mammographie nur fuer wenige Frauen in Frage, in der Regel bei nachgewiesenen BRCA-1- oder BRCA-2-Mutationen oder bei sonstiger Brustkrebsdisposition. (orig.)

  18. Sesquiterpene dimmer (DSF-27) inhibits the release of neuroinflammatory mediators from microglia by targeting spleen tyrosine kinase (Syk) and Janus kinase 2 (Jak2): Two major non-receptor tyrosine signaling proteins involved in inflammatory events

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Ke-Wu [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China); Wang, Shu [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China); Department of Medicinal Chemistry and Pharmaceutical Analysis, Logistics College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Dong, Xin; Jiang, Yong; Jin, Hong-Wei [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China); Tu, Peng-Fei, E-mail: pengfeitu@vip.163.com [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China)

    2014-03-15

    Non-receptor protein tyrosine kinases (NRPTKs)-dependent inflammatory signal transduction cascades play key roles in immunoregulation. However, drug intervention through NRPTKs-involved immunoregulation mechanism in microglia (the major immune cells of the central nervous system) has not been widely investigated. A main aim of the present study is to elucidate the contribution of two major NRPTKs (Syk and Jak2) in neuroinflammation suppression by a bioactive sesquiterpene dimmer (DSF-27). We found that LPS-stimulated BV-2 cells activated Syk and further initiated Akt/NF-κB inflammatory pathway. This Syk-dependent Akt/NF-κB inflammatory pathway can be effectively ameliorated by DSF-27. Moreover, Jak2 was activated by LPS, which was followed by transcriptional factor Stat3 activation. The Jak2/Stat3 signal was suppressed by DSF-27 through inhibition of Jak2 and Stat3 phosphorylation, promotion of Jak/Stat3 inhibitory factors PIAS3 expression, and down-regulation of ERK and p38 MAPK phosphorylation. Furthermore, DSF-27 protected cortical and mesencephalic dopaminergic neurons against neuroinflammatory injury. Taken together, our findings indicate NRPTK signaling pathways including Syk/NF-κB and Jak2/Stat3 cascades are potential anti-neuroinflammatory targets in microglia, and may also set the basis for the use of sesquiterpene dimmer as a therapeutic approach for neuroinflammation via interruption of these pathways. - Highlights: • Sesquiterpene dimmer DSF-27 inhibits inflammatory mediators' production in microglia. • Syk-dependent Akt/NF-κB pathway is important for DSF-27's anti-inflammation activity. • Jak2/Stat3 pathway is important for DSF-27's anti-inflammation activity. • Jak2/Stat3 signaling pathway is partly regulated by ERK and p38 MAPKs and PIAS3. • DSF-27 protects neurons against microglia-mediated neuroinflammatory injury.

  19. 78 FR 62716 - Pacific Life Insurance Company, et al; Notice of Application

    Science.gov (United States)

    2013-10-22

    ... objective of the Replaced Portfolio is to maximize total return consistent with its Investment Adviser's... Replaced Portfolio; (2) the historical performance of the Replacement Portfolio is generally better than..., approving the substitution of Service Shares of the Janus Aspen Balanced Portfolio, a series of Janus Aspen...

  20. Elements of a Reversible Object-Oriented Language

    DEFF Research Database (Denmark)

    Schultz, Ulrik Pagh; Axelsen, Holger Bock

    2016-01-01

    This paper presents initial ideas for the design and implementation of a reversible object-oriented language based on extending Janus with object-oriented concepts such as classes that encapsulate behavior and state, inheritance, virtual dispatching, as well as constructors. We show that virtual...... dispatching is a reversible decision mechanism easily translatable to a standard reversible programming model such as Janus, and we argue that reversible management of state can be accomplished using reversible constructors. The language is implemented in terms of translation to standard Janus programs....

  1. Skype has changed the telecommunications market / Lauri Levo

    Index Scriptorium Estoniae

    Levo, Lauri

    2005-01-01

    Eestlaste kaasabil loodud programmist Skype, millega saab Interneti vahendusel teha tasuta telefonikõnesid üle maailma. Meelis Kuusbergi kommentaar. Lisad: Ajalugu; Niklas Zennström; Janus Friis. Vt. samas intervjuud Sten Tamkiviga

  2. Journal of Chemical Sciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    The antibacterial and antifungal activities of the prepared compounds were also evaluated against the Klubsellia pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillius subtilis and Aspergillius janus and Pencillium glabrum strains, respectively. The formation and antimicrobial ...

  3. Can research be visual?

    DEFF Research Database (Denmark)

    Martiny, Kristian Moltke

    2014-01-01

    Short film interviews with for instance researchers Birger Lindberg Møller and Andreas Roepstorff and film directors Phie Ambo, Janus Metz and Joshua Oppenheimer, about the collaboration between documentary and research: http://vimeo.com/99909839...

  4. Ocean Drilling Program: Web Site Access Statistics

    Science.gov (United States)

    web site ODP/TAMU Science Operator Home Ocean Drilling Program Web Site Access Statistics* Overview See statistics for JOIDES members. See statistics for Janus database. 1997 October November December

  5. Integrated Criteria Document Chromium

    NARCIS (Netherlands)

    Slooff W; Cleven RFMJ; Janus JA; van der Poel P; van Beelen P; Boumans LJM; Canton JH; Eerens HC; Krajnc EI; de Leeuw FAAM; Matthijsen AJCM; van de Meent D; van der Meulen A; Mohn GR; Wijland GC; de Bruijn PJ; van Keulen A; Verburgh JJ; van der Woerd KF

    1990-01-01

    Betreft de engelse versie van rapport 758701001
    Bij dit rapport behoort een appendix onder hetzelfde nummer getiteld: "Integrated Criteria Document Chromium: Effects" Auteurs: Janus JA; Krajnc EI
    (appendix: see 710401002A)

  6. Journal of Chemical Sciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    The antibacterial and antifungal activities of the synthesized compounds were also evaluated against the Klubsellia pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillius subtilis and Aspergillius janus, Aspergillus niger and Pencillium glabrum, respectively. The antimicrobial behaviour ...

  7. Muusikaäri otsib uusi müügiideid / Kuldar Kullasepp

    Index Scriptorium Estoniae

    Kullasepp, Kuldar, 1980-

    2009-01-01

    IT- valdkonna muusiakäri uutest võimalustest. USA firmast Rdio, Niklas Zennströmi ja Janus Friisi pakutavast tensuest, millega pakutakse muusikat nii arvuti kui ka mobiiltelefoniaskutajatele pakkuda. Digitaalsetest plaadipoodidest Eestis

  8. Ajalooõpiku autor kirjutas võistluse parima romaani / Rein Veidemann

    Index Scriptorium Estoniae

    Veidemann, Rein, 1946-

    2009-01-01

    Romaanivõistluse võitjaks kuulutati romaan "Liblikad janus", autoriks ajalooharidusega Milvi Martina Piir, kelle sulest on varem ilmunud 5. klassi ajalooõpik "Inimesed ajas" ja luulekogu "Kõrkjavaas"

  9. Metals on graphene and carbon nanotube surfaces: From mobile atoms to atomtronics to bulk metals to clusters and catalysts

    KAUST Repository

    Sarkar, Santanu C.; Moser, Matthew L.; Tian, Xiaojuan; Zhang, Xixiang; Al-Hadeethi, Yas Fadel; Haddon, Robert C.

    2014-01-01

    , and the next generation energy devices. We touch on chemical vapor deposition (CVD) graphene grown on metals, the reactivity of its surface, and its use as a template for asymmetric graphene functionalization chemistry (ultrathin Janus discs). We highlight some

  10. Det danske landskab. De danske malere på J.C. Dahls tid

    DEFF Research Database (Denmark)

    Monrad, Kasper

    Om værker af Jens Juel, C.W. Eckersberg, J.C. Dahl, Thomas Fearnley, Christen Købke, Johan Thomas Lundbye, Peter Christian Skovgaard, Dankvart Dreyer, Vilhelm Kyhn, Janus la Cour......Om værker af Jens Juel, C.W. Eckersberg, J.C. Dahl, Thomas Fearnley, Christen Købke, Johan Thomas Lundbye, Peter Christian Skovgaard, Dankvart Dreyer, Vilhelm Kyhn, Janus la Cour...

  11. Molecular mechanisms of thyroid tumorigenesis; Molekulare Mechanismen der Schilddruesentumorgenese

    Energy Technology Data Exchange (ETDEWEB)

    Krause, K.; Fuehrer, D. [Universitaetsklinikum Leipzig (Germany). Abt. fuer Endokrinolgoie, Diabetologie und Nephrologie

    2008-09-15

    Thyroid nodules are the most frequent endocrine disorder and occur in approximately 30% of the German population. Thyroid nodular disease constitutes a very heterogeneous entity. A striking diversity of possible functional and morphological features of a thyroid tumour derived from the same thyroid ancestor cell, is a hallmark of thyroid tumorigenesis and is due to specific genetic alterations. Defects in known candidate genes can be found in up to 70% of differentiated thyroid carcinomas and determine the respective cancer phenotype. Papillary thyroid cancers (PTC) harbour BRAF (or much less frequently RAS) mutations in sporadically occurring tumours, while radiation-induced PTC display chromosomal rearrangements such as RET, TRK, APR9 / BRAF. These genetic events results in constitutive MAPKinase activation. Follicular thyroid cancers (FTC) harbour RAS mutations or PAX8/ PPAR{gamma} rearrangements, both of which, however have also been identified in follicular adenoma. In addition, recent studies show, that activation of PI3K/AKT signalling occurs with high frequency in follicular thyroid tumours. Undifferentiated (anaplastic) thyroid cancers (ATC) display genetic features of FTC or PTC, in addition to aberant activation of multiple tyrosinkinase pathways (overexpression or mutations in PI3K and MAPK pathways). This underscores the concept of a sequential evolution of ATC from differentiated thyroid cancer, a process widely conceived to be triggered by p53 inactivation. In contrast, the molecular pathogenesis of benign thyroid tumours, in particular cold thyroid nodules is less known, except for toxic thyroid nodules, which arise from constitutive activation of cAMP signalling, predominantly through TSHR mutations. (orig.)

  12. Molecular mechanisms of thyroid tumorigenesis

    International Nuclear Information System (INIS)

    Krause, K.; Fuehrer, D.

    2008-01-01

    Thyroid nodules are the most frequent endocrine disorder and occur in approximately 30% of the German population. Thyroid nodular disease constitutes a very heterogeneous entity. A striking diversity of possible functional and morphological features of a thyroid tumour derived from the same thyroid ancestor cell, is a hallmark of thyroid tumorigenesis and is due to specific genetic alterations. Defects in known candidate genes can be found in up to 70% of differentiated thyroid carcinomas and determine the respective cancer phenotype. Papillary thyroid cancers (PTC) harbour BRAF (or much less frequently RAS) mutations in sporadically occurring tumours, while radiation-induced PTC display chromosomal rearrangements such as RET, TRK, APR9 / BRAF. These genetic events results in constitutive MAPKinase activation. Follicular thyroid cancers (FTC) harbour RAS mutations or PAX8/ PPARγ rearrangements, both of which, however have also been identified in follicular adenoma. In addition, recent studies show, that activation of PI3K/AKT signalling occurs with high frequency in follicular thyroid tumours. Undifferentiated (anaplastic) thyroid cancers (ATC) display genetic features of FTC or PTC, in addition to aberant activation of multiple tyrosinkinase pathways (overexpression or mutations in PI3K and MAPK pathways). This underscores the concept of a sequential evolution of ATC from differentiated thyroid cancer, a process widely conceived to be triggered by p53 inactivation. In contrast, the molecular pathogenesis of benign thyroid tumours, in particular cold thyroid nodules is less known, except for toxic thyroid nodules, which arise from constitutive activation of cAMP signalling, predominantly through TSHR mutations. (orig.)

  13. Green Synthesis of Ag-Cu Nanoalloys Using Opuntia ficus- indica

    Science.gov (United States)

    Rocha-Rocha, O.; Cortez-Valadez, M.; Hernández-Martínez, A. R.; Gámez-Corrales, R.; Alvarez, Ramón A. B.; Britto-Hurtado, R.; Delgado-Beleño, Y.; Martinez-Nuñez, C. E.; Pérez-Rodríguez, A.; Arizpe-Chávez, H.; Flores-Acosta, M.

    2017-02-01

    Bimetallic Ag/Cu nanoparticles have been obtained by green synthesis using Opuntia ficus- indica plant extract. Two synthesis methods were applied to obtain nanoparticles with core-shell and Janus morphologies by reversing the order of precursors. Transmission electronic microscopy revealed size of 10 nm and 20 nm for the core-shell and Janus nanoparticles, respectively. Other small particles with size of up to 2 nm were also observed. Absorption bands attributed to surface plasmon resonance were detected at 440 nm and 500 nm for the core-shell and Janus nanoparticles, respectively. Density functional theory predicted a breathing mode type (BMT) located at low wavenumber due to small, low-energy clusters of (AgCu) n with n = 2 to 9, showing a certain correlation with the experimental one (at 220 cm-1). The dependence of the BMT on the number of atoms constituting the cluster is also studied.

  14. Gene expression profiling with principal component analysis depicts the biological continuum from essential thrombocythemia over polycythemia vera to myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Thomassen, Mads; Riley, Caroline H

    2012-01-01

    The recent discovery of the Janus activating kinase 2 V617F mutation in most patients with polycythemia vera (PV) and half of those with essential thrombocythemia (ET) and primary myelofibrosis (PMF) has favored the hypothesis of a biological continuum from ET over PV to PMF. We performed gene...... with biological relevant overlaps between the different entities. Moreover, the analysis separates Janus activating kinase 2-negative ET patients from Janus activating kinase 2-positive ET patients. Functional annotation analysis demonstrates that clusters of gene ontology terms related to inflammation, immune...... system, apoptosis, RNA metabolism, and secretory system were the most significantly deregulated terms in the three different disease groups. Our results yield further support for the hypothesis of a biological continuum originating from ET over PV to PMF. Functional analysis suggests an important...

  15. Redistribution of charged aluminum nanoparticles on oil droplets in water in response to applied electrical field

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mengqi; Li, Dongqing, E-mail: dongqing@mme.uwaterloo.ca [University of Waterloo, Department of Mechanical and Mechatronics Engineering (Canada)

    2016-05-15

    Janus droplets with two opposite faces of different physical or chemical properties have great potentials in many fields. This paper reports a new method for making Janus droplets by covering one side of the droplet with charged nanoparticles in an externally applied DC electric field. In this paper, aluminum oxide nanoparticles on micro-sized and macro-sized oil droplets were studied. In order to control the surface area covered by the nanoparticles on the oil droplets, the effects of the concentration of nanoparticle suspension, the droplet size as well as the strength of electric field on the final accumulation area of the nanoparticles are studied.Graphical abstract.

  16. Photopolymerization of complex emulsions with irregular shapes fabricated by multiplex coaxial flow focusing

    Science.gov (United States)

    Wu, Qiang; Yang, Chaoyu; Yang, Jianxin; Huang, Fangsheng; Liu, Guangli; Zhu, Zhiqiang; Si, Ting; Xu, Ronald X.

    2018-02-01

    We fabricate complex emulsions with irregular shapes in the microscale by a simple but effective multiplex coaxial flow focusing process. A multiphase cone-jet structure is steadily formed, and the compound liquid jet eventually breaks up into Janus microdroplets due to the perturbations propagating along the jet interfaces. The microdroplet shapes can be exclusively controlled by interfacial tensions of adjacent phases. Crescent-moon-shaped microparticles and microcapsules with designated structural characteristics are further produced under ultraviolet light of photopolymerization after removing one hemisphere of the Janus microdroplets. These complex emulsions have potential applications in bioscience, food, functional materials, and controlled drug delivery.

  17. Design of super-efficient mixer based on induced charge electroosmotic

    Directory of Open Access Journals (Sweden)

    Zhang Kai

    2012-01-01

    Full Text Available The super-efficient sample mixing induced by the induced-charge electrokinetic flow around conducting/Janus cylinder was numerically studied in a confined |U-shaped microchannel with suddenly applied DC weak electric filed. It’s found that there are four large circulations around the conducting cylinder and two smaller circulations around the Janus cylinder. The results show that samples can still be well mixed with high flux due to the induced electroosmosis. It is demonstrated that the local flow circulations provide effective means to enhance the flow mixing between different solutions. The dependence of the degree of mixing enhancement on the electric field is also predicted.

  18. Novel targeted therapies for inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Vermeire, Severine; Nielsen, Ole Haagen

    2017-01-01

    emerging novel and easily administered therapeutics that may be viable candidates for the management of IBD, such as antibodies against interleukin 6 (IL-6) and IL-12/23, small molecules including Janus kinase inhibitors, antisense oligonucleotide against SMAD7 mRNA, and inhibitors of leukocyte trafficking...

  19. The role of signal transducer and activator of transcription 5 in the inhibitory effects of GH on adipocyte differentiation

    DEFF Research Database (Denmark)

    Richter, H E; Albrektsen, T; Billestrup, Nils

    2003-01-01

    GH inhibits primary rat preadipocyte differentiation and expression of late genes required for terminal differentiation. Here we show that GH-mediated inhibition of fatty acid-binding protein aP2 gene expression correlates with the activation of the Janus kinase-2/signal transducer and activator ...

  20. Regulation of pancreatic beta-cell mass and proliferation by SOCS-3

    DEFF Research Database (Denmark)

    Lindberg, K; Rønn, S G; Tornehave, D

    2005-01-01

    Growth hormone and prolactin are important growth factors for pancreatic beta-cells. The effects exerted by these hormones on proliferation and on insulin synthesis and secretion in beta-cells are largely mediated through the Janus kinase (JAK)/signal transducer and activator of transcription (ST...

  1. Welcome to the home page of the Decontamination and Decommissioning Program at Argonne National Laboratory

    International Nuclear Information System (INIS)

    1996-01-01

    This report presents the details of the Argonne National Laboratory Home Page. Topics discussed include decontamination and decommissioning of the following: hot cells; remedial action; Experimental Boiling Water Reactor; glove boxes; the Chicago Pile No. 5 Research Reactor Facility; the Janus Reactor; Building 310 Retention Tanks; Zero Power Reactors 6 and 9; Argonne Thermal Source Reactor; cyclotron facility; and Juggernaut reactor

  2. Multidetector CT findings of bowel Transection in blunt abdominal trauma

    International Nuclear Information System (INIS)

    Cho, Hyun Suk; Woo, Ji Young; Hong, Hye Suk; Park, Mee Hyun; Yang, Ik; Lee, Yul; Jung, Ah Young; Hwang, Ji Young; Ha, Hong Il

    2013-01-01

    Though a number of CT findings of bowel and mesenteric injuries in blunt abdominal trauma are described in literature, no studies on the specific CT signs of a transected bowel have been published. In the present study we describe the incidence and new CT signs of bowel transection in blunt abdominal trauma. We investigated the incidence of bowel transection in 513 patients admitted for blunt abdominal trauma who underwent multidetector CT (MDCT). The MDCT findings of 8 patients with a surgically proven complete bowel transection were assessed retrospectively. We report novel CT signs that are unique for transection, such as complete cutoff sign (transection of bowel loop), Janus sign (abnormal dual bowel wall enhancement, both increased and decreased), and fecal spillage. The incidence of bowel transection in blunt abdominal trauma was 1.56%. In eight cases of bowel transection, percentage of CT signs unique for bowel transection were as follows: complete cutoff in 8 (100%), Janus sign in 6 (100%, excluding duodenal injury), and fecal spillage in 2 (25%). The combination of complete cutoff and Janus sign were highly specific findings in patients with bowel transection. Complete cut off and Janus sign are the unique CT findings to help detect bowel transection in blunt abdominal trauma and recognition of these findings enables an accurate and prompt diagnosis for emergency laparotomy leading to reduced mortality and morbidity.

  3. Leptin receptor 170 kDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance

    DEFF Research Database (Denmark)

    Fuentes, T; Ara, I; Guadalupe-Grau, A

    2010-01-01

    To examine whether obesity-associated leptin resistance could be due to down-regulation of leptin receptors (OB-Rs) and/or up-regulation of suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle, which blunt janus kinase 2-dependent leptin...

  4. Impedance-match experiments using high intensity lasers

    International Nuclear Information System (INIS)

    Holmes, N.C.; Trainor, R.J.; Anderson, R.A.; Veeser, L.R.; Reeves, G.A.

    1981-01-01

    The results of a series of impedance-match experiments using copper-aluminum targets irradiated using the Janus Laser Facility are discussed. The results are compared to extrapolations of data obtained at lower pressures using impact techniques. The sources of errors are described and evaluated. The potential of lasers for high accuracy equation of state investigations are discussed

  5. A Conformal, Fully-Conservative Approach for Predicting Blast Effects on Ground Vehicles

    Science.gov (United States)

    2014-02-09

    Government or the DoA, and shall not be used for advertising or product endorsement purposes. REFERENCES [1] Thompson, D., Luke, E., Newman III, J., Janus...of a Loading Model for Simulating Blast Mine Effects on Armoured Vehicles,” 7th International LS-DYNA Users Conference, Detroit, MI, 2002. [6

  6. Detection of TET2 , KRAS and CBL variants by Next Generation ...

    African Journals Online (AJOL)

    Aim: In this study, we aimed to find possible genetic markers for molecular analysis in childhood AML by screening hot-spot exons of TET2, KRAS, and CBL using Next Generation Sequencing (NGS) analysis. In addition, association between found variants and mutations of Januse Kinase-2 (JAK2) and Fms Related ...

  7. Children and the New 3 Rs (Reduce, Reuse, Recycle): Attitudes toward the Environment.

    Science.gov (United States)

    Malkus, Amy J.; Musser, Lynn M.

    This study examined the relationship between children's environmental attitudes and their perceived competence and locus of control. The study sample consisted of 171 children in grades 3, 4, and 5. Children completed the Children's Attitudes Toward the Environment Scale (CATES) and the Janus Environmental Attitudes Scale (JEAS), which assessed…

  8. The GHR mutations related to individual’s dwarf

    Science.gov (United States)

    Growth hormone (GH) promotes body’s growth through binding with two receptors (GHRs) at the cell surface to interact with Janus kinase and signal transducers and activators of transcription, and then to stimulate metabolic effects and insulin-like growth factor (IGF) synthesis. However, the disorder...

  9. Sugared biomaterial binding lectins: achievements and perspectives

    Czech Academy of Sciences Publication Activity Database

    Bojarová, Pavla; Křen, Vladimír

    2016-01-01

    Roč. 4, č. 8 (2016), s. 1142-1160 ISSN 2047-4830 R&D Projects: GA ČR GC15-02578J Institutional support: RVO:61388971 Keywords : C-TYPE LECTINS * AMPHIPHILIC JANUS GLYCODENDRIMERS * BIOMEDICALLY RELEVANT LECTINS Subject RIV: CE - Biochemistry Impact factor: 4.210, year: 2016

  10. Motion-based, high-yielding, and fast separation of different charged organics in water.

    Science.gov (United States)

    Xuan, Mingjun; Lin, Xiankun; Shao, Jingxin; Dai, Luru; He, Qiang

    2015-01-12

    We report a self-propelled Janus silica micromotor as a motion-based analytical method for achieving fast target separation of polyelectrolyte microcapsules, enriching different charged organics with low molecular weights in water. The self-propelled Janus silica micromotor catalytically decomposes a hydrogen peroxide fuel and moves along the direction of the catalyst face at a speed of 126.3 μm s(-1) . Biotin-functionalized Janus micromotors can specifically capture and rapidly transport streptavidin-modified polyelectrolyte multilayer capsules, which could effectively enrich and separate different charged organics in water. The interior of the polyelectrolyte multilayer microcapsules were filled with a strong charged polyelectrolyte, and thus a Donnan equilibrium is favorable between the inner solution within the capsules and the bulk solution to entrap oppositely charged organics in water. The integration of these self-propelled Janus silica micromotors and polyelectrolyte multilayer capsules into a lab-on-chip device that enables the separation and analysis of charged organics could be attractive for a diverse range of applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis

    DEFF Research Database (Denmark)

    Wolk, Robert; Armstrong, Ehrin J; Hansen, Peter R

    2017-01-01

    BACKGROUND: Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. OBJECTIVE: The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional ...

  12. Screening for calreticulin mutations in a cohort of patients suspected ...

    African Journals Online (AJOL)

    Background. The discovery of calreticulin (CALR) has shown it to be the second most frequent mutation after the Janus Kinase 2 (JAK2) mutation in myeloproliferative neoplasms (MPNs). Its structure indicates various functions, of which two are to ensure calcium homeostasis and proper folding of other target proteins.

  13. Learning to cope with uncertainty: on the spatial distributions of financial innovation and its fallout

    NARCIS (Netherlands)

    Engelen, E.; Clark, G.L.; Dixon, A.D.; Monk, A.H.B.

    2009-01-01

    The final year of the boom will enter financial history books as a Janus-faced year. While the problems that were ultimately to unlock the triumphant course that the financial markets had taken since 2003 had been brewing for quite some time, disaster nevertheless struck like lightning. The

  14. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2

    NARCIS (Netherlands)

    Nangalia, J.; Massie, C.E.; Baxter, E.J.; Nice, F.L.; Gundem, G.; Wedge, D.C.; Avezov, E.; Li, J.; Kollmann, K.; Kent, D.G.; Aziz, A.; Godfrey, A.L.; Hinton, J.; Martincorena, I.; Loo, P. Van; Jones, A.V.; Guglielmelli, P.; Tarpey, P.; Harding, H.P.; Fitzpatrick, J.D.; Goudie, C.T.; Ortmann, C.A.; Loughran, S.J.; Raine, K.; Jones, D.R.; Butler, A.P.; Teague, J.W.; O'Meara, S.; McLaren, S.; Bianchi, M.; Silber, Y.; Dimitropoulou, D.; Bloxham, D.; Mudie, L.; Maddison, M.; Robinson, B.; Keohane, C.; Maclean, C.; Hill, K.; Orchard, K.; Tauro, S.; Du, M.Q.; Greaves, M.; Bowen, D.; Huntly, B.J.; Harrison, C.N.; Cross, N.C.; Ron, D.; Vannucchi, A.M.; Papaemmanuil, E.; Campbell, P.J.; Green, A.R.

    2013-01-01

    BACKGROUND: Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. METHODS: We performed exome sequencing

  15. Micromotor-based on-off fluorescence detection of sarin and soman simulants.

    Science.gov (United States)

    Singh, Virendra V; Kaufmann, Kevin; Orozco, Jahir; Li, Jinxing; Galarnyk, Michael; Arya, Gaurav; Wang, Joseph

    2015-06-30

    Self-propelled micromotor-based fluorescent "On-Off" detection of nerve agents is described. The motion-based assay utilizes Si/Pt Janus micromotors coated with fluoresceinamine toward real-time "on-the-fly" field detection of sarin and soman simulants.

  16. Multi-functional micromotor: microfluidic fabrication and water treatment application.

    Science.gov (United States)

    Chen, Anqi; Ge, Xue-Hui; Chen, Jian; Zhang, Liyuan; Xu, Jian-Hong

    2017-12-05

    Micromotors are important for a wide variety of applications. Here, we develop a microfluidic approach for one-step fabrication of a Janus self-propelled micromotor with multiple functions. By fine tuning the fabrication parameters and loading functional nanoparticles, our micromotor reaches a high speed and achieves an oriented function to promote the water purification efficiency and recycling process.

  17. “Deus está sonhando você”: Narrativa como Imitatio Dei em Miguel de Unamuno

    Directory of Open Access Journals (Sweden)

    Jaimir Conte

    2010-09-01

    Full Text Available Traduçáo do artigo "'God is dreaming you': Narrative as Imitatio Dei in Miguel de Unamuno," artigo publicado originalmente Janus Head –Interdisciplinary Studies in Continental Philosophy, Literature, and the Arts, Volume 7, Issue 2

  18. Complete staining of human spermatozoa and immature germ cells combined with phase contrast microscopy

    DEFF Research Database (Denmark)

    Michael, A Y; Drejer, J O; Bagger, P V

    1987-01-01

    A method combining Janus green B and Thymol blue stains the anterior part of the head, the nuclear membrane, middle piece, and tail of spermatozoa light green and the nucleus deep purple. The method provides excellent stained preparations for the evaluation of sperm morphology by phase contrast...

  19. The rhizosphere zoo: An overview of plant-associated communities of microorganisms, including phages, bacteria, archaea, and fungi, and some of their structuring factors

    NARCIS (Netherlands)

    Buée, M.; Boer, de W.; Martin, F.; Overbeek, van L.S.; Jurkevitch, E.

    2009-01-01

    Rhizosphere microorganisms have two faces, like Janus the Roman god of gates and doors who symbolizes changes and transitions, from one condition to another. One face looks at the plant root, the other sees the soil. The ears and the nose sense the other gods around and the mouths are wide open,

  20. Beyond Testing: Assessment for Teaching and Learning. Viewpoints. [Booklet and Audio Compact Discs].

    Science.gov (United States)

    North Central Regional Educational Lab., Naperville, IL.

