Sample records for font4 ilc prototype
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Electroweak precision data and gravitino dark matter
NASA Astrophysics Data System (ADS)
Heinemeyer, S.
2007-11-01
Electroweak precision measurements can provide indirect information about the possible scale of supersymmetry already at the present level of accuracy. We review present day sensitivities of precision data in mSUGRA-type models with the gravitino as the lightest supersymmetric particle (LSP). The c2 fit is based on MW, sin2 qeff, (g-2)m , BR (b xAE sl) and the lightest MSSM Higgs boson mass, Mh. We find indications for relatively light soft supersymmetry-breaking masses, offering good prospects for the LHC and the ILC, and in some cases also for the Tevatron.
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NASA Astrophysics Data System (ADS)
Irles, A.
2018-02-01
High precision physics at future colliders as the International Linear Collider (ILC) require unprecedented high precision in the determination of the energy of final state particles. The needed precision will be achieved thanks to the Particle Flow algorithms (PF) which require highly granular and hermetic calorimeters systems. The physical proof of concept of the PF was performed in the previous campaign of beam tests of physic prototypes within the CALICE collaboration. One of these prototypes was the physics prototype of the Silicon-Tungsten Electromagnetic Calorimeter (SiW-ECAL) for the ILC. In this document we present the latest news on R&D of the next generation prototype, the technological prototype with fully embedded very front-end (VFE) electronics, of the SiW-ECAL. Special emphasis is given to the presentation and discussion of the first results from the beam test done at DESY in June 2017. The physics program for such beam test consisted in the calibration and commissioning of the current set of available SiW ECAL modules; the test of performance of individual slabs under 1T magnetic fields; and the study of electromagnetic showers events.
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The Yin and Yang of Innate Lymphoid Cells in Cancer.
Carrega, Paolo; Campana, Stefania; Bonaccorsi, Irene; Ferlazzo, Guido
2016-11-01
The recent appreciation of novel subsets of innate lymphoid cells (ILCs) as important regulators of tissue homeostasis, inflammation and repair, raise questions regarding the presence and role of these cells in cancer tissues. In addition to natural killer and fetal lymphoid tissue inducer (LTi) cells, the ILC family comprises non-cytolytic, cytokine-producing cells that are classified into ILC1, ILC2 and ILC3 based on phenotypic and functional characteristics. Differently from natural killer cells, which are the prototypical members of ILC1 and whose role in tumors is better established, the involvement of other ILC subsets in cancer progression or resistance is still fuzzy and in several instances controversial, since current studies indicate both context-dependent beneficial or pathogenic effects. Here, we review the current knowledge regarding the involvement of these novel ILC subsets in the context of tumor immunology, highlighting how ILC subsets might behave either as friends or foes. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
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A CMOS pixel sensor prototype for the outer layers of linear collider vertex detector
NASA Astrophysics Data System (ADS)
Zhang, L.; Morel, F.; Hu-Guo, C.; Himmi, A.; Dorokhov, A.; Hu, Y.
2015-01-01
The International Linear Collider (ILC) expresses a stringent requirement for high precision vertex detectors (VXD). CMOS pixel sensors (CPS) have been considered as an option for the VXD of the International Large Detector (ILD), one of the detector concepts proposed for the ILC. MIMOSA-31 developed at IPHC-Strasbourg is the first CPS integrated with 4-bit column-level ADC for the outer layers of the VXD, adapted to an original concept minimizing the power consumption. It is composed of a matrix of 64 rows and 48 columns. The pixel concept combines in-pixel amplification with a correlated double sampling (CDS) operation in order to reduce the temporal noise and fixed pattern noise (FPN). At the bottom of the pixel array, each column is terminated with a self-triggered analog-to-digital converter (ADC). The ADC design was optimized for power saving at a sampling frequency of 6.25 MS/s. The prototype chip is fabricated in a 0.35 μm CMOS technology. This paper presents the details of the prototype chip and its test results.
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Innate lymphoid cells in secondary lymphoid organs.
Bar-Ephraïm, Yotam E; Mebius, Reina E
2016-05-01
The family of innate lymphoid cells (ILCs) has attracted attention in recent years as its members are important regulators of immunity, while they can also cause pathology. In both mouse and man, ILCs were initially discovered in developing lymph nodes as lymphoid tissue inducer (LTi) cells. These cells form the prototypic members of the ILC family and play a central role in the formation of secondary lymphoid organs (SLOs). In the absence of LTi cells, lymph nodes (LN) and Peyer's Patches (PP) fail to form in mice, although the splenic white pulp can develop normally. Besides LTi cells, the ILC family encompasses helper-like ILCs with functional distinctions as seen by T-helper cells, as well as cytotoxic natural killer (NK) cells. ILCs are still present in adult SLOs where they have been shown to play a role in lymphoid tissue regeneration. Furthermore, ILCs were implicated to interact with adaptive lymphocytes and influence the adaptive immune response. Here, we review the recent literature on the role of ILCs in secondary lymphoid tissue from the formation of SLOs to mature SLOs in adults, during homeostasis and pathology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Measuring the Magnetic Center Behavior of an ILC Superconducting Quadrupole Prototype
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spencer, Cherrill M.; Adolphsen, Chris; Berndt, Martin
2011-02-07
The main linacs of the proposed International Linear Collider (ILC) consist of superconducting cavities operated at 2K. The accelerating cavities are contained in a contiguous series of cryogenic modules that also house the main linac quadrupoles, thus the quadrupoles also need to be superconducting. In an early ILC design, these magnets are about 0.6 m long, have cos (2{theta}) coils, and operate at constant field gradients up to 60 T/m. In order to preserve the small beam emittances in the ILC linacs, the e+ and e- beams need to traverse the quadrupoles near their magnetic centers. A quadrupole shunting techniquemore » is used to measure the quadrupole alignment with the beams; this process requires the magnetic centers move by no more than about 5 micrometers when their strength is changed. To determine if such tight stability is achievable in a superconducting quadrupole, we at SLAC measured the magnetic center motions in a prototype ILC quadrupole built at CIEMAT in Spain. A rotating coil technique was used with a better than 0.1 micrometer precision in the relative field center position, and less than a 2 micrometer systematic error over 30 minutes. This paper describes the warm-bore cryomodule that houses the quadrupole in its Helium vessel, the magnetic center measurement system, the measured center data and strength and harmonics magnetic data.« less
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Study of a Large Prototype TPC for the ILC using Micro-Pattern Gas Detectors
NASA Astrophysics Data System (ADS)
Münnich, A.; LCTPC Collaboration
2016-04-01
In the last decade, R&D for detectors for the future International Linear Collider (ILC) has been performed by the community. The International Large Detector (ILD) is one of two detector concepts at the ILC. Its tracking system consists of a Si vertex detector, forward tracking disks and a large volume Time Projection Chamber (TPC). Within the LCTPC collaboration, a Large Prototype (LP) TPC has been built as a demonstrator. Its endplate is able to house up to seven identical modules with Micro-Pattern Gas Detectors (MPGD) amplification. Recently, the LP has been equipped with resistive anode Micromegas (MM) or Gas Electron Multiplier (GEM) modules. Both the MM and GEM technologies have been studied with an electron beam up to 6 GeV in a 1 Tesla solenoid magnet. After introducing the current R&D status, recent results will be presented including field distortions, ion gating and spatial resolution as well as future plans of the LCTPC R&D.
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NASA Technical Reports Server (NTRS)
Cadogan, Dave; Lingo, Bob
1996-01-01
In July of 1996, ILC Dover was awarded Phase 1 of a contract for NASA to develop a prototype Power Assisted Space Suit glove to enhance the performance of astronauts during Extra-Vehicular Activity (EVA). This report summarizes the work performed to date on Phase 1, and details the work to be conducted on Phase 2 of the program. Phase 1 of the program consisted of research and review of related technical sources, concept brainstorming, baseline design development, modeling and analysis, component mock-up testing, and test data analysis. ILC worked in conjunction with the University of Maryland's Space Systems Laboratory (SSL) to develop the power assisted glove. Phase 2 activities will focus on the design maturation and the manufacture of a working prototype system. The prototype will be tested and evaluated in conjunction with existing space suit glove technology to determine the performance enhancement anticipated with the implementation of the power assisted joint technology in space suit gloves.
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Noval Rivas, Magali; Burton, Oliver T; Oettgen, Hans C; Chatila, Talal
2016-09-01
Food allergy is a major health issue, but its pathogenesis remains obscure. Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation. However their role in food allergy is largely unknown. We sought to investigate the role of ILC2s in food allergy. Food allergy-prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) were orally sensitized with food allergens, and the ILC2 compartment was analyzed. The requirement for ILC2s in food allergy was investigated by using Il4raF709, IL-33 receptor-deficient (Il1rl1(-/-)), IL-13-deficient (Il13(-/-)), and IL-4-deficient (Il4(-/-)) mice and by adoptive transfer of in vitro-expanded ILC2s. Direct effects of ILC2s on regulatory T (Treg) cells and mast cells were analyzed in coculture experiments. Treg cell control of ILC2s was assessed in vitro and in vivo. Il4raF709 mice with food allergy exhibit increased numbers of ILC2s. IL-4 secretion by ILC2s contributes to the allergic response by reducing allergen-specific Treg cell and activating mast cell counts. IL-33 receptor deficiency in Il4raF709 Il1rl1(-/-) mice protects against allergen sensitization and anaphylaxis while reducing ILC2 induction. Adoptive transfer of wild-type and Il13(-/-) but not Il4(-/-) ILC2s restored sensitization in Il4raF709 Il1rl1(-/-) mice. Treg cells suppress ILC2s in vitro and in vivo. IL-4 production by IL-33-stimulated ILC2s blocks the generation of allergen-specific Treg cells and favors food allergy. Strategies to block ILC2 activation or the IL-33/IL-33 receptor pathway can lead to innovative therapies in the treatment of food allergy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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CCD-based vertex detector for ILC
NASA Astrophysics Data System (ADS)
Stefanov, Konstantin D.
2006-12-01
Charge Coupled Devices (CCDs) have been successfully used in several high-energy physics experiments over the last 20 years. Their small pixel size and excellent precision provide a superb tool for studying of short-lived particles and understanding the nature at fundamental level. Over the last few years the Linear Collider Flavour Identification (LCFI) collaboration has developed Column-Parallel CCDs (CPCCD) and CMOS readout chips, to be used for the vertex detector at the International Linear Collider (ILC). The CPCCDs are very fast devices capable of satisfying the challenging requirements imposed by the beam structure of the superconducting accelerator. The first set of prototype devices have been successfully designed, manufactured and tested, with second generation chips on the way. Another idea for CCD-based device, the In-situ Storage Image Sensor (ISIS) is also under development and the first prototype has been manufactured.
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NASA Astrophysics Data System (ADS)
Adloff, C.; Blaha, J.; Blaising, J.-J.; Drancourt, C.; Espargilière, A.; Gaglione, R.; Geffroy, N.; Karyotakis, Y.; Prast, J.; Vouters, G.; Bilki, B.; Francis, K.; Repond, J.; Smith, J.; Xia, L.; Baldolemar, E.; Li, J.; Park, S. T.; Sosebee, M.; White, A. P.; Yu, J.; Buanes, T.; Eigen, G.; Mikami, Y.; Watson, N. K.; Mavromanolakis, G.; Thomson, M. A.; Ward, D. R.; Yan, W.; Benchekroun, D.; Hoummada, A.; Khoulaki, Y.; Benyamna, M.; Cârloganu, C.; Fehr, F.; Gay, P.; Manen, S.; Royer, L.; Blazey, G. C.; Boona, S.; Chakraborty, D.; Dyshkant, A.; Hedin, D.; Lima, J. G. R.; Powell, J.; Rykalin, V.; Scurti, N.; Smith, M.; Tran, N.; Zutshi, V.; Hostachy, J.-Y.; Morin, L.; Cornett, U.; David, D.; Dietrich, J.; Falley, G.; Gadow, K.; Göttlicher, P.; Günter, C.; Hermberg, B.; Karstensen, S.; Krivan, F.; Lucaci-Timoce, A.-I.; Lu, S.; Lutz, B.; Marchesini, I.; Morozov, S.; Morgunov, V.; Reinecke, M.; Sefkow, F.; Smirnov, P.; Terwort, M.; Vargas-Trevino, A.; Feege, N.; Garutti, E.; Eckert, P.; Kaplan, A.; Schultz-Coulon, H.-Ch; Shen, W.; Stamen, R.; Tadday, A.; Norbeck, E.; Onel, Y.; Wilson, G. W.; Kawagoe, K.; Uozumi, S.; Dauncey, P. D.; Magnan, A.-M.; Bartsch, V.; Wing, M.; Salvatore, F.; Calvo Alamillo, E.; Fouz, M.-C.; Puerta-Pelayo, J.; Bobchenko, B.; Chadeeva, M.; Danilov, M.; Epifantsev, A.; Markin, O.; Mizuk, R.; Novikov, E.; Rusinov, V.; Tarkovsky, E.; Kirikova, N.; Kozlov, V.; Soloviev, Y.; Buzhan, P.; Dolgoshein, B.; Ilyin, A.; Kantserov, V.; Kaplin, V.; Karakash, A.; Popova, E.; Smirnov, S.; Frey, A.; Kiesling, C.; Seidel, K.; Simon, F.; Soldner, C.; Weuste, L.; Bonis, J.; Bouquet, B.; Callier, S.; Cornebise, P.; Doublet, Ph; Dulucq, F.; Faucci Giannelli, M.; Fleury, J.; Li, H.; Martin-Chassard, G.; Richard, F.; de la Taille, Ch; Pöschl, R.; Raux, L.; Seguin-Moreau, N.; Wicek, F.; Anduze, M.; Boudry, V.; Brient, J.-C.; Jeans, D.; Mora de Freitas, P.; Musat, G.; Reinhard, M.; Ruan, M.; Videau, H.; Bulanek, B.; Zacek, J.; Cvach, J.; Gallus, P.; Havranek, M.; Janata, M.; Kvasnicka, J.; Lednicky, D.; Marcisovsky, M.; Polak, I.; Popule, J.; Tomasek, L.; Tomasek, M.; Ruzicka, P.; Sicho, P.; Smolik, J.; Vrba, V.; Zalesak, J.; Belhorma, B.; Ghazlane, H.; Takeshita, T.
2012-04-01
A prototype module for an International Linear Collider (ILC) detector was built, installed, and tested between 2006 and 2009 at CERN and Fermilab as part of the CALICE test beam program, in order to study the possibilities of extending energy sampling behind a hadronic calorimeter and to study the possibilities of providing muon tracking. The ``tail catcher/muon tracker'' (TCMT) is composed of 320 extruded scintillator strips (dimensions 1000 × 50 × 5 mm3) packaged in 16 one-meter square planes interleaved between steel plates. The scintillator strips were read out with wavelength shifting fibers and silicon photomultipliers. The planes were arranged with alternating horizontal and vertical strip orientations. Data were collected for muons and pions in the energy range 6 GeV to 80 GeV. Utilizing data taken in 2006, this paper describes the design and construction of the TCMT, performance characteristics, and a beam-based evaluation of the ability of the TCMT to improve hadronic energy resolution in a prototype ILC detector. For a typical configuration of an ILC detector with a coil situated outside a calorimeter system with a thickness of 5.5 nuclear interaction lengths, a TCMT would improve relative energy resolution by 6-16% for pions between 20 and 80 GeV.
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Evaluation of an Integrated Read-Out Layer Prototype
DOE Office of Scientific and Technical Information (OSTI.GOV)
Abu-Ajamieh, Fayez
2011-07-01
This thesis presents evaluation results of an Integrated Read-out Layer (IRL), a proposed concept in scintillator-based calorimetry intended to meet the exceptional calorimetric requirements of the envisaged International Linear Collider (ILC). This study presents a full characterization of the prototype IRL, including exploration of relevant parameters, calibration performance, and the uniformity of response. The study represents proof of the IRL concept. Finally, proposed design enhancements are presented.
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Evaluation of an Integrated Read-Out Layer Prototype
DOE Office of Scientific and Technical Information (OSTI.GOV)
Abu-Ajamieh, Fayez; /NIU
2011-08-18
This thesis presents evaluation results of an Integrated Read-out Layer (IRL), a proposed concept in scintillator-based calorimetry intended to meet the exceptional calorimetric requirements of the envisaged International Linear Collider (ILC). This study presents a full characterization of the prototype IRL, including exploration of relevant parameters, calibration performance, and the uniformity of response. The study represents proof of the IRL concept. Finally, proposed design enhancements are presented.
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Salimi, Maryam; Stöger, Linda; Liu, Wei; Go, Simei; Pavord, Ian; Klenerman, Paul; Ogg, Graham; Xue, Luzheng
2017-10-01
Group 2 innate lymphoid cells (ILC2s) are a potential innate source of type 2 cytokines in the pathogenesis of allergic conditions. Epithelial cytokines (IL-33, IL-25, and thymic stromal lymphopoietin [TSLP]) and mast cell mediators (prostaglandin D 2 [PGD 2 ]) are critical activators of ILC2s. Cysteinyl leukotrienes (cysLTs), including leukotriene (LT) C 4 , LTD 4 , and LTE 4 , are metabolites of arachidonic acid and mediate inflammatory responses. Their role in human ILC2s is still poorly understood. We sought to determine the role of cysLTs and their relationship with other ILC2 stimulators in the activation of human ILC2s. For ex vivo studies, fresh blood from patients with atopic dermatitis and healthy control subjects was analyzed with flow cytometry. For in vitro studies, ILC2s were isolated and cultured. The effects of cysLTs, PGD 2 , IL-33, IL-25, TSLP, and IL-2 alone or in combination on ILC2s were defined by using chemotaxis, apoptosis, ELISA, Luminex, quantitative RT-PCR, and flow cytometric assays. The effect of endogenous cysLTs was assessed by using human mast cell supernatants. Human ILC2s expressed the LT receptor CysLT 1 , levels of which were increased in atopic subjects. CysLTs, particularly LTE 4 , induced migration, reduced apoptosis, and promoted cytokine production in human ILC2s in vitro. LTE 4 enhanced the effect of PGD 2 , IL-25, IL-33, and TSLP, resulting in increased production of type 2 and other proinflammatory cytokines. The effect of LTE 4 was inhibited by montelukast, a CysLT 1 antagonist. Interestingly, addition of IL-2 to LTE 4 and epithelial cytokines significantly amplified ILC2 activation and upregulated expression of the receptors for IL-33 and IL-25. CysLTs, particularly LTE 4 , are important contributors to the triggering of human ILC2s in inflammatory responses, particularly when combined with other ILC2 activators. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules
Elemam, Noha Mousaad
2017-01-01
Innate lymphoid cells (ILCs) are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK) cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce TH2 cytokines while ILC3s and lymphoid tissue inducer (LTis) are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation. PMID:29232860
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Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules.
Elemam, Noha Mousaad; Hannawi, Suad; Maghazachi, Azzam A
2017-12-10
Innate lymphoid cells (ILCs) are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK) cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce T H 2 cytokines while ILC3s and lymphoid tissue inducer (LTis) are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation.
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Power pulsing of the CMOS sensor Mimosa 26
NASA Astrophysics Data System (ADS)
Kuprash, Oleg
2013-12-01
Mimosa 26 is a monolithic active pixel sensor developed by IPHC (Strasbourg) & IRFU (Saclay) as a prototype for the ILC vertex detector studies. The resolution requirements for the ILC tracking detector are very extreme, demanding very low material in the detector, thus only air cooling can be considered. Power consumption has to be reduced as far as possible. The beam structure of the ILC allows the possibility of power pulsing: only for about the 1 ms long bunch train full power is required, and during the 199 ms long pauses between the bunch trains the power can be reduced to a minimum. Not being adapted for the power pulsing, the sensor shows in laboratory tests a good performance under power pulsing. The power pulsing allows to significantly reduce the heating of the chip and divides power consumption approximately by a factor of 6. In this report a summary of power pulsing studies using the digital readout of Mimosa 26 is given.
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Charge shielding in the In-situ Storage Image Sensor for a vertex detector at the ILC
NASA Astrophysics Data System (ADS)
Zhang, Z.; Stefanov, K. D.; Bailey, D.; Banda, Y.; Buttar, C.; Cheplakov, A.; Cussans, D.; Damerell, C.; Devetak, E.; Fopma, J.; Foster, B.; Gao, R.; Gillman, A.; Goldstein, J.; Greenshaw, T.; Grimes, M.; Halsall, R.; Harder, K.; Hawes, B.; Hayrapetyan, K.; Heath, H.; Hillert, S.; Jackson, D.; Pinto Jayawardena, T.; Jeffery, B.; John, J.; Johnson, E.; Kundu, N.; Laing, A.; Lastovicka, T.; Lau, W.; Li, Y.; Lintern, A.; Lynch, C.; Mandry, S.; Martin, V.; Murray, P.; Nichols, A.; Nomerotski, A.; Page, R.; Parkes, C.; Perry, C.; O'Shea, V.; Sopczak, A.; Tabassam, H.; Thomas, S.; Tikkanen, T.; Velthuis, J.; Walsh, R.; Woolliscroft, T.; Worm, S.
2009-08-01
The Linear Collider Flavour Identification (LCFI) collaboration has successfully developed the first prototype of a novel particle detector, the In-situ Storage Image Sensor (ISIS). This device ideally suits the challenging requirements for the vertex detector at the future International Linear Collider (ILC), combining the charge storing capabilities of the Charge-Coupled Devices (CCD) with readout commonly used in CMOS imagers. The ISIS avoids the need for high-speed readout and offers low power operation combined with low noise, high immunity to electromagnetic interference and increased radiation hardness compared to typical CCDs. The ISIS is one of the most promising detector technologies for vertexing at the ILC. In this paper we describe the measurements on the charge-shielding properties of the p-well, which is used to protect the storage register from parasitic charge collection and is at the core of device's operation. We show that the p-well can suppress the parasitic charge collection by almost two orders of magnitude, satisfying the requirements for the application.
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Development of monolithic pixel detector with SOI technology for the ILC vertex detector
NASA Astrophysics Data System (ADS)
Yamada, M.; Ono, S.; Tsuboyama, T.; Arai, Y.; Haba, J.; Ikegami, Y.; Kurachi, I.; Togawa, M.; Mori, T.; Aoyagi, W.; Endo, S.; Hara, K.; Honda, S.; Sekigawa, D.
2018-01-01
We have been developing a monolithic pixel sensor for the International Linear Collider (ILC) vertex detector with the 0.2 μm FD-SOI CMOS process by LAPIS Semiconductor Co., Ltd. We aim to achieve a 3 μm single-point resolution required for the ILC with a 20×20 μm2 pixel. Beam bunch crossing at the ILC occurs every 554 ns in 1-msec-long bunch trains with an interval of 200 ms. Each pixel must record the charge and time stamp of a hit to identify a collision bunch for event reconstruction. Necessary functions include the amplifier, comparator, shift register, analog memory and time stamp implementation in each pixel, and column ADC and Zero-suppression logic on the chip. We tested the first prototype sensor, SOFIST ver.1, with a 120 GeV proton beam at the Fermilab Test Beam Facility in January 2017. SOFIST ver.1 has a charge sensitive amplifier and two analog memories in each pixel, and an 8-bit Wilkinson-type ADC is implemented for each column on the chip. We measured the residual of the hit position to the reconstructed track. The standard deviation of the residual distribution fitted by a Gaussian is better than 3 μm.
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CXCR6 Expression Is Important for Retention and Circulation of ILC Precursors.
Chea, Sylvestre; Possot, Cécilie; Perchet, Thibaut; Petit, Maxime; Cumano, Ana; Golub, Rachel
2015-01-01
Innate lymphoid cells are present at mucosal sites and represent the first immune barrier against infections, but what contributes to their circulation and homing is still unclear. Using Rag2(-/-) Cxcr6(Gfp/+) reporter mice, we assessed the expression and role of CXCR6 in the circulation of ILC precursors and their progeny. We identify CXCR6 expressing ILC precursors in the bone marrow and characterize their significant increase in CXCR6-deficient mice at steady state, indicating their partial retention in the bone marrow after CXCR6 ablation. Circulation was also impaired during embryonic life as fetal liver from CXCR6-deficient embryos displayed decreased numbers of ILC3 precursors. When injected, fetal CXCR6-deficient ILC3 precursors also fail to home and reconstitute ILC compartments in vivo. We show that adult intestinal ILC subsets have heterogeneous expression pattern of CXCR6, integrin α 4 β 7, CD62L, CD69, and CD44, with ILC1 and ILC3 being more likely tissue resident lymphocytes. Intestinal ILC subsets were unchanged in percentages and numbers in both mice. We demonstrate that the ILC frequency is maintained due to a significant increase of ILC peripheral proliferation, as well as an increased proliferation of the in situ ILC precursors to compensate their retention in the bone marrow.
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Cortez, Victor S; Ulland, Tyler K; Cervantes-Barragan, Luisa; Bando, Jennifer K; Robinette, Michelle L; Wang, Qianli; White, Andrew J; Gilfillan, Susan; Cella, Marina; Colonna, Marco
2017-09-01
Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of 'imprinting' by cytokines of the TGF-β family. We studied mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-β family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-β signaling mediated by the cytokine receptor TGFβR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-β. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-β signaling in NK cells.
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Cortez, Victor S; Ulland, Tyler K; Cervantes-Barragan, Luisa; Bando, Jennifer K; Robinette, Michelle L; Wang, Qianli; White, Andrew J; Gilfillan, Susan; Cella, Marina; Colonna, Marco
2017-01-01
Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of ‘imprinting’ by cytokines of the TGF-β family. We examined mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-β family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-β signaling mediated by the cytokine receptor TGF-βR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-β. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-β signaling in NK cells. PMID:28759002
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Compact, Intelligent, Digitally Controlled IGBT Gate Drivers for a PEBB-Based ILC Marx Modulator
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nguyen, M.N.; Burkhart, C.; Olsen, J.J.
2010-06-07
SLAC National Accelerator Laboratory has built and is currently operating a first generation prototype Marx klystron modulator to meet ILC specifications. Under development is a second generation prototype, aimed at improving overall performance, serviceability, and manufacturability as compared to its predecessor. It is designed around 32 cells, each operating at 3.75 kV and correcting for its own capacitor droop. Due to the uniqueness of this application, high voltage gate drivers needed to be developed for the main 6.5 kV and droop correction 1.7 kV IGBTs. The gate driver provides vital functions such as protection of the IGBT from over-voltage andmore » over-current, detection of gate-emitter open and short circuit conditions, and monitoring of IGBT degradation (based on collector-emitter saturation voltage). Gate drive control, diagnostic processing capabilities, and communication are digitally implemented using an FPGA. This paper details the design of the gate driver circuitry, component selection, and construction layout. In addition, experimental results are included to illustrate the effectiveness of the protection circuit.« less
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Barrier Epithelial Cells and the Control of Type 2 Immunity.
Hammad, Hamida; Lambrecht, Bart N
2015-07-21
Type-2-cell-mediated immunity, rich in eosinophils, basophils, mast cells, CD4(+) T helper 2 (Th2) cells, and type 2 innate lymphoid cells (ILC2s), protects the host from helminth infection but also drives chronic allergic diseases like asthma and atopic dermatitis. Barrier epithelial cells (ECs) represent the very first line of defense and express pattern recognition receptors to recognize type-2-cell-mediated immune insults like proteolytic allergens or helminths. These ECs mount a prototypical response made up of chemokines, innate cytokines such as interleukin-1 (IL-1), IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), as well as the alarmins uric acid, ATP, HMGB1, and S100 proteins. These signals program dendritic cells (DCs) to mount Th2-cell-mediated immunity and in so doing boost ILC2, basophil, and mast cell function. Here we review the general mechanisms of how different stimuli trigger type-2-cell-mediated immunity at mucosal barriers and how this leads to protection or disease. Copyright © 2015 Elsevier Inc. All rights reserved.
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CXCR6 Expression Is Important for Retention and Circulation of ILC Precursors
Chea, Sylvestre; Possot, Cécilie; Perchet, Thibaut; Petit, Maxime; Cumano, Ana; Golub, Rachel
2015-01-01
Innate lymphoid cells are present at mucosal sites and represent the first immune barrier against infections, but what contributes to their circulation and homing is still unclear. Using Rag2 −/− Cxcr6 Gfp/+ reporter mice, we assessed the expression and role of CXCR6 in the circulation of ILC precursors and their progeny. We identify CXCR6 expressing ILC precursors in the bone marrow and characterize their significant increase in CXCR6-deficient mice at steady state, indicating their partial retention in the bone marrow after CXCR6 ablation. Circulation was also impaired during embryonic life as fetal liver from CXCR6-deficient embryos displayed decreased numbers of ILC3 precursors. When injected, fetal CXCR6-deficient ILC3 precursors also fail to home and reconstitute ILC compartments in vivo. We show that adult intestinal ILC subsets have heterogeneous expression pattern of CXCR6, integrin α 4 β 7, CD62L, CD69, and CD44, with ILC1 and ILC3 being more likely tissue resident lymphocytes. Intestinal ILC subsets were unchanged in percentages and numbers in both mice. We demonstrate that the ILC frequency is maintained due to a significant increase of ILC peripheral proliferation, as well as an increased proliferation of the in situ ILC precursors to compensate their retention in the bone marrow. PMID:26494947
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Isolation and analysis of group 2 innate lymphoid cells in mice.
Moro, Kazuyo; Ealey, Kafi N; Kabata, Hiroki; Koyasu, Shigeo
2015-05-01
Recent studies have identified distinct subsets of innate lymphocytes, collectively called innate lymphoid cells (ILCs), which lack antigen receptor expression but produce various effector cytokines. Group 2 ILCs (ILC2s) respond to epithelial cell-derived cytokines such as interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), produce large amounts of type 2 cytokines, and have a key role in anti-helminth innate immunity and in the pathophysiology of allergic inflammation. The reported phenotypic characteristics of mouse ILC2s vary, depending on the tissue source and preparation method. This protocol describes improved methods for tissue-specific isolation and analysis of mouse ILC2s of high purity and yield from fat tissue, lung, bronchoalveolar lavage fluid (BALF) and small intestine. These improved methods are the result of our thorough investigation of enzymes used for tissue digestion, methods for the elimination of undesired cells, and a combination of antibodies for the detection and isolation of ILC2s. In addition, this new protocol now enables the isolation of ILC2s of high yield, even from inflamed tissues. Depending on the tissue being analyzed, it takes ∼2-4 h for isolation and flow cytometric analysis of ILC2s from the various tissues of a single mouse and ∼4-8 h to sort purified ILC2s from pooled tissues of multiple mice.
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Chen, Ruchong; Smith, Steven G; Salter, Brittany; El-Gammal, Amani; Oliveria, John Paul; Obminski, Caitlin; Watson, Rick; O'Byrne, Paul M; Gauvreau, Gail M; Sehmi, Roma
2017-09-15
Group 2 innate lymphoid cells (ILC2), a major source of type 2 cytokines, initiate eosinophilic inflammatory responses in murine models of asthma. To investigate the role of ILC2 in allergen-induced airway eosinophilic responses in subjects with atopy and asthma. Using a diluent-controlled allergen challenge crossover study, where all subjects (n = 10) developed allergen-induced early and late responses, airway eosinophilia, and increased methacholine airway responsiveness, bone marrow, blood, and sputum samples were collected before and after inhalation challenge. ILC2 (lin - FcεRI - CD45 + CD127 + ST2 + ) and CD4 + T lymphocytes were enumerated by flow cytometry, as well as intracellular IL-5 and IL-13 expression. Steroid sensitivity of ILC2 and CD4 + T cells was investigated in vitro. A significant increase in total, IL-5 + , IL-13 + , and CRTH2 + ILC2 was found in sputum, 24 hours after allergen, coincident with a significant decrease in blood ILC2. Total, IL-5 + , and IL-13 + , but not CRTH2 + , CD4 + T cells significantly increased at 24 and 48 hours after allergen in sputum. In blood and bone marrow, only CD4 + cells demonstrated increased activation after allergen. Airway eosinophilia correlated with IL-5 + ILC2 at all time points and allergen-induced changes in IL-5 + CD4 + cells at 48 hours after allergen. Dexamethasone significantly attenuated IL-2- and IL-33-stimulated IL-5 and IL-13 production by both cell types. Innate and adaptive immune cells are increased in the airways associated with allergic asthmatic responses. Total and type 2 cytokine-positive ILC2 are increased only within the airways, whereas CD4 + T lymphocytes demonstrated local and systemic increases. Steroid sensitivity of both cells may explain effectiveness of this therapy in those with mild asthma.
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Analysis of actual healthcare costs of early versus interval cholecystectomy in acute cholecystitis.
Tan, Cheryl H M; Pang, Tony C Y; Woon, Winston W L; Low, Jee Keem; Junnarkar, Sameer P
2015-03-01
Healthcare cost modeling have favored early (ELC) over interval laparoscopic cholecystectomy (ILC) for acute cholecystitis (AC). However, actual costs of treatment have never been studied. The aim of the present study was to compare actual hospital costs involved in ELC and ILC in patients with AC. Retrospective study of patients who underwent laparoscopic cholecystectomy for AC was conducted. Demographic, clinical, operative data and costs were extracted and analyzed. Between 2011 and 2013, 201 had laparoscopic surgery for AC at Tan Tock Seng Hospital, Singapore. One hundred and thirty-four (67%) patients underwent ELC (≤7 days of presentation, within index admission). Median total length of stay (LOS) was 4.6 and 6.8 days for ELC and ILC groups, respectively (P = 0.006). Patients who had ELC also had significantly lesser total number of admissions (P < 0.001). The median (IQR) total inpatient costs were €4.4 × 10(3) (3.6-5.6) and €5.5 × 10(3) (4.0-7.5) for ELC and ILC patients, respectively (P < 0.007). Costs associated with investigations were significantly higher in the ILC group (P = 0.039), of which serological costs made most difference (P < 0.005). The ward costs were also significantly higher in the ILC group. The cost differences reflect the significantly increased total LOS, and repeat presentations associated with ILC. Therefore, ELC should be the preferred management strategy for AC. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
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Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S
2015-12-01
Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7Rα(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (∼ 63%) and aryl hydrocarbon receptor and produced IL-17 (∼ 63%), IL-22 (∼ 36%), and TNF-α (∼ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P < 0.001). Notably, ILC3 could be induced to undergo apoptosis by microbial products through the TLR2 (lipoteichoic acid) and/or TLR4 (LPS) pathway. These findings indicated that persistent microbial translocation may result in loss of ILC3 in lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues. © FASEB.
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Group 2 innate lymphoid cells promote beiging of adipose and limit obesity
Brestoff, Jonathan R.; Kim, Brian S.; Saenz, Steven A.; Stine, Rachel R.; Monticelli, Laurel A.; Sonnenberg, Gregory F.; Thome, Joseph J.; Farber, Donna L.; Lutfy, Kabirullah; Seale, Patrick; Artis, David
2015-01-01
Obesity is an increasingly prevalent disease regulated by genetic and environmental factors. Emerging studies indicate that immune cells, including monocytes, granulocytes and lymphocytes, regulate metabolic homeostasis and are dysregulated in obesity1,2. Group 2 innate lymphoid cells (ILC2s) can regulate adaptive immunity3,4 and eosinophil and alternatively-activated macrophage responses5, and were recently identified in murine white adipose tissue (WAT)5 where they may act to limit the development of obesity6. However, ILC2s have not been identified in human adipose tissue, and the mechanisms by which ILC2s regulate metabolic homeostasis remain unknown. Here, we identify ILC2s in human WAT and demonstrate that decreased ILC2 responses in WAT are a conserved characteristic of obesity in humans and mice. Interleukin (IL)-33 was found to be critical for the maintenance of ILC2s in WAT and in limiting adiposity in mice by increasing caloric expenditure. This was associated with recruitment of uncoupling protein 1 (UCP1)+ beige adipocytes in WAT, a process known as beiging or browning that regulates caloric expenditure7–9. IL-33-induced beiging was dependent on ILC2s, and IL-33 treatment or transfer of IL-33-elicited ILC2s was sufficient to drive beiging independently of the adaptive immune system, eosinophils or IL-4 receptor signaling. We found that ILC2s produce methionine-enkephalin peptides that can act directly on adipocytes to upregulate Ucp1 expression in vitro and that promote beiging in vivo. Collectively, these studies indicate that in addition to responding to infection or tissue damage, ILC2s can regulate adipose function and metabolic homeostasis in part via production of enkephalin peptides that elicit beiging. PMID:25533952
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Michaut, Magali; Chin, Suet-Feung; Majewski, Ian; Severson, Tesa M.; Bismeijer, Tycho; de Koning, Leanne; Peeters, Justine K.; Schouten, Philip C.; Rueda, Oscar M.; Bosma, Astrid J.; Tarrant, Finbarr; Fan, Yue; He, Beilei; Xue, Zheng; Mittempergher, Lorenza; Kluin, Roelof J.C.; Heijmans, Jeroen; Snel, Mireille; Pereira, Bernard; Schlicker, Andreas; Provenzano, Elena; Ali, Hamid Raza; Gaber, Alexander; O’Hurley, Gillian; Lehn, Sophie; Muris, Jettie J.F.; Wesseling, Jelle; Kay, Elaine; Sammut, Stephen John; Bardwell, Helen A.; Barbet, Aurélie S.; Bard, Floriane; Lecerf, Caroline; O’Connor, Darran P.; Vis, Daniël J.; Benes, Cyril H.; McDermott, Ultan; Garnett, Mathew J.; Simon, Iris M.; Jirström, Karin; Dubois, Thierry; Linn, Sabine C.; Gallagher, William M.; Wessels, Lodewyk F.A.; Caldas, Carlos; Bernards, Rene
2016-01-01
Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies. PMID:26729235
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Innate lymphoid cells in normal and disease: An introductory overview.
Moretta, Lorenzo; Locatelli, Franco
2016-11-01
Innate lymphoid cells (ILC) represent a novel group of lymphocytes that, different from T and B-lymphocytes lack recombinant activating genes (RAG-1 or RAG-2) and thus do not express rearranged antigen-specific receptors. Members of this family, i.e. NK cells, have been known since long time, while the other ILCs have been discovered only in recent years, possibly because of their predominant localization in tissues, primarily in mucosal tissues, skin and mucosa-associated lymphoid organs. ILC have been grouped in three major subsets on the basis of their phenotypic and functional features as well as of their dependency on given transcription factors (TF). Briefly, ILC-1 are dependent on T-bet TF and produce interferon (IFN)-γ. Group 2 ILC (ILC2) express GATA-3 TF and produce IL-5, IL-4 and IL-13 (Type 2) cytokines while group 3 ILC (ILC3) express RORγt TF and produce IL-17 and IL-22. ILC provide early defenses against pathogens and intervene in the repair of damaged tissues. ILC activation is mediated by cytokines (specifically acting on different ILC groups) and/or by activating receptors that are, at least in part, the same that had been previously identified in NK cells [1]. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
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Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.
2015-01-01
Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit+IL-7Rα+ (CD117+CD127+) cells. These ILC3 cells highly expressed CD90 (∼63%) and aryl hydrocarbon receptor and produced IL-17 (∼63%), IL-22 (∼36%), and TNF-α (∼72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4+ T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P < 0.001). Notably, ILC3 could be induced to undergo apoptosis by microbial products through the TLR2 (lipoteichoic acid) and/or TLR4 (LPS) pathway. These findings indicated that persistent microbial translocation may result in loss of ILC3 in lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536
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The FONT5 Bunch-by-Bunch Position and Angle Feedback System at ATF2
NASA Astrophysics Data System (ADS)
Apsimon, R. J.; Bett, D. R.; Burrows, P. N.; Christian, G. B.; Constance, B.; Davis, M. R.; Gerbershagen, A.; Perry, C.; Resta-Lopez, J.
The FONT5 upstream beam-based feedback system at ATF2 is designed to correct the position and angle jitter at the entrance to the ATF2 final-focus system, and also to demonstrate a prototype intra-train feedback system for the International Linear Collider interaction point. We discuss the hardware, from stripline BPMs to kickers, and RF and digital signal processing, as well as presenting results from the latest beam tests at ATF2.
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Oliphant, Christopher J.; Hwang, You Yi; Walker, Jennifer A.; Salimi, Maryam; Wong, See Heng; Brewer, James M.; Englezakis, Alexandros; Barlow, Jillian L.; Hams, Emily; Scanlon, Seth T.; Ogg, Graham S.; Fallon, Padraic G.; McKenzie, Andrew N.J.
2014-01-01
Summary Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity. PMID:25088770
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Flyback CCM inverter for AC module applications: iterative learning control and convergence analysis
NASA Astrophysics Data System (ADS)
Lee, Sung-Ho; Kim, Minsung
2017-12-01
This paper presents an iterative learning controller (ILC) for an interleaved flyback inverter operating in continuous conduction mode (CCM). The flyback CCM inverter features small output ripple current, high efficiency, and low cost, and hence it is well suited for photovoltaic power applications. However, it exhibits the non-minimum phase behaviour, because its transfer function from control duty to output current has the right-half-plane (RHP) zero. Moreover, the flyback CCM inverter suffers from the time-varying grid voltage disturbance. Thus, conventional control scheme results in inaccurate output tracking. To overcome these problems, the ILC is first developed and applied to the flyback inverter operating in CCM. The ILC makes use of both predictive and current learning terms which help the system output to converge to the reference trajectory. We take into account the nonlinear averaged model and use it to construct the proposed controller. It is proven that the system output globally converges to the reference trajectory in the absence of state disturbances, output noises, or initial state errors. Numerical simulations are performed to validate the proposed control scheme, and experiments using 400-W AC module prototype are carried out to demonstrate its practical feasibility.
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A Proinflammatory Role of Type 2 Innate Lymphoid Cells in Murine Immune-Mediated Hepatitis.
Neumann, Katrin; Karimi, Khalil; Meiners, Jana; Voetlause, Ruth; Steinmann, Silja; Dammermann, Werner; Lüth, Stefan; Asghari, Farahnaz; Wegscheid, Claudia; Horst, Andrea K; Tiegs, Gisa
2017-01-01
Type 2 innate lymphoid cells (ILC2) mediate inflammatory immune responses in the context of diseases triggered by the alarmin IL-33. In recent years, IL-33 has been implicated in the pathogenesis of immune-mediated liver diseases. However, the immunoregulatory function of ILC2s in the inflamed liver remains elusive. Using the murine model of Con A-induced immune-mediated hepatitis, we showed that selective expansion of ILC2s in the liver was associated with highly elevated hepatic IL-33 expression, severe liver inflammation, and infiltration of eosinophils. CD4 + T cell-mediated tissue damage and subsequent IL-33 release were responsible for the activation of hepatic ILC2s that produced the type 2 cytokines IL-5 and IL-13 during liver inflammation. Interestingly, ILC2 depletion correlated with less severe hepatitis and reduced accumulation of eosinophils in the liver, whereas adoptive transfer of hepatic ILC2s aggravated liver inflammation and tissue damage. We further showed that, despite expansion of hepatic ILC2s, 3-d IL-33 treatment before Con A challenge potently suppressed development of immune-mediated hepatitis. We found that IL-33 not only activated hepatic ILC2s but also expanded CD4 + Foxp3 + regulatory T cells (Treg) expressing the IL-33 receptor ST2 in the liver. This Treg subset also accumulated in the liver during resolution of immune-mediated hepatitis. In summary, hepatic ILC2s are poised to respond to the release of IL-33 upon liver tissue damage through expression of type 2 cytokines thereby participating in the pathogenesis of immune-mediated hepatitis. Inflammatory activity of ILC2s might be regulated by IL-33-elicited ST2 + Tregs that also arise in immune-mediated hepatitis. Copyright © 2016 by The American Association of Immunologists, Inc.
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Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.
Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela
2016-03-15
Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.
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Type 2 innate lymphoid cells: at the cross-roads in allergic asthma.
van Rijt, Leonie; von Richthofen, Helen; van Ree, Ronald
2016-07-01
Allergic asthma is a chronic inflammatory disease of the lower airways that affects millions of people worldwide. Allergic asthma is a T helper 2 cell (Th2)-mediated disease, in which Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 are closely associated with the symptoms. IL-4 is needed by B cells to switch toward an IgE response, IL-5 recruits and activates eosinophils while IL-13 increases mucus production. The identification of type 2 innate lymphoid cells (ILC2), which are able to rapidly produce large amounts of IL-5 and IL-13 in response to epithelial derived cytokines, implicated a new key player besides Th2 cells. ILCs constitute a family of innate lymphocytes distinct from T and B cells. ILC2s are located in various epithelial compartments in mice and human, including the lung. The recent finding of increased numbers of ILC2s in the airways of severe asthma patients prompts further research to clarify their immunological function. Murine studies have shown that ILC2s are an early innate source of IL-5 and IL-13 after allergen exposure, which induce airway eosinophilic infiltration, mucus hyperproduction, and airway hyperresponsiveness but not allergen-specific IgE production. ILC2s contribute to the initiation as well as to the maintenance of the adaptive type 2 immune response. Here, we review the recent progress on our understanding of the role of ILC2s in the immunopathology of allergic asthma, in particular by studies using murine models which have elucidated fundamental mechanisms by which ILC2s act.