    This multimedia package, which contains two audio CDs and a short informative booklet, examines the use of assessment to improve teaching and learning. The booklet contains the essay "Assessment-Driven Reform: A Leadership Approach" (Rhetta L. Detrich with Ed Janus and Sabrina W. M. Laine). It discusses the increasing importance of…

  1. Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies

    NARCIS (Netherlands)

    Fleischmann, Roy; Wollenhaupt, Jürgen; Takiya, Liza; Maniccia, Anna; Kwok, Kenneth; Wang, Lisy; van Vollenhoven, Ronald F.

    2017-01-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post hoc analysis evaluated patients receiving tofacitinib monotherapy or combination therapy, as well as those who switched from monotherapy to combination therapy (mono→combo) or vice versa (combo→mono)

  2. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial

    NARCIS (Netherlands)

    Bachelez, Hervé; van de Kerkhof, Peter C. M.; Strohal, Robert; Kubanov, Alexey; Valenzuela, Fernando; Lee, Joo-Heung; Yakusevich, Vladimir; Chimenti, Sergio; Papacharalambous, Jocelyne; Proulx, James; Gupta, Pankaj; Tan, Huaming; Tawadrous, Margaret; Valdez, Hernan; Wolk, Robert; Kogan, Nora Noemi; Schmuth, Matthias; Hintner, Helmut; Ghislain, Pierre-Dominique; Alendar, Faruk; Kadurina, Miroslava; Marina, Sonya; Kuzeva, Vasilka; Gospodinov, Dimitar; Tsankov, Nikolay; de La Cruz, Claudia; Valdes, Pilar; Guglielmetti, Antonio; Yeung, Chi Keung; Chun-Yin, Johnny; Moreno, Edgar; Rojas, Ricardo Flaminio; Melendez, Esperanza Maria; Castillo, David; Mejia, Hernando; Londono, Angela M.; Bulic, Suzana Ozanic; Ceovic, Romana; Biljan, Darko; Pizinger, Karel; Horazdovsky, Jiri; Filipovska, Olga; Ettler, Karel; Arenberger, Petr; Iversen, Lars; Bang, Bo; Otkjaer, Aksel; Dreno, Brigitte; Guillet, Gerard; Spuls, Phyllis I.

    2015-01-01

    Background New therapeutic options are needed for patients with psoriasis. Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis. In this study, we aimed to compare two tofacitinib doses with high-dose etanercept or placebo

  3. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial

    NARCIS (Netherlands)

    Bachelez, H.; Kerkhof, P.C.M. van de; Strohal, R.; Kubanov, A.; Valenzuela, F.; Lee, J.H. van der; Yakusevich, V.; Chimenti, S.; Papacharalambous, J.; Proulx, J.; Gupta, P.; Tan, H.; Tawadrous, M.; Valdez, H.; Wolk, R.

    2015-01-01

    BACKGROUND: New therapeutic options are needed for patients with psoriasis. Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis. In this study, we aimed to compare two tofacitinib doses with high-dose etanercept or placebo

  4. Switching from adalimumab to tofacitinib in the treatment of patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Genovese, Mark C.; van Vollenhoven, Ronald F.; Wilkinson, Bethanie; Wang, Lisy; Zwillich, Samuel H.; Gruben, David; Biswas, Pinaki; Riese, Richard; Takiya, Liza; Jones, Thomas V.

    2016-01-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The aim of this study was to explore the safety and efficacy of open-label tofacitinib following blinded treatment with adalimumab or tofacitinib for moderate to severe RA. Analyses included patients

  5. Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials

    NARCIS (Netherlands)

    Panés, Julian; Sandborn, William J.; Schreiber, Stefan; Sands, Bruce E.; Vermeire, Séverine; D'Haens, Geert; Panaccione, Remo; Higgins, Peter D. R.; Colombel, Jean-Frederic; Feagan, Brian G.; Chan, Gary; Moscariello, Michele; Wang, Wenjin; Niezychowski, Wojciech; Marren, Amy; Healey, Paul; Maller, Eric

    2017-01-01

    Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). We conducted two randomised, double-blind,

  6. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

    NARCIS (Netherlands)

    Fleischmann, Roy M.; Huizinga, Tom W. J.; Kavanaugh, Arthur F.; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F.

    2016-01-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult

  7. Will novel oral formulations change the management of inflammatory bowel disease?

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Seidelin, Jakob Benedict; Ainsworth, Mark Andrew

    2016-01-01

    the current approaches with promising new oral drugs with distinct modes of action, including: the Janus kinase inhibitors (i.e., tofacitinib, filgotinib and peficitinib); the immunomodulatory drug (laquinimod); a small α4 antagonist (AJM300); agonists for sphingosine-phosphate receptors (i.e., ozanimod, APD...

  8. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

    NARCIS (Netherlands)

    Sandborn, William J.; Su, Chinyu; Sands, Bruce E.; D'Haens, Geert R.; Vermeire, Séverine; Schreiber, Stefan; Danese, Silvio; Feagan, Brian G.; Reinisch, Walter; Niezychowski, Wojciech; Friedman, Gary; Lawendy, Nervin; Yu, Dahong; Woodworth, Deborah; Mukherjee, Arnab; Zhang, Haiying; Healey, Paul; Panés, Julian

    2017-01-01

    Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. We conducted three phase 3, randomized,

  9. Staphylococcus aureus enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Willerslev-Olsen, Andreas; Krejsgaard, Thorbjørn; Lindahl, Lise Maria

    2016-01-01

    cells. The response is induced via IL-2 receptor common g chain cytokines and a Janus kinase 3 (JAK3)-dependent pathway in malignant T cells, and blocked by tofacitinib, a clinical-grade JAK3 inhibitor. In conclusion, we demonstrate that SEA induces cell cross talk-dependent activation of STAT3...

  10. Nye molekylaere markører ved de kroniske myeloproliferative sygdomme

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Pallisgaard, Niels; Christensen, Jacob Haaber

    2006-01-01

    The Philadelphia-negative chronic myeloproliferative disorders feature autonomous myeloid hyperproliferation and hypersensitivity to a number of growth factors, which most recently have been shown to be explained by a guanine-to-thymidine mutation in the Janus tyrosine kinase (JAK2) gene, implica...

  11. Does the EDI Measure School Readiness in the Same Way across Different Groups of Children?

    Science.gov (United States)

    Guhn, Martin; Gadermann, Anne; Zumbo, Bruno D.

    2007-01-01

    The present study investigates whether the Early Development Instrument (Offord & Janus, 1999) measures school readiness similarly across different groups of children. We employ ordinal logistic regression to investigate differential item functioning, a method of examining measurement bias. For 40,000 children, our analysis compares groups…

  12. 77 FR 3810 - New York Life Insurance and Annuity Corporation, et al., Notice of Application

    Science.gov (United States)

    2012-01-25

    ... Eck Assets Fund--Initial Global Hard Assets Class. Portfolio--Initial Class 2 Janus Aspen Balanced... Accounts'' and, together with NYLIAC, the ``Section 26 Applicants''); and Mainstay VP Funds Trust (``MVPFT... investment companies (the ``Existing Portfolios'') held by the Separate Accounts to fund certain group and...

  13. Fulltext PDF

    Indian Academy of Sciences (India)

    coccus aureus, Bacillius subtilis and Aspergillius janus, Aspergillus niger and Pencillium glabrum, respectively. The antimicrobial behaviour of the bispyrazolines 3a–3h is found to be dependent on the length of internal spacer unit. Keywords. Cyclization reactions; bischalcones; internal spacer; bispyrazolines; alkyl chains ...

  14. Cancellation of the central singularity of the Schwarzschild solution with natural mass inversion process

    Science.gov (United States)

    Petit, Jean-Pierre; D'Agostini, G.

    2015-03-01

    We reconsider the classical Schwarzschild solution in the context of a Janus cosmological model. We show that the central singularity can be eliminated through a simple coordinate change and that the subsequent transit from one fold to the other is accompanied by mass inversion. In such scenario matter swallowed by black holes could be ejected as invisible negative mass and dispersed in space.

  15. Methods and Systems for Use of an Acoustic Doppler Current Profiler for Measurement of Compact Jets

    National Research Council Canada - National Science Library

    Hendricks, Peter J

    2007-01-01

    ... an Acoustic Doppler Current Profiler (ADCP). The ADCP is a four-beam, Janus-type ADCP having beams aligned so that each of the beams is at an angle of about 200 to 300 to vertical and at 450 to the fore and aft axis of the vessel, such that two...

  16. Many Modernities and Utopia : From Thomas More to South Asian Utopian Writings

    NARCIS (Netherlands)

    Bagchi, B.

    2016-01-01

    This chapter sees Utopia as at once a place of dreams, a place of the good, and a place which is nowhere to be found: paradox, ambiguity, and janus-facedness are embedded in a very modern punning coupling of the good, ‘eu’, and the nonexistent, ‘ou’, made by Thomas More in his Greek neologism

  17. Critical Arts - Vol 18, No 1 (2004)

    African Journals Online (AJOL)

    Danie Jordaan. Transforming the media: A cultural approach. Lynette Steenveld. The Righteousness of self-centred royals: The world according to Disney animation. Lee Artz. Unifying and Dividing Processes in National Media: The Janus Face of South Africa. Kristin Skare Orgeret. Intellectuals Under Fire. Jonathan Jansen ...

  18. GSK2586184, a JAK1 selective inhibitor, in two patients with ulcerative colitis

    NARCIS (Netherlands)

    de Vries, Leonie C. S.; Ludbrook, Valerie J.; Hicks, Kirsty J.; D'Haens, Geert R.

    2017-01-01

    Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC). Tofacitinib inhibits cytokine signalling through blockade of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Adverse events including

  19. State of the art of the therapeutic perspective of sorafenib against hematological malignancies.

    Science.gov (United States)

    Zauli, G; Voltan, R; Tisato, V; Secchiero, P

    2012-01-01

    The bi-aryl urea multi-kinase inhibitor Sorafenib (BAY 43-9006, Nexavar) was initially approved for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma. Eleven years after its first description in PubMed, the therapeutic potential of Sorafenib has been evaluated in an increasing number of studies, mainly focused on solid tumors. More recently, the potential usefullness of Sorafenib has started to emerge also against hematological malignancies. At the molecular level, besides the RAF kinase pathway, which represents the first therapeutic target of Sorafenib, additional kinases, in particular the vascular endothelial growth factor receptor, have been identified as important targets of Sorafenib. A great interest for the potential use of Sorafenib against acute myeloid leukemia (AML) arose when it was demonstrated that a specific mutation of a kinase gene, called FMS-like tyrosin-kinase-3- internal tandem duplication (FLT-3-ITD) and occurring in more than 30% of AML, represents a molecular target of Sorafenib. However, recent phase I and II clinical studies showed that, in spite of its ability to suppress the activity of this mutated kinase, resistence to Sorafenib rapidly occurs in AML, suggesting that Sorafenib will be more effective in combined therapy than used as single drug. Another critical molecular target of Sorafenib is the anti-apoptotic protein Mcl-1. The ability of Sorafenib to rapidly shut-off Mcl-1 in virtually all the hematological malignancies investigated, including the B-chronic lymphocytic leukemia, represents a key element for its antileukemic activity as well as for therapeutic combinations based on Sorafenib. In this respect, it is of particular interest that many chemotherapeutic drugs or innovative anti-neoplastic compounds, such as recombinant TRAIL or inibitors of MDM2 protein, are either unable to down-regulate Mcl-1 or in some instances promote a paradoxical induction of Mcl-1. In this review, the

  20. Full-spectrum volumetric solar thermal conversion via photonic nanofluids.

    Science.gov (United States)

    Liu, Xianglei; Xuan, Yimin

    2017-10-12

    Volumetric solar thermal conversion is an emerging technique for a plethora of applications such as solar thermal power generation, desalination, and solar water splitting. However, achieving broadband solar thermal absorption via dilute nanofluids is still a daunting challenge. In this work, full-spectrum volumetric solar thermal conversion is demonstrated over a thin layer of the proposed 'photonic nanofluids'. The underlying mechanism is found to be the photonic superposition of core resonances, shell plasmons, and core-shell resonances at different wavelengths, whose coexistence is enabled by the broken symmetry of specially designed composite nanoparticles, i.e., Janus nanoparticles. The solar thermal conversion efficiency can be improved by 10.8% compared with core-shell nanofluids. The extinction coefficient of Janus dimers with various configurations is also investigated to unveil the effects of particle couplings. This work provides the possibility to achieve full-spectrum volumetric solar thermal conversion, and may have potential applications in efficient solar energy harvesting and utilization.

  1. Evaluation of proposed degradation algorithms for multiburst environments

    International Nuclear Information System (INIS)

    Olness, D.U.; Warshawsky, A.S.

    1993-01-01

    This work is part of an ongoing effort of the Defense Nuclear Agency's Intermediate Dose Program to investigate the effects of intermediate radiation doses on combat unit performance. The objective of this study is to develop an improved technique for applying performance degradation factors to combat crews in simulated battles following multiple radiation doses on the tactical battlefield. A further objective of the study is to quantify differences in Janus results when crew performance factors, following multiple radiation doses, are obtained from the improved technique instead of from the technique used previously. In this paper, the authors describe and evaluate three methods previously identified for determining performance degradation from multiple exposures. They also present the observed quantitative differences in outcomes of conventional battles begun a few hours after multiple radiation exposures when alternate techniques for calculating combat crew performance degradation factors are included in the Janus combat simulation

  2. Now comes the time to defuzzify neuro-fuzzy models

    International Nuclear Information System (INIS)

    Bersini, H.; Bontempi, G.

    1996-01-01

    Fuzzy models present a singular Janus-faced : on one hand, they are knowledge-based software environments constructed from a collection of linguistic IF-THEN rules, and on the other hand, they realize nonlinear mappings which have interesting mathematical properties like low-order interpolation and universal function approximation. Neuro-fuzzy basically provides fuzzy models with the capacity, based on the available data, to compensate for the missing human knowledge by an automatic self-tuning of the structure and the parameters. A first consequence of this hybridization between the architectural and representational aspect of fuzzy models and the learning mechanisms of neural networks has been to progressively increase and fuzzify the contrast between the two Janus faces: readability or performance

  3. Structural-Phase States of Fe-Cu and Fe-Ag Bimetallic Particles Produced by Electric Explosion of Two Wires

    Science.gov (United States)

    Lerner, M. I.; Bakina, O. V.; Pervikov, A. V.; Glazkova, E. A.; Lozhkomoev, A. S.; Vorozhtsov, A. B.

    2018-05-01

    X-ray phase analysis, transmission electron microscopy, and X-ray microanalysis were used to examine the structural-phase states of Fe-Cu and Fe-Ag bimetallic nanoparticles. The nanoparticles were obtained by the electric explosion of two twisted metal wires in argon atmosphere. It was demonstrated that the nanoparticles have the structure of Janus particles. Presence of the Janus particle structure in the samples indicates formation of binary melt under conditions of combined electric explosion of two wires. Phases based on supersaturated solid solutions were not found in the examined samples. The data obtained allow arguing that it is possible to achieve uniform mixing of the two-wire explosion products under the described experiment conditions.

  4. Motion Control of Urea-Powered Biocompatible Hollow Microcapsules.

    Science.gov (United States)

    Ma, Xing; Wang, Xu; Hahn, Kersten; Sánchez, Samuel

    2016-03-22

    The quest for biocompatible microswimmers powered by compatible fuel and with full motion control over their self-propulsion is a long-standing challenge in the field of active matter and microrobotics. Here, we present an active hybrid microcapsule motor based on Janus hollow mesoporous silica microparticles powered by the biocatalytic decomposition of urea at physiological concentrations. The directional self-propelled motion lasts longer than 10 min with an average velocity of up to 5 body lengths per second. Additionally, we control the velocity of the micromotor by chemically inhibiting and reactivating the enzymatic activity of urease. The incorporation of magnetic material within the Janus structure provides remote magnetic control on the movement direction. Furthermore, the mesoporous/hollow structure can load both small molecules and larger particles up to hundreds of nanometers, making the hybrid micromotor an active and controllable drug delivery microsystem.

  5. Transient Micromotors That Disappear When No Longer Needed.

    Science.gov (United States)

    Chen, Chuanrui; Karshalev, Emil; Li, Jinxing; Soto, Fernando; Castillo, Roxanne; Campos, Isaac; Mou, Fangzhi; Guan, Jianguo; Wang, Joseph

    2016-11-22

    Transient self-destroyed micromotors that autonomously disappear in biological media at controlled rates upon completing their task, without leaving a toxic residue, are presented. The propulsion and degradation characteristics of the self-destroyed Mg/ZnO, Mg/Si, and Zn/Fe Janus micromotors and single-component Zn micromotors are described. The degradation of the Janus micromotors relies on the different corrosion rates of their core-shell components. Inductively coupled plasma optical emission spectrometry measurements are used to probe the time-dependent degradation of the different constituents of the micromotors. The toxicity of the transient micromotors is discussed toward their potential use in biomedical applications. This concept of transient micromotors offers considerable potential for diverse practical applications in the near future.

  6. Bioinspired Chemical Communication between Synthetic Nanomotors.

    Science.gov (United States)

    Chen, Chuanrui; Chang, Xiaocong; Teymourian, Hazhir; Ramírez-Herrera, Doris E; Esteban-Fernández de Ávila, Berta; Lu, Xiaolong; Li, Jinxing; He, Sha; Fang, Chengcheng; Liang, Yuyan; Mou, Fangzhi; Guan, Jianguo; Wang, Joseph

    2018-01-02

    While chemical communication plays a key role in diverse natural processes, the intelligent chemical communication between synthetic nanomotors remains unexplored. The design and operation of bioinspired synthetic nanomotors is presented. Chemical communication between nanomotors is possible and has an influence on propulsion behavior. A chemical "message" is sent from a moving activator motor to a nearby activated (receiver) motor by release of Ag + ions from a Janus polystyrene/Ni/Au/Ag activator motor to the activated Janus SiO 2 /Pt nanomotor. The transmitted silver signal is translated rapidly into a dramatic speed change associated with the enhanced catalytic activity of activated motors. Selective and successive activation of multiple nanomotors is achieved by sequential localized chemical communications. The concept of establishing chemical communication between different synthetic nanomotors paves the way to intelligent nanoscale robotic systems that are capable of cooperating with each other. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Exploding pusher targets illuminated using f/1 lenses at approx. 0.4 TW

    International Nuclear Information System (INIS)

    Storm, E.K.; Ahlstrom, H.G.; Holzrichter, J.F.

    1976-01-01

    A series of laser fusion microimplosion experiments have been performed with the LLL two beam laser system JANUS. The JANUS laser is capable of focusing up to 400 gigawatts of 1.06 μm laser power (32J in 80 psec) on microscopic laser fusion targets, producing intensities in excess of 10 17 w/cm 2 . In these experiments the targets were Deuterium--Tritium (DT) gas filled, thin walled (.5 to 1.0 μm) SiO 2 microshells with diameters of 40 to 100 μm. Targets with these dimensions, properties and laser powers operate in what has become known as the exploding pusher mode. A summary of the salient points of each design limit is illustrated

  8. Principles of a reversible programming language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    The principles of reversible programming languages are explicated and illustrated with reference to the design of a high-level imperative language, Janus. The fundamental properties for such languages include backward as well as forward determinism and reversible updates of data. The unique design...... languages, and demonstrate this for Janus. We show the practicality of the language by implementation of a reversible fast Fourier transform. Our results indicate that the reversible programming paradigm has fundamental properties that are relevant to many different areas of computer science....... features of the language include explicit post-condition assertions, direct access to an inverse semantics and the possibility of clean (i.e., garbage-free) computation of injective functions. We suggest the clean simulation of reversible Turing machines as a criterion for computing strength of reversible...

  9. Interior properties of the inner Saturnian moons from space astrometry data

    Science.gov (United States)

    Lainey, Valery; Noyelles, Benoît; Cooper, Nick; Murray, Carl; Park, Ryan; Rambaux, Nicolas

    2018-04-01

    During thirteen years in orbit around Saturn before its final plunge, the Cassini spacecraft provided more than ten thousand astrometric measurements. Such large amounts of accurate data enable the search for extremely faint signals in the orbital motion of the moons. Among those, the detection of the dynamical feedback of the rotation of the inner moons of Saturn on their respective orbits becomes possible. Using all the currently available astrometric data associated with Atlas, Prometheus, Pandora, Janus and Epimetheus, we provide a detailed analysis of the ISS data, with special emphasis on their statistical behavior and source of biases. Then, we try quantifying the physical librations of Prometheus, Pandora, Epimetheus and Janus from the monitoring of their orbits. Last, we show how introducing measurements directly derived from imaging can provide tighter constraints on these quantities.

  10. The Coast Artillery Journal. Volume 69, Number 5, November 1928

    Science.gov (United States)

    1928-11-01

    States-Artillery: Today and Tomorrou’~Alexander: A Ro- mantic Biography-Janus: The Conquest of War- Kitchener : Soldier and Statesman-Spy and Counter-Spy...another had to be moved from the latter division to the former, and the two companies exchanged disignations . One can scarce imagine a more awkward or...Statesmen; Sedgwick’s Lafayette; Seitz’s Braxton Bragg, General of the Confederacy; Starritt’s Kitchener : Soldier and Statesman; Wilson’s Napoleon, the Man

  11. “Cybercrime”: Fenomena Kejahatan melalui Internet di Indonesia

    OpenAIRE

    Muhammad E. Fuady

    2005-01-01

    It had been long known that technology, as Janus, has two side of coins: the good side,and the bad side. Everybody knows the benefit of technology development. But there aren’t much who realize the negative potent of technology. Cybercrime discussed in this article is an example of how crime was developed sophisticatedly by using technological means. Cybercrime, simply defined as criminal acts using cyber and Internet, has faced a new challenge for lawmaker and law enforcement mission. In Ind...

  12. “Cybercrime”: Fenomena Kejahatan Melalui Internet Di Indonesia

    OpenAIRE

    Fuady, Muhammad E

    2005-01-01

    It had been long known that technology, as Janus, has two side of coins: the good side,and the bad side. Everybody knows the benefit of technology development. But there aren't much who realize the negative potent of technology. Cybercrime discussed in this article is an example of how crime was developed sophisticatedly by using technological means. Cybercrime, simply defined as criminal acts using cyber and Internet, has faced a new challenge for lawmaker and law enforcement mission. In Ind...

  13. Teratogenic and embryolethal effects in mice of fission-spectrum neutrons and γ-rays

    International Nuclear Information System (INIS)

    Cairnie, A.B.; Grahn, D.; Rayburn, H.B.; Williamson, F.S.; Brown, R.J.

    1974-01-01

    Fission-spectrum neutrons from the Janus reactor at Argonne National Laboratory were compared with γ-rays in terms of their relative biological effectiveness (RBE) for embryolethal and teratogenic effects in mice. No evidence was found of any processes that were abnormally sensitive to neutrons. The RBE for killing embryos and producing abnormal embryos or specific abnormalities was between 2 and 3. This is close to the values found in other systems for processes involving cell killing. (U.S.)

  14. Reactor D and D at Argonne National Laboratory - lessons learned

    International Nuclear Information System (INIS)

    Fellhauer, C. R.

    1998-01-01

    This paper focuses on the lessons learned during the decontamination and decommissioning (D and D) of two reactors at Argonne National Laboratory-East (ANL-E). The Experimental Boiling Water Reactor (EBWR) was a 100 MW(t), 5 MSV(e) proof-of-concept facility. The Janus Reactor was a 200 kW(t) reactor located at the Biological Irradiation Facility and was used to study the effects of neutron radiation on animals

  15. Mechanochemically-Active Polymer Composites

    Science.gov (United States)

    2013-09-13

    Technology (KAIST), Daejeon, South Korea, June 4, 2013 Bielawski, C. W. MIT, Merck- Karl Pfister Lectures, October 17, 2012 Bielawski, C. W. Northwestern...Submitted Patents Awarded Awards C. Bielawski: Merck- Karl Pfister Visiting Professorship, MIT Milliken Graduate Research Lecturer (to J. N. Brantley...2013, Submitted. 9 Dopieralski, P.; Ribas-Arino, J.; Anjukandi, P.; Krupicka, M.; Kiss, J.; Marx , D. The Janus-faced role of external forces in

  16. Chorea disclosing a polycythemia vera

    OpenAIRE

    Liu, Guidong; Chang, Jie; Liu, Zhijun; Qiang, Qiang; Gu, Chunhui; Zhang, Yingying; Wei, Wenshi

    2014-01-01

    Guidong Liu, Jie Chang, Zhijun Liu, Qiang Qiang, Chunhui Gu, Yingying Zhang, Wenshi Wei Department of Neurology, Huadong Hospital, Fudan University, Shanghai, People's Republic of China Abstract: Chorea is a rare complication of polycythemia. We report the case of a 70 year-old woman whose polycythemia vera (PV), with Janus Kinase-2 (JAK2) mutation, presented as chorea. Chorea resolved quickly after hydroxyurea therapy. Keywords: chorea, polycythemia vera, elderly, JAK2

  17. BCR-ABL1- positive chronic myeloid leukemia with erythrocytosis presenting as polycythemia vera: a case report.

    Science.gov (United States)

    Cornea, Mihaela I Precup; Levrat, Emmanuel; Pugin, Paul; Betticher, Daniel C

    2015-04-08

    The World Health Organization classification of chronic myeloproliferative disease encompasses eight entities of bone marrow neoplasms, among them Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1-positive chronic myeloid leukemia and polycythemia vera. Polycythemia vera requires, in the majority of cases (95%), the negativity of Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 rearrangement and the presence of the Janus kinase 2 mutation. We report a case of erythrocytosis as the primary manifestation of a chronic myeloid leukemia, with the presence of the Philadelphia chromosome and the Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion gene, and in the absence of any Janus kinase 2 mutation. A 68-year-old Caucasian woman, with a history of cigarette consumption and obstructive sleep apnoea syndrome (undergoing continuous positive airway pressure treatment) had presented to our institution with fatigue and a hemoglobin level of 18.6g/L, with slight leukocytosis at 16G/L, and no other anomalies on her complete blood cell count. Examination of her arterial blood gases found only a slight hypoxemia; erythropoietin and ferritin levels were very low and could not explain a secondary erythrocytosis. Further analyses revealed the absence of any Janus kinase 2 mutation, thus excluding polycythemia vera. Taken together with a high vitamin B12 level, we conducted a Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 gene analysis and bone marrow cytogenetic analysis, both of which returned positive, leading to the diagnosis of chronic myeloid leukemia. To date, this case is the first description of a Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1-positive chronic myeloid leukemia, presenting with erythrocytosis as the initial manifestation, and mimicking a Janus kinase 2 V617F-negative polycythemia vera. Her impressive response to imatinib

  18. Poloidal and toroidal plasmons and fields of multilayer nanorings

    OpenAIRE

    Garapati, Kumar Vijay; Salhi, Marouane; Kouchekian, Sherwin; Siopsis, George; Passian, Ali

    2017-01-01

    Composite and janus type metallo-dielectric nanoparticles are increasingly considered as a means to control the spatial and temporal behavior of electromagnetic fields in diverse applications such as coupling to quantum emitters, achieve invisibility cloaks, and obtain quantum correlations between qubits. We investigate the surface modes of a toroidal nano-structure and obtain the canonical plasmon dispersion relations and resonance modes for arbitrarily layered nanorings. Unlike particle pla...

  19. Alopecia areata: Update on management

    OpenAIRE

    Julie S Kranseler; Robert Sidbury

    2017-01-01

    Alopecia areata (AA) is a common autoimmune nonscarring alopecia. AA presents heterogeneously and is influenced by both environmental and genetic factors. Diagnosis is clinical after ruling out other local or systemic causes of alopecia. Standard first-line therapy is typically topical steroids, but the response can be frustrating. Novel treatment options have shown great promise in the management of the refractory disease. We review initial data on topical and systemic Janus kinase inhibitor...

  20. Igavesti uuesti üllatav romaanivõistlus / Peeter Helme

    Index Scriptorium Estoniae

    Helme, Peeter, 1978-

    2009-01-01

    2008. a. romaanivõistlusel 1. auhinda välja ei antud. 2. auhinna võitis Milvi Martina Piiri romaan "Liblikad janus". 3. auhinna võitjaid oli kaks: Birk Rohelend romaaniga "Minu sõraline sõber" ja Marion Andra "Algolagnia". Ergutusauhinna võitnud romaanid: Liina Lüecke "Sügismüsteerium", Robert Kurvitza "Püha ja õudne lõhn", Robert Randma "Sigaret" ja Helju Petsi "Õnneõiteta sirelid"

  1. Romaanivõistlus 2008 - naised ruulivad! / Peeter Helme

    Index Scriptorium Estoniae

    Helme, Peeter, 1978-

    2009-01-01

    2008. a. romaanivõistlusel 1. auhinda välja ei antud. 2. auhinna võitis Milvi Martina Piiri romaan "Liblikad janus". 3. auhinna võitjaid oli kaks: Birk Rohelend romaaniga "Minu sõraline sõber" ja Marion Andra "Algolagnia". Ergutusauhinna võitnud romaanid: Liina Lüecke "Sügismüsteerium", Robert Kurvitza "Püha ja õudne lõhn", Robert Randma "Sigaret" ja Helju Petsi "Õnneõiteta sirelid"

  2. Tofacitinib with conventional synthetic disease‐modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis: Patient‐reported outcomes from a Phase 3 randomized controlled trial

    OpenAIRE

    Li, Zhanguo; An, Yuan; Su, Houheng; Li, Xiangpei; Xu, Jianhua; Zheng, Yi; Li, Guiye; Kwok, Kenneth; Wang, Lisy; Wu, Qizhe

    2018-01-01

    Abstract Aim Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assess the effect of tofacitinib + conventional synthetic disease‐modifying anti rheumatic drugs (csDMARDs) on patient‐reported outcomes in Chinese patients with RA and inadequate response to DMARDs. Methods This analysis of data from the Phase 3 study ORAL Sync included Chinese patients randomized 4 : 4 : 1 : 1 to receive tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, p...

  3. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

    OpenAIRE

    Fleischmann, Roy M; Huizinga, Tom W J; Kavanaugh, Arthur F; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F

    2016-01-01

    Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24?months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration

  4. Efficacy and safety of tofacitinib in patients with active rheumatoid arthritis: review of key Phase 2 studies

    OpenAIRE

    Fleischmann, Roy; Kremer, Joel; Tanaka, Yoshiya; Gruben, David; Kanik, Keith; Koncz, Tamas; Krishnaswami, Sriram; Wallenstein, Gene; Wilkinson, Bethanie; Zwillich, Samuel H.; Keystone, Edward

    2016-01-01

    Abstract Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here, the safety and efficacy data from five Phase 2 studies of tofacitinib in patients with RA are summarized. Tofacitinib 1?30 mg twice daily was investigated, as monotherapy and in combination with methotrexate, in patients with RA. Tofacitinib 20 mg once daily was investigated in one study. Tofacitinib 5 and 10 mg twice daily were selected for investigation in Phase 3 studies; therefore,...

  5. A categorical foundation for structured reversible flowchart languages: Soundness and adequacy

    OpenAIRE

    Glück, Robert; Kaarsgaard, Robin

    2017-01-01

    Structured reversible flowchart languages is a class of imperative reversible programming languages allowing for a simple diagrammatic representation of control flow built from a limited set of control flow structures. This class includes the reversible programming language Janus (without recursion), as well as more recently developed reversible programming languages such as R-CORE and R-WHILE. In the present paper, we develop a categorical foundation for this class of languages based on inve...

  6. Novel competition 2008 - women's and genre literature / Peeter Helme

    Index Scriptorium Estoniae

    Helme, Peeter, 1978-

    2009-01-01

    2008. a. romaanivõistlusel 1. auhinda välja ei antud. 2. auhinna võitis Milvi Martina Piiri romaan "Liblikad janus". 3. auhinna võitjaid oli kaks: Birk Rohelend romaaniga "Minu sõraline sõber" ja Marion Andra "Algolagnia". Ergutusauhinna võitnud romaanid: Liina Lüecke "Sügismüsteerium", Robert Kurvitza "Püha ja õudne lõhn", Robert Randma "Sigaret" ja Helju Petsi "Õnneõiteta sirelid"

  7. A look back and a look forward

    International Nuclear Information System (INIS)

    McDonald, J. C.

    2012-01-01

    Roman mythology described Janus as the god of beginnings and transitions. Janus was depicted as having two heads facing in opposite directions that could be thought of as the future and the past. Therefore, it is altogether appropriate that the first month of our calendar should be named after Janus because it is a time of passage from the old to the new year. There were a number of significant events and developments during the past year, and one can look forward to a number of new and, perhaps, unexpected developments during the year to come. The year 2011 saw the tragedy of a major earthquake and Tsunami in Japan resulting in a disastrous series of explosions at the Fukushima I Nuclear Power Plant. Releases of radionuclides to the atmosphere and depositions in the immediate vicinity of the plant have required remediation efforts on the part of the Japanese government, with help from a number of other nations. This accident was classified as Level 7, the highest level, on the International Nuclear Event Scale. (author)

  8. Mimosa Origami: A nanostructure-enabled directional self-organization regime of materials

    Science.gov (United States)

    Wong, William S. Y.; Li, Minfei; Nisbet, David R.; Craig, Vincent S. J.; Wang, Zuankai; Tricoli, Antonio

    2016-01-01

    One of the innate fundamentals of living systems is their ability to respond toward distinct stimuli by various self-organization behaviors. Despite extensive progress, the engineering of spontaneous motion in man-made inorganic materials still lacks the directionality and scale observed in nature. We report the directional self-organization of soft materials into three-dimensional geometries by the rapid propagation of a folding stimulus along a predetermined path. We engineer a unique Janus bilayer architecture with superior chemical and mechanical properties that enables the efficient transformation of surface energy into directional kinetic and elastic energies. This Janus bilayer can respond to pinpoint water stimuli by a rapid, several-centimeters-long self-assembly that is reminiscent of the Mimosa pudica’s leaflet folding. The Janus bilayers also shuttle water at flow rates up to two orders of magnitude higher than traditional wicking-based devices, reaching velocities of 8 cm/s and flow rates of 4.7 μl/s. This self-organization regime enables the ease of fabricating curved, bent, and split flexible channels with lengths greater than 10 cm, demonstrating immense potential for microfluidics, biosensors, and water purification applications. PMID:28861471

  9. Selecting the swimming mechanisms of colloidal particles: bubble propulsion versus self-diffusiophoresis.

    Science.gov (United States)

    Wang, Sijia; Wu, Ning

    2014-04-01

    Bubble propulsion and self-diffusiophoresis are two common mechanisms that can drive autonomous motion of microparticles in hydrogen peroxide. Although microtubular particles, when coated with platinum in their interior concave surfaces, can propel due to the formation and release of bubbles from one end, the convex Janus particles usually do not generate any visible bubble. They move primarily due to the self-diffusiophoresis. Coincidentally, the platinum films on those particles were typically coated by physical evaporation. In this paper, we use a simple chemical deposition method to make platinum-polystyrene Janus dimers. Surprisingly, those particles are propelled by periodic growth and collapse of bubbles on the platinum-coated lobes. We find that both high catalytic activity and rough surface are necessary to change the propulsion mode from self-diffusiophoresis to bubble propulsion. Our Janus dimers, with combined geometric and interfacial anisotropy, also exhibit distinctive motions at the respective stages of bubble growth and collapse, which differ by 5-6 orders of magnitude in time. Our study not only provides insight into the link between self-diffusiophoresis and bubble propulsion but also reveals the intriguing impacts of the combined geometric and interfacial anisotropy on self-propulsion of particles.

  10. The Enhanced Catalytic Activities of Asymmetric Au-Ni Nanoparticle Decorated Halloysite-Based Nanocomposite for the Degradation of Organic Dyes

    Science.gov (United States)

    Jia, Lei; Zhou, Tao; Xu, Jun; Li, Xiaohui; Dong, Kun; Huang, Jiancui; Xu, Zhouqing

    2016-02-01

    Janus particles (JPs) are unique among the nano-/microobjects because they provide asymmetry and can thus impart drastically different chemical or physical properties. In this work, we have fabricated the magnetic halloysite nanotube (HNT)-based HNTs@Fe3O4 nanocomposite (NCs) and then anchored the Janus Au-Ni or isotropic Au nanoparticles (NPs) to the surface of external wall of sulfydryl modified magnetic nanotubes. The characterization by physical methods authenticates the successful fabrication of two different magnetic HNTs@Fe3O4@Au and HNTs@Fe3O4@Au-Ni NCs. The catalytic activity and recyclability of the two NCs have been evaluated considering the degradation of Congo red (CR) and 4-nitrophenol (4-NP) using sodium borohydride as a model reaction. The results reveal that the symmetric Au NPs participated NCs display low activity in the degradation of the above organic dyes. However, a detailed kinetic study demonstrates that the employ of bimetallic Janus Au-Ni NPs in the NCs indicates enhanced catalytic activity, owing to the structurally specific nature. Furthermore, the magnetic functional NCs reported here can be used as recyclable catalyst which can be recovered simply by magnet.

  11. Interfacial functionalization and engineering of nanoparticles

    Science.gov (United States)

    Song, Yang

    The intense research interest in nanoscience and nanotechnology is largely fueled by the unique properties of nanoscale materials. In this dissertation, the research efforts are focused on surface functionalization and interfacial engineering of functional nanoparticles in the preparation of patchy nanoparticles (e.g., Janus nanoparticles and Neapolitan nanoparticles) such that the nanoparticle structures and properties may be manipulated to an unprecedented level of sophistication. Experimentally, Janus nanoparticles were prepared by an interfacial engineering method where one hemisphere of the originally hydrophobic nanoparticles was replaced with hydrophilic ligands at the air|liquid or solid|liquid interface. The amphiphilic surface characters of the Janus nanoparticles were verified by contact angle measurements, as compared to those of the bulk-exchange counterparts where the two types of ligands were distributed rather homogeneously on the nanoparticle surface. In a further study, a mercapto derivative of diacetylene was used as the hydrophilic ligands to prepare Janus nanoparticles by using hydrophobic hexanethiolate-protected gold nanoparticles as the starting materials. Exposure to UV irradiation led to effective covalent cross-linking between the diacetylene moieties of neighboring ligands and hence marked enhancement of the structural integrity of the Janus nanoparticles, which was attributable to the impeded surface diffusion of the thiol ligands on the nanoparticle surface, as manifested in fluorescence measurements of aged nanoparticles. More complicated bimetallic AgAu Janus nanoparticles were prepared by interfacial galvanic exchange reactions of a Langmuir-Blodgett monolayer of 1-hexanethiolate-passivated silver nanoparticles on a glass slide with gold(I)-mercaptopropanediol complex in a water/ethanol solution. The resulting nanoparticles exhibited an asymmetrical distribution not only of the organic capping ligands on the nanoparticle surface but

  12. Design and development of anisotropic inorganic/polystyrene nanocomposites by surface modification of zinc oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Han, Xiao [School of Materials Science and Engineering, Tongji University, Shanghai 200092 (China); Research Center for Translational Medicine, East Hospital, the Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092 (China); Huang, Shiming [Department of Physics, Tongji University, Shanghai 200092 (China); Wang, Yilong, E-mail: yilongwang@tongji.edu.cn [Research Center for Translational Medicine, East Hospital, the Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092 (China); Shi, Donglu, E-mail: shid@ucmail.uc.edu [Research Center for Translational Medicine, East Hospital, the Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092 (China); The Materials Science and Engineering Program, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH 45221 (United States)

    2016-07-01

    Anisotropic yolk/shell or Janus inorganic/polystyrene nanocomposites were prepared by combining miniemulsion polymerization and sol–gel reaction. The morphologies of the anisotropic composites were found to be greatly influenced by surface modification of zinc oxide (ZnO) nanoparticle seeds. Two different types of the oleic acid modified ZnO nanoparticles (OA-ZnO) were prepared by post-treatment of commercial ZnO powder and homemade OA-ZnO nanoparticles. The morphologies and properties of the nanocomposites were investigated by transmission electron microscope (TEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), and energy dispersive X-ray spectroscopy (EDX). It was found that both post-treated OA-ZnO and in-situ prepared OA-ZnO nanoparticles resulted in the yolk–shell and Janus structure nanocomposites, but with varied size and morphology. These nanocomposites showed stable and strong fluorescence by introducing quantum dots as the co-seeds. The fluorescent anisotropic nanocomposites were decorated separately with surface carboxyl and hydroxyl groups. These composites with unique anisotropic properties will have high potential in biomedical applications, particularly in bio-detection. - Graphical abstract: Design and development of anisotropic inorganic/polystyrene nanocomposites by surface modification of zinc oxide nanoparticles. - Highlights: • Non-magnetic anisotropic yolk/shell or Janus nanocomposites are prepared and characterized. • Different surface modification of zinc oxide (ZnO) nanoparticles results in varied morphology and size of the final product. • Fluorescent anisotropic nanocomposites embodying quantum dots are an ideal candidate for bio-detection applications.

  13. The erotic transference: dream or delusion?

    Science.gov (United States)

    De Masi, Franco

    2012-12-01

    The erotic transference can be seen as the Janus face of clinical work in psychoanalysis: it may either arise out of the positive emotions necessary for the building of new shared realities, or be fueled by falsified and distorted constructions. In the former case, the erotic transference expresses the capacity to anticipate, or "dream," the emotional relationship with the object-which is why Freud valued its transformative aspect as one of the "forces impelling [the patient] to . . . make changes"-whereas in the latter it is equivalent to a flight from psychic reality and may be imperceptibly transformed into an actual delusion.

  14. Holographic complexity and fidelity susceptibility as holographic information dual to different volumes in AdS

    Directory of Open Access Journals (Sweden)

    N.S. Mazhari

    2017-03-01

    Full Text Available The holographic complexity and fidelity susceptibility have been defined as new quantities dual to different volumes in AdS. In this paper, we will use these new proposals to calculate both of these quantities for a variety of interesting deformations of AdS. We obtain the holographic complexity and fidelity susceptibility for an AdS black hole, Janus solution, a solution with cylindrical symmetry, an inhomogeneous background and a hyperscaling violating background. It is observed that the holographic complexity depends on the size of the subsystem for all these solutions and the fidelity susceptibility does not have any such dependence.

  15. The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells

    DEFF Research Database (Denmark)

    Rønn, Sif G; Hansen, Johnny A; Lindberg, Karen

    2002-01-01

    GH is an important regulator of cell growth and metabolism. In the pancreas, GH stimulates mitogenesis as well as insulin production in beta-cells. The cellular effects of GH are exerted mainly through activation of the Janus kinase-signal transducer and activator of transcription (STAT) pathway...... stable transfection of the beta-cell lines with plasmids expressing SOCS-3 under the control of an inducible promoter, a time- and dose-dependent expression of SOCS-3 in the cells was obtained. EMSA showed that SOCS-3 is able to inhibit GH-induced DNA binding of both STAT3 and STAT5 in RIN-5AH cells...

  16. Application of high-power lasers to equation-of-state research at ultrahigh pressures

    International Nuclear Information System (INIS)

    Trainor, R.J.; Graboske, H.C.; Long, K.S.; Shaner, J.W.

    1978-01-01

    The application of high-power pulsed lasers to ultrahigh pressure equation-of-state (EOS) experiments is discussed. It is shown that pressures along the principal Hugoniot between 1 and 10 TPa can be produced with existing lasers used for inertial-confinement fusion research. The relevance of measurements in this pressure regime to improving our understanding of condensed matter physics is also discussed. New experimental techniques as well as potential experimental problems are described, and EOS experiments on the Janus and Argus laser systems are proposed

  17. Mutation of the SHP-2 binding site in growth hormone (GH) receptor prolongs GH-promoted tyrosyl phosphorylation of GH receptor, JAK2, and STAT5B

    DEFF Research Database (Denmark)

    Stofega, M R; Herrington, J; Billestrup, Nils

    2000-01-01

    phosphorylation. Consistent with the effects on STAT5B phosphorylation, tyrosine-to-phenylalanine mutation of tyrosine 595 prolongs the duration of tyrosyl phosphorylation of GHR and JAK2. These data suggest that tyrosine 595 is a major site of interaction of GHR with SHP-2, and that GHR-bound SHP-2 negatively......Binding of GH to GH receptor (GHR) rapidly and transiently activates multiple signal transduction pathways that contribute to the growth-promoting and metabolic effects of GH. While the events that initiate GH signal transduction, such as activation of the Janus tyrosine kinase JAK2, are beginning...

  18. Expanding the Bethe/Gauge dictionary

    Science.gov (United States)

    Bullimore, Mathew; Kim, Hee-Cheol; Lukowski, Tomasz

    2017-11-01

    We expand the Bethe/Gauge dictionary between the XXX Heisenberg spin chain and 2d N = (2, 2) supersymmetric gauge theories to include aspects of the algebraic Bethe ansatz. We construct the wave functions of off-shell Bethe states as orbifold defects in the A-twisted supersymmetric gauge theory and study their correlation functions. We also present an alternative description of off-shell Bethe states as boundary conditions in an effective N = 4 supersymmetric quantum mechanics. Finally, we interpret spin chain R-matrices as correlation functions of Janus interfaces for mass parameters in the supersymmetric quantum mechanics.

  19. Theory-Based Evaluation Meets Ambiguity

    DEFF Research Database (Denmark)

    Dahler-Larsen, Peter

    2017-01-01

    As theory-based evaluation (TBE) engages in situations where multiple stakeholders help develop complex program theory about dynamic phenomena in politically contested settings, it becomes difficult to develop and use program theory without ambiguity. The purpose of this article is to explore...... ambiguity as a fruitful perspective that helps TBE face current challenges. Literatures in organization theory and political theory are consulted in order to cultivate the concept of ambiguity. Janus variables (which work in two ways) and other ambiguous aspects of program theories are classified...... and exemplified. Stances towards ambiguity are considered, as are concrete steps that TBE evaluators can take to identify and deal with ambiguity in TBE....

  20. Development of a Smart Diagnostics Platform for Early-Stage Screening of Breast Cancer

    Science.gov (United States)

    2007-04-01

    H H H H O H O HO OH OH H H H H OH F3 COCO O CO CF3 O H H H H O CF3 O F3 C O HO O CO CF 3 O H H H H O HF3 C O LiAlH4 /THF (CF3 CO )2 O NaHCO 3 THF/MeOH...Novel Fabrication of Janus Particles from the Surfaces of Electrospun Polymer Fibers . Langmuir 2008, 24, 5663–5666. 50. Chen, H. Y.; Rouillard, J. M

  1. Diagnostic measurements related to laser driven inertial confinement fusion

    International Nuclear Information System (INIS)

    Campbell, D.E.

    1979-01-01

    Scientists at the Lawrence Livermore Laboratory have been conducting laser driven inertial confinement fusion experiments for over five years. The first proof of the thermonuclear burn came at the Janus target irradiation facility in the spring of 1975. Since that time three succeedingly higher energy facilities have been constructed at Livermore, Cyclops, Argus and Shiva, where increased fusion efficiency has been demonstrated. A new facility, called Nova, is now in the construction phase and we are hopeful that scientific break even (energy released compared to incident laser energy on target) will be demonstrated here in early 1980's. Projected progress of the Livermore program is shown

  2. Musik for folket! http://www.aabenraa-lokal-tv.dk/wp/2010/11/22/22-november-%E2%80%93-29-november-musik-for-folket/

    DEFF Research Database (Denmark)

    Grund, Cynthia M.; Araghipour, Janus Høgfeldt; Bonne, Jane

    2010-01-01

    The TV-documentary "Musik for folket!" (in Danish) was filmed during the November 11 lunchtime concert and through a series of interviews with Carsten Sjødahl, Jane Bonne, Leif Jensen, Søren R. Frimodt-Møller, Janus Høgfeldt Araghipour and Cynthia M. Grund, it recounts the story behind the luncht...... the lunchtime concert series at SDU. The program aired November 22-29, 2010 on ALTV and is permanently available from November 22, 2010 onwards at http://www.aabenraa-lokal-tv.dk/wp/2010/11/22/22-november-%E2%80%93-29-november-musik-for-folket/...

  3. Special AT rich-binding1 protein (SATB1) in malignant T cells

    DEFF Research Database (Denmark)

    Fredholm, Simon; Willerslev-Olsen, Andreas; Met, Özcan

    2018-01-01

    Deficient expression of Suppressor Special AT-rich Binding-1 (SATB1) hampers thymocyte development and results in inept T cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides (MF), the most frequent variant of cutaneous T cell lymphoma (CTCL......) whereas increased SATB1 expression had the opposite effect indicating that the mir-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5, and its upstream activator Janus Kinase-3 (Jak3), triggered increased SATB1 expression and a concomitant suppression...

  4. Searching for a traveling feature in Saturn's rings in Cassini Imaging Science Subsystem data

    Science.gov (United States)

    Aye, Klaus-Michael; Rehnberg, Morgan; Brown, Zarah; Esposito, Larry W.

    2016-10-01

    Introduction: Using Cassini UVIS occultation data, a traveling wave feature has been identified in the Saturn rings that is most likely caused by the radial positions swap of the moons Janus and Epimetheus [1]. The hypothesis is that non-linear interferences between the linear density waves when being relocated by the moon swap create a solitary wave that is traveling outward through the rings. The observations in [1] further lead to the derivation of values for the radial travel speeds of the identified traveling features, from 39.6 km/yr for the Janus 5:4 resonance up to 45.8 for the Janus 4:3 resonance.Previous confirmations in ISS data: Work in [1] also identified the feature in Cassini Imaging Science Subsystem (ISS) data that was taken around the time of the UVIS occultations where the phenomenon was first discovered, so far one ISS image for each Janus resonances 2:1, 4:3, 5:4, and 6:5.Search guided by predicted locations: Using the observation-fitted radial velocities from [1], we can extrapolate these to identify Saturn radii at which the traveling feature should be found at later times. Using this and new image analysis and plotting tools available in [2], we have identified a potential candidate feature in an ISS image that was taken 2.5 years after the feature causing moon swap in January 2006. We intend to expand our search by identifying candidate ISS data by a meta-database search constraining the radius at future times corresponding to the predicted future locations of the hypothesized solitary wave and present our findings at this conference.References: [1] Rehnberg, M.E., Esposito, L.W., Brown, Z.L., Albers, N., Sremčević, M., Stewart, G.R., 2016. A Traveling Feature in Saturn's Rings. Icarus, accepted in June 2016. [2] K.-Michael Aye. (2016). pyciss: v0.5.0. Zenodo. 10.5281/zenodo.53092

  5. Confirmation of a traveling feature in Saturn's rings in Cassini Imaging Science Subsystem data

    Science.gov (United States)

    Aye, K. M.; Rehnberg, M.; Esposito, L. W.

    2017-12-01

    Introduction: Using Cassini UVIS occultation data, a traveling wave feature has been identified in the Saturn rings that is most likely caused by the radial positions swap of the moons Janus and Epimetheus [1]. The hypothesis is that non-linear interferences between the density waves when being relocated by the moon swap create a solitary wave that is traveling outward through the rings. The observations in [1] further lead to the derivation of values for the radial travel speeds of the identified traveling features, from 39.6 km/yr for the Janus 5:4 resonance up to 45.8 for the Janus 4:3 resonance. Previous confirmations in ISS data: Work in [1] also identified the feature in Cassini Imaging Science Subsystem (ISS) data that was taken around the time of the UVIS occultations where the phenomenon was first discovered, so far one ISS image for each Janus resonances 2:1, 4:3, 5:4, and 6:5. Searches performed in ISS data: Filtering all existing ISS data down to the best resolutions that include both a clearly identifiable minimum and maximum ring radius, we have visually inspected approx. 200 images, both with and without known resonances within the image, but unbeknownst to the inspector. Identification of a feature of interest happens when train waves are being interrupted by anomalies. Comparing the radial locations of identified ISS features with those in UV data of [1], we have identified several at the same radii. Considering the vast differences in radial resolution, we conclude that the traveling feature causes observable anomalies at both small scales of meters, up to large scales of hundreds of meters to kilometers.References: [1] Rehnberg, M.E., Esposito, L.W., Brown, Z.L., Albers, N., Sremčević, M., Stewart, G.R., 2016. A Traveling Feature in Saturn's Rings. Icarus, accepted in June 2016. [2] K.-Michael Aye (2016, November 11). michaelaye/pyciss: . v0.6.0 Zenodo. https://doi.org/10.5281/zenodo.596802

  6. Closure phenomena in pinholes irradiated by Nd laser pulses

    Energy Technology Data Exchange (ETDEWEB)

    Auerbach, J.M.; Holmes, N.C.; Hunt, J.T.; Linford, G.J.

    1979-07-15

    An experimental investigation has been made on plasma closure in pinholes irradiated by Nd glass laser pulses; 300--500-..mu..m diam pinholes of various materials and thicknesses have been irradiated by 20--100-J 300-psec FWHM pulses on the Janus laser system. Calorimetry measurements have yielded data on pinhole energy transmission and intensity loading on the periphery of the pinhole. Ultrafast streak photography measurements indicate effective closure velocities of 2--5 x 10/sup 7/ cm/sec. Scattered light measurements have shown the transmission loss through a typical spatial filter configuration to be primarily refractive in nature.

  7. Life shortening, tumor induction, and tissue dose for fission-neutron and gamma-ray irradiations

    International Nuclear Information System (INIS)

    Grahn, D.; Duggal, K.; Lombard, L.S.

    1985-01-01

    The primary focus of this program is to obtain information on the late effects of whole body exposure to low doses of a high linear-energy-transfer (LET) and a low-LET ionizing radiation in experimental animals to provide guidance for the prediction of radiation hazards to man. The information obtained takes the form of dose-response curves for life shortening and for the induction of numerous specific types of tumors. The animals are irradiated with fission neutrons from the Janus reactor and with 60 Co gamma rays, delivered as single, weekly, or duration-of-life exposures covering the range of doses and dose rates. 6 refs

  8. Self-propelled magnesium based micromotors: synthesis and magnetic steering

    Directory of Open Access Journals (Sweden)

    Jin Dongdong

    2015-01-01

    Full Text Available In this work the magnesium based Janus micromotors were prepared by an asymmetric coating of Co-Au bilayer on the surface of Mg microparticles. The micromotor could efficiently self-propel in phosphate buffer saline (PBS with a highest speed of 221 μm·s−1 without any extra additives through the macrogalvanic corrosion and pitting corrosion mechanism. The influence of pH value of PBS buffer on the motion of micromotor was also investigated. Moreover, we demonstrated that the motion of micromotor could be controlled by an external magnetic field rapidly and accurately, indicating the potential application in biomedicine.

  9. Bubble Driven Quasioscillatory Translational Motion of Catalytic Micromotors

    Science.gov (United States)

    Manjare, Manoj; Yang, Bo; Zhao, Y.-P.

    2012-09-01

    A new quasioscillatory translational motion has been observed for big Janus catalytic micromotors with a fast CCD camera. Such motional behavior is found to coincide with both the bubble growth and burst processes resulting from the catalytic reaction, and the competition of the two processes generates a net forward motion. Detailed physical models have been proposed to describe the above processes. It is suggested that the bubble growth process imposes a growth force moving the micromotor forward, while the burst process induces an instantaneous local pressure depression pulling the micromotor backward. The theoretic predictions are consistent with the experimental data.

  10. The Ambivalent Relations between Bureaucracy and Public Innovation:

    DEFF Research Database (Denmark)

    Schultz Larsen, Troels

    2015-01-01

    Building on a growing body of literature on public innovation and the rediscovery of bureaucracy, this article explores the relations between innovation and bureaucracy. A framework for studying innovation in a bureaucratic context is developed and its relevance assessed through a case study...... of the successful implementation but failed diffusion of an innovation project. The case study demonstrates how a bureaucratic context represents not only barriers to innovation but also a number of complex drivers. The outline of these ambivalent relations is used to tease out the Janus face of the new spirit...... of innovation in public administration....

  11. Holographic complexity and fidelity susceptibility as holographic information dual to different volumes in AdS

    Energy Technology Data Exchange (ETDEWEB)

    Mazhari, N.S., E-mail: najmemazhari86@gmail.com [Eurasian International Center for Theoretical Physics and Department of General & Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan); Momeni, Davood, E-mail: davoodmomeni78@gmail.com [Eurasian International Center for Theoretical Physics and Department of General & Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan); Bahamonde, Sebastian, E-mail: sebastian.beltran.14@ucl.ac.uk [Department of Mathematics, University College London, Gower Street, London, WC1E 6BT (United Kingdom); Faizal, Mir, E-mail: mirfaizalmir@googlemail.com [Irving K. Barber School of Arts and Sciences, University of British Columbia - Okanagan, 3333 University Way, Kelowna, British Columbia, V1V 1V7 (Canada); Department of Physics and Astronomy, University of Lethbridge, Lethbridge, Alberta, T1K 3M4 (Canada); Myrzakulov, Ratbay, E-mail: rmyrzakulov@gmail.com [Eurasian International Center for Theoretical Physics and Department of General & Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan)

    2017-03-10

    The holographic complexity and fidelity susceptibility have been defined as new quantities dual to different volumes in AdS. In this paper, we will use these new proposals to calculate both of these quantities for a variety of interesting deformations of AdS. We obtain the holographic complexity and fidelity susceptibility for an AdS black hole, Janus solution, a solution with cylindrical symmetry, an inhomogeneous background and a hyperscaling violating background. It is observed that the holographic complexity depends on the size of the subsystem for all these solutions and the fidelity susceptibility does not have any such dependence.