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ADC interface for data server with data preselection for luminosity detector in AIDA-2020 project
NASA Astrophysics Data System (ADS)
Daniluk, W.; Dziedzic, B.; Korcyl, G.; Wojtoń, T.; Zawiejski, L.
2017-08-01
Main aim of the AIDA-2020 project is development of detectors for future accelerators. In FCAL Colaboration we are working on forward subdetectors for ILC and CLIC accelerators. My team is developing prototype module which receives data from ADC, provides the data preselection, and transmits them as packages to the data server for further their analysis. Common prototype is based on AC701 evaluation board which contains Artix-7 FPGA and is equipped with SMA connectors for gigabit transceivers and ethernet connector. In my talk I will describe architecture of the device and current state of module development.
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Reliability of Upright and Supine Power Measurements Using an Inertial Load Cycle Ergometer
NASA Technical Reports Server (NTRS)
Wickwire, P. J.; Leach, M.; Ryder, J.; Ploutz-Snyder, R.; Ploutz-Snyder, L.
2011-01-01
Practical, reliable, and time efficient methods of measuring muscular power are desirable for both research and applied testing situations. The inertial-load cycling method (ILC; Power/Cycle, Austin, TX) requires subjects to pedal as fast as possible against the inertial load of a flywheel for only 3-5 seconds, which could help reduce the time and effort required for maximal power testing. PURPOSE: 1) To test the intramachine reliability of ILC over 3 separate sessions, 2) to compare postural stance (upright vs. supine) during testing, and 3) to compare the maximal power (Pmax) output measured using ILC to that obtained from traditional isokinetic and leg press testing. METHODS: Subjects (n = 12) were tested on 4 non-consecutive days. The following tests were done on the first day of testing: isometric knee extension, isokinetic knee extension at several speeds, isokinetic power/endurance at 180/sec (Biodex System 4), leg press maximal isometric force, and leg press power/endurance. The other 3 days consisted exclusively of ILC testing. Subjects performed 6 ILC tests in an upright position and 6 ILC tests in a supine position on each day. The starting position was counterbalanced. Mixed-effects linear modeling was used to determine if any differences existed between testing days and between upright and supine for Pmax and revolutions per minute at Pmax (RPMpk). Mixed-modeling was also used to calculate intraclass correlation coefficients (ICC) to determine the reliability of the ILC on each testing day for Pmax and RPMpk (ICCs were calculated separately for upright and supine). gKendall fs Tau a h was used to determine the association between ILC Pmax and isokinetic and leg press data. RESULTS: For Pmax, significant differences were found between days 1 and 2 (upright: p = 0.018; supine: p = 0.014) and between days 1 and 3 (upright: p = 0.001; supine: p = 0.002), but not between days 2 and 3 (upright: p = 0.422; supine: p = 0.501). Pmax ICC values were greater than or equal to 0.97 for all days in both positions. Also, no significant differences between upright and supine postures were found for Pmax. No significant differences between days were found for RPMpk; however, there was a significant posture effect (upright greater than supine). Moderate correlations were observed between ILC Pmax and isokinetic and leg press tests (upright: 0.64-0.79, supine: 0.52-0.82). CONCLUSIONS: Overall, ILC is a very reliable test. Since a significant difference was found between day 1 and the other ILC testing days, it is suggested that day 1 of ILC testing should be used as a familiarization session to allow for subject learning. No significant difference in Pmax was seen from test 3 to test 6. However, an increase of 1.3% was observed from test 4 to test 6. Therefore, although 4 tests may be sufficient for most subjects to produce Pmax, in some cases 6 tests may be required. PRACTICAL APPLICATIONS: No differences were seen in Pmax between upright and supine positions despite differing RPMpk. This suggests that ILC testing can be used to provide reliable testing both in an upright position (appropriate for athletes) and in research (e.g., bed rest) or rehabilitation settings where supine testing is necessary. Future research should evaluate whether peak power measurements obtained with the ILC are sensitive to changes such as that observed with training and de-training.
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Thermal Analysis of the ILC Superconductin Quadrupole
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ross, Ian; /Rose-Hulman Inst., Terre Haute /SLAC
2006-09-13
Critical to a particle accelerator's functioning, superconducting magnets serve to focus and aim the particle beam. The Stanford Linear Accelerator Center (SLAC) has received a prototype superconducting quadrupole designed and built by the Centro de Investigaciones Energ{acute e}ticas, Medioambientales y Tecnol{acute o}gicas (CIEMAT) to be evaluated for the International Linear Collider (ILC) project. To ensure proper functioning of the magnet, the device must be maintained at cryogenic temperatures by use of a cooling system containing liquid nitrogen and liquid helium. The cool down period of a low temperature cryostat is critical to the success of an experiment, especially a prototypemore » setup such as this one. The magnet and the dewar each contain unique heat leaks and material properties. These differences can lead to tremendous thermal stresses. The system was analyzed mathematically, leading to ideal liquid helium and liquid nitrogen flow rates during the magnet's cool-down to 4.2 K, along with a reasonable estimate of how long this cool-down will take. With a flow rate of ten gaseous liters of liquid nitrogen per minute, the nitrogen shield will take approximately five hours to cool down to 77 K. With a gaseous helium flow rate of sixty liters per minute, the magnet will take at least nineteen hours to cool down to a temperature of 4.2 K.« less
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Oliphant, Christopher J; Hwang, You Yi; Walker, Jennifer A; Salimi, Maryam; Wong, See Heng; Brewer, James M; Englezakis, Alexandros; Barlow, Jillian L; Hams, Emily; Scanlon, Seth T; Ogg, Graham S; Fallon, Padraic G; McKenzie, Andrew N J
2014-08-21
Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.
Weiner, Joshua; Zuber, Julien; Shonts, Brittany; Yang, Suxiao; Fu, Jianing; Martinez, Mercedes; Farber, Donna L; Kato, Tomoaki; Sykes, Megan
2017-10-01
Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Intestinal samples were taken from 4 isolated intestine and 3 multivisceral transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor-specific or recipient-specific HLA marker to analyze chimerism. Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be lymphoid tissue inducer cells among donor ILCs was far higher than that among recipient ILCs. Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human lymphoid tissue inducer cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study.
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Transcription factors controlling innate lymphoid cell fate decisions.
Klose, Christoph S N; Diefenbach, Andreas
2014-01-01
The mucosal epithelium is in direct contact with symbiotic and pathogenic microorganisms. Therefore, the mucosal surface is the principal portal of entry for invading pathogens and immune cells accumulated in the intestine to prevent infections. In addition to these conventional immune system functions, it has become clear that immune cells during steady-state continuously integrate microbial and nutrient-derived signals from the environment to support organ homeostasis. A major role in both processes is played by a recently discovered group of lymphocytes referred to as innate lymphoid cells (ILCs) Innate lymphoid cells (ILCs) that are specifically enriched at mucosal surfaces but are rather rare in secondary lymphoid organs. In analogy to the dichotomy between CD8 and CD4 T cells, we propose to classify ILCs into interleukin-7 receptor α-negative cytotoxic ILCs and IL-7Rα(+) helper-like ILCs. Dysregulated immune responses triggered by the various ILC subsets have been linked to inflammatory diseases such as inflammatory bowel disease, atopic dermatitis and airway hyperresponsiveness. Here, we will review recent progress in determining the transcriptional and developmental programs that control ILC fate decisions.
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Detectors for Linear Colliders: Detector design for a Future Electron-Positron Collider (4/4)
Thomson, Mark
2018-05-21
In this lecture I will discuss the issues related to the overall design and optimization of a detector for ILC and CLIC energies. I will concentrate on the two main detector concepts which are being developed in the context of the ILC. Here there has been much recent progress in developing realistic detector models and in understanding the physics performance of the overall detector concept. In addition, I will discuss the how the differences in the detector requirements for the ILC and CLIC impact the overall detector design.
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Friedmann, David; Keller, Baerbel; Harder, Ina; Schupp, Jonas; Tanriver, Yakup; Unger, Susanne; Warnatz, Klaus
2017-11-01
Over a third of patients with common variable immunodeficiency (CVID) suffer from secondary complications like inflammatory organ disease, autoimmune manifestations, or lymphoproliferation contributing to increased morbidity and mortality in affected patients. Innate lymphoid cells (ILCs) have emerging roles in setting the milieu for physiological, but also pathological, immune responses and inflammation. We therefore sought to correlate the recently identified disturbed homeostasis of ILCs with alterations of the adaptive immune system in complex CVID patients (CVIDc). We quantified peripheral blood ILC and T helper cell subsets of 58 CVID patients by flow cytometry and compared the results to the clinical and immunological phenotype. Total ILCs were significantly reduced in peripheral blood of CVIDc patients compared to healthy individuals, but not to CVID patients who suffered only from infections (CVIDio). This reduction was mainly due to a decrease in ILC2s, while ILC3s were relatively increased in CVIDc compared to CVIDio patients. This alteration in ILC phenotype was more prominent in patients with an expansion of CD21 low B cells, but we could not detect an association of the altered ILC phenotype with a T H 1-shift among circulating CD4 T cells, which was also prominent in CVIDc patients. We confirm a relative shift in ILCs of CVIDc patients towards ILC3s which was associated with the expansion of CD21 low B cells, but not overtly with the relative expansion of T H 1-like T cells. Given the relative abundance of T H 1-like T cells compared to ILCs, these probably represent a more prominent source of the observed IFNγ-signature in CVIDc patients.
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Adjustable typography: an approach to enhancing low vision text accessibility.
Arditi, Aries
2004-04-15
Millions of people have low vision, a disability condition caused by uncorrectable or partially correctable disorders of the eye. The primary goal of low vision rehabilitation is increasing access to printed material. This paper describes how adjustable typography, a computer graphic approach to enhancing text accessibility, can play a role in this process, by allowing visually-impaired users to customize fonts to maximize legibility according to their own visual needs. Prototype software and initial testing of the concept is described. The results show that visually-impaired users tend to produce a variety of very distinct fonts, and that the adjustment process results in greatly enhanced legibility. But this initial testing has not yet demonstrated increases in legibility over and above the legibility of highly legible standard fonts such as Times New Roman.
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Chen, Xiangyu; Li, Lingyun; Khan, Muhammad Noman; Shi, Lifeng; Wang, Zhongyan; Zheng, Fang; Gong, Feili; Fang, Min
2016-11-01
In inflammatory bowel diseases (IBD), high mobility group box 1 (HMGB1), as an endogenous inflammatory molecule, can promote inflammatory cytokines secretion by acting on TLR2/4 resulting in tissue damage. The underlying mechanisms remain unclear. Here we report a novel role of HMGB1 in controlling the maintenance and function of intestine-resident group-3 innate lymphoid cells (ILC3s) that are important innate effector cells implicated in mucosal homeostasis and IBD pathogenesis. We showed that mice treated with anti-HMGB1 Ab, or genetically deficient for TLR2 -/- or TLR4 -/- mice, displayed reduced intestinal inflammation. In these mice, the numbers of colonic ILC3s were significantly reduced, and the levels of IL-17 and IL-22 that can be secreted by ILC3s were also decreased in the colon tissues. Furthermore, HMGB1 promoted DCs via TLR2/4 signaling to produce IL-23, activating ILC3s to produce IL-17 and IL-22. Our data thus indicated that the HMGB1-TLR2/4-DCs-IL-23 cascade pathway enhances the functions of ILC3s to produce IL-17 and IL-22, and this signal way might play a vital role in the development of IBD.
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Kumagai, Kazuyoshi; Lewandowski, Ryan P; Jackson-Humbles, Daven N; Buglak, Nicholas; Li, Ning; White, Kaylin; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R
2017-08-01
Exposure to elevated levels of ambient ozone in photochemical smog is associated with eosinophilic airway inflammation and nonatopic asthma in children. In the present study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced nonatopic asthma by using lymphoid cell-sufficient C57BL/6 mice, ILC-sufficient Rag2 -/- mice (devoid of T and B cells), and ILC-deficient Rag2 -/- Il2rg -/- mice (depleted of all lymphoid cells including ILCs). Mice were exposed to 0 or 0.8 parts per million ozone for 1 day or 9 consecutive weekdays (4 hr/day). A single exposure to ozone caused neutrophilic inflammation, airway epithelial injury, and reparative DNA synthesis in all strains of mice, irrespective of the presence or absence of ILCs. In contrast, 9-day exposures induced eosinophilic inflammation and mucous cell metaplasia only in the lungs of ILC-sufficient mice. Repeated ozone exposures also elicited increased messenger RNA expression of transcripts associated with type 2 immunity and airway mucus production in ILC-sufficient mice. ILC-deficient mice repeatedly exposed to ozone had no pulmonary pathology or increased gene expression related to type 2 immunity. These results suggest a new paradigm for the biologic mechanisms underlying the development of a phenotype of childhood nonatopic asthma that has been linked to ambient ozone exposures.
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BCG vaccination drives accumulation and effector function of innate lymphoid cells in murine lungs.
Steigler, Pia; Daniels, Naomi J; McCulloch, Tim R; Ryder, Brin M; Sandford, Sarah K; Kirman, Joanna R
2018-04-01
The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) prevents disseminated childhood TB; however, it fails to protect against the more prevalent pulmonary TB. Limited understanding of the immune response to Mycobacterium tuberculosis, the causative agent of TB, has hindered development of improved vaccines. Although memory CD4 T cells are considered the main mediators of protection against TB, recent studies suggest there are other key subsets that contribute to antimycobacterial immunity. To that end, innate cells may be involved in the protective response. In this study, we investigated the primary response of innate lymphoid cells (ILCs) to BCG exposure. Using a murine model, we showed that ILCs increased in number in the lungs and lymph nodes in response to BCG vaccination. Additionally, there was significant production of the antimycobacterial cytokine IFN-γ by ILCs. As ILCs are located at mucosal sites, it was investigated whether mucosal vaccination (intranasal) stimulated an enhanced response compared to the traditional vaccination approach (intradermal or subcutaneous). Indeed, in response to intranasal vaccination, the number of ILCs, and IFN-γ production in NK cells and ILC1s in the lungs and lymph nodes, were higher than that provoked through intradermal or subcutaneous vaccination. This work provides the first evidence that BCG vaccination activates ILCs, paving the way for future research to elucidate the protective potential of ILCs against mycobacterial infection. Additionally, the finding that lung ILCs respond rigorously to mucosal vaccination may have implications for the delivery of novel TB vaccines. © 2018 Australasian Society for Immunology Inc.
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Leonardi, Maria Cristina; Maisonneuve, Patrick; Mastropasqua, Mauro Giuseppe; Cattani, Federica; Fanetti, Giuseppe; Morra, Anna; Lazzari, Roberta; Bazzani, Federica; Caputo, Mariangela; Rotmensz, Nicole; Gerardi, Marianna Alessandra; Ricotti, Rosalinda; Enrica Galimberti, Viviana; Veronesi, Paolo; Dicuonzo, Samantha; Viale, Giuseppe; Jereczek-Fossa, Barbara Alicja; Orecchia, Roberto
2017-09-01
To investigate the local outcome of patients after accelerated partial breast irradiation with intraoperative electrons (IORT) for invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC). From 1999 to 2007, 2173 patients were treated with breast-conserving surgery and IORT (21 Gy/1 fraction) as the sole local treatment: 252 patients with ILC (11.6%) were compared with 1921 patients with IDC in terms of local control. Compared with the IDC subgroup, patients with ILC had a low-risk profile and were more hormone responsive. The 5- and 10-year in-breast tumor reappearance (IBTR) rates were 5.5% and 14.4%, respectively, for the IDC group and 7.5% and 21.8%, respectively, for the ILC group (log-rank P=.03). The excess risk of IBTR associated with ILC was particularly high for small tumors (≤1 cm: hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.03-4.85), elderly patients (60-69 years: HR, 2.27; 95% CI, 1.11-4.63; ≥70 years: HR, 3.28; 95% CI, 1.08-10.0), low-grade tumors (grade 1: HR, 3.50; 95% CI, 1.05-11.7), and luminal A molecular subtype (HR, 3.18; 95% CI, 1.49-6.77). Among the ILC histologic variants, no difference between classic and nonclassic subgroups was observed, although the signet ring cell and solid variants had the worst local control. Despite a favorable tumor profile, accelerated partial breast irradiation with IORT led to a higher incidence of IBTRs in patients with ILC compared with those with IDC. Our institutional experience emphasized the importance of the size of the irradiation field, pointing to the use of larger collimators, even when dealing with small tumors, to improve local control. Copyright © 2017 Elsevier Inc. All rights reserved.
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Cao, Qi; Wang, Yiping; Niu, Zhiguo; Wang, Chengshi; Wang, Ruifeng; Zhang, Zhiqiang; Chen, Titi; Wang, Xin Maggie; Li, Qing; Lee, Vincent W S; Huang, Qingsong; Tan, Jing; Guo, Minghao; Wang, Yuan Min; Zheng, Guoping; Yu, Di; Alexander, Stephen I; Wang, Hui; Harris, David C H
2018-03-01
The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33-treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo -expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo -expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33-ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy. Copyright © 2018 by the American Society of Nephrology.
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Cutting Edge: Notch Signaling Promotes the Plasticity of Group-2 Innate Lymphoid Cells.
Zhang, Kangning; Xu, Xingyuan; Pasha, Muhammad Asghar; Siebel, Christian W; Costello, Angelica; Haczku, Angela; MacNamara, Katherine; Liang, Tingbo; Zhu, Jinfang; Bhandoola, Avinash; Maillard, Ivan; Yang, Qi
2017-03-01
The mechanisms underlying lymphocyte lineage stability and plasticity remain elusive. Recent work indicates that innate lymphoid cells (ILC) possess substantial plasticity. Whereas natural ILC2 (nILC2) produce type-2 cytokines, plastic inflammatory ILC2 (iILC2) can coproduce both type-2 cytokines and the ILC3-characteristic cytokine, IL-17. Mechanisms that elicit this lineage plasticity, and the importance in health and disease, remain unclear. In this study we show that iILC2 are potent inducers of airway inflammation in response to acute house dust mite challenge. We find that Notch signaling induces lineage plasticity of mature ILC2 and drives the conversion of nILC2 into iILC2. Acute blockade of Notch signaling abolished functional iILC2, but not nILC2, in vivo. Exposure of isolated nILC2 to Notch ligands induced Rorc expression and elicited dual IL-13/IL-17 production, converting nILC2 into iILC2. Together these results reveal a novel role for Notch signaling in eliciting ILC2 plasticity and driving the emergence of highly proinflammatory innate lymphocytes. Copyright © 2017 by The American Association of Immunologists, Inc.
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Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in humans and mice.
Montaldo, Elisa; Juelke, Kerstin; Romagnani, Chiara
2015-08-01
Since their discovery, innate lymphoid cells (ILCs) have been the subject of intense research. As their name implies, ILCs are innate cells of lymphoid origin, and can be grouped into subsets based on their cytotoxic activity, cytokine profile, and the transcriptional requirements during ILC differentiation. The main ILC groups are "killer" ILCs, comprising NK cells, and "helper-like" ILCs (including ILC1s, ILC2s, and ILC3s). This review examines the origin, differentiation stages, and plasticity of murine and human ILC3s. ILC3s express the retinoic acid receptor (RAR) related orphan receptor RORγt and the signature cytokines IL-22 and IL-17. Fetal ILC3s or lymphoid tissue inducer cells are required for lymphoid organogenesis, while postnatally developing ILC3s are important for the generation of intestinal cryptopatches and isolated lymphoid follicles as well as for the defence against pathogens and epithelial homeostasis. Here, we discuss the transcription factors and exogenous signals (including cytokines, nutrients and cell-to-cell interaction) that drive ILC3 lineage commitment and acquisition of their distinctive effector program. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Electronic Document Delivery: OCLC's Prototype System.
ERIC Educational Resources Information Center
Hickey, Thomas B.; Calabrese, Andrew M.
1986-01-01
Describes development of system for retrieval of documents from magnetic storage that uses stored font definition codes to control an inexpensive laser printer in the production of copies that closely resemble original document. Trends in information equipment and printing industries that will govern future application of this technology are…
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Satoh-Takayama, Naoko; Serafini, Nicolas; Verrier, Thomas; Rekiki, Abdessalem; Renauld, Jean-Christophe; Frankel, Gad; Di Santo, James P
2014-11-20
Interleukin-22 (IL-22) plays a critical role in mucosal defense, although the molecular mechanisms that ensure IL-22 tissue distribution remain poorly understood. We show that the CXCL16-CXCR6 chemokine-chemokine receptor axis regulated group 3 innate lymphoid cell (ILC3) diversity and function. CXCL16 was constitutively expressed by CX3CR1(+) intestinal dendritic cells (DCs) and coexpressed with IL-23 after Citrobacter rodentium infection. Intestinal ILC3s expressed CXCR6 and its ablation generated a selective loss of the NKp46(+) ILC3 subset, a depletion of intestinal IL-22, and the inability to control C. rodentium infection. CD4(+) ILC3s were unaffected by CXCR6 deficiency and remained clustered within lymphoid follicles. In contrast, the lamina propria of Cxcr6(-/-) mice was devoid of ILC3s. The loss of ILC3-dependent IL-22 epithelial stimulation reduced antimicrobial peptide expression that explained the sensitivity of Cxcr6(-/-) mice to C. rodentium. Our results delineate a critical CXCL16-CXCR6 crosstalk that coordinates the intestinal topography of IL-22 secretion required for mucosal defense. Copyright © 2014 Elsevier Inc. All rights reserved.
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Topps, A; Clay, V; Absar, M; Howe, M; Lim, Y; Johnson, R; Bundred, N
2014-07-01
Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC). Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND). A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001). AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Optimalisatie Draagsysteem (Optimization of the Load Carriage System)
2008-06-01
nadelige gevolgen beeft voor de beweeglijkheid. In bet prototype draagsysteem uit figuur 9 ’hangt’ bet scberfwerende vest met kogelwerende platen niet...Soesterberg TNO-rapport wwton T +31 346 35 62 11 TNO-DV 2008 A230 F +31 346 35 39 77Info-DenV@tno.nI Optimalisatie draagsysteem D)atun juni 2008 0 Autcur(s...de draagconstructie. Bij bet ILCS- 11 is gevarieerd met de hoeveelheid afsteuning op heupen en Beschrijving van de werkzaamhleden schouders, alsmede
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Fano Resonance of Eu2+ and Eu3+ in (Eu,Gd)Te MBE Layers
NASA Astrophysics Data System (ADS)
Orlowski, B. A.; Kowalski, B. J.; Dziawa, P.; Pietrzyk, M.; Mickievicius, S.; Osinniy, V.; Taliashvili, B.; Kowalik, I. A.; Story, T.; Johnson, R. L.
2006-11-01
Resonant photoemission spectroscopy, with application of synchrotron radiation, was used to study the valence band electronic structure of clean surface of (EuGd)Te layers. Fano-type resonant photoemission spectra corresponding to the Eu 4d-4f transition were measured to determine the contribution of 4f electrons of Eu2+ and Eu3+ ions to the valence band. The resonant and antiresonant photon energies of Eu2+ ions were found as equal to 141 V and 132 eV, respectively and for Eu3+ ions were found as equal to 146 eV and 132 eV, respectively. Contribution of Eu2+4f electrons was found at the valence band edge while for Eu3+ it was located in the region between 3.5 eV and 8.5 eV below the valence band edge.
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Cryogenic system configuration for the International Linear Collider (ILC) at mountainous site
NASA Astrophysics Data System (ADS)
Nakai, H.; Okamura, T.; Delikaris, D.; Peterson, T.; Yamamoto, A.
2017-02-01
The International Linear Collider (ILC) plans to make use of ten cryoplants for its main linacs, each providing 19 kW at 4.5 K equivalent and among of it 3.6 kW at 2 K. Each cryoplant will consist of various cryogenic components such as a 4.5 K refrigerator cold box, a 2 K refrigerator cold box, and helium compressors and so on. In the technical design report (TDR) of the ILC, due to the mountainous topology, almost all cryogenic components would be installed in underground cryogenic caverns next to the main linac tunnels and only cooling towers on surface area. However, we would like to find a more effective and sophisticated configuration of the cryoplant components (cryogenic configuration). Under several constraints of technical, geographical, and environmental points of view, the cryogenic configuration should be considered carefully to satisfy such various conditions. After discussions on this topic conducted at various workshops and conferences, an updated cryogenic configuration is suggested. The proposed updated configuration may affect the total construction cost of the ILC and the entire structure of the ILC conventional facilities. The updated cryogenic configuration is presented and the on-going discussions with the conventional facilities and siting (CFS) colleagues for further improvement of the cryogenic configuration is introduced.
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Innate lymphoid cells and the MHC.
Robinette, M L; Colonna, M
2016-01-01
Innate lymphoid cells (ILCs) are a new class of immune cells that include natural killer (NK) cells and appear to be the innate counterparts to CD4(+) helper T cells and CD8(+) cytotoxic T cells based on developmental and functional similarities. Like T cells, both NK cells and other ILCs also show connections to the major histocompatibility complex (MHC). In human and mouse, NK cells recognize and respond to classical and nonclassical MHC I molecules as well as structural homologues, whereas mouse ILCs have recently been shown to express MHC II. We describe the history of MHC I recognition by NK cells and discuss emerging roles for MHC II expression by ILC subsets, making comparisons between both mouse and human when possible. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Innate lymphoid cells in atherosclerosis.
Engelbertsen, Daniel; Lichtman, Andrew H
2017-12-05
The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.
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Development, differentiation and diversity of innate lymphoid cells
Diefenbach, Andreas; Colonna, Marco; Koyasu, Shigeo
2014-01-01
Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILC). ILC are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILC has been linked to the pathogenesis of inflammatory and autoimmune disorders. Recent evidence suggests that ILC can be grouped into two separate lineages, cytotoxic ILC represented by conventional natural killer (cNK) cells and cytokine-producing helper-like ILC (i.e., ILC1, ILC2, ILC3). We will focus here on current work in humans and mice that has identified core transcriptional circuitry required for the commitment of lymphoid progenitors to the ILC lineage. The striking similarities in transcriptional control of ILC and T cell lineages reveal important insights into the evolution of transcriptional programs required to protect multicellular organisms against infections and to fortify barrier surfaces. PMID:25238093
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Developmental acquisition of regulomes underlies innate lymphoid cell functionality
USDA-ARS?s Scientific Manuscript database
Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis, and they mirror adaptive CD4+ T helper (Th) cell subtypes in both usages of effector molecules and ·transcription factors. To better understand ILC subsets and their relationship with Th cells, we measur...
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The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing.
Björklund, Åsa K; Forkel, Marianne; Picelli, Simone; Konya, Viktoria; Theorell, Jakob; Friberg, Danielle; Sandberg, Rickard; Mjösberg, Jenny
2016-04-01
Innate lymphoid cells (ILCs) are increasingly appreciated as important participants in homeostasis and inflammation. Substantial plasticity and heterogeneity among ILC populations have been reported. Here we have delineated the heterogeneity of human ILCs through single-cell RNA sequencing of several hundreds of individual tonsil CD127(+) ILCs and natural killer (NK) cells. Unbiased transcriptional clustering revealed four distinct populations, corresponding to ILC1 cells, ILC2 cells, ILC3 cells and NK cells, with their respective transcriptomes recapitulating known as well as unknown transcriptional profiles. The single-cell resolution additionally divulged three transcriptionally and functionally diverse subpopulations of ILC3 cells. Our systematic comparison of single-cell transcriptional variation within and between ILC populations provides new insight into ILC biology during homeostasis, with additional implications for dysregulation of the immune system.
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Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.
Kumagai, Kazuyoshi; Lewandowski, Ryan; Jackson-Humbles, Daven N; Li, Ning; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R
2016-06-01
Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure.
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Geier, Christoph B; Kraupp, Sophie; Bra, David; Eibl, Martha M; Farmer, Jocelyn R; Csomos, Krisztian; Walter, Jolan E; Wolf, Hermann M
2017-11-01
Recent studies identified an emerging role of group 2 and 3 innate lymphoid cells (ILCs) as key players in the generation of T-dependent and T-independent antibody production. In this retrospective case-control study, CD117 + ILCs (including the majority of ILC2 and ILC3) were reduced in patients with common variable immunodeficiency (CVID). The reduction in CD117 + ILCs was distinctive to CVID and could not be observed in patients with X-linked agammaglobulinemia. Patients with a more pronounced reduction in CD117 + ILC numbers showed significantly lower numbers of peripheral MZ-like B cells and an increased prevalence of chronic, non-infectious enteropathy. Subsequent phenotyping of ILC subsets in CVID revealed that the reduction in CD117 + ILC numbers is due to a reduction in ILC2 numbers. In vitro expansion of CVID ILC2 in response to IL-2, IL-7, IL-25 and IL-33 was impaired. Furthermore, upregulation of MHCII and IL-2RA in response to IL-2, IL-7, IL-25 and IL-33 was impaired in CVID ILC2. Thus, our results indicate a dysregulation of ILC subsets with a reduction in ILC2 numbers in CVID, however, further studies are needed to explore whether ILC abnormalities are a primary finding or secondary to disease complications encountered in CVID. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast
Petridis, Christos; Brook, Mark N.; Nowinski, Salpie; Papouli, Efterpi; Fletcher, Olivia; Pinder, Sarah; Hanby, Andrew; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne; Gillett, Cheryl; Houlston, Richard; Ross, Gillian; De Ieso, Paolo; Southey, Melissa C.; Hopper, John L.; Provenzano, Elena; Apicella, Carmel; Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Fasching, Peter A.; Jud, Sebastian M.; Ekici, Arif B.; Beckmann, Matthias W.; Kerin, Michael J.; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Benitez, Javier; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Lochmann, Magdalena; Brauch, Hiltrud; Fischer, Hans-Peter; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Investigators, kConFab; Lambrechts, Diether; Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona A.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Tollenaar, Rob A. E. M.; Seynaeve, Caroline M.; Kriege, Mieke; Figueroa, Jonine; Chanock, Stephen J.; Sherman, Mark E.; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; van Deurzen, Carolien H. M.; Li, Jingmei; Czene, Kamila; Humphreys, Keith; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Shah, Mitul; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Couch, Fergus J.; Hallberg, Emily; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M.; Hall, Per; Easton, Doug; Pharoah, Paul; Schmidt, Marjanka K.; Tomlinson, Ian; Garcia-Closas, Montserrat
2014-01-01
Invasive lobular breast cancer (ILC) accounts for 10–15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09–1.18), P = 6.0×10−10; P-het for ILC vs IDC ER+ tumors = 1.8×10−4). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes. PMID:24743323
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Camelo, Ana; Rosignoli, Guglielmo; Ohne, Yoichiro; Stewart, Ross A; Overed-Sayer, Catherine; Sleeman, Matthew A; May, Richard D
2017-04-11
Innate lymphoid cells (ILCs) represent a distinct branch of the lymphoid lineage composed of 3 major subpopulations: ILC1, ILC2, and ILC3. ILCs are mainly described as tissue-resident cells but can be detected at low levels in human blood. However, unlike mouse ILCs, there is still no consistent methodology to purify and culture these cells that enables in-depth analysis of their intrinsic biology. Here, we describe defined culture conditions for ILC2s, which allowed us to dissect the roles of interleukin 2 (IL-2), IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) individually, or in combination, in modulating ILC2 phenotype and function. We show that TSLP is important for ILC2 survival, while ILC2 activation is more dependent on IL-33, especially when in combination with IL-2 or TSLP. We found that activation of ILC2s by IL-33 and TSLP dramatically upregulated their surface expression of c-Kit and downregulated expression of the canonical markers IL-7Rα and CRTH2. IL-2 further amplified ILC2 production of IL-5, IL-13, and granulocyte-macrophage colony-stimulating factor but also induced a more natural killer (NK)-like phenotype in ILC2, with upregulation of granzyme B production by these cells. Furthermore, ILC2 plasticity was observed in serum-free SFEM II media in response to IL-33, IL-25, and TSLP stimulation and independently of IL-12 and IL-1β. This is the first comprehensive report of an in vitro culture system for human ILC2s, without the use of feeder layers, which additionally evaluates the impact of IL-25, IL-33, and TSLP alone or in combination on ILC2 surface phenotype and activation status.
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Isolation of Human Innate Lymphoid Cells.
Krabbendam, Lisette; Nagasawa, Maho; Spits, Hergen; Bal, Suzanne M
2018-06-29
Innate lymphoid cells (ILCs) are innate immune cells of lymphoid origin that have important effector and regulatory functions in the first line of defense against pathogens, but also regulate tissue homeostasis, remodeling, and repair. Their function mirrors T helper cells and cytotoxic CD8 + T lymphocytes, but they lack expression of rearranged antigen-specific receptors. Distinct ILC subsets are classified in group 1 ILCs (ILC1s), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s and lymphoid tissue-inducer cells), based on the expression of transcription factors and the cytokines they produce. As the frequency of ILCs is low, their isolation requires extensive depletion of other cell types. The lack of unique cell surface antigens further complicates the identification of these cells. Here, methods for ILC isolation and characterization from human peripheral blood and different tissues are described. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.
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The Role of Innate Lymphoid Cells in Immune-Mediated Liver Diseases
Liu, Meifang; Zhang, Cai
2017-01-01
Innate lymphoid cells (ILCs) are a recently identified group of innate immune cells lacking antigen-specific receptors that can mediate immune responses and regulate tissue homeostasis and inflammation. ILCs comprise group 1 ILCs, group 2 ILCs, and group 3 ILCs. These ILCs usually localize at mucosal surfaces and combat pathogens by the rapid release of certain cytokines. However, the uncontrolled activation of ILCs can also lead to damaging inflammation, especially in the gut, lung, and skin. Although the physiological and pathogenic roles of ILCs in liver diseases have been attracting increasing attention recently, there has been no systematic review regarding the roles of ILCs in immune-mediated liver diseases. Here, we review the relationships between the ILC subsets and their functions in immune-mediated liver diseases, and discuss their therapeutic potential based on current knowledge about the functional roles of these cells in liver diseases. PMID:28659927
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CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.
Hardman, Clare S; Chen, Yi-Ling; Salimi, Maryam; Jarrett, Rachael; Johnson, David; Järvinen, Valtteri J; Owens, Raymond J; Repapi, Emmanouela; Cousins, David J; Barlow, Jillian L; McKenzie, Andrew N J; Ogg, Graham
2017-12-22
Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation.
Cephus, Jacqueline-Yvonne; Stier, Matthew T; Fuseini, Hubaida; Yung, Jeffrey A; Toki, Shinji; Bloodworth, Melissa H; Zhou, Weisong; Goleniewska, Kasia; Zhang, Jian; Garon, Sarah L; Hamilton, Robert G; Poloshukin, Vasiliy V; Boyd, Kelli L; Peebles, R Stokes; Newcomb, Dawn C
2017-11-28
Sex hormones regulate many autoimmune and inflammatory diseases, including asthma. As adults, asthma prevalence is 2-fold greater in women compared to men. The number of group 2 innate lymphoid cells (ILC2) is increased in patients with asthma, and we investigate how testosterone attenuates ILC2 function. In patients with moderate to severe asthma, we determine that women have an increased number of circulating ILC2 compared to men. ILC2 from adult female mice have increased IL-2-mediated ILC2 proliferation versus ILC2 from adult male mice, as well as pre-pubescent females and males. Further, 5α-dihydrotestosterone, a hormone downstream of testosterone, decreases lung ILC2 numbers and IL-5 and IL-13 expression from ILC2. In vivo, testosterone attenuated Alternaria-extract-induced IL-5+ and IL-13+ ILC2 numbers and lung eosinophils by intrinsically decreasing lung ILC2 numbers, as well as by decreasing expression of IL-33 and thymic stromal lymphopoietin (TSLP), ILC2-stimulating cytokines. Collectively, these findings provide a foundational understanding of sexual dimorphism in ILC2 function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Interactive laboratory classes enhance neurophysiological knowledge in Thai medical students.
Wongjarupong, Nicha; Niyomnaitham, Danai; Vilaisaktipakorn, Pitchamol; Suksiriworaboot, Tanawin; Qureshi, Shaun Peter; Bongsebandhu-Phubhakdi, Saknan
2018-03-01
Interactive laboratory class (ILC) is a two-way communication teaching method that encourages students to correlate laboratory findings with materials from lectures. In Thai medical education, active learning methods are uncommon. This paper aims to establish 1) if ILCs would effectively promote physiology learning; 2) if effectiveness would be found in both previously academically high-performing and low-performing students; and 3) the acceptability of ILCs to Thai medical students as a novel learning method. Two hundred seventy-eight second-year medical students were recruited to this study. We conducted three ILC sessions, which followed corresponding lectures. We carried out multiple-choice pre- and post-ILC assessments of knowledge and compared by repeated-measures ANOVA and unpaired t-test. Subgroup analysis was performed to compare high-performance (HighP) and low-performance (LowP) students. After the ILCs, participants self-rated their knowledge and satisfaction. Post-ILC test scores increased significantly compared with pre-ILC test scores in all three sessions. Mean scores of each post-ILC test increased significantly from pre-ILC test in both LowP and HighP groups. More students self-reported a "very high" and "high" level of knowledge after ILCs. Most students agreed that ILCs provided more discussion opportunity, motivated their learning, and made lessons more enjoyable. As an adjunct to lectures, ILCs can enhance knowledge in medical students, regardless of previous academic performance. Students perceived ILC as useful and acceptable. This study supports the active learning methods in physiology education, regardless of cultural context.
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Hepworth, Matthew R.; Fung, Thomas C.; Masur, Samuel H.; Kelsen, Judith R.; McConnell, Fiona M.; Dubrot, Juan; Withers, David R.; Hugues, Stephanie; Farrar, Michael A.; Reith, Walter; Eberl, Gerard; Baldassano, Robert N.; Laufer, Terri M.; Elson, Charles O.; Sonnenberg, Gregory F.
2015-01-01
Inflammatory CD4+ T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. While selection of self-specific T cells in the thymus limits responses to tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells, and that MHCII+ ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on human colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4+ T cells in the intestine, and suggest that this process is dysregulated in human IBD. PMID:25908663
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Kadel, Sapana; Ainsua-Enrich, Erola; Hatipoglu, Ibrahim; Turner, Sean; Singh, Simar; Khan, Sohaib; Kovats, Susan
2018-02-01
Humans show significant sex differences in the incidence and severity of respiratory diseases, including asthma and virus infection. Sex hormones contribute to the female sex bias in type 2 inflammation associated with respiratory diseases, consistent with recent reports that female lungs harbor greater numbers of GATA-3-dependent group 2 innate lymphoid cells (ILC2s). In this study, we determined whether sex hormone levels govern sex differences in the numbers, phenotype, and function of ILC2s in the murine lung and bone marrow (BM). Our data show that lungs of female mice harbor significantly greater ILC2 numbers in homeostasis, in part due to a major subset of ILC2s lacking killer-cell lectin like receptor G1 (KLRG1), a population largely absent in male lungs. The KLRG1 - ILC2s were capable of type 2 cytokine production and increased with age after sexual maturity, suggesting that a unique functional subset exists in females. Experiments with gonadectomized mice or mice bearing either global or lymphocyte restricted estrogen receptor α ( Esr1 ) deficiency showed that androgens rather than estrogens regulated numbers of the KLRG1 - ILC2 subset and ILC2 functional capacity in the lung and BM, as well as levels of GATA-3 expression in BM ILC2s. Furthermore, the frequency of BM PLZF + ILC precursors was higher in males and increased by excess androgens, suggesting that androgens act to inhibit the transition of ILC precursors to ILC2s. Taken together, these data show that a functional subset of KLRG1 - ILC2s in females contributes to the sex bias in lung ILC2s that is observed after reproductive age.
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T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation.
Kwong, Brandon; Rua, Rejane; Gao, Yuanyuan; Flickinger, John; Wang, Yan; Kruhlak, Michael J; Zhu, Jinfang; Vivier, Eric; McGavern, Dorian B; Lazarevic, Vanja
2017-10-01
The transcription factor T-bet has been associated with increased susceptibility to systemic and organ-specific autoimmunity, but the mechanism by which T-bet expression promotes neuroinflammation remains unknown. In this study, we demonstrate a cardinal role of T-bet-dependent NKp46 + innate lymphoid cells (ILCs) in the initiation of CD4 + T H 17-mediated neuroinflammation. Loss of T-bet specifically in NKp46 + ILCs profoundly impaired the ability of myelin-reactive T H 17 cells to invade central nervous system (CNS) tissue and protected the mice from autoimmunity. T-bet-dependent NKp46 + ILCs localized in the meninges and acted as chief coordinators of meningeal inflammation by inducing the expression of proinflammatory cytokines, chemokines and matrix metalloproteinases, which together facilitated T cell entry into CNS parenchyma. Our findings uncover a detrimental role of T-bet-dependent NKp46 + ILCs in the development of CNS autoimmune disease.
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Cavagnero, Kellen; Doherty, Taylor A
2017-08-01
The recent discovery of group 2 innate lymphoid cells (ILC2s) has caused a paradigm shift in the understanding of allergic airway disease pathogenesis. Prior to the discovery of ILC2s, Th2 cells were largely thought to be the primary source of type 2 cytokines; however, activated ILC2s have since been shown to contribute significantly, and in some cases, dominantly to type 2 cytokine production. Since the discovery of ILC2s in 2010, many mediators have been shown to regulate their effector functions. Initial studies identified the epithelial derived cytokines IL-25, IL-33, and TSLP as activators of ILC2s, and recent studies have identified many additional cytokine and lipid mediators that are involved in ILC2 regulation. ILC2s and their mediators represent novel therapeutic targets for allergic airway diseases and intensive investigation is underway to better understand ILC2 biology and upstream and downstream pathways that lead to ILC2-driven airway pathology. In this review, we will focus on the cytokine and lipid mediators that regulate ILC2s in human allergic airway disease, as well as highlight newly discovered mediators of mouse ILC2s that may eventually translate to humans.
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Identification of innate lymphoid cells in single-cell RNA-Seq data.
Suffiotti, Madeleine; Carmona, Santiago J; Jandus, Camilla; Gfeller, David
2017-07-01
Innate lymphoid cells (ILCs) consist of natural killer (NK) cells and non-cytotoxic ILCs that are broadly classified into ILC1, ILC2, and ILC3 subtypes. These cells recently emerged as important early effectors of innate immunity for their roles in tissue homeostasis and inflammation. Over the last few years, ILCs have been extensively studied in mouse and human at the functional and molecular level, including gene expression profiling. However, sorting ILCs with flow cytometry for gene expression analysis is a delicate and time-consuming process. Here we propose and validate a novel framework for studying ILCs at the transcriptomic level using single-cell RNA-Seq data. Our approach combines unsupervised clustering and a new cell type classifier trained on mouse ILC gene expression data. We show that this approach can accurately identify different ILCs, especially ILC2 cells, in human lymphocyte single-cell RNA-Seq data. Our new model relies only on genes conserved across vertebrates, thereby making it in principle applicable in any vertebrate species. Considering the rapid increase in throughput of single-cell RNA-Seq technology, our work provides a computational framework for studying ILC2 cells in single-cell transcriptomic data and may help exploring their conservation in distant vertebrate species.
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Ambiguous roles of innate lymphoid cells in chronic development of liver diseases.
Shen, Yue; Li, Jing; Wang, Si-Qi; Jiang, Wei
2018-05-14
Innate lymphoid cells (ILCs) are defined as a distinct arm of innate immunity. According to their profile of secreted cytokines and lineage-specific transcriptional factors, ILCs can be categorized into the following three groups: group 1 ILCs (including natural killer (NK) cells and ILC1s) are dependent on T-bet and can produce interferon-γ; group 2 ILCs (ILC2s) are dependent on GATA3 and can produce type 2 cytokines, including interleukin (IL)-5 and IL-13; and, group 3 ILCs (including lymphoid tissue-like cells and ILC3s) are dependent on RORγt and can produce IL-22 and IL-17. Collaborative with adaptive immunity, ILCs are highly reactive innate effectors that promptly orchestrate immunity, inflammation and tissue repair. Dysregulation of ILCs might result in inflammatory disorders. Evidence regarding the function of intrahepatic ILCs is emerging from longitudinal studies of inflammatory liver diseases wherein they exert both physiological and pathological functions, including immune homeostasis, defenses and surveillance. Their overall effect on the liver depends on the balance of their proinflammatory and antiinflammatory populations, specific microenvironment and stages of immune responses. Here, we review the current data about ILCs in chronic liver disease progression, to reveal their roles in different stages as well as to discuss their therapeutic potency as intervention targets.