  12. Climate change - the impacts

    International Nuclear Information System (INIS)

    Reysset, Bertrand; Billes-Garabedian, Laurent; Henique, Julien; Pascal, Mathilde; Pirard, Philippe; Motreff, Yvon; Barbault, Robert; Weber, Jacques; Gate, Philippe; Salagnac, Jean-Luc; Desplat, Julien; Kounkou-Arnaud, Raphaelle

    2012-01-01

    This special dossier about the impacts of climate change is made of 6 contributions dealing with: the mitigation of climate effects and how to deal with them (Bertrand Reysset); how to dare and transmit (Laurent Billes-Garabedian); littoral risks, the Pas-de-Calais example (Julien Henique); extreme meteorological events and health impacts (Mathilde Pascal, Philippe Pirard, Yvon Motreff); Biodiversity and climate: the janus of global change (Robert Barbault, Jacques Weber); adapting agriculture to dryness and temperatures (Philippe Gate); Paris and the future heats of the year 2100 (Jean-Luc Salagnac, Julien Desplat, Raphaelle Kounkou-Arnaud)

  13. Recoil-proton polarization in πp elastic scattering at 547 and 625 MeV/c

    International Nuclear Information System (INIS)

    Seftor, C.J.; Adrian, S.D.; Briscoe, W.J.; Mokhtari, A.; Taragin, M.F.; Sadler, M.E.; Barlow, D.B.; Nefkens, B.M.K.; Pillai, C.

    1989-01-01

    The polarization of the recoil proton in π + p and π - p elastic scattering using a liquid-hydrogen target has been measured for backward angles at 547 and 625 MeV/c. The scattered pion and recoil proton were detected in coincidence using the large-acceptance spectrometer to detect and analyze the momentum of the pions and the JANUS polarimeter to identify and measure the polarization of the protons. Results from this experiment agree with other measurements of the recoil polarization, with analyzing-power data previously taken by this group, and with predictions of partial-wave analyses

  14. Alopecia areata: Update on management

    Directory of Open Access Journals (Sweden)

    Julie S Kranseler

    2017-01-01

    Full Text Available Alopecia areata (AA is a common autoimmune nonscarring alopecia. AA presents heterogeneously and is influenced by both environmental and genetic factors. Diagnosis is clinical after ruling out other local or systemic causes of alopecia. Standard first-line therapy is typically topical steroids, but the response can be frustrating. Novel treatment options have shown great promise in the management of the refractory disease. We review initial data on topical and systemic Janus kinase inhibitors (tofacitinib, ruxolitinib, and baricitinib, topical bimatoprost, simvastatin/ezetimibe, and excimer laser therapy among others within the context of a general approach to AA management.

  15. Dual of big bang and big crunch

    International Nuclear Information System (INIS)

    Bak, Dongsu

    2007-01-01

    Starting from the Janus solution and its gauge theory dual, we obtain the dual gauge theory description of the cosmological solution by the procedure of double analytic continuation. The coupling is driven either to zero or to infinity at the big-bang and big-crunch singularities, which are shown to be related by the S-duality symmetry. In the dual Yang-Mills theory description, these are nonsingular as the coupling goes to zero in the N=4 super Yang-Mills theory. The cosmological singularities simply signal the failure of the supergravity description of the full type IIB superstring theory

  16. Stochastic localization of microswimmers by photon nudging.

    Science.gov (United States)

    Bregulla, Andreas P; Yang, Haw; Cichos, Frank

    2014-07-22

    Force-free trapping and steering of single photophoretically self-propelled Janus-type particles using a feedback mechanism is experimentally demonstrated. Realtime information on particle position and orientation is used to switch the self-propulsion mechanism of the particle optically. The orientational Brownian motion of the particle thereby provides the reorientation mechanism for the microswimmer. The particle size dependence of the photophoretic propulsion velocity reveals that photon nudging provides an increased position accuracy for decreasing particle radius. The explored steering mechanism is suitable for navigation in complex biological environments and in-depth studies of collective swimming effects.

  17. SH2B1 regulation of energy balance, body weight, and glucose metabolism

    OpenAIRE

    Rui, Liangyou

    2014-01-01

    The Src homology 2B (SH2B) family members (SH2B1, SH2B2 and SH2B3) are adaptor signaling proteins containing characteristic SH2 and PH domains. SH2B1 (also called SH2-B and PSM) and SH2B2 (also called APS) are able to form homo- or hetero-dimers via their N-terminal dimerization domains. Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins, including Janus kinase 2 (JAK2), TrkA, insulin receptors, insulin-like growth factor-1 receptors, insulin receptor substrate-1 (IRS1), and...

  18. Summary of 2016 Light Microscopy Module (LMM) Physical Science Experiments on ISS. Update of LMM Science Experiments and Facility Capabilities

    Science.gov (United States)

    Sicker, Ronald J.; Meyer, William V.; Foster, William M.; Fletcher, William A.; Williams, Stuart J.; Lee, Chang-Soo

    2016-01-01

    This presentation will feature a series of short, entertaining, and informative videos that describe the current status and science support for the Light Microscopy Module (LMM) facility on the International Space Station. These interviews will focus on current experiments and provide an overview of future capabilities. The recently completed experiments include nano-particle haloing, 3-D self-assembly with Janus particles and a model system for nano-particle drug delivery. The videos will share perspectives from the scientists, engineers, and managers working with the NASA Light Microscopy program.

  19. Rigorous symmetry adaptation of multiorbital rotationally invariant slave-boson theory with application to Hund's rules physics

    Science.gov (United States)

    Piefke, Christoph; Lechermann, Frank

    2018-03-01

    The theory of correlated electron systems on a lattice proves notoriously complicated because of the exponential growth of Hilbert space. Mean-field approaches provide valuable insight when the self-energy has a dominant local structure. Additionally, the extraction of effective low-energy theories from the generalized many-body representation is highly desirable. In this respect, the rotational-invariant slave-boson (RISB) approach in its mean-field formulation enables versatile access to correlated lattice problems. However, in its original form, due to numerical complexity, the RISB approach is limited to about three correlated orbitals per lattice site. We thus present a thorough symmetry-adapted advancement of RISB theory, suited to efficiently deal with multiorbital Hubbard Hamiltonians for complete atomic-shell manifolds. It is utilized to study the intriguing problem of Hund's physics for three- and especially five-orbital manifolds on the correlated lattice, including crystal-field terms as well as spin-orbit interaction. The well-known Janus-face phenomenology, i.e., strengthening of correlations at smaller-to-intermediate Hubbard U accompanied by a shift of the Mott transition to a larger U value, has a stronger signature and more involved multiplet resolution for five-orbital problems. Spin-orbit interaction effectively reduces the critical local interaction strength and weakens the Janus-face behavior. Application to the realistic challenge of Fe chalcogenides underlines the subtle interplay of the orbital degrees of freedom in these materials.

  20. Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth

    2010-01-01

    CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator of transcr......CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator...... of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T......-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

  1. Anisotropic Metal Deposition on TiO2 Particles by Electric-Field-Induced Charge Separation.

    Science.gov (United States)

    Tiewcharoen, Supakit; Warakulwit, Chompunuch; Lapeyre, Veronique; Garrigue, Patrick; Fourier, Lucas; Elissalde, Catherine; Buffière, Sonia; Legros, Philippe; Gayot, Marion; Limtrakul, Jumras; Kuhn, Alexander

    2017-09-11

    Deposition of metals on TiO 2 semiconductor particles (M-TiO 2 ) results in hybrid Janus objects combining the properties of both materials. One of the techniques proposed to generate Janus particles is bipolar electrochemistry (BPE). The concept can be applied in a straightforward way for the site-selective modification of conducting particles, but is much less obvious to use for semiconductors. Herein we report the bulk synthesis of anisotropic M-TiO 2 particles based on the synergy of BPE and photochemistry, allowing the intrinsic limitations, when they are used separately, to be overcome. When applying electric fields during irradiation, electrons and holes can be efficiently separated, thus breaking the symmetry of particles by modifying them selectively and in a wireless way on one side with either gold or platinum. Such hybrid materials are an important first step towards high-performance designer catalyst particles, for example for photosplitting of water. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. The effect of 2-[(aminopropyl)amino] ethanethiol on fission-neutron-induced DNA damage and repair.

    Science.gov (United States)

    Grdina, D. J.; Sigdestad, C. P.; Dale, P. J.; Perrin, J. M.

    1989-01-01

    The effect(s) of the radioprotector 2-[(aminopropyl)amino] ethanethiol (WR 1065) on fission-neutron-induced DNA damage and repair in V79 Chinese hamster cells was determined by using a neutral filter elution procedure (pH 7.2). When required, WR1065, at a final working concentration of 4 mM, was added to the culture medium, either 30 min before and during irradiation with fission spectrum neutrons (beam energy of 0.85 MeV) from the JANUS research reactor, or for selected intervals of time following exposure. The frequency of neutron-induced DNA strand breaks as measured by neutral elution as a function of dose equalled that observed for 60Co gamma-ray-induced damage (relative biological effectiveness of one). In contrast to the protective effect exhibited by WR1065 in reducing 60Co-induced DNA damage, WR1065 was ineffective in reducing or protecting against induction of DNA strand breaks by JANUS neutrons. The kinetics of DNA double-strand rejoining were measured following neutron irradiation. In the absence of WR1065, considerable DNA degradation by cellular enzymes was observed. This process was inhibited when WR1065 was present. These results indicate that, under the conditions used, the quality (i.e. nature), rather than quantity, of DNA lesions (measured by neutral elution) formed by neutrons was significantly different from that formed by gamma-rays. PMID:2667608

  3. Advances in Multicompartment Mesoporous Silica Micro/Nanoparticles for Theranostic Applications.

    Science.gov (United States)

    Liu, Jian; Liu, Tingting; Pan, Jian; Liu, Shaomin; Lu, G Q Max

    2018-04-04

    Mesoporous silica nanoparticles (MSNs) are promising functional nanomaterials for a variety of biomedical applications, such as bioimaging, drug/gene delivery, and cancer therapy. This is due to their low density, low toxicity, high biocompatibility, large specific surface areas, and excellent thermal and mechanical stability. The past decade has seen rapid advances in the development of MSNs with multiple compartments. These include hierarchical porous structures and core-shell, yolk-shell, and Janus structured particles for efficient diagnosis and therapeutic applications. We review advances in this area, covering the categories of multicompartment MSNs and their synthesis methods, with an emphasis on hierarchical structures and the incorporation of multiple functions. We classify multicompartment mesoporous silica micro/nanostructures, ranging from core-shell and yolk-shell structures to Janus and raspberry-like nanoparticles, and discuss their synthesis methods. We review applications of these multicompartment MSNs, including bioimaging, targeted drug/gene delivery, chemotherapy, phototherapy, and in vitro diagnostics. We also highlight the latest trends and new opportunities. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering Volume 9 is June 7, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  4. Microfluidic Fabrication of Morphology-Controlled Polymeric Microspheres of Blends of Poly(4-butyltriphenylamine and Poly(methyl methacrylate

    Directory of Open Access Journals (Sweden)

    Saki Yoshida

    2018-04-01

    Full Text Available Multicomponent polymer particles with specific morphology are promising materials exhibiting novel functionality which cannot be obtained with single-component polymer particles. Particularly, the preparation of such kinds of polymer particles involving electrically or optically active conjugated polymers with uniform size is a challenging subject due to their intense demands. Here, microspheres of binary polymer blend consisting of poly(4-butyltriphenylamine (PBTPA/poly(methyl methacrylate (PMMA (1:1 in weight were produced via a microfluidic emulsification with a Y-shaped microreactor, and a subsequent solvent evaporation method. The flow rate of the dispersed phase (polymer solution was fixed to 7 µL/min, and 140 or 700 µL/min of the flow rate of the continuous phase (aqueous 0.6 wt % of poly(vinyl alcohol (PVA solution was utilized to produce the dispersion with different diameter. The concentration of dispersed phase was adjusted to 0.1 or 1.0 w/v%. Core-shell, Janus and dumbbell type microspheres were obtained dependent on the flow rate of continuous phase. Incomplete core-shell type microspheres were produced for the blend involving low molecular weight PMMA. Complex Janus and core-shell type microspheres were fabricated by the addition of sodium dodecyl sulfate (SDS to continuous phase. It is found that final morphologies are strongly dependent on the initial conditions of dispersion including the particle size suggesting that the morphologies are governed by the kinetical factors together with the conventionally accepted thermodynamic ones.

  5. Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis

    Science.gov (United States)

    Cosgrove, Sallie B; Wren, Jody A; Cleaver, Dawn M; Martin, David D; Walsh, Kelly F; Harfst, Jessica A; Follis, Stacey L; King, Vickie L; Boucher, Joseph F; Stegemann, Michael R

    2013-01-01

    Background Oclacitinib (Apoquel®) inhibits the function of a variety of pro-inflammatory, pro-allergic and pruritogenic cytokines that are dependent on Janus kinase enzyme activity. Oclacitinib selectively inhibits Janus kinase 1. Hypothesis/Objectives We aimed to evaluate the safety and efficacy of oclacitinib for the control of pruritus associated with allergic dermatitis in a randomized, double-blinded, placebo-controlled trial. Methods Client-owned dogs (n = 436) with moderate to severe owner-assessed pruritus and a presumptive diagnosis of allergic dermatitis were enrolled. Dogs were randomized to either oclacitinib at 0.4–0.6 mg/kg orally twice daily or an excipient-matched placebo. An enhanced 10 cm visual analog scale (VAS) was used by the owners to assess the severity of pruritus from day 0 to 7 and by veterinarians to assess the severity of dermatitis on days 0 and 7. Dogs could remain on the study for 28 days. Results Pretreatment owner and veterinary VAS scores were similar for the two treatment groups. Oclacitinib produced a rapid onset of efficacy within 24 h. Mean oclacitinib Owner Pruritus VAS scores were significantly better than placebo scores (P Dermatitis VAS scores were also significantly better (P dermatitis, with owners and veterinarians noting substantial improvements in pruritus and dermatitis VAS scores. PMID:23829933

  6. Differential effect of ionizing radiation on transcription in repair-deficient and repair-proficient mice

    International Nuclear Information System (INIS)

    Munson, G.P.; Woloschak, G.E.

    1990-01-01

    Experiments were designed to examine in vivo changes in total transcription and in the expression of the c-fos gene following whole-body exposure of mice to JANUS fission-spectrum neutrons. Radiation repair-deficient (wst/wst) and -proficient (wst/., C57BL/6 x C3H F1) mice were exposed to JANUS fission-spectrum neutrons calibrated to deliver a gut dose of 50 cGy. Animals were sacrificed less than 10 or at 60 min postirradiation, and gut tissues were removed for study. Our results revealed that, in repair-proficient mice, an immediate depression (relative to untreated control) in total transcription was evident that continued through 1 h postirradiation. Conversely, radiation-sensitive wst/wst mice displayed doubled transcription levels postirradiation. Expression of c-fos was consistently depressed following radiation exposure in control and wst/wst mice. However, the depression of c-fos mRNA was delayed in wst/wst mice relative to controls. These results demonstrate abnormal regulation of transcription and of c-fos mRNA accumulation in repair-deficient wasted mice following exposure to ionizing radiation. In addition, this work documents rapid total transcriptional depression in normal mice following radiation exposure

  7. Chemical/Light-Powered Hybrid Micromotors with "On-the-Fly" Optical Brakes.

    Science.gov (United States)

    Chen, Chuanrui; Tang, Songsong; Teymourian, Hazhir; Karshalev, Emil; Zhang, Fangyu; Li, Jinxing; Mou, Fangzhi; Liang, Yuyan; Guan, Jianguo; Wang, Joseph

    2018-07-02

    Hybrid micromotors capable of both chemically powered propulsion and fuel-free light-driven actuation and offering built-in optical brakes for chemical propulsion are described. The new hybrid micromotors are designed by combining photocatalytic TiO 2 and catalytic Pt surfaces into a Janus microparticle. The chemical reactions on the different surfaces of the Janus particle hybrid micromotor can be tailored by using chemical or light stimuli that generate counteracting propulsion forces on the catalytic Pt and photocatalytic TiO 2 sides. Such modulation of the surface chemistry on a single micromotor leads to switchable propulsion modes and reversal of the direction of motion that reflect the tuning of the local ion concentration and hence the dominant propulsion force. An intermediate Au layer (under the Pt surface) plays an important role in determining the propulsion mechanism and operation of the hybrid motor. The built-in optical braking system allows "on-the-fly" control of the chemical propulsion through a photocatalytic reaction on the TiO 2 side to counterbalance the chemical propulsion force generated on the Pt side. The adaptive dual operation of these chemical/light hybrid micromotors, associated with such control of the surface chemistry, holds considerable promise for designing smart nanomachines that autonomously reconfigure their propulsion mode for various on-demand operations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Self-assembly of three-dimensional open structures using patchy colloidal particles.

    Science.gov (United States)

    Rocklin, D Zeb; Mao, Xiaoming

    2014-10-14

    Open structures can display a number of unusual properties, including a negative Poisson's ratio, negative thermal expansion, and holographic elasticity, and have many interesting applications in engineering. However, it is a grand challenge to self-assemble open structures at the colloidal scale, where short-range interactions and low coordination number can leave them mechanically unstable. In this paper we discuss the self-assembly of three-dimensional open structures using triblock Janus particles, which have two large attractive patches that can form multiple bonds, separated by a band with purely hard-sphere repulsion. Such surface patterning leads to open structures that are stabilized by orientational entropy (in an order-by-disorder effect) and selected over close-packed structures by vibrational entropy. For different patch sizes the particles can form into either tetrahedral or octahedral structural motifs which then compose open lattices, including the pyrochlore, the hexagonal tetrastack and the perovskite lattices. Using an analytic theory, we examine the phase diagrams of these possible open and close-packed structures for triblock Janus particles and characterize the mechanical properties of these structures. Our theory leads to rational designs of particles for the self-assembly of three-dimensional colloidal structures that are possible using current experimental techniques.

  9. Bifunctional Phosphorus Dendrimers and Their Properties.

    Science.gov (United States)

    Caminade, Anne-Marie; Majoral, Jean-Pierre

    2016-04-23

    Dendrimers are hyperbranched and monodisperse macromolecules, generally considered as a special class of polymers, but synthesized step-by-step. Most dendrimers have a uniform structure, with a single type of terminal function. However, it is often desirable to have at least two different functional groups. This review will discuss the case of bifunctional phosphorus-containing dendrimers, and the consequences for their properties. Besides the terminal functions, dendritic structures may have also a function at the core, or linked off-center to the core, or at the core of dendrons (dendritic wedges). Association of two dendrons having different terminal functions leads to Janus dendrimers (two faces). The internal structure can also possess functional groups on one layer, or linked to one layer, or on several layers. Finally, there are several ways to have two types of terminal functions, besides the case of Janus dendrimers: either each terminal function bears two functions sequentially, or two different functions are linked to each terminal branching point. Examples of each type of structure will be given in this review, as well as practical uses of such sophisticated structures in the fields of fluorescence, catalysis, nanomaterials and biology.

  10. Self-Assembled Colloidal Particle Clusters from In Situ Pickering-Like Emulsion Polymerization via Single Electron Transfer Mechanism.

    Science.gov (United States)

    Yuan, Jinfeng; Zhao, Weiting; Pan, Mingwang; Zhu, Lei

    2016-08-01

    A simple route is reported to synthesize colloidal particle clusters (CPCs) from self-assembly of in situ poly(vinylidene fluoride)/poly(styrene-co-tert-butyl acrylate) [PVDF/P(St-co-tBA)] Janus particles through one-pot seeded emulsion single electron transfer radical polymerization. In the in situ Pickering-like emulsion polymerization, the tBA/St/PVDF feed ratio and polymerization temperature are important for the formation of well-defined CPCs. When the tBA/St/PVDF feed ratio is 0.75 g/2.5 g/0.5 g and the reaction temperature is 35 °C, relatively uniform raspberry-like CPCs are obtained. The hydrophobicity of the P(St-co-tBA) domains and the affinity of PVDF to the aqueous environment are considered to be the driving force for the self-assembly of the in situ formed PVDF/P(St-co-tBA) Janus particles. The resultant raspberry-like CPCs with PVDF particles protruding outward may be promising for superhydrophobic smart coatings. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Hvad kan de nu?

    DEFF Research Database (Denmark)

    Gredsted, Leif; Rasmussen, Per Arne

    toårigt udviklingsarbejde i deres klasser. Janus-projektet, der havde ?Skolefag og edb? som undertitel, havde til hensigt at tilvejebringe viden om, hvorledes en undervisning i et skolefag kunne tilrettelægges og gennemføres, således at både den it-faglige og den såkaldt fag-faglige side af integrationen......I skoleåret 1995/96 blev der i forbindelse med udviklingsarbejdet Janus gennemført en undersøgelse af elevernes viden og erfaringer med brug af computer i skolen og hjemme. Undersøgelsen blev gennemført i to 2. klasser på Hjortespring skole, hvor i alt 20 elever blev interviewet som start på et...... af edb blev tilgodeset. Desuden skulle der tilvejebringes viden om, hvorledes integrationen af edb i undervisningen kunne tænkes at indvirke på udvalgte skolefags indhold og metoder. Det er en almindeligt udbredt antagelse, at der i de forløbne 10 år er sket en væsentlig ændring i den generelle it...

  12. Tofacitinib for the treatment of alopecia areata and variants in adolescents.

    Science.gov (United States)

    Craiglow, Brittany G; Liu, Lucy Y; King, Brett A

    2017-01-01

    There are no reliably effective therapies for alopecia areata (AA). We sought to evaluate the benefit and adverse effects of the Janus kinase 1/3 inhibitor, tofacitinib, in a series of adolescent patients with AA. We reviewed the records of 13 adolescent patients with AA treated with tofacitinib. Severity of disease was assessed using the Severity of Alopecia Tool (SALT). Adverse events were evaluated by laboratory monitoring, physical examinations, and review of systems. Thirteen patients, aged 12 to 17 years, with AA were treated with tofacitinib. Nine patients experienced clinically significant hair regrowth. Median percent change in SALT score was 93% (mean 61%; 1%-100%) at an average of 6.5 months of treatment. Adverse events were mild. Limitations include the retrospective nature of the data, small sample size, and lack of a control group. Tofacitinib is a promising therapy for AA in adolescents. The use of tofacitinib and other Janus kinase inhibitors for the treatment of AA in this age group should be further evaluated in prospective clinical trials. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  13. Clinical utility of the oral JAK inhibitor tofacitinib in the treatment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Cutolo M

    2013-11-01

    Full Text Available Maurizio Cutolo, Marianna Meroni Research Laboratories and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy Abstract: Immune/inflammatory cells act in rheumatoid arthritis (RA-affected patients by synthesizing several inflammatory mediators, including cytokines that initiate intracellular signaling. Recently, small molecule inhibitors of transduction and transcription signals that influence the intracellular pathways (such as the Janus kinase [JAK] family of tyrosine kinases have been tested for RA treatment. Four members of the JAK family are known: JAK1, JAK2, JAK3, and TyK2. JAK1/JAK3 constitutively binds to the cytoplasmic portion of the cytokine receptor – the common gamma chain – that represents a common subunit of several cytokines involved in T-cell and natural killer cell development, as well as in B-cell activation. Tofacitinib is an oral JAK inhibitor that is now available and effective in RA treatment, as shown in multiple Phase II and Phase III clinical trials. However, long-term safety data and comparisons with other disease-modifying antirheumatic drugs and small molecule inhibitors are necessary to better determine the role of tofacitinib in RA. Keywords: Janus kinase inhibitors, tofacitinib, rheumatoid arthritis, kinases, small molecules inhibitors, intracellular signaling

  14. The Effects of Radiation and Dose-Fractionation on Cancer and Non-Tumor Disease Development

    Directory of Open Access Journals (Sweden)

    Gayle E. Woloschak

    2012-12-01

    Full Text Available The Janus series of radiation experiments, conducted from 1970 to 1992, explored the effects of gamma and neutron radiation on animal lifespan and disease development. Data from these experiments presents an opportunity to conduct a large scale analysis of both tumor and non-tumor disease development. This work was focused on a subset of animals from the Janus series of experiments, comparing acute or fractionated exposures of gamma or neutron radiation on the hazards associated with the development of tumor and non-tumor diseases of the liver, lung, kidney or vascular system. This study also examines how the co-occurrence of non-tumor diseases may affect tumor-associated hazards. While exposure to radiation increases the hazard of dying with tumor and non-tumor diseases, dose fractionation modulates these hazards, which varies across different organ systems. Finally, the effect that concurrent non-cancer diseases have on the hazard of dying with a tumor also differs by organ system. These results highlight the complexity in the effects of radiation on the liver, lung, kidney and vascular system.

  15. Poloidal and toroidal plasmons and fields of multilayer nanorings

    International Nuclear Information System (INIS)

    Garapati, K. V.; Salhi, M.; Kouchekian, S.; Siopsis, G.

    2017-01-01

    Composite and janus type metallodielectric nanoparticles are increasingly considered as a means to control the spatial and temporal behavior of electromagnetic fields in diverse applications such as coupling to quantum emitters, achieving invisibility cloaks, and obtaining quantum correlations between qubits. We investigate the surface modes of a toroidal nanostructure and obtain the canonical plasmon dispersion relations and resonance modes for arbitrarily layered nanorings. Unlike particle plasmon eigenmodes in other geometries, the amplitudes of the eigenmodes of tori exhibit a distinct forward and backward coupling. We present the plasmon dispersion relations for several relevant toroidal configurations in the quasistatic limit and obtain the dominant retarded dispersion relations of a single ring for comparison, discuss mode complementarity and hybridization, and introduce two new types of toroidal particles in the form of janus nanorings. The resonance frequencies for the first few dominant modes of a ring composed of plasmon supporting materials such as gold, silver, and aluminum are provided and compared to those for a silicon ring. A generalized Green's function is obtained for multilayer tori allowing for calculation of the scattering response to interacting fields. Employing the Green's function, the scalar electric potential distribution corresponding to individual poloidal and toroidal modes in response to an arbitrarily polarized external field and the field of electrons is obtained. The results are applied to obtain the local density of states and decay rate of a dipole near the center of the torus.

  16. Poloidal and toroidal plasmons and fields of multilayer nanorings

    Science.gov (United States)

    Garapati, K. V.; Salhi, M.; Kouchekian, S.; Siopsis, G.; Passian, A.

    2017-04-01

    Composite and janus type metallodielectric nanoparticles are increasingly considered as a means to control the spatial and temporal behavior of electromagnetic fields in diverse applications such as coupling to quantum emitters, achieving invisibility cloaks, and obtaining quantum correlations between qubits. We investigate the surface modes of a toroidal nanostructure and obtain the canonical plasmon dispersion relations and resonance modes for arbitrarily layered nanorings. Unlike particle plasmon eigenmodes in other geometries, the amplitudes of the eigenmodes of tori exhibit a distinct forward and backward coupling. We present the plasmon dispersion relations for several relevant toroidal configurations in the quasistatic limit and obtain the dominant retarded dispersion relations of a single ring for comparison, discuss mode complementarity and hybridization, and introduce two new types of toroidal particles in the form of janus nanorings. The resonance frequencies for the first few dominant modes of a ring composed of plasmon supporting materials such as gold, silver, and aluminum are provided and compared to those for a silicon ring. A generalized Green's function is obtained for multilayer tori allowing for calculation of the scattering response to interacting fields. Employing the Green's function, the scalar electric potential distribution corresponding to individual poloidal and toroidal modes in response to an arbitrarily polarized external field and the field of electrons is obtained. The results are applied to obtain the local density of states and decay rate of a dipole near the center of the torus.

  17. Holdup Measurement System II (HMSII): Version 2.1. User's guide and software documentation

    International Nuclear Information System (INIS)

    Smith, S.E.

    1995-01-01

    The Holdup Measurement System II (HMSII) software is a database management package for doing Holdup Measurements. It is based on the generalized geometry holdup (GGH) methodology taught in the US Department of Energy Safeguards Technology Training Program, ''Nondestructive Assay of Special Nuclear Materials Holdup.'' This program was developed and taught by Los Alamos National Laboratory (LANL). The HMSII was developed as a joint effort between LANL and the Oak Ridge Y-12 Plant, managed for the US Department of Energy by Lockheed Martin Energy Systems, Inc. The system is designed specifically for use with three types of Multichannel Analyzer (MCA): a Davidson Portable MultiChannel Analyzer (MCA); a EG ampersand G Ortec MicroNOMAD (μNOMAD); or a new Miniature Modular MultiChannel Analyzer (M 3 CA) under development at LANL. It is also designed assuming a 512 channel spectrum from a low resolution (e.g., NaI) detector measuring Uranium or Plutonium. Another important hardware component of the system is a portable bar code reader (also called a DataLogger or Trakker), by Intermec Corporation. The 944X series and the JANUS 2OXX series readers are compatible models with the HMSII. The JANUS series is a bar code reader which is also a 386 compatible palmtop PC with MS-DOS 5.0 built-in. Both series readers are programmable and control all the aspects of field holdup data collection from the MCAs

  18. Bipolar electrochemistry: from materials science to motion and beyond.

    Science.gov (United States)

    Loget, Gabriel; Zigah, Dodzi; Bouffier, Laurent; Sojic, Neso; Kuhn, Alexander

    2013-11-19

    Bipolar electrochemistry, a phenomenon which generates an asymmetric reactivity on the surface of conductive objects in a wireless manner, is an important concept for many purposes, from analysis to materials science as well as for the generation of motion. Chemists have known the basic concept for a long time, but it has recently attracted additional attention, especially in the context of micro- and nanoscience. In this Account, we introduce the fundamentals of bipolar electrochemistry and illustrate its recent applications, with a particular focus on the fields of materials science and dynamic systems. Janus particles, named after the Roman god depicted with two faces, are currently in the heart of many original investigations. These objects exhibit different physicochemical properties on two opposite sides. This makes them a unique class of materials, showing interesting features. They have received increasing attention from the materials science community, since they can be used for a large variety of applications, ranging from sensing to photosplitting of water. So far the great majority of methods developed for the generation of Janus particles breaks the symmetry by using interfaces or surfaces. The consequence is often a low time-space yield, which limits their large scale production. In this context, chemists have successfully used bipolar electrodeposition to break the symmetry. This provides a single-step technique for the bulk production of Janus particles with a high control over the deposit structure and morphology, as well as a significantly improved yield. In this context, researchers have used the bipolar electrodeposition of molecular layers, metals, semiconductors, and insulators at one or both reactive poles of bipolar electrodes to generate a wide range of Janus particles with different size, composition and shape. In using bipolar electrochemistry as a driving force for generating motion, its intrinsic asymmetric reactivity is again the

  19. Controlling nuclear JAKs and STATs for specific gene activation by IFNγ

    International Nuclear Information System (INIS)

    Noon-Song, Ezra N.; Ahmed, Chulbul M.; Dabelic, Rea; Canton, Johnathan; Johnson, Howard M.

    2011-01-01

    Highlights: → Gamma interferon (IFNγ) and its receptor subunit, IFNGR1, interact with the promoter region of IFNγ-associated genes along with transcription factor STAT1α. → We show that activated Janus kinases pJAK2 and pJAK1 also associate with IFNGR1 in the nucleus. → The activated Janus kinases are responsible for phosphorylation of tyrosine 41 on histone H3, an important epigenetic event for specific gene activation. -- Abstract: We previously showed that gamma interferon (IFNγ) and its receptor subunit, IFNGR1, interacted with the promoter region of IFNγ-activated genes along with transcription factor STAT1α. Recent studies have suggested that activated Janus kinases pJAK2 and pJAK1 also played a role in gene activation by phosphorylation of histone H3 on tyrosine 41. This study addresses the question of the role of activated JAKs in specific gene activation by IFNγ. We carried out chromatin immunoprecipitation (ChIP) followed by PCR in IFNγ treated WISH cells and showed association of pJAK1, pJAK2, IFNGR1, and STAT1 on the same DNA sequence of the IRF-1 gene promoter. The β-actin gene, which is not activated by IFNγ, did not show this association. The movement of activated JAK to the nucleus and the IRF-1 promoter was confirmed by the combination of nuclear fractionation, confocal microscopy and DNA precipitation analysis using the biotinylated GAS promoter. Activated JAKs in the nucleus was associated with phosphorylated tyrosine 41 on histone H3 in the region of the GAS promoter. Unphosphorylated JAK2 was found to be constitutively present in the nucleus and was capable of undergoing activation in IFNγ treated cells, most likely via nuclear IFNGR1. Association of pJAK2 and IFNGR1 with histone H3 in IFNγ treated cells was demonstrated by histone H3 immunoprecipitation. Unphosphorylated STAT1 protein was associated with histone H3 of untreated cells. IFNγ treatment resulted in its disassociation and then re-association as pSTAT1. The

  20. DNA-imprinted polymer nanoparticles with monodispersity and prescribed DNA-strand patterns

    Science.gov (United States)

    Trinh, Tuan; Liao, Chenyi; Toader, Violeta; Barłóg, Maciej; Bazzi, Hassan S.; Li, Jianing; Sleiman, Hanadi F.

    2018-02-01

    As colloidal self-assembly increasingly approaches the complexity of natural systems, an ongoing challenge is to generate non-centrosymmetric structures. For example, patchy, Janus or living crystallization particles have significantly advanced the area of polymer assembly. It has remained difficult, however, to devise polymer particles that associate in a directional manner, with controlled valency and recognition motifs. Here, we present a method to transfer DNA patterns from a DNA cage to a polymeric nanoparticle encapsulated inside the cage in three dimensions. The resulting DNA-imprinted particles (DIPs), which are 'moulded' on the inside of the DNA cage, consist of a monodisperse crosslinked polymer core with a predetermined pattern of different DNA strands covalently 'printed' on their exterior, and further assemble with programmability and directionality. The number, orientation and sequence of DNA strands grafted onto the polymeric core can be controlled during the process, and the strands are addressable independently of each other.

  1. Activation of Stat-3 is involved in the induction of apoptosis after ligation of major histocompatibility complex class I molecules on human Jurkat T cells

    DEFF Research Database (Denmark)

    Skov, S; Nielsen, M; Bregenholt, S

    1998-01-01

    Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators of transcription (Stat) after ligation of major histocompatibility complex class I (MHC-I) was explored in Jurkat T cells. Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3......-probe derived from the interferon-gamma activated site (GAS) in the c-fos promoter, a common DNA sequence for Stat protein binding. An association between hSIE and Stat-3 after MHC-I ligation was directly demonstrated by precipitating Stat-3 from nuclear extracts with biotinylated hSIE probe and avidin......-coupled agarose. To investigate the function of the activated Stat-3, Jurkat T cells were transiently transfected with a Stat-3 isoform lacking the transactivating domain. This dominant-negative acting Stat-3 isoform significantly inhibited apoptosis induced by ligation of MHC-I. In conclusion, our data suggest...

  2. Coexistance of JAK2V617F mutation and BCR/ABL translocation in one patient

    Directory of Open Access Journals (Sweden)

    Murat Albayrak

    2010-09-01

    Full Text Available Dear Editor,The myeloproliferative disorders (MPDs constitute a subcategory of chronic myeloid disorders and include chronic myeloid leukemia (CML, essential thrombocytemia (ET, polycythemia vera (PV and myelofibrosis (MF. In 1960, the discovery of the Philadelphia chromosome (Ph became a cornerstone in CML treatment and led to the development of moleculary targeted therapy. Recently, an acquired mutation in the Janus kinase 2 (JAK2 gene has been discovered in nearly all patents with PV and approximately half of the patients with primary MF and ET. Subsequently, the mutation has been demonstrated in atypical MPDs (chronic neutrophilic leukemia, unclassified, de novo myelodysplastic syndrome or acute myeloid leukemia.1 It has been hoped that targeted inhibition of JAK2V617F should achieve similar disease control as thyrosine kinases has produced in CML.

  3. How Do You Feel?

    DEFF Research Database (Denmark)

    Rosfort, René; Stanghellini, Giovanni

    2014-01-01

    are Janus-faced in the sense that they bring out the complex interplay of impersonal, biological and personal features of mental illness. We propose a framework for understanding emotional experience that is grounded in four key points: a general concept of “affectivity”, the definition of “emotion” as felt...... motivation to move, the distinction between “affect” and “mood” according to their intentional structure and the dialectics between affects and moods. The reason why emotions matter in psychiatry is that mental suffering brings out an emotional fragility that we argue is constitutive of personal identity......This article argues for the importance of investigating emotions in psychiatry. In a time dominated by striding naturalistic explanations of mental illness, phenomenological psychopathology provides a crucial investigation into the subjective aspect of the disordered mind. Emotional phenomena...

  4. Roles of STATs signaling in cardiovascular diseases.

    Science.gov (United States)

    Kishore, Raj; Verma, Suresh K

    2012-04-01

    In cardiac and many other systems, chronic stress activates avfamily of structurally and functionally conserved receptors and their downstream signaling molecules that entail tyrosine, serine or threonine phosphorylation to transfer the messages to the genetic machinery. However, the activation of the Janus kinases (JAKs) and their downstream signal transducer and activator of transcription (STATs) proteins is both characteristic of and unique to cytokine and growth factor signaling which plays a central role in heart physiology. Dysregulation of JAK-STAT signaling is associated with various cardiovascular diseases. The molecular signaling and specificity of the JAK-STAT pathway are modulated at many levels by distinct regulatory proteins. Here, we review recent studies on the regulation of the STAT signaling pathway that will enhance our ability to design rational therapeutic strategies for stress-induced heart failure.

  5. Let the sun shine in: mechanisms and potential for therapeutics in skin photodamage.

    Science.gov (United States)

    Wondrak, Georg T

    2007-05-01

    Photoaging and photocarcinogenesis are the two Janus faces of skin photodamage. Reactivity-based design of prototype agents that antagonize, modulate and reverse the chemistry of skin photodamage holds promise in delivering unprecedented therapeutic benefit. In contrast to structure-based approaches that use selective ligands to target macromolecules, reactivity-based drug discovery uses chemical reagents as therapeutics to target reactive chemical species as key mediators of skin photo-oxidative stress. The following classes of reactivity-based agents for skin photoprotection can be distinguished based on their mechanism of action: direct antagonists of photo-oxidative stress (sunscreens, quenchers of photo-excited states, antioxidants, redox modulators and glycation inhibitors) and skin photo-adaptation inducers (nuclear factor erythroid 2-related factor 2 [Nrf2] activators, heat-shock response inducers and metallothionein inducers).

  6. Deformation of N = 4 SYM with varying couplings via fluxes and intersecting branes

    Science.gov (United States)

    Choi, Jaewang; Fernández-Melgarejo, José J.; Sugimoto, Shigeki

    2018-03-01

    We study deformations of N = 4 supersymmetric Yang-Mills theory with space-time dependent couplings by embedding probe D3-branes in supergravity backgrounds with non-trivial fluxes. The effective action on the world-volume of the D3-branes is analyzed and a map between the deformation parameters and the fluxes is obtained. As an explicit example, we consider D3-branes in a background corresponding to ( p, q) 5-branes intersecting them and show that the effective theory on the D3-branes precisely agrees with the supersymmetric Janus configuration found by Gaiotto and Witten in [1]. D3-branes in an intersecting D3-brane background is also analyzed and the D3-brane effective action reproduces one of the supersymmetric configurations with ISO(1 , 1) × SO(2) × SO(4) symmetry found in our previous paper [2].

  7. Prevalence and clinical correlates of JAK2 mutations in Down syndrome acute lymphoblastic leukemia

    Science.gov (United States)

    Gaikwad, Amos; Rye, Cassia L.; Devidas, Meenakshi; Heerema, Nyla A.; Carroll, Andrew J.; Izraeli, Shai; Plon, Sharon E.; Basso, Giuseppe; Pession, Andrea; Rabin, Karen R.

    2009-01-01

    Summary Recurrent, prognostically significant chromosomal abnormalities occur in approximately 75% of pediatric acute lymphoblastic leukemia (ALL), but only infrequently in children with Down syndrome (DS) and ALL. Recently, novel somatic activating mutations in Janus kinase 2 (JAK2) were reported in 18% of DS ALL. Here we report identification and clinical correlates of JAK2 mutations in an independent cohort. JAK2 activating mutations occurred in 10 of 53 DS ALL cases (18.9%). Mutations were overrepresented in males (p<0.03), occurred once in association with high hyperdiploidy, and were not significantly correlated with age, initial white blood count, or event-free survival. Our results confirm significance of JAK-STAT pathway activation in DS ALL. PMID:19120350

  8. Bevalac operations update: Pub. 496, No. 5

    International Nuclear Information System (INIS)

    1989-03-01

    This report contains information on the following experiments: Beam 30-1 (Dilepton Spectrometer); Beam 30-2 (Janus Spectrometer); Beam 39 I Low Energy Program; Beam 39 II Irradiation Station; Beam 39 III Irradiation Station; Beam 40 I RTE; Beam 40 II NASA; Beam 42 I EOS; Beam 42 II Radioactive Beams-Nuclear Radii; Beam 42 III Fragmentation; Beam 42 IV TPC; Beam 42 V Time of Flight Wall; Beam 44 I Low Energy Program; Beam 44 II Radioactive Beams-Magnetic Moments; Beam 44 III Antiprotons; AIP 86-Uranium Intensity; AIP 87-SHILAC Drift Tubes; AIP 88-Computer Control Upgrade I; AIP 89-Computer Control Upgrade II; AIP 90-External Particle Beam Lines Control; AIP 91-Power Supplies; BEVAX Developments; Spiller Control; and, New Pulsed Switching Magnet. 20 figs

  9. “Cybercrime”: Fenomena Kejahatan melalui Internet di Indonesia

    Directory of Open Access Journals (Sweden)

    Muhammad E. Fuady

    2005-12-01

    Full Text Available It had been long known that technology, as Janus, has two side of coins: the good side,and the bad side. Everybody knows the benefit of technology development. But there aren’t much who realize the negative potent of technology. Cybercrime discussed in this article is an example of how crime was developed sophisticatedly by using technological means. Cybercrime, simply defined as criminal acts using cyber and Internet, has faced a new challenge for lawmaker and law enforcement mission. In Indonesia, carding become serious issues to be combated. Another type of cybercrime frequently occur in Indonesia are hacking and deface. Although Internet user in Indonesia is estimated no more than 5% of total population (4.38 million persons, everybody must attended cybercrime issues seriously. The loss of cybercrime reached unspeakable heights and damaged public safety in communication and information flows.

  10. The metastasis-promoting S100A4 protein confers neuroprotection in brain injury

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Pankratova, Stanislava; Owczarek, Sylwia

    2012-01-01

    and downregulating the neuroprotective protein metallothionein I+II. We identify two neurotrophic motifs in S100A4 and show that these motifs are neuroprotective in animal models of brain trauma. Finally, we find that S100A4 rescues neurons via the Janus kinase/STAT pathway and, partially, the interleukin-10......Identification of novel pro-survival factors in the brain is paramount for developing neuroprotective therapies. The multifunctional S100 family proteins have important roles in many human diseases and are also upregulated by brain injury. However, S100 functions in the nervous system remain...... unclear. Here we show that the S100A4 protein, mostly studied in cancer, is overexpressed in the damaged human and rodent brain and released from stressed astrocytes. Genetic deletion of S100A4 exacerbates neuronal loss after brain trauma or excitotoxicity, increasing oxidative cell damage...

  11. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko

    2011-08-01

    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  12. Isolation of microorganisms from red pepper powder and their radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Choi, E H; Kim, Y B; Lee, S R [Korea Atomic Energy Research Inst., Seoul (Republic of Korea)

    1977-01-01

    From samples of red pepper powder sold in Korea were isolated and identified 13 species of molds (Aspergillus amsteodami, Asp. chevalieri, Asp. clavatus, Asp. Flavus, Asp. janus var. effusus, Asp. oryzae, Asp. oryzae var. brevis, Asp. repens, Asp. sydowi, Asp. thomii, Asp. tubingensis, Penicillium thomii, Scopulariopsis brevicaulis) and 5 species of bacteria (Bacillus pumilus, Bac. subtilis, Micrococus luteus, M. varians, Staphylococcus aureus). Radiosensitivity of these microorganisms was examined to give D/sub 10/ values of 14-41 krad for molds, 11-24 krad for bacterial vegetative cells and 190-250 krad for bacterial spores. The red pepper powder was contaminated with 2-3x10/sup 2/ mold counts/g and 3-6x10/sup 7/ bacterial counts/g, which would be sufficiently destroyed by irradiating 200 krad r-rays.

  13. Flow chemistry to control the synthesis of nano and microparticles for biomedical applications.

    Science.gov (United States)

    Hassan, Natalia; Oyarzun-Ampuero, Felipe; Lara, Pablo; Guerrero, Simón; Cabuil, Valérie; Abou-Hassan, Ali; Kogan, Marcelo J

    2014-03-01

    In this article we review the flow chemistry methodologies for the controlled synthesis of different kind of nano and microparticles for biomedical applications. Injection mechanism has emerged as new alternative for the synthesis of nanoparticles due to this strategy allows achieving superior levels of control of self-assemblies, leading to higher-ordered structures and rapid chemical reactions. Self-assembly events are strongly dependent on factors such as the local concentration of reagents, the mixing rates, and the shear forces, which can be finely tuned, as an example, in a microfluidic device. Injection methods have also proved to be optimal to elaborate microsystems comprising polymer solutions. Concretely, extrusion based methods can provide controlled fluid transport, rapid chemical reactions, and cost-saving advantages over conventional reactors. We provide an update of synthesis of nano and microparticles such as core/shell, Janus, nanocrystals, liposomes, and biopolymeric microgels through flow chemistry, its potential bioapplications and future challenges in this field are discussed.

  14. Pain modulation by nitric oxide in the spinal cord.

    Directory of Open Access Journals (Sweden)

    Marco Aurelio M Freire

    2009-09-01

    Full Text Available Nitric oxide (NO is a versatile messenger molecule first associated with endothelial relaxing effects. In the central nervous system (CNS, NO synthesis is primarily triggered by activation of N-methyl-D-aspartate (NMDA receptors and has a Janus face, with both beneficial and harmful properties, depending on concentration and the identity of its synthetic enzyme isoform. There are three isoforms of the NO synthesizing enzyme nitric oxide synthase (NOS: neuronal (nNOS, endothelial (eNOS, and inducible nitric oxide synthase (iNOS, each one involved with specific events in the brain. In CNS, nNOS is involved with modulation of synaptic transmission through long-term potentiation in several regions, including nociceptive circuits in the spinal cord. Here, we review the role played by NO on central pain sensitization.

  15. Massive upper gastrointestinal bleeding due to splenoportal axis thrombosis in a patient with a tested JAK2 mutation: A case report and review literature

    Directory of Open Access Journals (Sweden)

    Isabel Macías, PhD

    2016-01-01

    Full Text Available Portal hypertension is a clinical syndrome defined as a portal venous pressure that exceeds 10 mmHg. Cirrhosis is the most common cause of portal hypertension and thrombosis of the splenoportal axis not associated with liver cirrhosis is the second cause of portal hypertension in the Western world. The primary myeloproliferative disorders are the main cause of portal venous thrombosis and somatic mutation of Janus Kinase 2 gene (JAK2 V617F can be found in approximately 90% of polycythemia vera, 50% of essential thrombocyrosis and 50% primary myelofibrosis. A a 55-year-old man with JAK2 mutation-associated splenoportal axis hypertension and bleeding complications due to oesophageal varices is reported. A massive upper bleeding episode made an emergent surgery to be done immediatelly at seventh day. The patient was discharged home at fifteenth day after surgery.

  16. Le règne de Louis XIV, ou la rupture définitive entre la société française et la monarchie

    OpenAIRE

    Bouveresse, Jacques

    2018-01-01

    Le règne de Louis XIV, comme Janus, présente deux faces. La première de ces faces qui correspond au vingt-cinq premières années du règne est brillante et lumineuse. Tout s’ordonne autour du roi dans un bel ordonnancement classique. Louis XIV est le maître de la guerre et de la paix. Il est entouré d’une cour brillante où il n’y a pas que des courtisans mais aussi beaucoup d’hommes capables et compétents. À partir des années 1680 – et à cet égard la révocation de l’Édit de Nantes en 1685 est u...

  17. Studies of closure phenomena in pinholes irradiated by Nd laser pulses

    Energy Technology Data Exchange (ETDEWEB)

    Auerbach, J.M.; Holmes, N.C.; Hunt, J.T.; Linford, G.J.

    1978-08-21

    The plasma closure of spatial filter pinholes is a critical parameter in the performance of high energy glass laser systems. Using 50 to 100 J, 300 psec FWHM laser pulses on the Janus laser, an investigation has been made on closure effects in 300 ..mu..m to 500 ..mu..m diameter pinholes of various materials and thicknesses. Calorimetry measurements have yielded data on pinhole transmission and intensity loading on the periphery of the pinhole. Ultrafast streak photography measurements indicate effective closure velocities of 2 x 10/sup 7/ cm/sec to 5 x 10/sup 7/ cm/sec. Scattered light measurements have shown the transmission loss through a typical spatial filter configuration to be primarily refractive in nature.

  18. Studies of closure phenomena in pinholes irradiated by Nd laser pulses

    International Nuclear Information System (INIS)

    Auerbach, J.M.; Holmes, N.C.; Hunt, J.T.; Linford, G.J.

    1978-01-01

    The plasma closure of spatial filter pinholes is a critical parameter in the performance of high energy glass laser systems. Using 50 to 100 J, 300 psec FWHM laser pulses on the Janus laser, an investigation has been made on closure effects in 300 μm to 500 μm diameter pinholes of various materials and thicknesses. Calorimetry measurements have yielded data on pinhole transmission and intensity loading on the periphery of the pinhole. Ultrafast streak photography measurements indicate effective closure velocities of 2 x 10 7 cm/sec to 5 x 10 7 cm/sec. Scattered light measurements have shown the transmission loss through a typical spatial filter configuration to be primarily refractive in nature

  19. Cross-talk between KLF4 and STAT3 regulates axon regeneration

    Science.gov (United States)

    Qin, Song; Zou, Yuhua; Zhang, Chun-Li

    2013-10-01

    Cytokine-induced activation of signal transducer and activator of transcription 3 (STAT3) promotes the regrowth of damaged axons in the adult central nervous system (CNS). Here we show that KLF4 physically interacts with STAT3 upon cytokine-induced phosphorylation of tyrosine 705 (Y705) on STAT3. This interaction suppresses STAT3-dependent gene expression by blocking its DNA-binding activity. The deletion of KLF4 in vivo induces axon regeneration of adult retinal ganglion cells (RGCs) via Janus kinase (JAK)-STAT3 signalling. This regeneration can be greatly enhanced by exogenous cytokine treatment, or removal of an endogenous JAK-STAT3 pathway inhibitor called suppressor of cytokine signalling 3 (SOCS3). These findings reveal an unexpected cross-talk between KLF4 and activated STAT3 in the regulation of axon regeneration that might have therapeutic implications in promoting repair of injured adult CNS.

  20. Concluding Remarks: The Current Status and Future Prospects for GRB Astronomy

    Science.gov (United States)

    Gehrels, Neil

    2009-01-01

    We are in a remarkable period of discovery in GRB astronomy. The current satellites including Swift, Fermi. AGILE and INTEGRAL are detecting and observing bursts of all varieties. Increasing capabilities for follow-up observations on the ground and in space are leading to rapid and deep coverage across the electromagnetic spectrum, The future will see continued operation of the current experiments and with future missions like SVOM plus possible rni_Ssions like JANUS and EXIST. An exciting expansion of capabilities is occurring in areas of gravitational waves and neutrinos that could open new windows on the GRB phenomenon. Increased IR capabilities on the ground and with missions like JWST will enable further exploration of high redshift bursts. The future is bright.

  1. Advanced CCD camera developments

    Energy Technology Data Exchange (ETDEWEB)

    Condor, A. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    Two charge coupled device (CCD) camera systems are introduced and discussed, describing briefly the hardware involved, and the data obtained in their various applications. The Advanced Development Group Defense Sciences Engineering Division has been actively designing, manufacturing, fielding state-of-the-art CCD camera systems for over a decade. These systems were originally developed for the nuclear test program to record data from underground nuclear tests. Today, new and interesting application for these systems have surfaced and development is continuing in the area of advanced CCD camera systems, with the new CCD camera that will allow experimenters to replace film for x-ray imaging at the JANUS, USP, and NOVA laser facilities.

  2. Diagnostics of ytterbium/aluminium laser plasmas

    International Nuclear Information System (INIS)

    Bailey, J.; Lee, R.W.; Landen, O.L.; Kilkenny, J.D.; Lewis, C.L.; Busquet, M.

    1986-11-01

    Microdot spectroscopy was used to study the x-ray emission from laser-produced plasmas consisting of 10% ytterbium, 90% aluminium. Spectra were recorded with a space-resolving flat crystal (PET) mini-spectrometer in the 4.0-8.0 A range. The Janus research laser at LLNL irradiated the targets with green (0.53 μm) light in a 1 nsec pulse. The power density was varied between 4x10 13 and 3x10 14 W/cm 2 . The plasma electron density and temperature were determined from the aluminium XI, XII and XIII line emission. By examining correlations between changes in the plasma conditions with changes in the ytterbium spectra, we will determine the potential for using ytterbium line emission as a plasma diagnostic

  3. Role of Ubiquitylation in Controlling Suppressor of Cytokine Signalling 3 (SOCS3 Function and Expression

    Directory of Open Access Journals (Sweden)

    Jamie J. L. Williams

    2014-05-01

    Full Text Available The realisation that unregulated activation of the Janus kinase–signal transducer and activator of transcription (JAK–STAT pathway is a key driver of a wide range of diseases has identified its components as targets for therapeutic intervention by small molecule inhibitors and biologicals. In this review, we discuss JAK-STAT signalling pathway inhibition by the inducible inhibitor “suppressor of cytokine signaling 3 (SOCS3, its role in diseases such as myeloproliferative disorders, and its function as part of a multi-subunit E3 ubiquitin ligase complex. In addition, we highlight potential applications of these insights into SOCS3-based therapeutic strategies for management of conditions such as vascular re-stenosis associated with acute vascular injury, where there is strong evidence that multiple processes involved in disease progression could be attenuated by localized potentiation of SOCS3 expression levels.

  4. Bridging the gap between legacy services and Web Services

    DEFF Research Database (Denmark)

    Bissyandé, Tegawendé; Réveillère, Laurent; Bromberg, Yérom-David

    2010-01-01

    itself. In this paper, we introduce a generative language based approach for constructing wrappers to facilitate the migration of legacy service functionalities to Web Services. To this end, we have designed the Janus domain-specific language, which provides developers with a high-level way to describe......Web Services is an increasingly used instantiation of Service-Oriented Architectures (SOA) that relies on standard Internet protocols to produce services that are highly interoperable. Other types of services, relying on legacy application layer protocols, however, cannot be composed directly....... A promising solution is to implement wrappers to translate between the application layer protocols and the WS protocol. Doing so manually, however, requires a high level of expertise, in the relevant application layer protocols, in low-level network and system programming, and in the Web Service paradigm...

  5. SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer

    DEFF Research Database (Denmark)

    Iglesias Gato, Diego; Chuan, Yin Choy; Wikström, Pernilla

    2014-01-01

    ) as mediator of the cross talk between androgens and GH signals in the prostate and its potential role as tumor suppressor in prostate cancer (PCa). We observed that SOCS2 protein levels assayed by immunohistochemistry are elevated in hormone therapy-naive localized prostatic adenocarcinoma in comparison...... of transcription 5 protein (STAT5) and androgen receptor-dependent transcription. Consequentially, SOCS2 inhibits GH activation of Janus kinase 2, Src and STAT5 as well as both cell invasion and cell proliferation in vitro. In vivo, SOCS2 limits proliferation and production of IGF-1 in the prostate in response......Anabolic signals such as androgens and the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis play an essential role in the normal development of the prostate but also in its malignant transformation. In this study, we investigated the role of suppressor of cytokine signaling 2 (SOCS2...

  6. Embodying multilingual interaction

    DEFF Research Database (Denmark)

    Hazel, Spencer; Mortensen, Janus

    this linguistic diversity is managed in situ by participants engaged in dialogue with one another, and what it is used for in these transient multilingual communities. This paper presents CA-based micro-ethnographic analyses of language choice in an informal social setting – a kitchen – of an international study...... literature on language choice in interaction, our findings emphasize that analyses of language choice in multilingual settings need to take into account social actions beyond the words that are spoken. We show that facial, spatial and postural configurations, gaze orientation and gestures as well as prosodic...... in the particular community of practice that we are investigating. Reference Hazel, Spencer, and Janus Mortensen. forthcoming. Kitchen talk: Exploring linguistic practices in liminal institutional interactions in a multilingual university setting. in Language Alternation, Language Choice, and Language Encounter...

  7. Spatially and temporally resolved x-ray emission from imploding laser fusion targets

    International Nuclear Information System (INIS)

    Attwood, D.T.; Coleman, L.W.; Boyle, M.J.; Phillion, D.W.; Swain, J.E.; Manes, K.R.; Larsen, J.T.

    1976-09-01

    The Livermore 15 psec x-ray streak camera has been used in conjunction with 6 μm diameter pinholes to record well resolved implosion histories of DT filled laser fusion targets. The space-time compression data provide clearly identified implosion velocities, typically 3 x 10 7 cm/sec for two-sided clamshell irradiation of a 70 μm/sup D/, .5 μm wall DT filled glass microshell. Single-sided irradiation results show hydrodynamic convergence at the target center, followed by an asymmetric but two-sided target disassembly. These experiments were performed at the two arm Janus Laser facility, which typically delivered a total of 0.4 TW in a 70 psec pulse for these experiments

  8. Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity.