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Ambiguous roles of innate lymphoid cells in chronic development of liver diseases
Shen, Yue; Li, Jing; Wang, Si-Qi; Jiang, Wei
2018-01-01
Innate lymphoid cells (ILCs) are defined as a distinct arm of innate immunity. According to their profile of secreted cytokines and lineage-specific transcriptional factors, ILCs can be categorized into the following three groups: group 1 ILCs (including natural killer (NK) cells and ILC1s) are dependent on T-bet and can produce interferon-γ; group 2 ILCs (ILC2s) are dependent on GATA3 and can produce type 2 cytokines, including interleukin (IL)-5 and IL-13; and, group 3 ILCs (including lymphoid tissue-like cells and ILC3s) are dependent on RORγt and can produce IL-22 and IL-17. Collaborative with adaptive immunity, ILCs are highly reactive innate effectors that promptly orchestrate immunity, inflammation and tissue repair. Dysregulation of ILCs might result in inflammatory disorders. Evidence regarding the function of intrahepatic ILCs is emerging from longitudinal studies of inflammatory liver diseases wherein they exert both physiological and pathological functions, including immune homeostasis, defenses and surveillance. Their overall effect on the liver depends on the balance of their proinflammatory and antiinflammatory populations, specific microenvironment and stages of immune responses. Here, we review the current data about ILCs in chronic liver disease progression, to reveal their roles in different stages as well as to discuss their therapeutic potency as intervention targets. PMID:29760540
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Technical instrumentation R&D for ILD SiW ECAL large scale device
NASA Astrophysics Data System (ADS)
Balagura, V.
2018-03-01
Calorimeters with silicon detectors have many unique features and are proposed for several world-leading experiments. We describe the R&D program of the large scale detector element with up to 12 000 readout channels for the International Large Detector (ILD) at the future e+e‑ ILC collider. The program is focused on the readout front-end electronics embedded inside the calorimeter. The first part with 2 000 channels and two small silicon sensors has already been constructed, the full prototype is planned for the beginning of 2018.
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Aptel, Florent; Beccat, Sylvain; Fortoul, Vincent; Denis, Philippe
2011-08-01
To compare anterior chamber volume (ACV), iris volume, and iridolenticular contact (ILC) area before and after laser peripheral iridotomy (LPI) in eyes with pigment dispersion syndrome (PDS) using anterior segment optical coherence tomography (AS OCT) and image processing software. Cross-sectional study. Eighteen eyes of 18 patients with PDS; 30 eyes of 30 controls matched for age, gender, and refraction. Anterior segment OCT imaging was performed in all eyes before LPI and 1, 4, and 12 weeks after LPI. At each visit, 12 cross-sectional images of the AS were taken: 4 in bright conditions with accommodation (accommodation), 4 in bright conditions without accommodation (physiological miosis), and 4 under dark conditions (physiologic mydriasis). Biometric parameters were estimated using AS OCT radial sections and customized image-processing software. Anterior chamber volume, iris volume-to-length ratio, ILC area, AS OCT anterior chamber depth, and A-scan ultrasonography axial length. Before LPI, PDS eyes had a significantly greater ACV and ILC area than control eyes (P<0.01) and a significantly smaller iris volume-to-length ratio than the controls (P<0.05). After LPI, ACV and ILC area decreased significantly in PDS eyes, but iris volume-to-length ratio increased significantly (P<0.02) and was not significantly different from that of controls. These biometric changes were stable over time. Iris volume-to-length ratio decreased significantly from accommodation to mydriasis and from miosis to mydriasis, both in PDS and control eyes (P<0.01). In PDS eyes, ILC area decreased significantly from accommodation to mydriasis, both before and after LPI (P<0.01). On multivariate analysis, greater anterior chamber (AC) volume (P<0.02) and larger AC depth (P<0.05) before LPI were significant predictors of a larger ILC area. Pigment dispersion syndrome eyes do not have an iris that is abnormally large, relative to the AS size, but have a weakly resistant iris that is stretched and pushed against the lens when there is a pressure difference across the iris. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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Nabatanzi, Rose; Cose, Stephen; Joloba, Moses; Jones, Sarah Rowland; Nakanjako, Damalie
2018-03-15
HIV infection causes upregulation of markers of inflammation, immune activation and apoptosis of host adaptive, and innate immune cells particularly monocytes, natural killer (NK) and innate lymphoid cells (ILCs). Although antiretroviral therapy (ART) restores CD4 T-cell counts, the persistent aberrant activation of monocytes, NK and ILCs observed likely contributes to the incomplete recovery of T-cell effector functions. A better understanding of the effects of HIV infection and ART on the phenotype and function of circulating monocytes, NK, and ILCs is required to guide development of novel therapeutic interventions to optimize immune recovery.
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Yazdani, Reza; Sharifi, Mehri; Shirvan, Aylar Saba; Azizi, Gholamreza; Ganjalikhani-Hakemi, Mazdak
2015-01-01
Innate lymphoid cells (ILCs) are a novel family of hematopoietic effectors and regulators of innate immunity. Although these cells are morphologically similar to B cells and T cells, however they do not express antigen receptors. ILCs seems to have emerging roles in innate immune responses against infectious or non-infectious microorganisms, protection of the epithelial barrier, lymphoid organogenesis and inflammation, tissue remodeling and regulating homeostasis of tissue stromal cells. In addition, it has recently been reported that ILCs have a crucial role in several disorders such as allergy and autoimmunity. Based on their phenotype and functions, ILCs are classified into three major groups called ILCs1, ILCs2, and ILCs3. Here we reviewed the most recent data concerning diverse ILC phenotypes, subclasses, functions in immune responses as well as in immune mediated disorders. Copyright © 2015 Elsevier Inc. All rights reserved.
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Regulation of Innate Lymphoid Cells by Aryl Hydrocarbon Receptor
Li, Shiyang; Bostick, John W.; Zhou, Liang
2018-01-01
With striking similarity to their adaptive T helper cell counterparts, innate lymphoid cells (ILCs) represent an emerging family of cell types that express signature transcription factors, including T-bet+ Eomes+ natural killer cells, T-bet+ Eomes− group 1 ILCs, GATA3+ group 2 ILCs, RORγt+ group 3 ILCs, and newly identified Id3+ regulatory ILC. ILCs are abundantly present in barrier tissues of the host (e.g., the lung, gut, and skin) at the interface of host–environment interactions. Active research has been conducted to elucidate molecular mechanisms underlying the development and function of ILCs. The aryl hydrocarbon receptor (Ahr) is a ligand-dependent transcription factor, best known to mediate the effects of xenobiotic environmental toxins and endogenous microbial and dietary metabolites. Here, we review recent progresses regarding Ahr function in ILCs. We focus on the Ahr-mediated cross talk between ILCs and other immune/non-immune cells in host tissues especially in the gut. We discuss the molecular mechanisms of the action of Ahr expression and activity in regulation of ILCs in immunity and inflammation, and the interaction between Ahr and other pathways/transcription factors in ILC development and function with their implication in disease. PMID:29354125
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DOE Office of Scientific and Technical Information (OSTI.GOV)
J.K. Sekutowicz, P. Kneisel
This paper reports about our efforts to develop a flangeable coaxial coupler for both HOM and fundamental coupling for 9-cell TESLA/ILC-type cavities. The cavities were designed in early 90‘s for pulsed operation with a low duty factor, less than 1 %. The proposed design of the coupler has been done in a way, that the magnetic flux B at the flange connection is minimized and only a field of <5 mT would be present at the accelerating field Eacc of ~ 36 MV/m (B =150 mT in the cavity). Even though we achieved reasonably high Q-values at low field, themore » cavity/coupler combination was limited in the cw mode to only ~ 7 MV/m, where a thermally initiated degradation occurred. We have improved the cooling conditions by initially drilling radial channels every 30 degrees, then every 15 degrees into the shorting plate. The modified prototype performed well up to 9 MV/m in cw mode. This paper reports about our experiences with the further modified coaxial coupler and about test results in cw and low duty cycle pulsed mode, similar to the TESLA/ILC operation conditions.« less
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Font group identification using reconstructed fonts
NASA Astrophysics Data System (ADS)
Cutter, Michael P.; van Beusekom, Joost; Shafait, Faisal; Breuel, Thomas M.
2011-01-01
Ideally, digital versions of scanned documents should be represented in a format that is searchable, compressed, highly readable, and faithful to the original. These goals can theoretically be achieved through OCR and font recognition, re-typesetting the document text with original fonts. However, OCR and font recognition remain hard problems, and many historical documents use fonts that are not available in digital forms. It is desirable to be able to reconstruct fonts with vector glyphs that approximate the shapes of the letters that form a font. In this work, we address the grouping of tokens in a token-compressed document into candidate fonts. This permits us to incorporate font information into token-compressed images even when the original fonts are unknown or unavailable in digital format. This paper extends previous work in font reconstruction by proposing and evaluating an algorithm to assign a font to every character within a document. This is a necessary step to represent a scanned document image with a reconstructed font. Through our evaluation method, we have measured a 98.4% accuracy for the assignment of letters to candidate fonts in multi-font documents.
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Isolation and characterization of mouse innate lymphoid cells.
Halim, Timotheus Y F; Takei, Fumio
2014-08-01
Innate lymphoid cells (ILCs) are rare populations of cytokine-producing lymphocytes and are divided into three groups, namely ILC1, ILC2, and ILC3, based on the cytokines that they produce. They comprise less than 1% of lymphocytes in mucosal tissues and express no unique cell surface markers. Therefore, they can only be identified by combinations of multiple cell surface markers and further characterized by cytokine production in vitro. Thus, multicolor flow cytometry is the only reliable method to purify and characterize ILCs. Here we describe the methods for cell preparation, flow cytometric analysis, and purification of murine ILC2 and ILC3. Copyright © 2014 John Wiley & Sons, Inc.
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Adachi, Yayoi; Sawaki, Masataka; Hattori, Masaya; Yoshimura, Akiyo; Gondo, Noami; Kotani, Haruru; Iwase, Madoka; Kataoka, Ayumi; Onishi, Sakura; Sugino, Kayoko; Terada, Mitsuo; Horisawa, Nanae; Mori, Makiko; Oze, Isao; Iwata, Hiroji
2018-03-13
Recent studies suggested that ALND (axillary lymph node dissection) can be avoided in breast cancer patients with limited SLN (sentinel lymph node) metastasis. However, these trials included only several invasive lobular carcinoma (ILC) cases, and the validity of omitting ALND for ILC remains controversial. Here, we examined whether omitting ALND is feasible in ILC treatment. A total of 3771 breast cancer patients underwent surgery for breast cancer at the Aichi Cancer Center Hospital between January 2006 and December 2015. We excluded patients with neoadjuvant therapy or without axillary management, and identified 184 ILC patients and 2402 invasive ductal carcinoma (IDC) patients. We compared SLN and non-SLN metastasis rates and the number of total ALN metastases between the ILC and IDC cohorts, and we examined the factors that influenced non-SLN metastasis in the SLN micrometastasis group. SLN biopsies were performed in 171 (93%) ILC and 2168 (90%) IDC cases, and 31 (18%) ILC and 457 (21%) IDC cases were SLN micrometastasis and macrometastasis (p = 0.36). Among SLN macrometastasis patients, 17 (68%) ILC cases and 163 (46%) IDC cases showed non-SLN metastasis (p = 0.03). The number of non-SLN metastases was greater in ILC cases compared with IDC cases. Multivariate analysis showed that ILC was the influential factor predicting non-SLN metastasis in patients with SLN macrometastasis. ILC cases had more non-SLN metastasis than IDC cases among SLN-positive cases, and ILC was an important factor for the prediction of non-SLN positivity in SLN macrometastasis cases. Omitting ALND for ILC with positive SLNs requires more consideration.
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CCD developments for particle colliders
NASA Astrophysics Data System (ADS)
Stefanov, Konstantin D.
2006-09-01
Charge Coupled Devices (CCDs) have been successfully used in several high-energy physics experiments over the last 20 years. Their small pixel size and excellent precision provide superb tool for studying of short-lived particles and understanding the nature at fundamental level. Over the last years the Linear Collider Flavour Identification (LCFI) collaboration has developed Column-Parallel CCDs (CPCCD) and CMOS readout chips to be used for the vertex detector at the International Linear Collider (ILC). The CPCCDs are very fast devices capable of satisfying the challenging requirements imposed by the beam structure of the superconducting accelerator. First set of prototype devices have been designed, manufactured and successfully tested, with second-generation chips on the way. Another idea for CCD-based device, the In-situ Storage Image Sensor (ISIS) is also under development and the first prototype is in production.
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Innate Lymphoid Cells in Intestinal Inflammation
Geremia, Alessandra; Arancibia-Cárcamo, Carolina V.
2017-01-01
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an increased risk of developing colorectal cancer. ILC may play an important amplifying role in IBD and IBD-associated cancer, through secretion of inflammatory cytokines and interaction with other immune and non-immune cells. Here, we will review the evidence indicating a role for ILC in the pathogenesis of chronic intestinal inflammation. PMID:29081776
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Montaldo, Elisa; Vacca, Paola; Vitale, Chiara; Moretta, Francesca; Locatelli, Franco; Mingari, Maria Cristina; Moretta, Lorenzo
2016-11-01
The interest in innate lymphoid cells (ILC) has rapidly grown during the last decade. ILC include distinct cell types that are collectively involved in host protection against pathogens and tumor cells and in the regulation of tissue homeostasis. Studies in mice enabled a broad characterization of ILC function and of their developmental requirements. In humans all mature ILC subsets have been characterized and their role in the pathogenesis of certain disease is emerging. Nonetheless, still limited information is available on human ILC development. Indeed, only the cell precursors committed toward NK cells or ILC3 have been described. Here, we review the most recent finding on human mature ILC, discussing their tissue localization and function. Moreover, we summarize the available data regarding human ILC development. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
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Group 2 innate lymphoid cells in disease
2016-01-01
Abstract Group 2 innate lymphoid cells (ILC2) are now recognized as an important innate source of type-2 effector cytokines. Although initially associated with mucosal tissues, it is clear that ILC2 are present in diverse anatomical locations. The function of ILC2 at these sites is equally varied, and although ILC2 represent a relatively minor population, they are fundamentally important regulators of innate and adaptive immune processes. As such, there is much interest to understand the role of ILC2 in diseases with a type-2 inflammatory component. This review explores the known roles of ILC2 in disease, and the diseases that show associations or other strong evidence for the involvement of ILC2. PMID:26306498
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Jeffery, Hannah C; McDowell, Patrick; Lutz, Philipp; Wawman, Rebecca E; Roberts, Sheree; Bagnall, Chris; Birtwistle, Jane; Adams, David H; Oo, Ye Htun
2017-01-01
Innate lymphoid cells (ILC) have been implicated in the initiation of inflammation and fibrosis in mice. However, ILC have not been characterized in inflamed human liver tissue. Human intrahepatic lymphocytes were isolated by mechanical digestion and phenotyped by flow cytometry. Conditioned medium from cultures of primary human biliary epithelial cells, stellate cells, fibroblasts and inflamed human liver tissue was used to model the effects of the inflammatory liver environment of ILC phenotype and function. All three ILC subsets were present in the human liver, with the ILC1 (CRTH2negCD117neg) subset constituting around 70% of intrahepatic ILCs. Both NCRpos (NKp44+) and NCRneg ILC3 (CRTH2negCD117pos) subsets were also detected. ILC2 (CRTH2pos) frequency correlated with disease severity measured by model of end stage liver disease (MELD) scoring leading us to study this subset in more detail. ILC2 displayed a tissue resident CD69+ CD161++ phenotype and expressed chemokine receptor CCR6 allowing them to respond to CCL20 secreted by cholangiocytes and stellate cells. ILC2 expressed integrins VLA-5 and VLA-6 and the IL-2 and IL-7 cytokine receptors CD25 and CD127 although IL-2 and IL-7 were barely detectable in inflamed liver tissue. Although biliary epithelial cells secrete IL-33, intrahepatic ILC2 had low expression of the ST2 receptor. Intrahepatic ILC2 secreted the immunoregulatory and repair cytokines IL-13 and amphiregulin. Intrahepatic ILC2 express receptors allowing them to be recruited to bile ducts in inflamed portal tracts. Their frequencies increased with worsening liver function. Their secretion of IL-13 and amphiregulin suggests they may be recruited to promote resolution and repair and thereby they may contribute to ongoing fibrogenesis in liver disease.
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Tosi, Isabella; Grys, Katarzyna; Sreeneebus, Hemawtee; Perera, Gayathri K; Chapman, Anna; Smith, Catherine H; Di Meglio, Paola; Nestle, Frank O
2013-01-01
Innate lymphoid cells (ILC) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterise the ILC in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in skin and blood of normal individuals and psoriasis patients are CD3 negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in blood of psoriasis patients compared to healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILC in skin compared to blood. Moreover the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared to normal skin. A detailed time course of a psoriasis patient treated with anti-TNF showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis. PMID:24352038
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GATA-3 function in innate and adaptive immunity.
Tindemans, Irma; Serafini, Nicolas; Di Santo, James P; Hendriks, Rudi W
2014-08-21
The zinc-finger transcription factor GATA-3 has received much attention as a master regulator of T helper 2 (Th2) cell differentiation, during which it controls interleukin-4 (IL-4), IL-5, and IL-13 expression. More recently, GATA-3 was shown to contribute to type 2 immunity through regulation of group 2 innate lymphoid cell (ILC2) development and function. Furthermore, during thymopoiesis, GATA-3 represses B cell potential in early T cell precursors, activates TCR signaling in pre-T cells, and promotes the CD4(+) T cell lineage after positive selection. GATA-3 also functions outside the thymus in hematopoietic stem cells, regulatory T cells, CD8(+) T cells, thymic natural killer cells, and ILC precursors. Here we discuss the varied functions of GATA-3 in innate and adaptive immune cells, with emphasis on its activity in T cells and ILCs, and examine the mechanistic basis for the dose-dependent, developmental-stage- and cell-lineage-specific activity of this transcription factor. Copyright © 2014 Elsevier Inc. All rights reserved.
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T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation
Kwong, Brandon; Rua, Rejane; Gao, Yuanyuan; Flickinger, John; Wang, Yan; Kruhlak, Michael J.; Zhu, Jinfang; Vivier, Eric; McGavern, Dorian B.; Lazarevic, Vanja
2017-01-01
The transcription factor T-bet has been linked to increased susceptibility to systemic and organ-specific autoimmunity, but the mechanism by which T-bet expression promotes neuroinflammation remains unknown. In this study, we demonstrate a cardinal role for T-bet-dependent NKp46+ innate lymphoid cells (ILCs) in the initiation of CD4+ TH17-mediated neuroinflammation. Loss of T-bet specifically in NKp46+ ILCs profoundly impaired the ability of myelin-reactive TH17 cells to invade the central nervous system (CNS) tissue and protected the mice from autoimmunity. T-bet-dependent NKp46+ ILCs were localized in the meninges and acted as chief coordinators of meningeal inflammation by inducing the expression of pro-inflammatory cytokines, chemokines and matrix metalloproteinases, which in a concerted fashion facilitated T cell entry into CNS parenchyma. Our findings uncover a detrimental role of T-bet-dependent NKp46+ ILCs in the development of CNS autoimmune disease. PMID:28805812
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Kotas, Maya E; Locksley, Richard M
2018-06-19
Innate lymphoid cells (ILCs) are positioned in tissues perinatally, constitutively express receptors responsive to their organ microenvironments, and perform an arsenal of effector functions that overlap those of adaptive CD4 + T cells. Based on knowledge regarding subsets of invariant-like lymphocytes (e.g., natural killer T [NKT] cells, γδ T cells, mucosal-associated invariant T [MAIT] cells, etc.) and fetally derived macrophages, we hypothesize that immune cells established during the perinatal period-including, but not limited to, ILCs-serve intimate roles in tissue that go beyond classical understanding of the immune system in microbial host defense. In this Perspective, we propose mechanisms by which the establishment of ILCs and the tissue lymphoid niche during early development may have consequences much later in life. Although definitive answers require better tools, efforts to achieve deeper understanding of ILC biology across the mammalian lifespan have the potential to lift the veil on the unknown breadth of immune cell functions. Copyright © 2018 Elsevier Inc. All rights reserved.
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Innate Lymphoid Cells in Tumor Immunity.
van Beek, Jasper J P; Martens, Anne W J; Bakdash, Ghaith; de Vries, I Jolanda M
2016-02-25
Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring.
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Innate Lymphoid Cells in Tumor Immunity
van Beek, Jasper J. P.; Martens, Anne W. J.; Bakdash, Ghaith; de Vries, I. Jolanda M.
2016-01-01
Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring. PMID:28536374
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Innate Lymphoid Cells in HIV/SIV Infections.
Shah, Spandan V; Manickam, Cordelia; Ram, Daniel R; Reeves, R Keith
2017-01-01
Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.
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Innate lymphoid cells in tissue homeostasis and diseases.
Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva
2017-08-18
Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.
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Innate Lymphoid Cells in HIV/SIV Infections
Shah, Spandan V.; Manickam, Cordelia; Ram, Daniel R.; Reeves, R. Keith
2017-01-01
Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections. PMID:29326704
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2017-01-01
CD4 T cells, including T regulatory cells (Treg cells) and effector T helper cells (Th cells), and recently identified innate lymphoid cells (ILCs) play important roles in host defense and inflammation. Both CD4 T cells and ILCs can be classified into distinct lineages based on their functions and the expression of lineage-specific genes, including those encoding effector cytokines, cell surface markers, and key transcription factors. It was first recognized that each lineage expresses a specific master transcription factor and the expression of these factors is mutually exclusive because of cross-regulation among these factors. However, recent studies indicate that the master regulators are often coexpressed. Furthermore, the expression of master regulators can be dynamic and quantitative. In this review, we will first discuss similarities and differences between the development and functions of CD4 T cell and ILC subsets and then summarize recent literature on quantitative, dynamic, and cell type–specific balance between the master transcription factors in determining heterogeneity and plasticity of these subsets. PMID:28630089
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Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.
Melo-Gonzalez, Felipe; Hepworth, Matthew R
2017-03-01
Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid-related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR + ILC3 and LTi-like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets. © 2016 The Authors. Immunology published by John Wiley & Sons Ltd.
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Ilic, Ivan R; Djordjevic, Nebojsa P; Randjelovic, Pavle J; Stojanovic, Nikola M; Radulovic, Niko S; Ilic, Ratko S
2016-01-01
The occurrence of different variants of invasive lobular carcinoma (ILC) of the breast is variable. For example, the pleomorphic variant of ILC has an incidence of around 5%; however, the number of analyzed cases of ILC is shadowed by the number of ductal type carcinoma (IDC). Thus, we aimed to analyze the classical and pleomorphic ILCs in women from southeastern Serbia. Analyzed were 296 cases (11.91%) diagnosed with ILC, out of 2486 cases of all breast cancers (BCs), during a 7-year period (2005-2011) from southeastern Serbia. The differences in clinicopathological and immunohistochemical features (estrogen receptor/ER, progesterone receptor/ PR, HER-2, Ki-67, BRCA-1, p53 and E-cadherin) of these cases of ILCs were assessed and compared. Pleomorphic ILC occurred relatively rarely compared to other variants, however almost one fifth of the ILC cases were pleomorphic. No statistically significant correlation was found between patient age, tumor stage and the presence/absence of multifocality (MFC), multicentricity (MCC) and bilaterality (BL) on one side, and ILC variant on the other. Only the expression of two prognostic and predictive immunohistochemical markers, important for endocrine therapy, ER and PR, showed significant correlation with the ILC variant. Although higher tumor stage, incidence of multicentricity, overexpression of HER2 and higher p53 positivity were deemed to be characteristic of pleomorphic ILC, in our study that included a much larger number of cases than previous studies did, such correlations were not observed. Thus, it appears that the only two features of pleomorphic ILCs is absence of ER and PR positivity.