    Science.gov (United States)

    Kim, Jongwan; Yun, Eun-Young; Quan, Fu-Shi; Park, Seung-Won; Goo, Tae-Won

    2017-01-01

    The α -glucosidase inhibitor, 1-deoxynojirimycin (DNJ), is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Results showed that intracerebroventricular (ICV) administration of DNJ reduced hypothalamic ER stress, which activated the leptin-induced Janus-activated kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway to cause appetite suppression. We conclude that DNJ may reduce obesity by moderating feeding behavior and ER stress in the hypothalamic portion of the central nervous system (CNS).

  9. Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Jongwan Kim

    2017-01-01

    Full Text Available The α-glucosidase inhibitor, 1-deoxynojirimycin (DNJ, is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Results showed that intracerebroventricular (ICV administration of DNJ reduced hypothalamic ER stress, which activated the leptin-induced Janus-activated kinase 2 (JAK2/signal transducers and activators of transcription 3 (STAT3 signaling pathway to cause appetite suppression. We conclude that DNJ may reduce obesity by moderating feeding behavior and ER stress in the hypothalamic portion of the central nervous system (CNS.

  10. Creating leptin-like biofunctions by active immunization against chicken leptin receptor in growing chickens.

    Science.gov (United States)

    Lei, M M; Wu, S Q; Shao, X B; Li, X W; Chen, Z; Ying, S J; Shi, Z D

    2015-01-01

    In this study, immunization against chicken leptin receptor (cLEPR) extracellular domain (ECD) was applied to investigate leptin regulation and LEPR biofunction in growing chicken pullets. A recombinant protein (cLEPR ECD) based on the cLEPR complemenary DNA sequence corresponding to the 582nd to 796th amino acid residues of cLEPR mature peptide was prepared and used as antigen. Immunization against cLEPR ECD in growing chickens increased anti-cLEPR ECD antibody titers in blood, enhanced proportions of phosphorylated janus kinase 2 (JAK2) and served as signal transducer and activator of transcription 3 (STAT3) protein in liver tissue. Chicken live weight gain and abdominal fat mass were significantly decreased (P chickens. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Iridium-catalyst-based autonomous bubble-propelled graphene micromotors with ultralow catalyst loading.

    Science.gov (United States)

    Wang, Hong; Sofer, Zdeněk; Eng, Alex Yong Sheng; Pumera, Martin

    2014-11-10

    A novel concept of an iridium-based bubble-propelled Janus-particle-type graphene micromotor with very high surface area and with very low catalyst loading is described. The low loading of Ir catalyst (0.54 at %) allows for fast motion of graphene microparticles with high surface area of 316.2 m(2)  g(-1). The micromotor was prepared with a simple and scalable method by thermal exfoliation of iridium-doped graphite oxide precursor composite in hydrogen atmosphere. Oxygen bubbles generated from the decomposition of hydrogen peroxide at the iridium catalytic sites provide robust propulsion thrust for the graphene micromotor. The high surface area and low iridium catalyst loading of the bubble-propelled graphene motors offer great possibilities for dramatically enhanced cargo delivery. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Being at war: Cognitive Approaches to Observational War Documentaries

    DEFF Research Database (Denmark)

    Bondebjerg, Ib

    2017-01-01

    : Janus Metz’s Danish ‘Armadillo’ (2010) following a group of soldiers to Afghanistan, and Andreas Dalsgaard and Obiada Zytoon’s Danish-Syrian ‘The War Show’ following a group of young Syrians during the Syrian spring to the civil war and beyond. Based on theories of cognition and emotion and evolutionary......In this article I primarily analyse observational war documentaries in order to deal with how this particular form of documentary contribute to our understanding of how it is to be at war as a soldier or as a civilian in a war zone. I analyse two very different observational war documentaries...... biology the article argues for the importance of this type of documentaries in developing and understanding of what war really is and it is experience, how it is to be at war. The article also puts the films in the broader context of both fictional and documentary war genres trying to map how...

  13. A defect in holographic interpretations of tensor networks

    Energy Technology Data Exchange (ETDEWEB)

    Czech, Bartłomiej [Institute for Advanced Study,Princeton, NJ 08540 (United States); Nguyen, Phuc H.; Swaminathan, Sivaramakrishnan [Theory Group, Department of Physics and Texas Cosmology Center,The University of Texas at Austin,Austin, TX 78712 (United States)

    2017-03-16

    We initiate the study of how tensor networks reproduce properties of static holographic space-times, which are not locally pure anti-de Sitter. We consider geometries that are holographically dual to ground states of defect, interface and boundary CFTs and compare them to the structure of the requisite MERA networks predicted by the theory of minimal updates. When the CFT is deformed, certain tensors require updating. On the other hand, even identical tensors can contribute differently to estimates of entanglement entropies. We interpret these facts holographically by associating tensor updates to turning on non-normalizable modes in the bulk. In passing, we also clarify and complement existing arguments in support of the theory of minimal updates, propose a novel ansatz called rayed MERA that applies to a class of generalized interface CFTs, and analyze the kinematic spaces of the thin wall and AdS{sub 3}-Janus geometries.

  14. Active Brownian motion in a narrow channel

    Science.gov (United States)

    Ao, X.; Ghosh, P. K.; Li, Y.; Schmid, G.; Hänggi, P.; Marchesoni, F.

    2014-12-01

    We review recent advances in rectification control of artificial microswimmers, also known as Janus particles, diffusing along narrow, periodically corrugated channels. The swimmer self-propulsion mechanism is modeled so as to incorporate a nonzero torque (propulsion chirality). We first summarize the effects of chirality on the autonomous current of microswimmers freely diffusing in channels of different geometries. In particular, left-right and upside-down asymmetric channels are shown to exhibit different transport properties. We then report new results on the dependence of the diffusivity of chiral microswimmers on the channel geometry and their own self-propulsion mechanism. The self-propulsion torque turns out to play a key role as a transport control parameter.

  15. Gene mutations in hepatocellular adenomas

    DEFF Research Database (Denmark)

    Raft, Marie B; Jørgensen, Ernö N; Vainer, Ben

    2015-01-01

    is associated with bi-allelic mutations in the TCF1 gene and morphologically has marked steatosis. β-catenin activating HCA has increased activity of the Wnt/β-catenin pathway and is associated with possible malignant transformation. Inflammatory HCA is characterized by an oncogene-induced inflammation due...... to alterations in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. In the diagnostic setting, sub classification of HCA is based primarily on immunohistochemical analyzes, and has had an increasing impact on choice of treatment and individual prognostic assessment....... This review offers an overview of the reported gene mutations associated with hepatocellular adenomas together with a discussion of the diagnostic and prognostic value....

  16. LOFT Engineering Simulator

    International Nuclear Information System (INIS)

    Venhuizen, J.R.

    1982-02-01

    The LOFT Engineering Simulator was developed to supply plant equivalent data for evaluating graphic aids and advanced control concepts for nuclear plant operators. The Simulator, a combination of hardware and software, combines some of the features of best estimate (safety analysis) computer codes with reactor operator training simulators. The LOFT Engineering Simulator represents an attempt to develop a simulation with sufficient physical detail (solution of the conservation equations) for moderate accident simulation, but which will still run in real time and provide an interface for the operator to interact with the model. As a result of this combination, a real time simulation of the LOFT plant has been developed which yields realistic transient results. These data can be used for evaluating reactor control room aids such as Safety Parameter Displays and Janus Predictive Displays

  17. Genetic loss of SH2B3 in acute lymphoblastic leukemia.

    Science.gov (United States)

    Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Hadler, Michael; Rigo, Isaura; LeDuc, Charles A; Kelly, Kara; Jalas, Chaim; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Paganin, Maddalena; Basso, Giuseppe; Tong, Wei; Chung, Wendy K; Ferrando, Adolfo A

    2013-10-03

    The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. Here, we report the identification of germline homozygous SH2B3 mutations in 2 siblings affected with developmental delay and autoimmunity, one in whom B-precursor acute lymphoblastic leukemia (ALL) developed. Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL. Moreover, extended mutation analysis showed homozygous somatic mutations in SH2B3 in 2 of 167 ALLs analyzed. Overall, these results demonstrate a Knudson tumor suppressor role for SH2B3 in the pathogenesis of ALL and highlight a possible link between genetic predisposition factors in the pathogenesis of autoimmunity and leukemogenesis.

  18. Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques

    DEFF Research Database (Denmark)

    Conaghan, Philip G.; Ostergaard, Mikkel; Bowes, Michael A.

    2016-01-01

    OBJECTIVES: To explore the effects of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)-with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand. METHODS: In this exploratory......, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score...... differences in RAMRIS bone marrow oedema (BME) at month 6 were -1.55 (90% CI -2.52 to -0.58) for tofacitinib + MTX and -1.74 (-2.72 to -0.76) for tofacitinib monotherapy (both ptofacitinib + MTX...

  19. Tofacitinib in psoriatic arthritis.

    Science.gov (United States)

    Wang, Ting-Shun; Tsai, Tsen-Fang

    2017-11-01

    Psoriatic arthritis is a heterogeneous disease that has been difficult to manage until the recent advent of biologics. However, there are still unmet medical needs for newer agents. Tofacitinib is a Janus family of kinases inhibitor approved for treating rheumatoid arthritis in many countries and psoriasis in Russia. We reviewed the evidences of tofacitinib in psoriatic arthritis treatment. The efficacy and safety profiles result from Phase III clinical trials (OPAL BROADEN and OPAL BEYOND) and one open-label extension study (OPAL BALANCE). Both tofacitinib 5 or 10 mg twice a day were superior to placebo for American College of Rheumatology 20% improvement criteria response at 3 months and showed significant improvement of skin, enthesitis and dactylitis. Tofacitinib is a promising treatment option for psoriatic arthritis.

  20. Transient Efficacy of Tofacitinib in Alopecia Areata Universalis

    Directory of Open Access Journals (Sweden)

    Florian Anzengruber

    2016-04-01

    Full Text Available Alopecia areata is a common autoimmune disorder that targets hair follicles. Swarms of lymphocytes surround the basis of the follicles, inducing loss of pigmented terminal hair and subsequently inhibit further hair growth. Depending on the extent of involvement, alopecia areata can be associated with a dramatic reduction of quality of life. Currently, no targeted treatment option is available, and topical immune therapies or immunosuppressive drugs are typically used with mixed success. Recently, several cases of alopecia areata responding to Janus kinase inhibitors were published. Here, we report on a businessman with alopecia areata universalis who was treated with tofacitinib. We observed initial signs of hair regrowth in the same timeframe as previously reported, but efficacy quickly waned again, leading to renewed effluvium. Thus, even though tofacitinib and ruxolitinib are a promising new treatment option, we have yet to learn more about their potential role in each particular patient's individual treatment strategy.

  1. Pathogenetic Role of JAK2 V617F Mutation in Chronic Myeloproliferative Disorders

    Directory of Open Access Journals (Sweden)

    Hui-Chi Hsu

    2007-03-01

    Full Text Available The molecular pathogenesis of chronic myeloproliferative disorders (MPDs is poorly understood. The hematopoietic progenitor cells of patients with polycythemia vera (PV or essential thrombocythemia (ET are characterized by hypersensitiv-ity to hematopoietic growth factors and formation of endogenous erythroid colonies. Recently, 4 groups reported almost simultaneously Janus kinase 2 (JAK2 V617F mutation in more than 80% of PV patients, 30% of patients with ET and in about 50% of patients with idiopathic myelofibrosis. The identification of the JAK2 mutation represents a major advance in the understanding of the molecular pathogenesis of MPDs that will likely permit a new classification and the development of novel therapeutic strategies for these diseases.

  2. Ligands Exchange Process on Gold Nanoparticles in Acetone Solution

    Science.gov (United States)

    Hu, C. L.; Mu, Y. Y.; Bian, Z. C.; Luo, Z. H.; Luo, K.; Huang, A. Z.

    2018-05-01

    The ligands exchange process on gold nanoparticles (GNPs) was proceeded by using hydrophobic group (PPh3) and hydrophilic group (THPO) in acetone solution. The FTIR and XPS results demonstrated that part of THPO was replaced by PPh3 which was dissolved in polar solution (acetone); the results were in accordance with the electrochemical analysis where the differential capacity decreased with increasing exchange time. After 12 h, the exchange process terminated and the final ratio of PPh3 and THPO was about 1.4: 1. This ratio remained unchanged although the PPh3 and THPO modified GNPs re-dispersed in the PPh3 acetone solution demonstrating the stable adsorption of both ligands after exchanging for 12 h. The TEM images showed that the gold nanoparticles were self-assembled from scattered to arranged morphology due to the existence of hydrophilic and hydrophobic ligands and led to Janus gold nanoparticles.

  3. Tofacitinib suppresses disease activity and febrile attacks in a patient with coexisting rheumatoid arthritis and familial Mediterranean fever.

    Science.gov (United States)

    Gök, Kevser; Cengiz, Gizem; Erol, Kemal; Ozgocmen, Salih

    2017-01-01

    Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory (periodic fever) syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK) inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA). Herein we report a female patient with coexisting RA and colchicine resistant FMF whose FMF attacks and disease activity were completely controlled after treatment with tofacitinib, a small-molecule JAK3 inhibitor.

  4. Tuning the wettability of calcite cubes by varying the sizes of the polystyrene nanoparticles attached to their surfaces

    International Nuclear Information System (INIS)

    He Yongjun; Li Tanliang; Yu Xiangyang; Zhao Shiyong; Lu Jianhua; He Jia

    2007-01-01

    The wettability of calcite cubes was tuned by varying the sizes of the polystyrene nanoparticles attached to their surfaces via a dispersion polymerization. The products were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersion spectrum (EDS) and Fourier transformation infrared spectrum (FTIR). The results showed that the hydrophobicity of the calcite cubes was enhanced with the increase of the size of the polystyrene nanoparticles attached. Using polystyrene nanoparticle-attached calcite cubes (PNACC) as emulsifiers, stable water-in-tricaprylin Pickering emulsions were produced. By gelling the water droplets of the Pickering emulsions, the hierarchical structures of polystyrene nanoparticle-attached calcite cube-armored microspheres were obtained. The polystyrene nanoparticle-attached calcite cubes were expected to have novel surface properties similar neither to traditional Pickering particles, nor to macroscopically asymmetrical Janus particles

  5. Animal facilities

    International Nuclear Information System (INIS)

    Fritz, T.E.; Angerman, J.M.; Keenan, W.G.; Linsley, J.G.; Poole, C.M.; Sallese, A.; Simkins, R.C.; Tolle, D.

    1981-01-01

    The animal facilities in the Division are described. They consist of kennels, animal rooms, service areas, and technical areas (examining rooms, operating rooms, pathology labs, x-ray rooms, and 60 Co exposure facilities). The computer support facility is also described. The advent of the Conversational Monitor System at Argonne has launched a new effort to set up conversational computing and graphics software for users. The existing LS-11 data acquisition systems have been further enhanced and expanded. The divisional radiation facilities include a number of gamma, neutron, and x-ray radiation sources with accompanying areas for related equipment. There are five 60 Co irradiation facilities; a research reactor, Janus, is a source for fission-spectrum neutrons; two other neutron sources in the Chicago area are also available to the staff for cell biology studies. The electron microscope facilities are also described

  6. Emerging treatments in alopecia.

    Science.gov (United States)

    Falto-Aizpurua, Leyre; Choudhary, Sonal; Tosti, Antonella

    2014-12-01

    Alopecia is a common concern encountered in the medical practice. Treatment approach varies according to the type and severity of alopecia. However, available treatment options have limited efficacy and several adverse effects. Presently, there are different treatment options being studied to overcome these limitations. Additionally, cellular pathways involved in the pathophysiology of alopecia are further being clarified to potentially target pathogenic molecules. We searched the literature for recently published articles discussing new treatment options as well as mechanisms involved in alopecia. We discuss the use of stem cells, growth factors, cellular pathways and robotic hair transplant, among other emerging therapies used for alopecia. Future looks very promising and new effective treatments such as janus kinase inhibitors could possibly be available for alopecia areata. The stem-cell technology is advancing and companies involved in hair follicle neogenesis are starting clinical trials on patients with androgenetic alopecia.

  7. New Treatments for Hair Loss.

    Science.gov (United States)

    Vañó-Galván, S; Camacho, F

    2017-04-01

    The treatment of hair loss is an important part of clinical dermatology given the prevalence of the problem and great impact on patients' quality of life. Many new treatments have been introduced in recent years. This review summarizes the main ones in 4 groups: a) For androgenetic alopecia, we discuss new excipients for oral minoxidil, dutasteride, and finasteride as well as new forms of topical application; prostaglandin agonists and antagonists; low-level laser therapy; and regenerative medicine with Wnt signaling activators and stem cell therapy. b) For alopecia areata, Janus kinase inhibitors are reviewed. c) For frontal fibrosing alopecia, we discuss the use of antiandrogens and, for some patients, pioglitazone. d) Finally, we mention new robotic devices for hair transplant procedures and techniques for optimal follicular unit extraction. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Nature of the spin-glass phase at experimental length scales

    International Nuclear Information System (INIS)

    Alvarez Baños, R; Cruz, A; Fernandez, L A; Gil-Narvion, J M; Gordillo-Guerrero, A; Maiorano, A; Martin-Mayor, V; Monforte-Garcia, J; Perez-Gaviro, S; Ruiz-Lorenzo, J J; Seoane, B; Tarancon, A; Guidetti, M; Mantovani, F; Schifano, S F; Tripiccione, R; Marinari, E; Parisi, G; Muñoz Sudupe, A; Navarro, D

    2010-01-01

    We present a massive equilibrium simulation of the three-dimensional Ising spin glass at low temperatures. The Janus special-purpose computer has allowed us to equilibrate, using parallel tempering, L = 32 lattices down to T ≈ 0.64T c . We demonstrate the relevance of equilibrium finite size simulations to understanding experimental non-equilibrium spin glasses in the thermodynamical limit by establishing a time-length dictionary. We conclude that non-equilibrium experiments performed on a timescale of 1 h can be matched with equilibrium results on L ≈ 110 lattices. A detailed investigation of the probability distribution functions of the spin and link overlap, as well as of their correlation functions, shows that Replica Symmetry Breaking is the appropriate theoretical framework for the physically relevant length scales. Besides, we improve over existing methodologies in ensuring equilibration in parallel tempering simulations

  9. Nuclear translocation and retention of growth hormone

    DEFF Research Database (Denmark)

    Mertani, Hichem C; Raccurt, Mireille; Abbate, Aude

    2003-01-01

    We have previously demonstrated that GH is subject to rapid receptor-dependent nuclear translocation. Here, we examine the importance of ligand activation of the GH-receptor (GHR)-associated Janus kinase (JAK) 2 and receptor dimerization for hormone internalization and nuclear translocation by use...... of cells stably transfected with cDNA for the GHR. Staurosporine and herbimycin A treatment of cells did not affect the ability of GH to internalize but resulted in increased nuclear accumulation of hormone. Similarly, receptor mutations, which prevent the association and activation of JAK2, did not affect...... the ability of the hormone to internalize or translocate to the nucleus but resulted in increased nuclear accumulation of GH. These results were observed both by nuclear isolation and confocal laser scanning microscopy. Staurosporine treatment of cells in which human GH (hGH) was targeted to the cytoplasm...

  10. Tofacitinib suppresses disease activity and febrile attacks in a patient with coexisting rheumatoid arthritis and familial Mediterranean fever

    Directory of Open Access Journals (Sweden)

    Kevser Gök

    2017-01-01

    Full Text Available Familial Mediterranean fever (FMF is the most common hereditary auto-inflammatory (periodic fever syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA. Herein we report a female patient with coexisting RA and colchicine resistant FMF whose FMF attacks and disease activity were completely controlled after treatment with tofacitinib, a small-molecule JAK3 inhibitor.

  11. Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice

    DEFF Research Database (Denmark)

    Alkharusi, Amira; Mirecki-Garrido, Mercedes; Ma, Zuheng

    2016-01-01

    Background: Diabetes type 1 is characterized by the failure of beta cells to produce insulin. Suppressor of cytokine signaling (SOCS) proteins are important regulators of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Previous studies have shown that GH can...... prevent the development of type I diabetes in mice and that SOCS2 deficiency mimics a state of increased GH sensitivity. Methodology: The elevated sensitivity of SOCS2-/- mice to GH and possibly to PRL was the rationale to analyze the effects of multiple low dose streptozotocin (MLDSTZ)-induced diabetes...... in SOCS2-/- mice. Results: We show that 6-month-old SOCS2-/- mice, but not 2-month-old mice, were less sensitive to MLDSTZ-induced diabetes, compared to controls. MLDSTZ treatment induced glucose intolerance in both SOCS2+/+ and SOCS2-/- mice, as shown by glucose tolerance tests, with SOCS2+/+ mice...

  12. Saturn satellites

    International Nuclear Information System (INIS)

    Ruskol, E.L.

    1981-01-01

    The characteristics of the Saturn satellites are discussed. The satellites close to Saturn - Janus, Mimas, Enceladus, Tethys, Dione and Rhea - rotate along the circular orbits. High reflectivity is attributed to them, and the density of the satellites is 1 g/cm 3 . Titan is one of the biggest Saturn satellites. Titan has atmosphere many times more powerful than that of Mars. The Titan atmosphere is a peculiar medium with a unique methane and hydrogen distribution in the whole Solar system. The external satellites - Hyperion, Japetus and Phoebe - are poorly investigated. Neither satellite substance density, nor their composition are known. The experimental data on the Saturn rings obtained on the ''Pioneer-11'' and ''Voyager-1'' satellites are presented [ru

  13. Isolation of microorganisms from red pepper powder and their radiosensitivity

    International Nuclear Information System (INIS)

    Choi, E.H.; Kim, Y.B.; Lee, S.R.

    1977-01-01

    From samples of red pepper powder sold in Korea were isolated and identified 13 species of molds (Aspergillus amsteodami, Asp. chevalieri, Asp. clavatus, Asp. Flavus, Asp. janus var. effusus, Asp. oryzae, Asp. oryzae var. brevis, Asp. repens, Asp. sydowi, Asp. thomii, Asp. tubingensis, Penicillium thomii, Scopulariopsis brevicaulis) and 5 species of bacteria (Bacillus pumilus, Bac. subtilis, Micrococus luteus, M. varians, Staphylococcus aureus). Radiosensitivity of these microorganisms was examined to give D 10 values of 14-41 krad for molds, 11-24 krad for bacterial vegetative cells and 190-250 krad for bacterial spores. The red pepper powder was contaminated with 2-3x10 2 mold counts/g and 3-6x10 7 bacterial counts/g, which would be sufficiently destroyed by irradiating 200 krad r-rays. (Author)

  14. Associations between generic substitution and patient-related factors

    DEFF Research Database (Denmark)

    Østergaard Rathe, Jette

    Associations between generic substitution and patient-related factors Jette Østergaard Rathe1, Pia V. Larsen1, Morten Andersen2, Janus L. Thomsen3, Maja S. Paulsen1, Jens Søndergaard1 1. Research Unit of General Practice, Institute of Public Health, University of Southern Denmark 2. Centre...... for Pharmacoepidemiology, Karolinska Institutet, Department of Medicine Solna, Stockholm, Sweden 3. Danish Quality Unit of General Practice, Odense, Denmark Background Generic substitution means that chemically equivalent but less expensive drugs are dispensed in place of a brand name product. Although generic medicines...... by definition are bioequivalent to their brand name counterparts there are concerns about whether generic substitution is always accompanied by clinical equivalence in terms of effectiveness and that it may cause concerns and thereby causing some skepticism towards generic substitution. There is, however...

  15. Advances in continuous gamma-ray spectrometry and applications

    International Nuclear Information System (INIS)

    Gold, R.; McNeece, J.P.; Kaiser, B.J.

    1984-07-01

    Recent advances and applications in continuous Compton recoil gamma-ray spectrometry are described. Applications of continuous gamma-ray spectrometry are presented for: (1) Characterization of light water reactor (LWR) pressures vessel (PV) environments. (2) Assessment of fuel distributions for Three Mile Island Unit 2 (TMI-2) reactor recovery. (3) Measurement of LWR-PV-neutron exposure. The latest improvements attained with the Janus probe, a special in-situ configuration of Si(Li) detectors, are presented. The status of current efforts to extend the domain of applicability of this method beyond 3 MeV is discussed with emphasis on recent work carried out with Si(Li) detectors of much larger volume

  16. Primary myelofibrosis: own experience and news from diagnostic and treatment

    Directory of Open Access Journals (Sweden)

    K. M. Abdulkadyrov

    2015-06-01

    Full Text Available The newest advances in primary myelofibrosis (PMF pathogenesis study, diagnostic and treatment approaches are presented in this article. The JAK-STAT signal pathway activation now recognized as main pathogenesis mechanism of PMF, it caused by JAK2, CALR, MPL genes mutations. Authors demonstrate their own data about epidemiology, clinical signs, diagnostic and treatment results of 315 PMF patients. The most frequent clinical symptoms are: anemia, leukocytosis, thrombocytosis, splenomegaly, constitutional symptoms. Diagnostic criteria, prognostic scales (including cytogenetic and molecular features issues are reviewed. Intermediate-1 risk grade is in the most proportion of patients. Therecommended PMF treatment algorithm is listed. The treatment methods, target drugs (Janus kinases inhibitors trials results are discussed.

  17. Primary myelofibrosis: own experience and news from diagnostic and treatment

    Directory of Open Access Journals (Sweden)

    K. M. Abdulkadyrov

    2015-01-01

    Full Text Available The newest advances in primary myelofibrosis (PMF pathogenesis study, diagnostic and treatment approaches are presented in this article. The JAK-STAT signal pathway activation now recognized as main pathogenesis mechanism of PMF, it caused by JAK2, CALR, MPL genes mutations. Authors demonstrate their own data about epidemiology, clinical signs, diagnostic and treatment results of 315 PMF patients. The most frequent clinical symptoms are: anemia, leukocytosis, thrombocytosis, splenomegaly, constitutional symptoms. Diagnostic criteria, prognostic scales (including cytogenetic and molecular features issues are reviewed. Intermediate-1 risk grade is in the most proportion of patients. Therecommended PMF treatment algorithm is listed. The treatment methods, target drugs (Janus kinases inhibitors trials results are discussed.

  18. Clean translation of an imperative reversible programming language

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock

    2011-01-01

    We describe the translation techniques used for the code generation in a compiler from the high-level reversible imperative programming language Janus to the low-level reversible assembly language PISA. Our translation is both semantics preserving (correct), in that target programs compute exactly...... the same functions as their source programs (cleanly, with no extraneous garbage output), and efficient, in that target programs conserve the complexities of source programs. In particular, target programs only require a constant amount of temporary garbage space. The given translation methods are generic......, and should be applicable to any (imperative) reversible source language described with reversible flowcharts and reversible updates. To our knowledge, this is the first compiler between reversible languages where the source and target languages were independently developed; the first exhibiting both...

  19. Design, synthesis, and evaluation of 4,6-diaminonicotinamide derivatives as novel and potent immunomodulators targeting JAK3.

    Science.gov (United States)

    Nakajima, Yutaka; Aoyama, Naohiro; Takahashi, Fumie; Sasaki, Hiroshi; Hatanaka, Keiko; Moritomo, Ayako; Inami, Masamichi; Ito, Misato; Nakamura, Koji; Nakamori, Fumihiro; Inoue, Takayuki; Shirakami, Shohei

    2016-10-01

    In organ transplantation, T cell-mediated immune responses play a key role in the rejection of allografts. Janus kinase 3 (JAK3) is specifically expressed in hematopoietic cells and associated with regulation of T cell development via interleukin-2 signaling pathway. Here, we designed novel 4,6-diaminonicotinamide derivatives as immunomodulators targeting JAK3 for prevention of transplant rejection. Our optimization of C4- and C6-substituents and docking calculations to JAK3 protein confirmed that the 4,6-diaminonicotinamide scaffold resulted in potent inhibition of JAK3. We also investigated avoidance of human ether-a-go-go related gene (hERG) inhibitory activity. Selected compound 28 in combination with tacrolimus prevented allograft rejection in a rat heterotopic cardiac transplantation model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Sustained Submicromolar H2O2 Levels Induce Hepcidin via Signal Transducer and Activator of Transcription 3 (STAT3)*

    Science.gov (United States)

    Millonig, Gunda; Ganzleben, Ingo; Peccerella, Teresa; Casanovas, Guillem; Brodziak-Jarosz, Lidia; Breitkopf-Heinlein, Katja; Dick, Tobias P.; Seitz, Helmut-Karl; Muckenthaler, Martina U.; Mueller, Sebastian

    2012-01-01

    The peptide hormone hepcidin regulates mammalian iron homeostasis by blocking ferroportin-mediated iron export from macrophages and the duodenum. During inflammation, hepcidin is strongly induced by interleukin 6, eventually leading to the anemia of chronic disease. Here we show that hepatoma cells and primary hepatocytes strongly up-regulate hepcidin when exposed to low concentrations of H2O2 (0.3–6 μm), concentrations that are comparable with levels of H2O2 released by inflammatory cells. In contrast, bolus treatment of H2O2 has no effect at low concentrations and even suppresses hepcidin at concentrations of >50 μm. H2O2 treatment synergistically stimulates hepcidin promoter activity in combination with recombinant interleukin-6 or bone morphogenetic protein-6 and in a manner that requires a functional STAT3-responsive element. The H2O2-mediated hepcidin induction requires STAT3 phosphorylation and is effectively blocked by siRNA-mediated STAT3 silencing, overexpression of SOCS3 (suppressor of cytokine signaling 3), and antioxidants such as N-acetylcysteine. Glycoprotein 130 (gp130) is required for H2O2 responsiveness, and Janus kinase 1 (JAK1) is required for adequate basal signaling, whereas Janus kinase 2 (JAK2) is dispensable upstream of STAT3. Importantly, hepcidin levels are also increased by intracellular H2O2 released from the respiratory chain in the presence of rotenone or antimycin A. Our results suggest a novel mechanism of hepcidin regulation by nanomolar levels of sustained H2O2. Thus, similar to cytokines, H2O2 provides an important regulatory link between inflammation and iron metabolism. PMID:22932892

  1. Evidence for Break-Up of Clumps in Dynamically Stirred Regions of Saturn's Rings

    Science.gov (United States)

    Colwell, J. E.; Sega, D. N.; Jerousek, R. G.; Cooney, J. H.; Esposito, L. W.