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Expansion of CD25+ Innate Lymphoid Cells Reduces Atherosclerosis
Engelbertsen, Daniel; Foks, Amanda C.; Alberts-Grill, Noah; Kuperwaser, Felicia; Chen, Tao; Lederer, James A.; Jarolim, Petr; Grabie, Nir; Lichtman, Andrew H.
2015-01-01
Objective Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. Approach and Results We demonstrate that CD25+ ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr−/−rag1−/− mice. To investigate the role of ILCs in atherosclerosis, ldlr−/−rag1−/− mice were concurrently fed an atherogenic diet and treated with either ILC-depleting anti-CD90.2 antibodies or with IL-2/anti-IL-2 complexes that expand CD25+ ILCs. Lesion development was not affected by anti-CD90.2 treatment, but was reduced in IL-2/anti-IL-2 -treated mice. These IL-2 treated mice had reduced VLDL cholesterol and increased triglycerides compared to controls and reduced apolipoprotein B100 gene expression in the liver. IL-2/anti-IL-2 treatment caused expansion of ILC2s in aorta and other tissues, elevated levels of IL-5, systemic eosinophila and hepatic eosinophilic inflammation. Blockade of IL-5 reversed the IL-2-complex-induced eosinophilia but did not change lesion size. Conclusions This study demonstrates that expansion of CD25-expressing ILCs by IL-2/anti-IL-2 complexes leads to a reduction in VLDL cholesterol and atherosclerosis. Global depletion of ILCs by anti-CD90.2 did not significantly affect lesion size indicating that different ILC subsets may have divergent effects on atherosclerosis. PMID:26494229
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Innate lymphoid cells at the interface between obesity and asthma.
Everaere, Laetitia; Ait Yahia, Saliha; Bouté, Mélodie; Audousset, Camille; Chenivesse, Cécile; Tsicopoulos, Anne
2018-01-01
Obesity and asthma prevalence has dramatically and concomitantly increased over the last 25 years, and many epidemiological studies have highlighted obesity as an important risk factor for asthma. Although many studies have been performed, the underlying mechanisms remain poorly understood. Innate mechanisms have been involved in both diseases, in particular through the recently described innate lymphoid cells (ILCs). ILCs are subdivided into three groups that are defined by their cytokine production and by their master transcription factor expression, in sharp correlation with their T helper counterparts. However, unlike T helper cells, ILCs do not express antigen-specific receptors, but respond to damage-induced signals. ILCs have been found in target tissues of both diseases, and data have implicated these cells in the pathogenesis of both diseases. In particular group 2 ILCs (ILC2) are activated in both the adipose and lung tissues under the effect of interleukin-33 and interleukin-25 expression. However, counter-intuitively to the well-known association between obesity and asthma, ILC2 are beneficial for obesity but deleterious for asthma. This review will examine the roles of ILCs in each disease and recent data highlighting ILCs as a putative link between obesity and asthma. © 2017 John Wiley & Sons Ltd.
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Mjösberg, Jenny; Spits, Hergen
2012-05-01
Type 2 innate lymphoid cells (ILC2s) are members of an ILC family, which contains NK cells and Rorγt(+) ILCs, the latter including lymphoid tissue inducer (LTi) cells and ILCs producing IL-17 and IL-22. ILC2s are dedicated to the production of IL-5 and IL-13 and, as such, ILC2s provide an early and important source of type 2 cytokines critical for helminth expulsion in the gut. Several studies have also demonstrated a role for ILC2s in airway inflammation. In this issue of the European Journal of Immunology, Klein Wolterink et al. [Eur. J. Immunol. 2012. 42: 1106-1116] show that ILC2s are instrumental in several models of experimental asthma where they significantly contribute to production of IL-5 and IL-13, key cytokines in airway inflammation. This study sheds light over the relative contribution of ILC2s versus T helper type 2 cells (Th2) in type 2 mediated allergen-specific inflammation in the airways as discussed in this commentary. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Innate lymphoid cells in graft-versus-host disease.
Konya, V; Mjösberg, J
2015-11-01
Innate lymphoid cells (ILC) are lymphocytes lacking rearranged antigen receptors such as those expressed by T and B cells. ILC are important effector and regulatory cells of the innate immune system, controlling lymphoid organogenesis, tissue inflammation, and homeostasis. The family of ILC consists of cytotoxic NK cells and the more recently described noncytotoxic group 1, 2, and 3 ILC. The classification of noncytotoxic ILC-in many aspects-mirrors that of T helper cells, which is based on the expression of master transcription factors and signature cytokines specific for each subset. The IL-22 producing RORγt(+) ILC3 subset was recently found to be critical in the prevention of intestinal graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT) via strengthening the intestinal mucosal barrier. In this review, we summarize the current view of the immunological functions of human noncytotoxic ILC subsets and discuss the potentially beneficial features of IL-22 producing ILC3 in improving allo-HCT efficacy by attenuating susceptibility to GVHD. In addition, we explore the possibility of other ILC subsets playing a role in GVHD. © 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.
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Group 2 Innate Lymphoid Cells Exhibit a Dynamic Phenotype in Allergic Airway Inflammation
Li, Bobby W. S.; Stadhouders, Ralph; de Bruijn, Marjolein J. W.; Lukkes, Melanie; Beerens, Dior M. J. M.; Brem, Maarten D.; KleinJan, Alex; Bergen, Ingrid; Vroman, Heleen; Kool, Mirjam; van IJcken, Wilfred F. J.; Rao, Tata Nageswara; Fehling, Hans Jörg; Hendriks, Rudi W.
2017-01-01
Group 2 innate lymphoid cells (ILC2) are implicated in allergic asthma as an early innate source of the type 2 cytokines IL-5 and IL-13. However, their induction in house dust mite (HDM)-mediated airway inflammation additionally requires T cell activation. It is currently unknown whether phenotypic differences exist between ILC2s that are activated in a T cell-dependent or T cell-independent fashion. Here, we compared ILC2s in IL-33- and HDM-driven airway inflammation. Using flow cytometry, we found that surface expression levels of various markers frequently used to identify ILC2s were dependent on their mode of activation, highly variable over time, and differed between tissue compartments, including bronchoalveolar lavage (BAL) fluid, lung, draining lymph nodes, and spleen. Whereas in vivo IL-33-activated BAL fluid ILC2s exhibited an almost uniform CD25+CD127+T1/ST2+ICOS+KLRG1+ phenotype, at a comparable time point after HDM exposure BAL fluid ILC2s had a very heterogeneous surface marker phenotype. A major fraction of HDM-activated ILC2s were CD25lowCD127+T1/ST2low ICOSlowKLRG1low, but nevertheless had the capacity to produce large amounts of type 2 cytokines. HDM-activated CD25low ILC2s in BAL fluid and lung rapidly reverted to CD25high ILC2s upon in vivo stimulation with IL-33. Genome-wide transcriptional profiling of BAL ILC2s revealed ~1,600 differentially expressed genes: HDM-stimulated ILC2s specifically expressed genes involved in the regulation of adaptive immunity through B and T cell interactions, whereas IL-33-stimulated ILC2s expressed high levels of proliferation-related and cytokine genes. In both airway inflammation models ILC2s were present in the lung submucosa close to epithelial cells, as identified by confocal microscopy. In chronic HDM-driven airway inflammation ILC2s were also found inside organized cellular infiltrates near T cells. Collectively, our findings show that ILC2s are phenotypically more heterogeneous than previously thought, whereby their surface marker and gene expression profile are highly dynamic. PMID:29250067
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Villanova, Federica; Flutter, Barry; Tosi, Isabella; Grys, Katarzyna; Sreeneebus, Hemawtee; Perera, Gayathri K; Chapman, Anna; Smith, Catherine H; Di Meglio, Paola; Nestle, Frank O
2014-04-01
Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterize the ILCs in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in the skin and blood of normal individuals and psoriasis patients are CD3-negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in the blood of psoriasis patients compared with healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen, indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILCs in the skin compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared with normal skin. A detailed time course of a psoriasis patient treated with anti-tumor necrosis factor showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis.
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Innate lymphoid cells in tissue homeostasis and diseases
Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva
2017-01-01
Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver. PMID:28878863
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Down-regulation of E protein activity augments an ILC2 differentiation program in the thymus
USDA-ARS?s Scientific Manuscript database
Innate lymphoid cells (ILCs) are important regulators in various immune responses. Current paradigm states that all newly-made ILCs originate from common lymphoid progenitors (CLP) in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation. Une...
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Zhu, Jinfang
2015-01-01
Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these “type 2 immune response-related” cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses. In this review, I will focus on the signaling pathways and key molecules that determine the differentiation of naïve CD4 T cells into Th2 cells, and how the expression of Th2 cytokines, especially IL-4 and IL-13, is regulated in Th2 cells. The similarities and differences in the differentiation of Th2 cells, IL-4-producing T follicular helper (Tfh) cells and ILC2s as well as their relationships will also be discussed. PMID:26044597
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NASA Astrophysics Data System (ADS)
Sun, Shu-Ting; Li, Xiao-Dong; Zhong, Ren-Xin
2017-10-01
For nonlinear switched discrete-time systems with input constraints, this paper presents an open-closed-loop iterative learning control (ILC) approach, which includes a feedforward ILC part and a feedback control part. Under a given switching rule, the mathematical induction is used to prove the convergence of ILC tracking error in each subsystem. It is demonstrated that the convergence of ILC tracking error is dependent on the feedforward control gain, but the feedback control can speed up the convergence process of ILC by a suitable selection of feedback control gain. A switched freeway traffic system is used to illustrate the effectiveness of the proposed ILC law.
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Innate lymphoid cells in asthma: Will they take your breath away?
Kim, Hye Young; Umetsu, Dale. T.; Dekruyff, Rosemarie H.
2016-01-01
Asthma is a complex and heterogeneous disease that is characterized by airway hyperreactivity (AHR) and airway inflammation. Although asthma was long thought to be driven by allergen-reactive Th2 cells, it has recently become clear that the pathogenesis of asthma is more complicated and associated with multiple pathways and cell types. A very exciting recent development was the discovery of innate lymphoid cells (ILCs) as key players in the pathogenesis of asthma. ILCs do not express antigen receptors but react promptly to “danger signals” from inflamed tissue and produce an array of cytokines that direct the ensuing immune response. The roles of ILCs may differ in distinct asthma phenotypes. ILC2s may be critical for initiation of adaptive immune responses in inhaled allergen-driven AHR, but may also function independently of adaptive immunity, mediating influenza-induced AHR. ILC2s also contribute to resolution of lung inflammation through their production of amphiregulin. Obesity-induced asthma, is associated with expansion of IL-17A-producing ILC3s in the lungs. Furthermore, ILCs may also contribute to steroid-resistant asthma. Although the precise roles of ILCs in different types of asthma are still under investigation, it is clear that inhibition of ILC function represents a potential target that could provide novel treatments for asthma. PMID:26891006
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Klein Wolterink, Roel G. J.; Serafini, Nicolas; van Nimwegen, Menno; Vosshenrich, Christian A. J.; de Bruijn, Marjolein J. W.; Fonseca Pereira, Diogo; Veiga Fernandes, Henrique; Hendriks, Rudi W.; Di Santo, James P.
2013-01-01
Group 2 innate lymphoid cells (ILC2s; also called nuocytes, innate helper cells, or natural helper cells) provide protective immunity during helminth infection and play an important role in influenza-induced and allergic airway hyperreactivity. Whereas the transcription factor GATA binding protein 3 (Gata3) is important for the production of IL-5 and -13 by ILC2s in response to IL-33 or -25 stimulation, it is not known whether Gata3 is required for ILC2 development from hematopoietic stem cells. Here, we show that chimeric mice generated with Gata3-deficient fetal liver hematopoietic stem cells fail to develop systemically dispersed ILC2s. In these chimeric mice, in vivo administration of IL-33 or -25 fails to expand ILC2 numbers or to induce characteristic ILC2-dependent IL-5 or -13 production. Moreover, cell-intrinsic Gata3 expression is required for ILC2 development in vitro and in vivo. Using mutant and transgenic mice in which Gata3 gene copy number is altered, we show that ILC2 generation from common lymphoid progenitors, as well as ILC2 homeostasis and cytokine production, is regulated by Gata3 expression levels in a dose-dependent fashion. Collectively, these results identify Gata3 as a critical early regulator of ILC2 development, thereby extending the paradigm of Gata3-dependent control of type 2 immunity to include both innate and adaptive lymphocytes. PMID:23733962
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NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation.
Vacca, Paola; Montaldo, Elisa; Croxatto, Daniele; Moretta, Francesca; Bertaina, Alice; Vitale, Chiara; Locatelli, Franco; Mingari, Maria Cristina; Moretta, Lorenzo
2016-01-01
Natural killer (NK) cells play a major role in the T-cell depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILCs). At variance with NK cells, the other ILC populations (ILC1/2/3) are non-cytolytic, while they secrete different patterns of cytokines. ILCs provide host defenses against viruses, bacteria, and parasites, drive lymphoid organogenesis, and contribute to tissue remodeling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD) but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defenses that are reconstituted more rapidly than the adaptive ones. In this context, ILCs may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodeling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILCs. Of note, CD34(+) cells isolated from different sources of HSC may differentiate in vitro toward various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g., IL-1β) may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.
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Group 2 ILCs: A way of enhancing immune protection against human helminths?
Nausch, N; Mutapi, F
2018-02-01
Group 2 innate lymphoid cells (ILC2s) play crucial roles in type 2 immune responses associated with allergic and autoimmune diseases, viral and helminth infections and tissue homoeostasis. Experimental models show that in helminth infections ILC2s provide an early source of type 2 cytokines and therefore are essential for the induction of potentially protective type 2 responses. Much of our knowledge of ILC2s in helminth infections has come from experimental mouse models with very few studies analysing ILC2s in natural human infections. In attempts to harness knowledge from paradigms of the development of protective immunity in human helminth infections for vaccine development, the role of ILC2 cells could be pivotal. So far, potential vaccines against human helminth infections have failed to provide effective protection when evaluated in human studies. In addition to appropriate antigen selection, it is apparent that more detailed knowledge on mechanisms of induction and maintenance of protective immune responses is required. Therefore, there is need to understand how ILC2 cells induce type 2 responses and subsequently support the development of a protective immune response in the context of immunizations. Within this review, we summarize the current knowledge of the biology of ILC2s, discuss the importance of ILC2s in human helminth infections and explore how ILC2 responses could be boosted to efficiently induce protective immunity. © 2017 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.
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Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome.
Arpino, Grazia; Bardou, Valerie J; Clark, Gary M; Elledge, Richard M
2004-01-01
Invasive lobular carcinoma (ILC) comprises approximately 10% of breast cancers and appears to have a distinct biology. Because it is less common than infiltrating ductal carcinoma (IDC), few data have been reported that address the biologic features of ILC in the context of their clinical outcome. In the present study we undertook an extensive comparison of ILC and IDC using a large database to provide a more complete and reliable assessment of their biologic phenotypes and clinical behaviors. The clinical and biological features of 4140 patients with ILC were compared with those of 45,169 patients with IDC (not otherwise specified). The median follow-up period was 87 months. In comparison with IDC, ILC was significantly more likely to occur in older patients, to be larger in size, to be estrogen and progesterone receptor positive, to have lower S-phase fraction, to be diploid, and to be HER-2, p53, and epidermal growth factor receptor negative. It was more common for ILC than for IDC to metastasize to the gastrointestinal tract and ovary. The incidence of contralateral breast cancer was higher for ILC patients than for IDC patients (20.9% versus 11.2%; P < 0.0001). Breast preservation was modestly less frequent in ILC patients than in IDC patients. The 5-year disease-free survival was 85.7% for ILC and 83.5% for IDC (P = 0.13). The 5-year overall survival was 85.6% for ILC and 84.1% for IDC (P = 0.64). Despite the fact that the biologic phenotype of ILC is quite favorable, these patients do not have better clinical outcomes than do patients with IDC. At present, management decisions should be based on individual patient and tumor biologic characteristics, and not on lobular histology.
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Ishimori, Ayako; Harada, Norihiro; Chiba, Asako; Harada, Sonoko; Matsuno, Kei; Makino, Fumihiko; Ito, Jun; Ohta, Shoichiro; Ono, Junya; Atsuta, Ryo; Izuhara, Kenji; Takahashi, Kazuhisa; Miyake, Sachiko
2017-04-01
A variety of innate subsets of lymphoid cells such as natural killer (NK) cells, several populations of innate lymphoid cells (ILCs), and mucosal-associated invariant T (MAIT) cells as innate-like T lymphocytes are involved in asthma and may have important effector functions in asthmatic immune responses. In the present study, we investigated whether NK cells, ILCs, and MAIT cells in the peripheral blood of patients with asthma would be associated with clinical asthma parameters. We recruited 75 adult patients with mild to severe asthma. The peripheral blood mononuclear cells in peripheral venous blood samples from the patients were purified and stained with different combinations of appropriate antibodies. The cells were analyzed by flow cytometry. The percentage of activated (i.e., CD69 + ) NK cells in the total NK cell population was negatively correlated with FEV 1 % which is calculated by the forced expiratory volume in 1 s (FEV 1 )/the forced vital capacity (FVC). The percentages of CD69 + ILC1s and ILC2s were negatively correlated with FEV 1 % and %FEV 1 . The percentage of CD69 + ILC3s was positively correlated with BMI, and the percentage of CD69 + MAIT cells was negatively correlated with FEV 1 %. Moreover, the percentage of CD69 + NK cells, ILC1s, ILC2s, ILC3s, and MAIT cells were positively correlated with each other. For the first time, our data showed that activated NK cells, ILC1s, ILC2s, ILC3s, and MAIT cells were positively correlated with each other and may be associated with airflow limitation in patients with asthma. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.
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Rigas, Diamanda; Lewis, Gavin; Aron, Jennifer L; Wang, Bowen; Banie, Homayon; Sankaranarayanan, Ishwarya; Galle-Treger, Lauriane; Maazi, Hadi; Lo, Richard; Freeman, Gordon J; Sharpe, Arlene H; Soroosh, Pejman; Akbari, Omid
2017-05-01
Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function. ILC2s and Treg cells were evaluated by using in vitro suppression assays, cell-contact assays, and gene expression panels. Also, human ILC2s and Treg cells were adoptively transferred into NOD SCID γC-deficient mice, which were given isotype or anti-inducible T-cell costimulator ligand (ICOSL) antibodies and then challenged with IL-33 and assessed for airway hyperreactivity. We show that induced Treg cells, but not natural Treg cells, effectively suppress the production of the ILC2-driven proinflammatory cytokines IL-5 and IL-13 both in vitro and in vivo. Mechanistically, our data reveal the necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated ILC2 suppression alongside the suppressive cytokines TGF-β and IL-10. Using a translational approach, we then demonstrate that human induced Treg cells suppress syngeneic human ILC2s through ICOSL to control airway inflammation in a humanized ILC2 mouse model. These findings suggest that peripheral expansion of induced Treg cells can serve as a promising therapeutic target against ILC2-dependent asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Komlósi, Zsolt I; Kovács, Nóra; van de Veen, Willem; Kirsch, Anna Isabella; Fahrner, Heinz Benedikt; Wawrzyniak, Marcin; Rebane, Ana; Stanic, Barbara; Palomares, Oscar; Rückert, Beate; Menz, Günter; Akdis, Mübeccel; Losonczy, György; Akdis, Cezmi A
2017-09-20
Type 3 innate lymphoid cells (ILC3s) are involved in maintenance of mucosal homeostasis; however, their role in immunoregulation has been unknown. Immature transitional regulatory B (itBreg) cells are innate-like B cells with immunosuppressive properties, and the in vivo mechanisms by which they are induced have not been fully clarified. We aimed to investigate the ILC3-B-cell interaction that probably takes place in human tonsils. ILC3s were isolated from peripheral blood and palatine tonsils, expanded, and cocultured with naive B cells. Tonsillar ILC3s and regulatory B cells were visualized with immunofluorescence histology. ILC3 frequencies were measured in tonsil tissue of allergic and nonallergic patients and in peripheral blood of allergic asthmatic patients and healthy control subjects. A mutually beneficial relationship was revealed between ILC3s and B cells: ILC3s induced IL-15 production in B cells through B cell-activating factor receptor, whereas IL-15, a potent growth factor for ILC3s, induced CD40 ligand (CD40L) expression on circulating and tonsillar ILC3s. IL-15-activated CD40L + ILC3s helped B-cell survival, proliferation, and differentiation of IL-10-secreting, PD-L1-expressing functional itBreg cells in a CD40L- and B cell-activating factor receptor-dependent manner. ILC3s and regulatory B cells were in close connection with each other in palatine tonsils. ILC3 frequency was reduced in tonsil tissue of allergic patients and in peripheral blood of allergic asthmatic patients. Human CD40L + ILC3s provide innate B-cell help and are involved in an innate immunoregulatory mechanism through induction of itBreg cell differentiation, which takes place in palatine tonsils in vivo. This mechanism, which can contribute to maintenance of immune tolerance, becomes insufficient in allergic diseases. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Innate lymphoid cells in the initiation, regulation and resolution of inflammation
Sonnenberg, Gregory F.; Artis, David
2016-01-01
A previously unappreciated cell type of the innate immune system, termed innate lymphoid cells (ILCs), has been characterized in mice and humans, and found to profoundly influence the induction, regulation and resolution of inflammation. ILCs play an important role in these processes in murine models of infection, inflammatory disease and tissue repair. Further, disease association studies in defined patient populations have identified significant alterations in ILC responses, suggesting a potential role for these cell populations in human health and disease. In this review, we discuss the emerging family of ILCs, the role of ILCs in inflammation, and how current or novel therapeutic strategies could be employed to selectively modulate ILC responses and limit chronic inflammatory diseases in patients. PMID:26121198
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Regulatory T cells and type 2 innate lymphoid cell-dependent asthma.