    2017-12-01

    Stellar occultations of Saturn's rings observed by the Cassini Ultraviolet Imaging Spectrograph (UVIS) High Speed Photometer (HSP) record stellar brightness seen through the rings as photon counts that are described by Poisson counting statistics in the absence of intervening ring material. The variance in the data increases above counting statistics due to the discrete sizes of the ring particles, with larger particles leading to a larger variance at a given optical depth. We take advantage of the high spatial resolution and multiple viewing geometries of the UVIS occultations to study variations in particle size near and within strongly perturbed regions of Saturn's A ring, in particular the strong first order Lindblad resonances with Janus and the Mimas 5:3 Lindblad resonance and inner vertical resonance. The variance shows changes in the area-weighted particle size between peaks and troughs in the density waves as well as an overall decrease in particle size in the broad "halo" regions that bracket the strong Janus Lindblad resonances in the A ring. In addition we see a decrease in particle size at the location of the Mimas 5:3 bending wave wavetrain itself, and an increase in optical depth at the location of the wave when viewed from high elevation angles out of the ring plane. Taken together, these observations suggest that clumps of particles, perhaps the ubiquitous A ring self-gravity wakes, are disaggregated in the bending wave, even though standard bending wave theory does not predict enhanced collision velocities. We also examine the skewness, a higher order moment of the occultation data, that is diagnostic of asymmetries in the particle size distribution. We use Monte Carlo simulations of occultations to match the first three moments of the data (the signal mean, or equivalently the optical depth, the variance, and the skewness) to illustrate differences in ring particle size in these perturbed regions.

  2. Manganese- and 1-methyl-4-phenylpyridinium-induced neurotoxicity display differences in morphological, electrophysiological and genome-wide alterations: implications for idiopathic Parkinson's disease.

    Science.gov (United States)

    Mythri, Rajeswara Babu; Raghunath, Narayana Reddy; Narwade, Santosh Chandrakant; Pandareesh, Mirazkar Dasharatha Rao; Sabitha, Kollarkandi Rajesh; Aiyaz, Mohamad; Chand, Bipin; Sule, Manas; Ghosh, Krittika; Kumar, Senthil; Shankarappa, Bhagyalakshmi; Soundararajan, Soundarya; Alladi, Phalguni Anand; Purushottam, Meera; Gayathri, Narayanappa; Deobagkar, Deepti Dileep; Laxmi, Thenkanidiyoor Rao; Srinivas Bharath, Muchukunte Mukunda

    2017-11-01

    Idiopathic Parkinson's disease and manganese-induced atypical parkinsonism are characterized by movement disorder and nigrostriatal pathology. Although clinical features, brain region involved and responsiveness to levodopa distinguish both, differences at the neuronal level are largely unknown. We studied the morphological, neurophysiological and molecular differences in dopaminergic neurons exposed to the Parkinson's disease toxin 1-methyl-4-phenylpyridinium ion (MPP + ) and manganese (Mn), followed by validation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and Mn mouse models. Morphological analysis highlighted loss of neuronal processes in the MPP + and not the Mn model. Cellular network dynamics of dopaminergic neurons characterized by spike frequency and inter-spike intervals indicated major neuronal population (~ 93%) with slow discharge rates (0-5 Hz). While MPP + exposure suppressed the firing of these neurons, Mn neither suppressed nor elevated the neuronal activity. High-throughput transcriptomic analysis revealed up-regulation of 694 and 603 genes and down-regulation of 428 and 255 genes in the MPP + and Mn models respectively. Many differentially expressed genes were unique to either models and contributed to neuroinflammation, metabolic/mitochondrial function, apoptosis and nuclear function, synaptic plasticity, neurotransmission and cytoskeleton. Analysis of the Janus kinase-signal transducer and activator of transcription pathway with implications for neuritogenesis and neuronal proliferation revealed contrasting profile in both models. Genome-wide DNA methylomics revealed differences between both models and substantiated the epigenetic basis of the difference in the Janus kinase-signal transducer and activator of transcription pathway. We conclude that idiopathic Parkinson's disease and atypical parkinsonism have divergent neurotoxicological manifestation at the dopaminergic neuronal level with implications for pathobiology and evolution

  3. Data taken from the review article “Radiation and circulatory disease” and used in the associated meta-analysis

    Directory of Open Access Journals (Sweden)

    Mark P. Little

    2016-12-01

    Full Text Available This WinZip archive ‘Combined R, EpiWin & datafiles (rev 2016-9-29.zip’ contains the basic data used in the meta-analysis of doi 10.1016/j.mrrev.2016.07.008 (M.P. Little, 2016 [1], complete with R (R Project version 3.2.2, 2015 [2] code used for meta-regression etc. The basic data is derived from the papers of Mulrooney et al. (D.A. Mulrooney, M.W. Yeazel, T. Kawashima, A.C. Mertens, P. Mitby, M. Stovall, S.S. Donaldson, D.M. Green, C.A. Sklar, L.L. Robison, W.M. Leisenring, 2009 [3], Cutter et al. (D.J. Cutter, M. Schaapveld, S.C. Darby, M. Hauptmann, F.A. van Nimwegen, A.D.G. Krol, C.P.M. Janus, F.E. van Leeuwen, B.M.P. Aleman, 2015 [4] and van Nimwegen et al. (F.A. van Nimwegen, M. Schaapveld, D.J. Cutter, C.P.M. Janus, A.D.G. krol, M. Hauptmann, K. Kooijman, J. Roesink, R. van der Maazen, S.C. Darby, B.M.P. Aleman, F.E. van Leeuwen, 2016 [5], and other data taken from various Tables in the papers summarized in Tables 2–4 of doi 10.1016/j.mrrev.2016.07.008 [1]. The archive also contains R [2] script files that perform the meta-analysis.

  4. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1993-01-01

    From 1971 to 1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF 1 mice irradiated with 60 Co γ rays or JANUS fission-spectrum neutrons; normal and tumor tissues from mice in these studies were preserved in paraffin blocks. A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma (mRb) gene in the paraffin-embedded tissues. Microtomed sections were used as the DNA source in PCR reaction mixtures. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments (relative to control PCR products) on a Southern blot indicated a deletion of that portion of the mRb gene. The tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice (569 cGy of 60 Co γ rays or 60 cGy of JANUS neutrons, doses that have been found to have approximately equal biological effectiveness in the BCF, mouse) were analyzed for mRb deletions. In all normal mouse tissues studies, all six mRb exon fragments were present on Southem blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, I of 6 tumors from γ-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice had a deletion in one or both mRb alleles. All deletions detected were in the 5' region of the mRb gene

  5. 4+ Dimensional nuclear systems engineering

    International Nuclear Information System (INIS)

    Suh, Kune Y.

    2009-01-01

    Nuclear power plants (NPPs) require massive quantity of data during the design, construction, operation, maintenance and decommissioning stages because of their special features like size, cost, radioactivity, and so forth. The system engineering thus calls for a fully integrated way of managing the information flow spanning their life cycle. This paper proposes digital systems engineering anchored in three dimensional (3D) computer aided design (CAD) models. The signature in the proposal lies with the four plus dimensional (4 + D) Technology TM , a critical know how for digital management. ESSE (Engineering Super Simulation Emulation) features a 4 + D Technology TM for nuclear energy systems engineering. The technology proposed in the 3D space and time plus cost coordinates, i.e. 4 + D, is the backbone of digital engineering in the nuclear systems design and management. Dased on an integrated 3D configuration management system, ESSE consists of solutions JANUS (Junctional Analysis Neodynamic Unit SoftPower), EURUS (Engineering Utilities Research Unit SoftPower), NOTUS (Neosystemic Optimization Technical Unit SoftPower), VENUS (Virtual Engineering Neocybernetic Unit SoftPower) and INUUS (Informative Neographic Utilities Unit SoftPower). NOTUS contributes to reducing the construction cost of the NPPs by optimizing the component manufacturing procedure and the plant construction process. Planning and scheduling construction projects can thus benefit greatly by integrating traditional management techniques with digital process simulation visualization. The 3D visualization of construction processes and the resulting products intrinsically afford most of the advantages realized by incorporating a purely schedule level detail based the 4 + D system. Problems with equipment positioning and manpower congestion in certain areas can be visualized prior to the actual operation, thus preventing accidents and safety problems such as collision between two machines and losses in

  6. 4+D TechnologyTM for nuclear systems soft solutions

    International Nuclear Information System (INIS)

    Suh, Kune Y.

    2010-10-01

    The signature in the proposal lies with the NSSS (Nuclear Systems Soft Solutions). NSSS proposed in the 3-dimensional space and time plus cost coordinates, i.e. 4 + dimensional technology, is the backbone of digital engineering in the nuclear system design and management. The NSSS is empowered by Janus (Junctional Analysis Neo dynamic Unit Soft Power), NOTUS (Neo systemic Optimization Technical Unit Soft Power), Venus (Virtual Engineering Neo cybernetic Unit Soft Power), EURUS (Engineering Utilities Research Unit Soft Power) and INUUS (Informative Neo graphic Utilities Unit Soft Power). Janus extracts the geometric data directly from the computer-aided design CAD files to import to multidimensional computational fluid and structural dynamics codes. Janus uses the joint-CAD analysis methods to eliminate the necessity of any pre- and post- processors. Starting from the 3-dimensional CAD, NOTUS contributes to reducing the construction cost of the nuclear power plants by optimizing the component manufacturing procedure and the plant construction process. Planning and scheduling construction projects can thus benefit greatly by integrating traditional management techniques with digital process simulation visualization. The 3-dimensional visualization of construction processes and resulting products intrinsically afford most of the advantages realized by the 4 + D technology. Problems with equipment positioning and manpower congestion in certain areas can readily be visualized prior to the actual operation, thus preventing accidents and safety problems such as collision between two machines and losses in productivity. Venus applied the virtual reality technology in nuclear industry. Virtual reality provides an interactive real time motion with sound and tactile and other forms of feedback. The management and workers can thus comprehend the work process crystal clear by visualizing precisely how activities relate to one another, whereby reducing conflicting

  7. 4+D digital engineering for advanced nuclear energy systems

    International Nuclear Information System (INIS)

    Jeong, S. G.; Suh, K. Y.; Nam, S. K.

    2007-01-01

    Nuclear power plants (NPPs) require massive quantity of data during the design, construction, operation, maintenance and decommissioning stages because of their special features like size, cost, radioactivity, and so forth. The system engineering thus calls for a fully automated way of managing the information flow spanning their life cycle. In line with practice in disciplines of naval architecture, aerospace engineering, and automotive manufacturing, the paper proposes total digital systems engineering based on three-dimensional (3D) computer-aided design (CAD) models. The signature in the proposal lies with the four-plus-dimensional (4 + D) Technology T M, a critical know-how for digital management. The so-called OPIUM (Optimized Plant Integrated Ubiquitous Management) features a 4 + D Technology T M for nuclear energy systems engineering. The technology proposed in the 3D space and time plus cost coordinates, i.e. 4 + D, is the backbone of digital engineering in the nuclear systems design and management. Based on an integrated 3D configuration management system, OPIUM consists of solutions NOTUS (Nuclear Optimization Technique Ubiquitous System), VENUS (Virtual Engineering Nuclear Ubiquitous System), INUUS (Informatics Nuclear Utilities Ubiquitous System), JANUS (Junctional Analysis Numerical Ubiquitous System) and EURUS (Electronic Unit Research Ubiquitous System). These solutions will help initial simulation capability for NPPs to supply the crucial information. NOTUS contributes to reducing the construction cost of the NPPs by optimizing the component manufacturing procedure and the plant construction process. Planning and scheduling construction projects can thus benefit greatly by integrating traditional management techniques with digital process simulation visualization. The 3D visualization of construction processes and the resulting products intrinsically afford most of the advantages realized by incorporating a purely schedule level detail based the 4

  8. Adsorption behavior of redox-active suppressor additives: Combined electrochemical and STM studies

    International Nuclear Information System (INIS)

    Hai, N.T.M.; Huynh, T.M.T.; Fluegel, A.; Mayer, D.; Broekmann, P.

    2011-01-01

    Highlights: → Janus Green B and safranine are prototypical redox-active leveler additives for copper electroplating. → Their redox-transitions lie within the copper potential window. → Reduced additives are identified as active species for the leveling effect. → Electro-reduction affects in particular the central aromatic cores of the additives. - Abstract: The redox chemistry and the related surface phase behavior of Safranine (SAF) and Janus Green B (JGB) have been studied by means of cyclic voltammetry in combination with in situ Scanning Tunneling Microscopy using HOPG (Highly Oriented Pyrolytic Graphite) and single crystalline Cu(1 0 0) as model substrates, both revealing different widths of the accessible potential windows. JGB and SAF serve as prototypical heterocyclic suppressor/leveler additives that are used for the metallization of 3D-TSVs (3D Through Silicon Vias) following a classical 'leveling' concept. SAF can be considered as the reductive decomposition product of JGB that is formed at the copper/electrolyte interface upon electroplating. Both additives reveal a pronounced pH-dependent redox-chemistry with redox-transitions lying close to or even beyond the anodic limit of the copper potential window. Affected by these redox-processes are in particular the aromatic cores of those heterocycles that can be (quasi)reversibly reduced by a two electron transfer process within the potential window of copper. Therefore we identify the reduced form of those dyes as the active components for the suppressing/leveling effect in copper plating. STM data clearly shows a dye surface phase behavior that is crucially determined by its potential-dependent redox-chemistry. This will be exemplarily discussed for the SAF dye. On chloride-modified Cu(1 0 0) mono-reduced SAF forms a structurally well-defined monolayer of cationic stacking polymers. However, this coupled anion/cation layer reveals only minor suppressing capabilities with respect to the copper

  9. Exceeding Conventional Photovoltaic Efficiency Limits Using Colloidal Quantum Dots

    Science.gov (United States)

    Pach, Gregory F.

    details the synthesis of PbS/CdS heterostructures in which the PbS and CdS domains exist on opposite sides of the nanocrystal and are termed "Janus particles". Transient absorption spectroscopy shows MEG quantum yields above unity very the thermodynamic limit of 2Eg for PbS/CdS Janus particles. We further explain a mechanism for enhanced MEG using photoluminescence studies.

  10. Synthetic Micro/Nanomachines and Their Applications: Towards 'Fantastic Voyage'

    Science.gov (United States)

    Gao, Wei

    The 1966 movie Fantastic Voyage captured the world's imagination, portraying a tiny submarine navigating through the human bloodstream and treating life-threatening medical conditions. My PhD research focuses on the synthetic nano/microscale machines to realize the Fantastic Voyage vision. Various biomedical and environmental areas would benefit from the developments of efficient fuel-free and fuel-driven nano/microscale machines. The polymer-based catalytic tubular microengine is synthesized using a template based electrodeposition method. The oxygen bubble propelled microengine harvests the energy from chemical fuels (such as H2O2) and displays very efficient propulsion. It can serve as an ideal platform for diverse biomedical and environmental applications. For example, lectin modified polyaniline based microengines can be used for selective bacteria (E. Coli) isolation from food, clinical and environmental samples; poly(3-aminophenylboronic acid)/Ni/Pt microengine itself provides the 'built in' glucose recognition capability for 'on-the-fly' capture, transport and release of yeast cells. A series of micromotors which can be self-propelled in natural environments without additional chemical fuels are developed, holding great promise for in vivo biomedical applications: the polyaniline/zinc microrockets display effective autonomous motion in extreme acidic environments (such as human stomach); the Al-Ga/Ti based Janus micromotor can be propelled by the hydrogen bubbles generated from the rapid aluminum and water reaction; alkanethiols modified seawater-driven Mg Janus micromotors, which utilize macrogalvanic corrosion and chloride pitting corrosion processes, can be used for environmental oil remediation. Magnetically powered nanoswimmers have attracted considerable attention due to their great biocompatibility. A high-speed magnetically-propelled nanowire swimmer which mimics swimming microorganisms by exploiting the flexible nanowire as artificial flagella

  11. Final report for project "Effects of Low-Dose Irradiation on NFkB Signaling Networks and Mitochondria"

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, Gayle E [Northwestern Univ., Evanston, IL (United States); Grdina, David [Univ. of Chicago, IL (United States); Li, Jian-Jian [Univ. of California, Davis, CA (United States)

    2017-06-12

    Low dose ionizing radiation effects are difficult to study in human population because of the numerous confounding factors such as genetic and lifestyle differences. Research in mammalian model systems and in vitro is generally used in order to overcome this difficulty. In this program project three projects have joined together to investigate effects of low doses of ionizing radiation. These are doses at and below 10 cGy of low linear energy transfer ionizing radiation such as X-ray and gamma rays. This project was focused on cellular signaling associated with nuclear factor kappa B (NFkB) and mitochondria - subcellular organelles critical for cell aging and aging-like changes induced by ionizing radiation. In addition to cells in culture this project utilized animal tissues accumulated in a radiation biology tissue archive housed at Northwestern University (http://janus.northwestern.edu/janus2/index.php). Major trust of Project 1 was to gather all of the DoE sponsored irradiated animal (mouse, rat and dog) data and tissues under one roof and investigate mitochondrial DNA changes and micro RNA changes in these samples. Through comparison of different samples we were trying to delineate mitochondrial DNA quantity alterations and micro RNA expression differences associated with different doses and dose rates of radiation. Historic animal irradiation experiments sponsored by DoE were done in several national laboratories and universities between 1950’s and 1990’s; while these experiments were closed data and tissues were released to Project 1. Project 2 used cells in culture to investigate effects that low doses or radiation have on NFκB and its target genes manganese superoxide dismutase (MnSOD) and genes involved in cell cycle: Cyclins (B1 and D1) and cyclin dependent kinases (CDKs). Project 3 used cells in culture such as “normal” human cells (breast epithelial cell line MCF10A cells and skin keratinocyte cells HK18) and mouse embryo fibroblast (mef

  12. Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study.

    Science.gov (United States)

    Krueger, James; Clark, James D; Suárez-Fariñas, Mayte; Fuentes-Duculan, Judilyn; Cueto, Inna; Wang, Claire Q; Tan, Huaming; Wolk, Robert; Rottinghaus, Scott T; Whitley, Maryann Z; Valdez, Hernan; von Schack, David; O'Neil, Shawn P; Reddy, Padmalatha S; Tatulych, Svitlana

    2016-04-01

    Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to elucidate the molecular mechanisms underlying the clinical efficacy of tofacitinib in patients with psoriasis. Twelve patients with plaque psoriasis were randomized (3:1) to receive 10 mg of tofacitinib or placebo twice daily for 12 weeks. Biopsy specimens were taken from nonlesional (baseline) and lesional (baseline, days 1 and 3, and weeks 1, 2, 4, and 12) skin. Biopsy specimens were examined for psoriatic epidermal features (thickness, Ki67(+) keratinocytes and keratin 16 [KRT16] mRNA expression, and phosphorylated signal transducer and activator of transcription [pSTAT](+) nuclei) and T-cell and dendritic cell (DC) subsets by using immunohistochemistry, and mRNA transcripts were quantified by using a microarray. In lesional skin keratinocyte pSTAT1 and pSTAT3 staining was increased at baseline but reduced after 1 day of tofacitinib (baseline, median of 1290 pSTAT1(+) cells/μm(2); day 1, median of 332 pSTAT1(+) cells/μm(2); and nonlesional, median of 155 pSTAT1(+) cells/μm(2)). Epidermal thickness and KRT16 mRNA expression were significantly and progressively reduced after days 1 and 3 of tofacitinib administration, respectively (eg, KRT16 decreased 2.74-fold, day 3 vs baseline, P = .016). Decreases in DC and T-cell numbers were observed after weeks 1 and 2, respectively. At week 4, significant decreases in IL-23/TH17 pathways were observed that persisted through week 12. Improvements in clinical and histologic features were strongly associated with changes in expression of psoriasis-related genes and reduction in IL-17 gene expression. Tofacitinib has a multitiered response in patients with psoriasis: (1) rapid attenuation of keratinocyte Janus kinase/STAT signaling; (2) removal of keratinocyte-induced cytokine signaling, leading to reductions in pathologic DC and T-cell numbers to nonlesional levels; and (3) inhibition of the IL-23/TH17 pathway. Copyright © 2016

  13. Interleukin-2-induced survival of natural killer (NK) cells involving phosphatidylinositol-3 kinase-dependent reduction of ceramide through acid sphingomyelinase, sphingomyelin synthase, and glucosylceramide synthase.

    Science.gov (United States)

    Taguchi, Yoshimitsu; Kondo, Tadakazu; Watanabe, Mitsumasa; Miyaji, Michihiko; Umehara, Hisanori; Kozutsumi, Yasunori; Okazaki, Toshiro

    2004-11-15

    Interleukin 2 (IL-2) rescued human natural killer (NK) KHYG-1 cells from apoptosis along with a reduction of ceramide. Conversely, an increase of ceramide inhibited IL-2-rescued survival. IL-2 deprivation-induced activation of acid sphingomyelinase (SMase) and inhibition of glucosylceramide synthase (GCS) and sphingomyelin synthase (SMS) were normalized by IL-2 supplementation. A phosphatidyl inositol-3 (PI-3) kinase inhibitor, LY294002, inhibited IL-2-rescued survival, but a mitogen-activated protein kinase inhibitor, PD98059, and an inhibitor of Janus tyrosine kinase/signal transducer and activator of transcription pathway, AG490, did not. LY294002 inhibited IL-2-induced reduction of ceramide through activation of acid SMase and inhibition of GCS and SMS, suggesting the positive involvement of PI-3 kinase in ceramide reduction through enzymatic regulation. Indeed, a constitutively active PI-3 kinase enhanced growth rate and ceramide reduction through inhibition of acid SMase and activation of GCS and SMS. Further, LY294002 inhibited IL-2-induced changes of transcriptional level as well as mRNA and protein levels in acid SMase and GCS but did not affect the stability of the mRNAs. These results suggest that PI-3 kinase-dependent reduction of ceramide through regulation of acid SMase, GCS, and SMS plays a role in IL-2-rescued survival of NK cells.

  14. Can (ReCentralization Be a Modern Governance in Rural Areas?

    Directory of Open Access Journals (Sweden)

    István BALÁZS

    2017-02-01

    Full Text Available Concentration and recentralization can be described as a European trend in the fi eld of local governance, especially in the fi eld of the administration of rural areas. An important tool of the concentration of the local administration is the intercommunal cooperation. The Hungarian rural areas have fragmented spatial structures. Because of the fragmentation and the small number of the voluntary associations these types of local cooperation were signifi cantly supported by the central budget in the 1990s and 2000s. The economic crisis resulted in a strong concentration trend in Hungary, as well. The new Hungarian Municipal Code introduced a Janus-faced model. The administration of the rural areas was strongly concentrated by the establishment of the mandatory common municipal offi ces of the small villages (under 2000 inhabitants while the forms of the intercommunal associations were simplifi ed. This reform reduced the number of local offi ces signifi cantly. This type of intercommunal cooperation became the main form of the j oined public service management as well, because the former signifi cant state aid of the voluntary associations has been reduced.

  15. Can (ReCentralization Be a Modern Governance in Rural Areas?

    Directory of Open Access Journals (Sweden)

    István BALÁZS

    2017-02-01

    Full Text Available Concentration and recentralization can be described as a European trend in the fi eld of local governance, especially in the fi eld of the administration of rural areas. An important tool of the concentration of the local administration is the intercommunal cooperation. The Hungarian rural areas have fragmented spatial structures. Because of the fragmentation and the small number of the voluntary associations these types of local cooperation were signifi cantly supported by the central budget in the 1990s and 2000s. The economic crisis resulted a strong concentration trend in Hungary, as well. The new Hungarian Municipal Code introduced a Janus-faced model. The administration of the rural areas was strongly concentrated by the establishment of the mandatory common municipal offi ces of the small villages (under 2000 inhabitants while the forms of the intercommunal associations were simplifi ed. This reform reduced the number of local offi ces signifi cantly. This type of intercommunal cooperation became the main form of the j oined public service management as well, because the former signifi cant state aid of the voluntary associations have been reduced.

  16. Generation of metal composition gradients by means of bipolar electrodeposition

    International Nuclear Information System (INIS)

    Tisserant, Gwendoline; Fattah, Zahra; Ayela, Cédric; Roche, Jérome; Plano, Bernard; Zigah, Dodzi; Goudeau, Bertrand; Kuhn, Alexander; Bouffier, Laurent

    2015-01-01

    Highlights: • A bipolar electrochemistry approach for the preparation of surface gradients is reported. • Several metals are simultaneously deposited on a bipolar electrode. • The elemental composition and thickness of the deposit varies alongside the bipolar electrode. • The deposit affects the surface properties and exhibits a barcode feature. - Abstract: Bipolar electrochemistry is an unconventional technique that currently encounters a renewal of interest due to modern applications in the fields of analytical chemistry or materials science. The approach is particularly relevant for the preparation of asymmetric objects or surfaces such as Janus particles for example. Bipolar electrochemistry allows spatially controlled deposition of various layers from electroactive precursors, selectively at one side of a bipolar electrode. We report here the concomitant cathodic deposition of up to three different metals at the same time in a single experiment. The deposits were characterized by optical and electron microscopy imaging as well as profilometry and energy dispersive X-ray spectroscopy. As a result, the deposited layer is composed of several areas exhibiting both a composition and a thickness gradient. Such a variation directly modifies the optical and electronic properties alongside the surface and gives access to the design of composite surfaces exhibiting a visual gradient feature.

  17. Cadmium affects the mitochondrial viability and the acid soluble thiols concentration in liver, kidney, heart and gills of Ancistrus brevifilis (Eigenmann, 1920

    Directory of Open Access Journals (Sweden)

    P. Velasquez-Vottelerd

    2015-11-01

    Full Text Available The freshwater fish Ancistrus brevifilis, which is found in Venezuelan rivers, is considered a potential sentinel fish in ecotoxicological studies. The cadmium (Cd effect on the mitochondrial viability (MV and acid soluble thiols levels (AST in A. brevifilis tissues (liver, kidney, heart, and gill was evaluated. Forty-two fish with similar sizes and weights were randomly selected, of which 7 fish (with their respective replicate were exposed for 7 and 30 days to a Cd sublethal concentration (0.1 mg.l-1. We determined the MV through a Janus Green B colorimetric assay and we obtained the concentration of AST by Ellman’s method. Mitochondrial viability decreased in fish exposed to Cd for 30 days with the liver being the most affected tissue. We also detected a significant decrease in AST levels was in fishes exposed to Cd for 7 days in liver and kidney tissues; these results suggests that AST levels are elevated in some tissues may act as cytoprotective and adaptive alternative mechanism related to the ROS detoxification, maintenance redox status and mitochondrial viability. Organ-specifics variations were observed in both assays. We conclude that the Cd exposure effect on AST levels and MV, vary across fish tissues and is related to the exposure duration, the molecule dynamics in different tissues, the organism and environmental conditions.