Aron, J L; Akbari, O
2017-08-01
Group 2 innate lymphoid cells (ILC2s) are a recently identified group of cells with the potent capability to produce Th2-type cytokines such as interleukin (IL)-5 and IL-13. Several studies suggest that ILC2s play an important role in the development of allergic diseases and asthma. Activation of pulmonary ILC2s in murine models lacking T and B cells induces eosinophilia and airway hyper-reactivity (AHR), which are cardinal features of asthma. More importantly, numerous recent studies have highlighted the role of ILC2s in asthma persistence and exacerbation among human subjects, and thus, regulation of pulmonary ILC2s is a major area of investigation aimed at curbing allergic lung inflammation and exacerbation. Emerging evidence reveals that a group of regulatory T cells, induced Tregs (iTregs), effectively suppress the production of ILC2-driven, pro-inflammatory cytokines IL-5 and IL-13. The inhibitory effects of iTregs are blocked by preventing direct cellular contact or by inhibiting the ICOS-ICOS-ligand (ICOSL) pathway, suggesting that both direct contact and ICOS-ICOSL interaction are important in the regulation of ILC2 function. Also, cytokines such as IL-10 and TGF-β1 significantly reduce cytokine secretion by ILC2s. Altogether, these new findings uncover iTregs as potent regulators of ILC2 activation and implicate their utility as a therapeutic approach for the treatment of ILC2-mediated allergic asthma and respiratory disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Paclik, Daniela; Stehle, Christina; Lahmann, Annette; Hutloff, Andreas; Romagnani, Chiara
2015-10-01
Group 2 innate lymphoid cells (ILC2s) are innate effectors playing an important role in the defense against helminthic infections and in the pathogenesis of allergic inflammation. Cytokines have been identified as the major stimuli driving ILC2 activation and expansion. Conversely, it is unclear whether costimulatory molecules contribute to regulation of ILC2 functions. ILC2s display high expression of inducible T-cell costimulator (ICOS), which belongs to the CD28 superfamily, and which has been shown to control late effector T-cell functions, and is of utmost importance for the humoral immune response. However, the biological function of ICOS expression on ILC2s is unknown. Here, we show that ICOS signaling in mice regulates ILC2 homeostasis independently of T cells and B cells, by promoting proliferation and accumulation of mature ILC2s in lung and intestine. In a model of IL-33-induced airway inflammation, ICOS controls ILC2 activation and eosinophil infiltration in the lung. Our data identify a role of ICOS in innate immunity and indicate that not only cytokines, but also costimulatory pathways such as those involving ICOS, can contribute to regulate the ILC2 pool. Thus, ICOS costimulation blockade, which is currently under clinical evaluation for inhibiting the humoral immune response, could also target innate inflammatory circuits. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Establishment and function of tissue-resident innate lymphoid cells in the skin.
Yang, Jie; Zhao, Luming; Xu, Ming; Xiong, Na
2017-07-01
Innate lymphoid cells (ILCs) are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.
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Pathological and therapeutic roles of innate lymphoid cells in diverse diseases.
Kim, Jisu; Kim, Geon; Min, Hyeyoung
2017-11-01
Innate lymphoid cells (ILCs) are a recently defined type of innate-immunity cells that belong to the lymphoid lineage and have lymphoid morphology but do not express an antigen-specific B cell or T-cell receptor. ILCs regulate immune functions prior to the formation of adaptive immunity and exert effector functions through a cytokine release. ILCs have been classified into three groups according to the transcription factors that regulate their development and function and the effector cytokines they produce. Of note, ILCs resemble T helper (Th) cells, such as Th1, Th2, and Th17 cells, and show a similar dependence on transcription factors and distinct cytokine production. Despite their short history in immunology, ILCs have received much attention, and numerous studies have revealed biological functions of ILCs including host defense against pathogens, inflammation, tissue repair, and metabolic homeostasis. Here, we describe recent findings about the roles of ILCs in the pathogenesis of various diseases and potential therapeutic targets.
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Migration and Tissue Tropism of Innate Lymphoid Cells
Kim, Chang H.; Hashimoto-Hill, Seika; Kim, Myunghoo
2016-01-01
Innate lymphoid cell (ILCs) subsets differentially populate various barrier and non-barrier tissues, where they play important roles in tissue homeostasis and tissue-specific responses to pathogen attack. Recent findings have provided insight into the molecular mechanisms that guide ILC migration into peripheral tissues, revealing common features among different ILC subsets as well as important distinctions. Recent studies have also highlighted the impact of tissue-specific cues on ILC migration, and the importance of the local immunological milieu. We review these findings here and discuss how the migratory patterns and tissue tropism of different ILC subsets relate to the development and differentiation of these cells, and to ILC-mediated tissue-specific regulation of innate and adaptive immune responses. In this context we outline open questions and important areas of future research. PMID:26708278
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ILC2 memory: Recollection of previous activation.
Martinez-Gonzalez, Itziar; Ghaedi, Maryam; Steer, Catherine A; Mathä, Laura; Vivier, Eric; Takei, Fumio
2018-05-01
Immunological memory, traditionally thought to belong to T and B cells, has now been extended to innate lymphocytes, including NK cells and ILC2s, myeloid cells such as macrophages, also termed "trained immunity" and more recently to epithelial stem cells. In this review, we discuss the mechanisms underlying memory generation on ILC2s and speculate about their potential role in human allergic diseases, such as asthma. Moreover, we examine the relevance of the spontaneous ILC2 activation in the lung during the neonatal period in order to efficiently respond to stimuli later in life. These "training" of neonatal ILC2s may have an impact on the generation of memory ILC2s in the adulthood. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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O'Sullivan, Timothy E; Sun, Joseph C
2018-01-01
Innate lymphoid cells are a heterogeneous family of tissue-resident and circulating lymphocytes that play an important role in host immunity. Recent studies have profiled the developmental pathways of mature ILCs and have identified ILC progenitors in the bone marrow through the use of transcription factor reporter mice. Here we describe methodology to identify and isolate bone marrow CHILP and ILC2 progenitor (ILC2P) cells based on cell surface marker expression for adoptive transfer into lymphopenic mice to track the fate of developing ILCs.
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Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.
Everaere, Laetitia; Ait-Yahia, Saliha; Molendi-Coste, Olivier; Vorng, Han; Quemener, Sandrine; LeVu, Pauline; Fleury, Sebastien; Bouchaert, Emmanuel; Fan, Ying; Duez, Catherine; de Nadai, Patricia; Staels, Bart; Dombrowicz, David; Tsicopoulos, Anne
2016-11-01
Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR). We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)-induced obesity. Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs. HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and T H 2 and T H 17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including T H 2 and T H 17 infiltration. These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Innate lymphoid cells: a paradigm for low SSI in cleft lip repair.
Simmerman, Erika; Qin, Xu; Marshall, Brendan; Perry, Libby; Cai, Lei; Wang, Tailing; Yu, Jack; Akbari, Omid; Baban, Babak
2016-10-01
Cleft lip and palate reconstructions demonstrate significantly lower surgical site infection rates compared with clean-contaminated cases, prompting investigation into the pathophysiology causing this discrepancy. Recent studies have identified a new group of innate lymphocytes called innate lymphoid cells (ILCs), located in barrier surfaces of the skin, airways, and intestine. Our objectives were to explore for the first time the presence of ILCs in the vermillion of neonates and young children undergoing cleft lip reconstruction and characterize their composition by measuring the three classes of ILCs. Lip tissue samples were collected from 13 subjects undergoing vermillion resection during cleft lip reconstructive surgery. Preparative, transmission electron microscopy, and analytical flow cytometry were performed. The functionality of ILCs was tested in terms of their capacity to produce type 1 (IFN-γ/TNF-α), type 2 (IL-5/IL-13), and type 3 (IL-17/IL-22) cytokines. Data were analyzed using Student t test or the analysis of variance to establish significance (P < 0.05) among groups for all other data. All three classes of ILCs were detected and visualized in the tissue samples. In all samples, the level of ILC2 subset was significantly higher than the other two ILC subsets (P < 0.01), followed by the ILC1 subset, which was present in significantly higher levels than the ILC3 subset (P < 0.05). Our data place ILCs for the first time in the interface of oral mucosal immunity, tissue microenvironment, and homeostasis during and after tissue development, possibly explaining lower infection rates in cleft lip or palate reconstructions. Copyright © 2016 Elsevier Inc. All rights reserved.
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Chikman, Bar; Davidson, Tima; Kais, Hasan; Jeroukhimov, Igor; Leshno, Ari; Sandbank, Judith; Halevy, Ariel; Lavy, Ron
2016-01-01
CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, <50 and ≥50 years. One thousand one hundred and sixty-seven patients with IDC and ILC entered the study. A family history of malignancies was reported in 21.6 % of patients with IDC as opposed to 37.8 % of patients with ILC (P < 0.001). A history of gastric cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P < 0.008. A family history of breast cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.
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Düster, Mathis; Becker, Martina; Gnirck, Ann-Christin; Wunderlich, Malte; Panzer, Ulf; Turner, Jan-Eric
2018-04-19
Innate lymphoid cells (ILCs) are important regulators of the immune response and play a crucial role in the restoration of tissue homeostasis after injury. GATA-3 + IL-13- and IL-5-producing group 2 innate lymphoid cells (ILC2s) have been shown to promote tissue repair in barrier organs, but despite extensive research on ILCs in the recent years, their potential role in autoimmune diseases is still incompletely understood. In the present study, we investigate the role of ILC2s in the MRL/MpJ-Fas lpr (MRL-lpr) mouse model for severe organ manifestation of systemic lupus erythematosus (SLE). We show that in these MRL-lpr mice, progression of lupus nephritis is accompanied with a reduction of ILC2 abundance in the inflamed renal tissue. Proliferation/survival and cytokine production of kidney-residing ILC2s was suppressed by IFN-γ and, to a lesser extent, by IL-27 which were produced by activated T cells and myeloid cells in the nephritic kidney, respectively. Most importantly, restoration of ILC2 numbers by IL-33-mediated expansion ameliorated lupus nephritis and prevented mortality in MRL-lpr mice. In summary, we show here that development of SLE-like kidney inflammation leads to a downregulation of the renal ILC2 response and identify an ILC2-expanding therapy as a promising treatment approach for autoimmune diseases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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IL-9-Producing Mast Cell Precursors and Food Allergy
2016-10-01
that Stat6-/- BM progenitors in sensitized wild type recipients that were competent in GFP- CD4+ST2+TH2 and ILC2s ( innate lymphoid cells ) generation, and...report demonstrated that type 2 innate lymphoid cells (ILC2s) lack cell lineage markers and have the potential to pro- duce IL-9 (Wilhelm et al., 2011...Fujii, H., and Koyasu, S. (2010). Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells . Nature 463, 540–544
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Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells
Mortha, Arthur; Burrows, Kyle
2018-01-01
Innate lymphoid cells (ILCs) are an essential component of the innate immune system in vertebrates. They are developmentally rooted in the lymphoid lineage and can diverge into at least three transcriptionally distinct lineages. ILCs seed both lymphoid and non-lymphoid tissues and are locally self-maintained in tissue-resident pools. Tissue-resident ILCs execute important effector functions making them key regulator in tissue homeostasis, repair, remodeling, microbial defense, and anti-tumor immunity. Similar to T lymphocytes, ILCs possess only few sensory elements for the recognition of non-self and thus depend on extrinsic cellular sensory elements residing within the tissue. Myeloid cells, including mononuclear phagocytes (MNPs), are key sentinels of the tissue and are able to translate environmental cues into an effector profile that instructs lymphocyte responses. The adaptation of myeloid cells to the tissue state thus influences the effector program of ILCs and serves as an example of how environmental signals are integrated into the function of ILCs via a tissue-resident immune cell cross talks. This review summarizes our current knowledge on the role of myeloid cells in regulating ILC functions and discusses how feedback communication between ILCs and myeloid cells contribute to stabilize immune homeostasis in order to maintain the healthy state of an organ. PMID:29467768
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Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells.
Mortha, Arthur; Burrows, Kyle
2018-01-01
Innate lymphoid cells (ILCs) are an essential component of the innate immune system in vertebrates. They are developmentally rooted in the lymphoid lineage and can diverge into at least three transcriptionally distinct lineages. ILCs seed both lymphoid and non-lymphoid tissues and are locally self-maintained in tissue-resident pools. Tissue-resident ILCs execute important effector functions making them key regulator in tissue homeostasis, repair, remodeling, microbial defense, and anti-tumor immunity. Similar to T lymphocytes, ILCs possess only few sensory elements for the recognition of non-self and thus depend on extrinsic cellular sensory elements residing within the tissue. Myeloid cells, including mononuclear phagocytes (MNPs), are key sentinels of the tissue and are able to translate environmental cues into an effector profile that instructs lymphocyte responses. The adaptation of myeloid cells to the tissue state thus influences the effector program of ILCs and serves as an example of how environmental signals are integrated into the function of ILCs via a tissue-resident immune cell cross talks. This review summarizes our current knowledge on the role of myeloid cells in regulating ILC functions and discusses how feedback communication between ILCs and myeloid cells contribute to stabilize immune homeostasis in order to maintain the healthy state of an organ.
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Chu, Coco; Moriyama, Saya; Li, Zhi; Zhou, Lei; Flamar, Anne-Laure; Klose, Christoph S N; Moeller, Jesper B; Putzel, Gregory G; Withers, David R; Sonnenberg, Gregory F; Artis, David
2018-06-26
The intestinal tract is constantly exposed to various stimuli. Group 3 innate lymphoid cells (ILC3s) reside in lymphoid organs and in the intestinal tract and are required for immunity to enteric bacterial infection. However, the mechanisms that regulate the ILC3s in vivo remain incompletely defined. Here, we show that GPR183, a chemotactic receptor expressed on murine and human ILC3s, regulates ILC3 migration toward its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) in vitro, and GPR183 deficiency in vivo leads to a disorganized distribution of ILC3s in mesenteric lymph nodes and decreased ILC3 accumulation in the intestine. GPR183 functions intrinsically in ILC3s, and GPR183-deficient mice are more susceptible to enteric bacterial infection. Together, these results reveal a role for the GPR183-7α,25-OHC pathway in regulating the accumulation, distribution, and anti-microbial and tissue-protective functions of ILC3s and define a critical role for this pathway in promoting innate immunity to enteric bacterial infection. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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Role of innate lymphoid cells in obesity and metabolic disease
Saetang, Jirakrit; Sangkhathat, Surasak
2018-01-01
The immune system has previously been demonstrated to be associated with the pathophysiological development of metabolic abnormalities. However, the mechanisms linking immunity to metabolic disease remain to be fully elucidated. It has previously been suggested that innate lymphoid cells (ILCs) may be involved in the progression of numerous types of metabolic diseases as these cells act as suppressors and promoters for obesity and associated conditions, and are particularly involved in adipose tissue inflammation, which is a major feature of metabolic imbalance. Group 2 ILCs (ILC2s) have been revealed as anti-obese immune regulators by secreting anti-inflammatory cytokines and promoting the polarization of M2 macrophages, whereas group 1 ILCs (ILC1s), including natural killer cells, may promote adipose tissue inflammation via production of interferon-γ, which in turn polarizes macrophages toward the M1 type. The majority of studies to date have demonstrated the pathological association between ILCs and obesity in the context of adipose tissue inflammation, whereas the roles of ILCs in other organs which participate in obesity development have not been fully characterized. Therefore, identifying the roles of all types of ILCs as central components mediating obesity-associated inflammation, is of primary concern, and may lead to the discovery of novel preventative and therapeutic interventions. PMID:29138853
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TSLP elicits IL-33–independent innate lymphoid cell responses to promote skin inflammation
Kim, Brian S.; Siracusa, Mark C.; Saenz, Steven A.; Noti, Mario; Monticelli, Laurel A.; Sonnenberg, Gregory F.; Hepworth, Matthew R.; Van Voorhees, Abby S.; Comeau, Michael R.
2013-01-01
Innate lymphoid cells (ILCs) are a recently identified family of heterogeneous immune cells that can be divided into three groups based on their differential developmental requirements and expression of effector cytokines. Among these, group 2 ILCs produce the type 2 cytokines IL-5 and IL-13 and promote type 2 inflammation in the lung and intestine. However, whether group 2 ILCs reside in the skin and contribute to skin inflammation has not been characterized. Here, we identify for the first time a population of skin-resident group 2 ILCs present in healthy human skin that are enriched in lesional human skin from atopic dermatitis (AD) patients. Group 2 ILCs were also found in normal murine skin and were critical for the development of inflammation in a murine model of AD-like disease. Remarkably, in contrast to group 2 ILC responses in the intestine and lung, which are critically regulated by IL-33 and IL-25, ILC responses in the skin and skin-draining lymph nodes were independent of these canonical cytokines but were critically dependent on thymic stromal lymphopoietin (TSLP). Collectively, these results demonstrate an essential role for IL-33– and IL-25–independent group 2 ILCs in promoting skin inflammation. PMID:23363980
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β2-adrenergic receptor-mediated negative regulation of group 2 innate lymphoid cell responses.
Moriyama, Saya; Brestoff, Jonathan R; Flamar, Anne-Laure; Moeller, Jesper B; Klose, Christoph S N; Rankin, Lucille C; Yudanin, Naomi A; Monticelli, Laurel A; Putzel, Gregory Garbès; Rodewald, Hans-Reimer; Artis, David
2018-03-02
The type 2 inflammatory response is induced by various environmental and infectious stimuli. Although recent studies identified group 2 innate lymphoid cells (ILC2s) as potent sources of type 2 cytokines, the molecular pathways controlling ILC2 responses are incompletely defined. Here we demonstrate that murine ILC2s express the β 2 -adrenergic receptor (β 2 AR) and colocalize with adrenergic neurons in the intestine. β 2 AR deficiency resulted in exaggerated ILC2 responses and type 2 inflammation in intestinal and lung tissues. Conversely, β 2 AR agonist treatment was associated with impaired ILC2 responses and reduced inflammation in vivo. Mechanistically, we demonstrate that the β 2 AR pathway is a cell-intrinsic negative regulator of ILC2 responses through inhibition of cell proliferation and effector function. Collectively, these data provide the first evidence of a neuronal-derived regulatory circuit that limits ILC2-dependent type 2 inflammation. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Geng, R. L.; Golden, B. A.; Kushnick, P.
2011-07-01
One of the major goals of ILC SRF cavity R&D is to develop industrial capabilities of cavity manufacture and processing in all three regions. In the past several years, Jefferson Lab, in collaboration with Fermi National Accelerator Laboratory, has processed and tested all the 9-cell cavities of the first batch (4 cavities) and second batch (6 cavities) production cavities manufactured by Advanced Energy Systems Inc. (AES). Over the course, close information feedback was maintained, resulting in changes in fabrication and processing procedures. A light buffered chemical polishing was introduced, removing the weld splatters that could not be effectively removed bymore » heavy EP alone. An 800 Celsius 2 hour vacuum furnace heat treatment procedure replaced the original 600 Celsius 10 hour procedure. Four out of the six 9-cell cavities of the second production bath achieved a gradient of 36-41 MV/m at a Q0 of more than 8E9 at 35 MV/m. This result validated AES as the first ''ILC certified'' industrial vendor in the US for ILC cavity manufacture.« less
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Verma, Mukesh; Liu, Sucai; Michalec, Lidia; Sripada, Anand; Gorska, Magdalena M; Alam, Rafeul
2017-11-10
IL-33 plays an important role in the development of experimental asthma. We sought to study the role of the IL-33 receptor suppressor of tumorigenicity 2 (ST2) in the persistence of asthma in a mouse model. We studied allergen-induced experimental asthma in ST2 knockout (KO) and wild-type control mice. We measured airway hyperresponsiveness by using flexiVent; inflammatory indices by using ELISA, histology, and real-time PCR; and type 2 innate lymphoid cells (ILC2s) in lung single-cell preparations by using flow cytometry. Airway hyperresponsiveness was increased in allergen-treated ST2 KO mice and comparable with that in allergen-treated wild-type control mice. Peribronchial and perivascular inflammation and mucus production were largely similar in both groups. Persistence of experimental asthma in ST2 KO mice was associated with an increase in levels of thymic stromal lymphopoietin (TSLP), IL-9, and IL-13, but not IL-5, in bronchoalveolar lavage fluid. Expectedly, ST2 deletion caused a reduction in IL-13 + CD4 T cells, forkhead box P3-positive regulatory T cells, and IL-5 + ILC2s. Unexpectedly, ST2 deletion led to an overall increase in innate lymphoid cells (CD45 + lin - CD25 + cells) and IL-13 + ILC2s, emergence of a TSLP receptor-positive IL-9 + ILC2 population, and an increase in intraepithelial mast cell numbers in the lung. An anti-TSLP antibody abrogated airway hyperresponsiveness, inflammation, and mucus production in allergen-treated ST2 KO mice. It also caused a reduction in innate lymphoid cell, ILC2, and IL-9 + and IL-13 + ILC2 numbers in the lung. Genetic deletion of the IL-33 receptor paradoxically increases TSLP production, which stimulates the emergence of IL-9 + and IL-13 + ILC2s and mast cells and leads to development of chronic experimental asthma. An anti-TSLP antibody abrogates all pathologic features of asthma in this model. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Yang, Jie; Hu, Shaomin; Zhao, Luming; Kaplan, Daniel H.; Perdew, Gary H.; Xiong, Na
2016-01-01
Innate lymphoid cells (ILCs) are preferentially localized into barrier tissues where they function in tissue protection but can also contribute to inflammatory diseases. The mechanisms regulating the establishment of ILCs in barrier tissues are poorly understood. Here we show that under steady-state conditions ILCs in skin-draining lymph nodes (sLNs) were continuously activated to acquire regulatory properties and high expression of the chemokine receptor CCR10 for localization into the skin. CCR10+ ILCs promoted the homeostasis of skin-resident T cells and reciprocally, their establishment in the skin required T cell-regulated homeostatic environments. Foxn1-expressing CD207+ dendritic cells were required for the proper generation of CCR10+ ILCs. These observations reveal mechanisms underlying the specific programming and priming of skin-homing CCR10+ ILCs in the sLNs. PMID:26523865
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Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation.