  18. Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth

    International Nuclear Information System (INIS)

    Patecki, Margret; Schaewen, Markus von; Tkachuk, Sergey; Jerke, Uwe; Dietz, Rainer; Dumler, Inna; Kusch, Angelika

    2007-01-01

    The urokinase (uPA)/uPA receptor (uPAR) system plays a role in the response of the vessel wall to injury, presumably by modulating vascular smooth muscle cell (VSMC) functional behaviour. The Jak/Stat signaling pathway has been implicated to mediate the uPA/uPAR-directed cell migration and proliferation in VSMC. We have therefore investigated the underlying molecular mechanisms, which remained not completely understood. In particular, we aimed at identification of the kinase involved in the signaling cascade leading to Stat1 phosphorylation by uPA and its impact on VSMC growth. We performed expression in VSMC of kinase-deficient mutant forms of the Janus kinases Jak1 and Tyk2 and used different cell culture models imitating the response to vascular injury. We provide evidence that Tyk2, but not Jak1, mediates uPA-induced Stat1 phosphorylation and VSMC growth inhibition and suggest a novel function for Tyk2 as an important modulator of the uPA-directed VSMC functional behaviour at the place of injury

  19. The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis.

    Science.gov (United States)

    Chang, Qing; Bournazou, Eirini; Sansone, Pasquale; Berishaj, Marjan; Gao, Sizhi Paul; Daly, Laura; Wels, Jared; Theilen, Till; Granitto, Selena; Zhang, Xinmin; Cotari, Jesse; Alpaugh, Mary L; de Stanchina, Elisa; Manova, Katia; Li, Ming; Bonafe, Massimiliano; Ceccarelli, Claudio; Taffurelli, Mario; Santini, Donatella; Altan-Bonnet, Gregoire; Kaplan, Rosandra; Norton, Larry; Nishimoto, Norihiro; Huszar, Dennis; Lyden, David; Bromberg, Jacqueline

    2013-07-01

    We have investigated the importance of interleukin-6 (IL-6) in promoting tumor growth and metastasis. In human primary breast cancers, increased levels of IL-6 were found at the tumor leading edge and positively correlated with advanced stage, suggesting a mechanistic link between tumor cell production of IL-6 and invasion. In support of this hypothesis, we showed that the IL-6/Janus kinase (JAK)/signal transducer and activator of transcription 3 (Stat3) pathway drives tumor progression through the stroma and metastatic niche. Overexpression of IL-6 in tumor cell lines promoted myeloid cell recruitment, angiogenesis, and induced metastases. We demonstrated the therapeutic potential of interrupting this pathway with IL-6 receptor blockade or by inhibiting its downstream effectors JAK1/2 or Stat3. These clinically relevant interventions did not inhibit tumor cell proliferation in vitro but had profound effects in vivo on tumor progression, interfering broadly with tumor-supportive stromal functions, including angiogenesis, fibroblast infiltration, and myeloid suppressor cell recruitment in both the tumor and pre-metastatic niche. This study provides the first evidence for IL-6 expression at the leading edge of invasive human breast tumors and demonstrates mechanistically that IL-6/JAK/Stat3 signaling plays a critical and pharmacologically targetable role in orchestrating the composition of the tumor microenvironment that promotes growth, invasion, and metastasis.

  20. The IL-6/JAK/Stat3 Feed-Forward Loop Drives Tumorigenesis and Metastasis12

    Science.gov (United States)

    Chang, Qing; Bournazou, Eirini; Sansone, Pasquale; Berishaj, Marjan; Gao, Sizhi Paul; Daly, Laura; Wels, Jared; Theilen, Till; Granitto, Selena; Zhang, Xinmin; Cotari, Jesse; Alpaugh, Mary L; de Stanchina, Elisa; Manova, Katia; Li, Ming; Bonafe, Massimiliano; Ceccarelli, Claudio; Taffurelli, Mario; Santini, Donatella; Altan-Bonnet, Gregoire; Kaplan, Rosandra; Norton, Larry; Nishimoto, Norihiro; Huszar, Dennis; Lyden, David; Bromberg, Jacqueline

    2013-01-01

    We have investigated the importance of interleukin-6 (IL-6) in promoting tumor growth and metastasis. In human primary breast cancers, increased levels of IL-6 were found at the tumor leading edge and positively correlated with advanced stage, suggesting a mechanistic link between tumor cell production of IL-6 and invasion. In support of this hypothesis, we showed that the IL-6/Janus kinase (JAK)/signal transducer and activator of transcription 3 (Stat3) pathway drives tumor progression through the stroma and metastatic niche. Overexpression of IL-6 in tumor cell lines promoted myeloid cell recruitment, angiogenesis, and induced metastases. We demonstrated the therapeutic potential of interrupting this pathway with IL-6 receptor blockade or by inhibiting its downstream effectors JAK1/2 or Stat3. These clinically relevant interventions did not inhibit tumor cell proliferation in vitro but had profound effects in vivo on tumor progression, interfering broadly with tumor-supportive stromal functions, including angiogenesis, fibroblast infiltration, and myeloid suppressor cell recruitment in both the tumor and pre-metastatic niche. This study provides the first evidence for IL-6 expression at the leading edge of invasive human breast tumors and demonstrates mechanistically that IL-6/JAK/Stat3 signaling plays a critical and pharmacologically targetable role in orchestrating the composition of the tumor microenvironment that promotes growth, invasion, and metastasis. PMID:23814496

  1. Comparative evaluation of the impact on endothelial cells induced by different nanoparticle structures and functionalization

    Directory of Open Access Journals (Sweden)

    Lisa Landgraf

    2015-01-01

    Full Text Available In the research field of nanoparticles, many studies demonstrated a high impact of the shape, size and surface charge, which is determined by the functionalization, of nanoparticles on cell viability and internalization into cells. This work focused on the comparison of three different nanoparticle types to give a better insight into general rules determining the biocompatibility of gold, Janus and semiconductor (quantum dot nanoparticles. Endothelial cells were subject of this study, since blood is the first barrier after intravenous nanoparticle application. In particular, stronger effects on the viability of endothelial cells were found for nanoparticles with an elongated shape in comparison to spherical ones. Furthermore, a positively charged nanoparticle surface (NH2, CyA leads to the strongest reduction in cell viability, whereas neutral and negatively charged nanoparticles are highly biocompatible to endothelial cells. These findings are attributed to a rapid internalization of the NH2-functionalized nanoparticles in combination with the damage of intracellular membranes. Interestingly, the endocytotic pathway seems to be a size-dependent process whereas nanoparticles with a size of 20 nm are internalized by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of nanoparticles on endothelial cells. Our findings will help to design new nanoparticles with optimized properties concerning biocompatibility and uptake behavior with respect to the respective intended application.

  2. Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses.

    Science.gov (United States)

    Majoros, Andrea; Platanitis, Ekaterini; Kernbauer-Hölzl, Elisabeth; Rosebrock, Felix; Müller, Mathias; Decker, Thomas

    2017-01-01

    Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported. These include kinase-independent JAK functions as well as extra- and intranuclear activities of U-STATs without phosphotyrosines. Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contributes to transcriptome changes in IFN-treated cells. Our review summarizes the contribution of non-canonical JAK-STAT signaling to the innate antimicrobial immunity imparted by IFN. Moreover, we touch upon functions of IFN pathway proteins beyond the IFN response. These include metabolic functions of IRF9 as well as the regulation of natural killer cell activity by kinase-dead TYK2 and different phosphorylation isoforms of STAT1.

  3. Canonical and Non-Canonical Aspects of JAK–STAT Signaling: Lessons from Interferons for Cytokine Responses

    Science.gov (United States)

    Majoros, Andrea; Platanitis, Ekaterini; Kernbauer-Hölzl, Elisabeth; Rosebrock, Felix; Müller, Mathias; Decker, Thomas

    2017-01-01

    Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported. These include kinase-independent JAK functions as well as extra- and intranuclear activities of U-STATs without phosphotyrosines. Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contributes to transcriptome changes in IFN-treated cells. Our review summarizes the contribution of non-canonical JAK–STAT signaling to the innate antimicrobial immunity imparted by IFN. Moreover, we touch upon functions of IFN pathway proteins beyond the IFN response. These include metabolic functions of IRF9 as well as the regulation of natural killer cell activity by kinase-dead TYK2 and different phosphorylation isoforms of STAT1. PMID:28184222

  4. Rational design and dynamics of self-propelled colloidal bead chains: from rotators to flagella.

    Science.gov (United States)

    Vutukuri, Hanumantha Rao; Bet, Bram; van Roij, René; Dijkstra, Marjolein; Huck, Wilhelm T S

    2017-12-01

    The quest for designing new self-propelled colloids is fuelled by the demand for simple experimental models to study the collective behaviour of their more complex natural counterparts. Most synthetic self-propelled particles move by converting the input energy into translational motion. In this work we address the question if simple self-propelled spheres can assemble into more complex structures that exhibit rotational motion, possibly coupled with translational motion as in flagella. We exploit a combination of induced dipolar interactions and a bonding step to create permanent linear bead chains, composed of self-propelled Janus spheres, with a well-controlled internal structure. Next, we study how flexibility between individual swimmers in a chain can affect its swimming behaviour. Permanent rigid chains showed only active rotational or spinning motion, whereas longer semi-flexible chains showed both translational and rotational motion resembling flagella like-motion, in the presence of the fuel. Moreover, we are able to reproduce our experimental results using numerical calculations with a minimal model, which includes full hydrodynamic interactions with the fluid. Our method is general and opens a new way to design novel self-propelled colloids with complex swimming behaviours, using different complex starting building blocks in combination with the flexibility between them.

  5. Detection of retinoblastoma gene deletions in spontaneous and radiation-induced mouse lung adenocarcinomas by polymerase chain reaction

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-01-01

    A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma gene using histological sections from radiation-induced and spontaneous tumors as the DNA source. Six mouse Rb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments relative to control PCR products on a Southern blot indicated a deletion of that portion of the mouse Rb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death. Spontaneous tumors as well as those from irradiated mice (5.69 Gy 60 Co γ rays or 0.6 Gy JANUS neutrons, which have been found to have approximately equal radiobiological effectiveness) were analyzed for mouse Rb deletions. Tumors in 6 neutron-irradiated mice had no mouse Rb deletions. However, 1 of 6 tumors from γ-irradiated mice (17%) and 6 of 18 spontaneous tumors from unirradiated mice (33%) showed a deletion in one or both mouse Rb alleles. All deletions detected were in the 5' region of the mouse Rb gene. 36 refs., 2 figs., 2 tabs

  6. Design, Construction and Calibration of a Near-Infrared Four-Color Pyrometry System for Laser-Driven High Pressure Experiments

    Science.gov (United States)

    Ali, S. J.; Jeanloz, R.; Collins, G.; Spaulding, D. K.

    2010-12-01

    Current dynamic compression experiments, using both quasi-isentropic and shock-compression, allow access to pressure-temperature states both on and off the principle Hugoniot and over a wide range of conditions of direct relevance to planetary interiors. Such studies necessitate reliable temperature measurements below 4000-5000 K. Such relatively low temperature states are also of particular interest for materials such as methane and water that do not experience much heating under shock compression. In order to measure these temperatures as a function of time across the sample, a four-color, near-infrared pyrometry system is being developed for use at the Janus laser facility (LLNL) with channels at wavelengths of 932nm-1008nm, 1008nm-1108nm, 1108nm-1208nm, and 1208nm-1300nm. Each color band is fiber-coupled to an InGaAs PIN photodiode with a rise time of less than 60 ps, read using an 18 GHz oscilloscope in order to ensure time resolutions of under 200 ps. This will allow for high temporal resolution measurements of laser-driven shock compression experiments with total durations of 5-15 ns as well as correlation with simultaneous time-resolved velocity interferometry and visual-wavelength pyrometry. Calibration of the system is being accomplished using quartz targets, as the EOS for quartz is well known, along with a calibrated integrating sphere of known spectral radiance.

  7. Securing the anonymity of content providers in the World Wide Web

    Science.gov (United States)

    Demuth, Thomas; Rieke, Andreas

    1999-04-01

    Nowadays the World Wide Web (WWW) is an established service used by people all over the world. Most of them do not recognize the fact that they reveal plenty of information about themselves or their affiliation and computer equipment to the providers of web pages they connect to. As a result, a lot of services offer users to access web pages unrecognized or without risk of being backtracked, respectively. This kind of anonymity is called user or client anonymity. But on the other hand, an equivalent protection for content providers does not exist, although this feature is desirable for many situations in which the identity of a publisher or content provider shall be hidden. We call this property server anonymity. We will introduce the first system with the primary target to offer anonymity for providers of information in the WWW. Beside this property, it provides also client anonymity. Based on David Chaum's idea of mixes and in relation to the context of the WWW, we explain the term 'server anonymity' motivating the system JANUS which offers both client and server anonymity.

  8. Acting Law | Law Acting: A Conversation with Dr Felix Nobis and Professor Gary Watt

    Directory of Open Access Journals (Sweden)

    Sean Alexander Mulcahy

    2017-04-01

    Full Text Available Dr Felix Nobis is a senior lecturer with the Centre for Theatre and Performance at Monash University. He has worked as a professional actor for many years. He previously played an assistant to the Crown Prosecutor in the Australian television series, Janus, which was set in Melbourne, Victoria and based on the true story of a criminal family allegedly responsible for police shootings. He also played an advisor to a medical defence firm in the Australian television series MDA. He is a writer and professional storyteller. He has toured his one-person adaptation of Beowulf (2004 and one-person show Once Upon a Barstool (2006 internationally and has written on these experiences. His most recent work Boy Out of the Country (2016 is written in an Australian verse style and has just completed a tour of regional Victoria. Professor Gary Watt is an academic in the School of Law at the University of Warwick where his teaching includes advocacy and mooting. He also regularly leads rhetoric workshops at the Royal Shakespeare Company. He is the author of Dress, Law and Naked Truth (2013 and, most recently, Shakespeare’s Acts of Will: Law, Testament and Properties of Performance (2016, which explores rhetoric in law and theatre. He also co-wrote A Strange Eventful History, which he performed with Australian choral ensemble, The Song Company, to mark the 400th anniversary of Shakespeare’s death.

  9. Treatment with Biologicals in Rheumatoid Arthritis: An Overview.

    Science.gov (United States)

    Rein, Philipp; Mueller, Ruediger B

    2017-12-01

    Management and therapy of rheumatoid arthritis (RA) has been revolutionized by the development and approval of the first biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumor necrosis factor (TNF) α at the end of the last century. Today, numerous efficacious agents with different modes of action are available and achievement of clinical remission or, at least, low disease activity is the target of therapy. Early therapeutic interventions aiming at a defined goal of therapy (treat to target) are supposed to halt inflammation, improving symptoms and signs, and preserving structural integrity of the joints in RA. Up to now, bDMARDs approved for therapy in RA include agents with five different modes of action: TNF inhibition, T cell co-stimulation blockade, IL-6 receptor inhibition, B cell depletion, and interleukin 1 inhibition. Furthermore, targeted synthetic DMARDs (tsDMARDs) inhibiting Janus kinase (JAK) and biosimilars also are approved for RA. The present review focuses on bDMARDs and tsDMARDS regarding similarities and possible drug-specific advantages in the treatment of RA. Furthermore, compounds not yet approved in RA and biosimilars are discussed. Following the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) recommendations, specific treatment of the disease will be discussed with respect to safety and efficacy. In particular, we discuss the question of favoring specific bDMARDs or tsDMARDs in the two settings of insufficient response to methotrexate and to the first bDMARD, respectively.

  10. Kinase inhibitors: a new class of antirheumatic drugs

    Directory of Open Access Journals (Sweden)

    Kyttaris VC

    2012-09-01

    Full Text Available Vasileios C KyttarisDivision of Rheumatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USAAbstract: The outlook for patients with rheumatoid arthritis has improved significantly over the last three decades with the use of disease-modifying antirheumatic drugs. However, despite the use of methotrexate, cytokine inhibitors, and molecules targeting T and B cells, a percentage of patients do not respond or lose their response over time. The autoimmune process in rheumatoid arthritis depends on activation of immune cells, which utilize intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. In the past decade, small molecules targeting several kinases, such as p38 MAPK, Syk, and JAK have been developed. Several p38 MAPK inhibitors proved ineffective in treating rheumatoid arthritis. The Syk inhibitor, fostamatinib, proved superior to placebo in Phase II trials and is currently under Phase III investigation. Tofacitinib, a JAK1/3 inhibitor, was shown to be efficacious in two Phase III trials, while VX-509, a JAK3 inhibitor, showed promising results in a Phase II trial. Fostamatinib and tofacitinib were associated with increased rates of infection, elevation of liver enzymes, and neutropenia. Moreover, fostamatinib caused elevations of blood pressure and diarrhea, while tofacitinib was associated with an increase in creatinine and elevation of lipid levels.Keywords: rheumatoid arthritis, kinase inhibitors, mitogen-activated phosphokinase p38, spleen tyrosine kinase, Janus kinases

  11. Two Decades (almost) of Keck Observations of Io

    Science.gov (United States)

    De Pater, I.; Davies, A. G.; de Kleer, K.

    2015-12-01

    We have regularly observed Io with the 10-m Keck Telescope since 1998, initially using the speckle imaging technique, and switching to Adaptive Optics techniques when this became available in 2001. In this talk we will discuss several eruptions that we witnessed, and present 20-30 year timelines of thermal emission from Pele, Pillan, Janus Patera, Kanehekili Fluctus, and Loki Patera, updating timelines in recent publications [1, 2] with additional Keck adaptive optics data obtained between 2002 and 2015. These new timelines are the most comprehensive plots ever produced of the volcanic thermal emission variability for these or any other locations on Io, utilizing data from multiple ground- and space-based assets. Our continuing multi-decadal observing program forms the basis for charting the variability of Io's volcanic activity, of great importance for understanding the evolution of the Galilean satellite system, and with the expectation of new missions to the jovian system in the next decade. Acknowledgements: This research is in part supported by NSF grant AST-1313485 to UC Berkeley. AGD is supported by a grant from the NASA OPR Program. References: [1] Davies et al. (2012) Icarus, 221, 466-470. [2] Rathbun and Spencer (2010) Icarus, 209, 625-630.

  12. Plasticity of regulatory T cells under cytokine pressure.

    Science.gov (United States)

    Diaconu, Carmen C; Neagu, Ana I; Lungu, Răzvan; Tardei, Graţiela; Alexiu, Irina; Bleotu, Coralia; Economescu, Mihaela Chivu; Bumbăcea, Roxana S; Pele, Irina; Bumbăcea, Dragoş

    2010-01-01

    CD4+ T helper (Th) cells have been divided into different subsets as defined by their cytokine products and functions after their activation. CD4+ T cell subsets are continuously discovered and until now Th1, Th2, Th9, Th17, and regulatory T (Treg) cells have been almost unanimously recognized but yet not completely characterized. The selective production of cytokines by each of the subsets is probably the master key of the mechanisms of immune regulation. The cytokine milieu is extremely important on deciding the fate of T cells. Generally, more than one cytokine is needed for differentiating to a particular lineage and just recently it was shown that this status quo of commitment could be challenged. It is well known that cytokines bind to Type I/II cytokine receptors signaling via Janus kinases (JAKs) followed by activation of Signal Transducer and Activator of Transcription (STAT). STAT molecules work together with other transcription factors (Foxp3, RORgammat and RORalpha, T-bet, GATA3, Runx 1, NFAT, etc.) also controlled by cytokines, in modulating the Th phenotype and functions. In this review, we analyze the plasticity of Treg population focusing on the most recent discoveries on how microenvironmental cytokines refine/modify Treg phenotype and function, thus changing their fate.

  13. Comparative Observation of Silver Nano and Microstructures Deposited from Aerosol and Fog

    Directory of Open Access Journals (Sweden)

    Zheltova Anna

    2017-01-01

    Full Text Available A comparative study of the structure and fractal properties of arrays of the silver nano-/micro-particles deposited on the silicon substrate both from the aerosol and fog showed that the form of the silver individual particles and nano-/microstructures greatly depends on the deposition conditions. By passing an aerosol through isopropyl alcohol, the formation of fractal aggregates of the silver nano-/micro-particles both in the air and in alcohol was observed. Deposition of the silver nano-/micro-particles in the atmosphere of the saturated isopropyl alcohol vapours led to formation of fog. Micro-droplets of the silver colloidal solution were deposited on the substrate. The further evaporation of alcohol created the silver nano/microstructures in the form of annular layers. It was found that the concerned annular layers contained silver particles of the same shape in the form of a Crescent (or Janus-nano-/microparticles. The nature of discovered effects is discussed.

  14. Tuning Amphiphilicity of Particles for Controllable Pickering Emulsion

    Directory of Open Access Journals (Sweden)

    Zhen Wang

    2016-11-01

    Full Text Available Pickering emulsions with the use of particles as emulsifiers have been extensively used in scientific research and industrial production due to their edge in biocompatibility and stability compared with traditional emulsions. The control over Pickering emulsion stability and type plays a significant role in these applications. Among the present methods to build controllable Pickering emulsions, tuning the amphiphilicity of particles is comparatively effective and has attracted enormous attention. In this review, we highlight some recent advances in tuning the amphiphilicity of particles for controlling the stability and type of Pickering emulsions. The amphiphilicity of three types of particles including rigid particles, soft particles, and Janus particles are tailored by means of different mechanisms and discussed here in detail. The stabilization-destabilization interconversion and phase inversion of Pickering emulsions have been successfully achieved by changing the surface properties of these particles. This article provides a comprehensive review of controllable Pickering emulsions, which is expected to stimulate inspiration for designing and preparing novel Pickering emulsions, and ultimately directing the preparation of functional materials.

  15. IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain.

    Science.gov (United States)

    Wang, H Y; Paul, W E; Keegan, A D

    1996-02-01

    IL-4 binds to a cell surface receptor complex that consists of the IL-4 binding protein (IL-4R alpha) and the gamma chain of the IL-2 receptor complex (gamma c). The receptors for IL-4 and IL-2 have several features in common; both use the gamma c as a receptor component, and both activate the Janus kinases JAK-1 and JAK-3. In spite of these similarities, IL-4 evokes specific responses, including the tyrosine phosphorylation of 4PS/IRS-2 and the induction of CD23. To determine whether sequences within the cytoplasmic domain of the IL-4R alpha specify these IL-4-specific responses, we transplanted the insulin IL-4 receptor motif (I4R motif) of the huIL-4R alpha to the cytoplasmic domain of a truncated IL-2R beta. In addition, we transplanted a region that contains peptide sequences shown to block Stat6 binding to DNA. We analyzed the ability of cells expressing these IL-2R-IL-4R chimeric constructs to respond to IL-2. We found that IL-4 function could be transplanted to the IL-2 receptor by these regions and that proliferative and differentiative functions can be induced by different receptor sequences.

  16. Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases.

    Science.gov (United States)

    Johnston, J A; Wang, L M; Hanson, E P; Sun, X J; White, M F; Oakes, S A; Pierce, J H; O'Shea, J J

    1995-12-01

    The signaling molecules insulin receptor substrate (IRS)-1 and the newly described IRS-2 (4PS) molecule are major insulin and interleukin 4 (IL-4)-dependent phosphoproteins. We report here that IL-2, IL-7, and IL-15, as well as IL-4, rapidly stimulate the tyrosine phosphorylation of IRS-1 and IRS-2 in human peripheral blood T cells, NK cells, and in lymphoid cell lines. In addition, we show that the Janus kinases, JAK1 and JAK3, associate with IRS-1 and IRS-2 in T cells. Coexpression studies demonstrate that these kinases can tyrosine-phosphorylate IRS-2, suggesting a possible mechanism by which cytokine receptors may induce the tyrosine phosphorylation of IRS-1 and IRS-2. We further demonstrate that the p85 subunit of phosphoinositol 3-kinase associates with IRS-1 in response to IL-2 and IL-4 in T cells. Therefore, these data indicate that IRS-1 and IRS-2 may have important roles in T lymphocyte activation not only in response to IL-4, but also in response to IL-2, IL-7, and IL-15.

  17. CAD/CAM–designed 3D-printed electroanalytical cell for the evaluation of nanostructured gas-diffusion electrodes

    International Nuclear Information System (INIS)

    Chervin, Christopher N; Parker, Joseph F; Nelson, Eric S; Rolison, Debra R; Long, Jeffrey W

    2016-01-01

    The ability to effectively screen and validate gas-diffusion electrodes is critical to the development of next-generation metal–air batteries and regenerative fuel cells. The limiting electrode in a classic two-terminal device such as a battery or fuel cell is difficult to discern without an internal reference electrode, but the flooded electrolyte characteristic of three-electrode electroanalytical cells negates the prime function of an air electrode—a void volume freely accessible to gases. The nanostructured catalysts that drive the energy-conversion reactions (e.g., oxygen reduction and evolution in the air electrode of metal–air batteries) are best evaluated in the electrode structure as-used in the practical device. We have designed, 3D-printed, and characterized an air-breathing, thermodynamically referenced electroanalytical cell that allows us to mimic the Janus arrangement of the gas-diffusion electrode in a metal–air cell: one face freely exposed to gases, the other wetted by electrolyte. (paper)

  18. The effects of electromagnetic irradiation on activation of microglia and JAKs in rat hippocampus

    International Nuclear Information System (INIS)

    Chen Chunhai; Yang Xuesen; Hao Yutong; Zhang Guangbin; Yu Zhengping

    2008-01-01

    Objective: To determine the activation of microglia and the phosphorylation of Jaks, the upstream factors of JAK/STAT(janus activated kinase/signal transducers and activators of transcription) signaling pathway, after electromagnetic irradiation. Methods: Rats were irradiated by 90 mW/cm 2 EMF for 20 min. The phosphorylation of Jaks was determined by western blot at different time after electromagnetic irradiation. The activation of microglia was determined by immuno- chemistry. Results: GSA-IB4 was upregulated in microglia, which indicated microglia was activated after electromagnetic irradiation. The phosphorylation of Jak1, Jak2 and Jak3 in rat hippocampus was upregulated after electromagnetic irradiation. The phosphorylation of Jakl was upregulated after microwave exposure and peaked at 12 h. Jak2 peaked at 0 h after electro-magnetic irradiation and sustained in a high level. Jak3 was slightly affected by electromagnetic irradiation. All the three members of JAKs return to normal at 72 h after electromagnetic irradiation. Conclusion: Microglia cells was activated after electromagnetic irradiation. The phosphorylation of Jaks was upregulated by electromagnetic irradiation. It suggested that JAK/ STAT singnaling pathway was activated after electromagnetic irradiation, which indicated that JAK/STAT signaling pathway may participate in brain microglia activation induced by electromagnetic irradiation. (authors)

  19. Photogrammetry-Based Head Digitization for Rapid and Accurate Localization of EEG Electrodes and MEG Fiducial Markers Using a Single Digital SLR Camera.

    Science.gov (United States)

    Clausner, Tommy; Dalal, Sarang S; Crespo-García, Maité

    2017-01-01

    The performance of EEG source reconstruction has benefited from the increasing use of advanced head modeling techniques that take advantage of MRI together with the precise positions of the recording electrodes. The prevailing technique for registering EEG electrode coordinates involves electromagnetic digitization. However, the procedure adds several minutes to experiment preparation and typical digitizers may not be accurate enough for optimal source reconstruction performance (Dalal et al., 2014). Here, we present a rapid, accurate, and cost-effective alternative method to register EEG electrode positions, using a single digital SLR camera, photogrammetry software, and computer vision techniques implemented in our open-source toolbox, janus3D . Our approach uses photogrammetry to construct 3D models from multiple photographs of the participant's head wearing the EEG electrode cap. Electrodes are detected automatically or semi-automatically using a template. The rigid facial features from these photo-based models are then surface-matched to MRI-based head reconstructions to facilitate coregistration to MRI space. This method yields a final electrode coregistration error of 0.8 mm, while a standard technique using an electromagnetic digitizer yielded an error of 6.1 mm. The technique furthermore reduces preparation time, and could be extended to a multi-camera array, which would make the procedure virtually instantaneous. In addition to EEG, the technique could likewise capture the position of the fiducial markers used in magnetoencephalography systems to register head position.

  20. Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 2.

    Science.gov (United States)

    Kettle, Jason G; Åstrand, Annika; Catley, Matthew; Grimster, Neil P; Nilsson, Magnus; Su, Qibin; Woessner, Richard

    2017-02-01

    Janus kinases (JAKs) are a family of four enzymes; JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2) that are critical in cytokine signalling and are strongly linked to both cancer and inflammatory diseases. There are currently two launched JAK inhibitors for the treatment of human conditions: tofacitinib for Rheumatoid arthritis (RA) and ruxolitinib for myeloproliferative neoplasms including intermediate or high risk myelofibrosis and polycythemia vera. Areas covered: This review covers patents claiming activity against one or more JAK family members in the period 2013-2015 inclusive, and covers 95 patents from 42 applicants, split over two parts. The authors have ordered recent patents according to the primary applicant's name, with part 2 covering J through Z. Expert opinion: Inhibition of JAK-family kinases is an area of growing interest, catalysed by the maturity of data on marketed inhibitors ruxolitinib and tofacitinib in late stage clinical trials. Many applicants are pursuing traditional fast-follower strategies around these inhibitors, with a range of chemical strategies adopted. The challenge will be to show sufficient differentiation to the originator compounds, since dose limiting toxicities with such agents appear to be on target and mechanism-related and also considering that such agents may be available as generic compounds by the time follower agents reach market.