Wang, Shuo; Xia, Pengyan; Chen, Yi; Qu, Yuan; Xiong, Zhen; Ye, Buqing; Du, Ying; Tian, Yong; Yin, Zhinan; Xu, Zhiheng; Fan, Zusen
2017-09-21
An emerging family of innate lymphoid cells (termed ILCs) has an essential role in the initiation and regulation of inflammation. However, it is still unclear how ILCs are regulated in the duration of intestinal inflammation. Here, we identify a regulatory subpopulation of ILCs (called ILCregs) that exists in the gut and harbors a unique gene identity that is distinct from that of ILCs or regulatory T cells (Tregs). During inflammatory stimulation, ILCregs can be induced in the intestine and suppress the activation of ILC1s and ILC3s via secretion of IL-10, leading to protection against innate intestinal inflammation. Moreover, TGF-β1 is induced by ILCregs during the innate intestinal inflammation, and autocrine TGF-β1 sustains the maintenance and expansion of ILCregs. Therefore, ILCregs play an inhibitory role in the innate immune response, favoring the resolution of intestinal inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Quast, Thorben
2018-02-01
As part of its HL-LHC upgrade program, CMS is developing a High Granularity Calorimeter (HGCAL) to replace the existing endcap calorimeters. The HGCAL will be realised as a sampling calorimeter, including an electromagnetic compartment comprising 28 layers of silicon pad detectors with pad areas of 0.5-1.0 cm2 interspersed with absorbers. Prototype modules, based on 6-inch hexagonal silicon pad sensors with 128 channels, have been constructed and include many of the features required for this challenging detector. In 2016, beam tests of sampling configurations made from these modules have been conducted both at FNAL and at CERN using the Skiroc2 front-end ASIC (designed by the CALICE collaboration for ILC). In 2017, the setup has been extended with CALICE's AHCAL prototype, a scinitillator based sampling calorimeter, and it was further tested in dedicated beam tests at CERN. There, the new Skiroc2-CMS front-end ASIC was used for the first time. We highlight final results from our studies in 2016, including position resolution as well as precision timing-measurements. Furthermore, the extended setup in 2017 is discussed and first results from beam tests with electrons and pions are shown.
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MICROROC: MICRO-mesh gaseous structure Read-Out Chip
NASA Astrophysics Data System (ADS)
Adloff, C.; Blaha, J.; Chefdeville, M.; Dalmaz, A.; Drancourt, C.; Dulucq, F.; Espargilière, A.; Gaglione, R.; Geffroy, N.; Jacquemier, J.; Karyotakis, Y.; Martin-Chassard, G.; Prast, J.; Seguin-Moreau, N.; de La Taille, Ch; Vouters, G.
2012-01-01
MICRO MEsh GAseous Structure (MICROMEGAS) and Gas Electron Multipliers (GEM) detectors are two candidates for the active medium of a Digital Hadronic CALorimeter (DHCAL) as part of a high energy physics experiment at a future linear collider (ILC/CLIC). Physics requirements lead to a highly granular hadronic calorimeter with up to thirty million channels with probably only hit information (digital readout calorimeter). To validate the concept of digital hadronic calorimetry with such small cell size, the construction and test of a cubic meter technological prototype, made of 40 planes of one square meter each, is necessary. This technological prototype would contain about 400 000 electronic channels, thus requiring the development of front-end ASIC. Based on the experience gained with previous ASIC that were mounted on detectors and tested in particle beams, a new ASIC called MICROROC has been developped. This paper summarizes the caracterisation campaign that was conducted on this new chip as well as its integration into a large area Micromegas chamber of one square meter.
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Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.
Trabanelli, Sara; Chevalier, Mathieu F; Martinez-Usatorre, Amaia; Gomez-Cadena, Alejandra; Salomé, Bérengère; Lecciso, Mariangela; Salvestrini, Valentina; Verdeil, Grégory; Racle, Julien; Papayannidis, Cristina; Morita, Hideaki; Pizzitola, Irene; Grandclément, Camille; Bohner, Perrine; Bruni, Elena; Girotra, Mukul; Pallavi, Rani; Falvo, Paolo; Leibundgut, Elisabeth Oppliger; Baerlocher, Gabriela M; Carlo-Stella, Carmelo; Taurino, Daniela; Santoro, Armando; Spinelli, Orietta; Rambaldi, Alessandro; Giarin, Emanuela; Basso, Giuseppe; Tresoldi, Cristina; Ciceri, Fabio; Gfeller, David; Akdis, Cezmi A; Mazzarella, Luca; Minucci, Saverio; Pelicci, Pier Giuseppe; Marcenaro, Emanuela; McKenzie, Andrew N J; Vanhecke, Dominique; Coukos, George; Mavilio, Domenico; Curti, Antonio; Derré, Laurent; Jandus, Camilla
2017-09-19
Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer.Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth.
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Kim, Sae-Hae; Cho, Byeol-Hee; Kiyono, Hiroshi; Jang, Yong-Suk
2017-06-21
The regional specialization of intestinal immune cells is affected by the longitudinal heterogeneity of environmental factors. Although the distribution of group 3 innate lymphoid cells (ILC3s) is well characterized in the lamina propria, it is poorly defined in Peyer's patches (PPs) along the intestine. Given that PP ILC3s are closely associated with mucosal immune regulation, it is important to characterize the regulatory mechanism of ILC3s. Here, we found that terminal ileal PPs of specific pathogen-free (SPF) mice have fewer NKp46 + ILC3s than jejunal PPs, while there was no difference in NKp46 + ILC3 numbers between terminal ileal and jejunal PPs in antibiotics (ABX)-treated mice. We also found that butyrate levels in the terminal ileal PPs of SPF mice were higher than those in the jejunal PPs of SPF mice and terminal ileal PPs of ABX-treated mice. The reduced number of NKp46 + ILC3s in terminal ileal PPs resulted in a decrease in Csf2 expression and, in turn, resulted in reduced regulatory T cells and enhanced antigen-specific T-cell proliferation. Thus, we suggest that NKp46 + ILC3s are negatively regulated by microbiota-derived butyrate in terminal ileal PPs and the reduced ILC3 frequency is closely associated with antigen-specific immune induction in terminal ileal PPs.
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Jung, Na Young; Kim, Sung Hoon; Kim, Sung Hun; Seo, Ye Young; Oh, Jin Kyoung; Choi, Hyun Su; You, Won Jong
2015-03-01
We evaluated the utility of magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for the preoperative staging of invasive lobular carcinoma (ILC) of the breast and compared the results with those of invasive ductal carcinoma (IDC). The study included pathologically proven 32 ILCs and 73 IDCs. We compared clinical and histopathological characteristics and the diagnostic performances of MRI and (18)F-FDG PET/CT for the primary mass, additional ipsilateral and/or contralateral lesion(s), and axillary lymph node metastasis between the ILC and IDC groups. Primary ILCs were greater in size, but demonstrated lower maximum standardized uptake values than IDCs. All primary masses were detected on MRI. The detection rate for ILCs (75.0%) was lower than that for IDCs (83.6%) on (18)F-FDG PET/CT, but the difference was not significant. For additional ipsilateral lesion(s), the sensitivities and specificities of MRI were 87.5% and 58.3% for ILC and 100.0% and 66.7% for IDC, respectively; whereas the sensitivities and specificities of (18)F-FDG PET/CT were 0% and 91.7% for ILC and 37.5% and 94.7% for IDC, respectively. The sensitivity of (18)F-FDG PET/CT for ipsilateral lesion(s) was significantly lower in the ILC group than the IDC group. The sensitivity for ipsilateral lesion(s) was significantly higher with MRI; however, specificity was higher with (18)F-FDG PET/CT in both tumor groups. There was no significant difference in the diagnostic performance for additional contralateral lesion(s) or axillary lymph node metastasis on MRI or (18)F-FDG PET/CT for ILC versus IDC. The MRI and (18)F-FDG PET/CT detection rates for the primary cancer do not differ between the ILC and IDC groups. Although (18)F-FDG PET/CT demonstrates lower sensitivity for primary and additional ipsilateral lesions, it shows higher specificity for additional ipsilateral lesions, and could play a complementary role in the staging of ILC as well as IDC.
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Triggianese, Paola; Conigliaro, Paola; Chimenti, Maria Sole; Biancone, Livia; Monteleone, Giovanni; Perricone, Roberto; Monteleone, Ivan
2016-01-01
Both the innate and the adaptive immune responses contribute to the onset of chronic inflammation in spondyloarthritis (SpA). The association between SpA and inflammatory bowel disease (IBD, enteropathic SpA-ESpA) has been largely established and suggests a shared pathophysiology. There is evidence that innate lymphoid cells (ILC) are involved in the pathogenesis of both SpA and IBD while no evidence has been reported to date on ESpA. We aimed to analyse for the first time the frequency and cytokine expression of ILC in peripheral blood from ESpA patients compared with both IBD and healthy subjects. Correlations between immunophenotyping and disease activity were also explored. ESpA patients (n=20) were prospectively enrolled. Healthy controls (HC, n=10) and IBD patients (n=10) served as control groups. Peripheral blood Interferon (IFN)-γ and interleukin (IL)-17 expressing T and non-T cells as well as ILC subsets (ILC-1: IFN- γ +; ILC-3: IL-17+; natural killer-NK) were characterised by flowcytometry. Correlations between IL-17+ cells and SpA disease activity were analysed. ESpA patients showed higher levels of ROR-γ expressing non T-cells with the respect to the controls. IL-17 producing non-T cells were higher than the HC and positively correlated with IFN-γ expressing cells levels as well as with SpA disease activity. ESpA showed higher levels of ILC-1 and ILC-3 than both IBD and HC. IFN-γ expressing NK cells were higher in ESpA than HC. Our preliminary findings indicate that peripheral blood of ESpA patients is enriched for IL-17 expressing ILC which distinguishes the blood compartment from both IBD and HC. The increased IL-17 production by ILC indicates a novel role for ILC in ESpA.
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Yang, Qi; Ge, Moyar Q.; Kokalari, Blerina; Redai, Imre G.; Wang, Xinxin; Kemeny, David M.; Bhandoola, Avinash; Haczku, Angela
2015-01-01
Background Patients with asthma are highly susceptible to air pollution and in particular, to the effects of ozone (O3) inhalation, but the underlying mechanisms remain unclear. Objective Using mouse models of O3-induced airway inflammation and hyperresponsiveness (AHR), we sought to investigate the role of the recently discovered group 2 innate lymphoid cells (ILC2). Methods C57BL/6 and Balb/c mice were exposed to Aspergillus fumigatus and/or O3 (2ppm, 2h). ILC2 were isolated by FACS sorting and studied for IL-5 and IL-13 mRNA expression. ILC2 were depleted with anti-Thy1.2 mAb and replaced by intratracheal transfer of ex vivo expanded Thy1.1 ILC2. Cytokines (ELISA, qPCR), inflammatory cell profile and AHR (FlexiVent) were assessed in the mice. Results In addition to neutrophil influx, O3 inhalation elicited the appearance of eosinophils and IL-5 in the airways of Balb/c but not C57BL/6 mice. Although O3 induced expression of IL-33, a known activator of ILC2 in the lung was similar between these strains, isolated pulmonary ILC2 from O3 exposed Balb/c mice had significantly greater IL-5 and IL-13 mRNA expression than those of C57BL/6 mice. This suggested that an altered ILC2 function in Balb/c mice may mediate the increased O3 responsiveness. Indeed, anti-Thy1.2 treatment abolished, whereas ILC2 add-back dramatically enhanced O3-induced AHR. Conclusions O3-induced activation of pulmonary ILC2 was necessary and sufficient to mediate asthma-like changes in Balb/c mice. This previously unrecognized role of ILC2 may help explain the heightened susceptibility of human asthmatic airways to O3 exposure. PMID:26282284
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Mjösberg, Jenny; Spits, Hergen
2016-11-01
Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis.
Mindt, Barbara C; Fritz, Jörg H; Duerr, Claudia U
2018-01-01
Group 2 innate lymphoid cells (ILC2) represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung.
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Emerging concepts and future challenges in innate lymphoid cell biology
Artis, David
2016-01-01
Innate lymphoid cells (ILCs) are innate immune cells that are ubiquitously distributed in lymphoid and nonlymphoid tissues and enriched at mucosal and barrier surfaces. Three major ILC subsets are recognized in mice and humans. Each of these subsets interacts with innate and adaptive immune cells and integrates cues from the epithelium, the microbiota, and pathogens to regulate inflammation, immunity, tissue repair, and metabolic homeostasis. Although intense study has elucidated many aspects of ILC development, phenotype, and function, numerous challenges remain in the field of ILC biology. In particular, recent work has highlighted key new questions regarding how these cells communicate with their environment and other cell types during health and disease. This review summarizes new findings in this rapidly developing field that showcase the critical role ILCs play in directing immune responses through their ability to interact with a variety of hematopoietic and nonhematopoietic cells. In addition, we define remaining challenges and emerging questions facing the field. Finally, this review discusses the potential application of basic studies of ILC biology to the development of new treatments for human patients with inflammatory and infectious diseases in which ILCs play a role. PMID:27811053
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Krishnamoorthy, Nandini; Burkett, Patrick R; Dalli, Jesmond; Abdulnour, Raja-Elie E; Colas, Romain; Ramon, Sesquile; Phipps, Richard P; Petasis, Nicos A; Kuchroo, Vijay K; Serhan, Charles N; Levy, Bruce D
2015-02-01
Asthma is a chronic inflammatory disease that fails to resolve. Recently, a key role for type 2 innate lymphoid cells (ILC2s) was linked to asthma pathogenesis; however, mechanisms for ILC2 regulation remain to be determined. In this study, metabololipidomics of murine lungs identified temporal changes in endogenous maresin 1 (MaR1) during self-limited allergic inflammation. Exogenous MaR1 reduced lung inflammation and ILC2 expression of IL-5 and IL-13 and increased amphiregulin. MaR1 augmented de novo generation of regulatory T cells (Tregs), which interacted with ILC2s to markedly suppress cytokine production in a TGF-β-dependent manner. Ab-mediated depletion of Tregs interrupted MaR1 control of ILC2 expression of IL-13 in vivo. Together, the findings uncover Tregs as potent regulators of ILC2 activation; MaR1 targets Tregs and ILC2s to restrain allergic lung inflammation, suggesting MaR1 as the basis for a new proresolving therapeutic approach to asthma and other chronic inflammatory diseases. Copyright © 2015 by The American Association of Immunologists, Inc.
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Colonization and effector functions of innate lymphoid cells in mucosal tissues
Kim, Myunghoo; Kim, Chang H.
2016-01-01
Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193
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van de Water, Willemien; Fontein, Duveken B Y; van Nes, Johanna G H; Bartlett, John M S; Hille, Elysée T M; Putter, Hein; Robson, Tammy; Liefers, Gerrit-Jan; Roumen, Rudi M H; Seynaeve, Caroline; Dirix, Luc Y; Paridaens, Robert; Kranenbarg, Elma Meershoek-Klein; Nortier, Johan W R; van de Velde, Cornelis J H
2013-01-01
Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas (IDC) than invasive lobular breast carcinomas (ILC). However, data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse. This study assessed endocrine therapy efficacy in IDC and ILC. The influence of semi-quantitative oestrogen receptor (ER) expression by Allred score was also investigated. Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were randomized to exemestane (25mg daily) alone or following tamoxifen (20mg daily) for 5 years. Inclusion was restricted to IDC and ILC patients. Histological subtype was assessed locally; ER expression was centrally reviewed according to Allred score (ER-poor (<7; n=235); ER-rich (7; n=1789)). Primary end-point was relapse-free survival (RFS), which was the time from randomization to disease relapse. Overall, 2140 (82%) IDC and 463 (18%) ILC patients were included. RFS was similar for both endocrine treatment regimens in IDC (hazard ratio (HR) for exemestane was 0.83 (95%confidence interval (CI) 0.67-1.03)), and ILC (HR 0.69 (95%CI 0.45-1.06)). Irrespective of histological subtype, patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS (multivariable HR 0.71 (95%CI 0.56-0.89)). In contrast, patients with ER-poor Allred scores allocated to exemestane had a worse RFS (multivariable HR 2.33 (95%CI 1.32-4.11)). Significant effect modification by ER-Allred score was confirmed (multivariable p=0.003). Efficacy of endocrine therapy regimens was similar for IDC and ILC. However, ER-rich patients showed superior efficacy to upfront exemestane, while ER-poor patients had better outcomes with sequential therapy, irrespective of histological subtype, emphasising the relevance of quantification of ER expression. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Distribution of Interleukin-22-secreting Immune Cells in Conjunctival Associated Lymphoid Tissue.
Yoon, Chang Ho; Lee, Daeseung; Jeong, Hyun Jeong; Ryu, Jin Suk; Kim, Mee Kum
2018-04-01
Interleukin (IL)-22 is a cytokine involved in epithelial cell regeneration. Currently, no research studies have analyzed the distribution of the three distinct IL-22-secreting cell populations in human or mouse conjunctiva. This study investigated the distribution of the three main populations of IL-22-secreting immune cells, αβ Th cells, γδ T cells, or innate cells (innate lymphoid cells [ILCs] or natural killer cells), in conjunctival associated lymphoid tissues (CALTs) in human and mouse models. We collected discarded cadaveric bulbar conjunctival tissue specimens after preservation of the corneo-limbal tissue for keratoplasty from four enucleated eyes of the domestic donor. The bulbar conjunctiva tissue, including the cornea from normal (n = 27) or abraded (n = 4) B6 mice, were excised and pooled in RPMI 1640 media. After the lymphoid cells were gated in forward and side scattering, the αβ Th cells, γδ T cells, or innate lymphoid cells were positively or negatively gated using anti-CD3, anti-γδ TCR, and anti-IL-22 antibodies, with a FACSCanto flow cytometer. In normal human conjunctiva, the percentage and number of cells were highest in αβ Th cells, followed by γδ T cells and CD3- γδ TCR- IL-22+ innate cells (presumed ILCs, pILCs) (Kruskal-Wallis test, p = 0.012). In normal mice keratoconjunctiva, the percentage and total number were highest in γδ T cells, followed by αβ Th cells and pILCs (Kruskal-Wallis test, p = 0.0004); in corneal abraded mice, the population of αβ Th cells and pILCs tended to increase. This study suggests that three distinctive populations of IL-22-secreting immune cells are present in CALTs of both humans and mice, and the proportions of IL-22+αβ Th cells, γδ T cells, and pILCs in CALTs in humans might be differently distributed from those in normal mice. © 2018 The Korean Ophthalmological Society.
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Wong, Hilda; Lau, Silvia; Cheung, Polly; Wong, Ting Ting; Parker, Andrew; Yau, Thomas; Epstein, Richard J
2014-11-10
Although invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma (IDC) in numerous respects - including its genetics, clinical phenotype, metastatic pattern, and chemosensitivity - most experts continue to manage ILC and IDC identically in the adjuvant setting. Here we address this discrepancy by comparing early-stage ILC and IDC in two breast cancer patient cohorts of differing nationality and ethnicity. The clinicopathologic features of 2029 consecutive breast cancer patients diagnosed in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between tumor histology and other clinicopathologic variables, including ER/PR and Ki67, were analysed. Two hundred thirty-nine patients were identified with ILC (11.8%) and 1790 patients with IDC. AUS patients were older (p <0.001) and more often postmenopausal (p <0.03) than HK patients. As expected, ILC tumors were lower in grade and proliferative rate, and more often ER-positive and HER2-negative, than IDC (p <0.002); yet despite this, ILC tumors were as likely as IDC to present with nodal metastases (p >0.7). Moreover, whereas IDC tumors exhibited a strongly negative relationship between ER/PR and Ki67 status (p <0.0005), ILC tumors failed to demonstrate any such inverse relationship (p >0.6). These data imply that the primary adhesion defect in ILC underlies a secondary stromal-epithelial disconnect between hormonal signaling and tumor growth, suggesting in turn that this peritumoral feedback defect could reduce both the antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic therapies for such tumors. Hence, we caution against assuming similar adjuvant chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and Ki67, whether based on immunohistochemical or gene expression assays.
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Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System.
Withers, David R; Hepworth, Matthew R
2017-01-01
The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of "exogenous" signals, such as dietary metabolites and commensal microbes, and "endogenous" host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a "communications hub" in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell-cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.
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Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System
Withers, David R.; Hepworth, Matthew R.
2017-01-01
The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases. PMID:29085366
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Innate Lymphoid Cells: a new paradigm in immunology
Eberl, Gérard; Colonna, Marco; Di Santo, James P.; McKenzie, Andrew N.J.
2016-01-01
Summary Innate lymphoid cells (ILCs) are a growing family of immune cells that mirror the phenotypes and functions of T cells. However, in contrast to T cells, ILCs do not express acquired antigen receptors or undergo clonal selection and expansion when stimulated. Instead, ILCs react promptly to signals from infected or injured tissues and produce an array of secreted proteins termed cytokines that direct the developing immune response into one that is adapted to the original insult. The complex crosstalk between microenvironment, ILCs and adaptive immunity remains to be fully deciphered. Only by understanding these complex regulatory networks can the power of ILCs be controlled or unleashed to regulate or enhance immune responses in disease prevention and therapy. PMID:25999512
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Okihira, K.; Hara, H.; Ikeda, N.
MHI have supplied several 9-cell cavities for STF (R&D of ILC project at KEK) and have been considering production method for stable quality and cost reduction, seamless dumb-bell cavity was one of them. We had fabricated a 2 cell seamless dumb-bell cavity for cost reduction and measured RF performance in collaboration with JLab, KEK and MHI. Surface treatment recipe for ILC was applied for MHI 2-cell cavity and vertical test was performed at JLab. The cavity reached Eacc=32.4MV/m after BCP and EP. Details of the result are reported.
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Complement and Immunoregulation in Tissue Injury
2015-12-01
and IL-8. Cells that produce IL-17A include TCRα/β T cells , TCRγ/δ T cells and CD45+CD4+TCR-IL-7R+ innate lymphoid cells (ILCs), which reside at...cytokine IL-23. In contrast, IL-17A production by TCRγ/δ T cells ILCs and other innate cell is directly driven by IL-23 and is rapid. IL-23 is a...amplifies IL-17A production by T cells and drives its production by innate cells . We investigated the potential role of IL-23 in small intestinal IRI
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Liu, Y; Liu, Z
2017-02-07
Type Ⅱ innate lymphoid cells (ILC2) is a family of innate immune lymphocytes, which provide effective immune responses to cytokines. ILC2 are regulated by the nuclear transcription factor ROR alpha and GATA3, secreting cytokines IL-5 and IL-13, etc. Animal models have shown that ILC2 are involved in allergic diseases, such as asthma and atopic dermatitis, and also play a very important role in the metabolic balance. In addition, recent reports suggest that ILC2 not only play a role in the initial stages of the disease, but also can lead to chronic pathological changes in the disease, such as fibrosis, and may have an effect on acquired immunity. This paper mainly focus in the role and regulation of ILC2 cells, and review the research status of ILC2 in the field of chronic upper airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.
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Group 1 innate lymphoid cells in Toxoplasma gondii infection.
Dunay, I R; Diefenbach, A
2018-02-01
Innate lymphoid cells (ILCs) are a group of lymphocytes that carry out important functions in immunity to infections and in organ homeostasis at epithelial barrier surfaces. ILCs are innate immune cells that provide an early source of cytokines to initiate immune responses against pathogens. Cytotoxic ILCs (i.e. conventional (c)NK cells) and several subsets of helper-like ILCs are the major branches of the ILC family. Conventional NK cells and group 1 ILCs share several characteristics such as surface receptors and the ability to produce IFN-γ upon activation, but they differ in their developmental paths and in their dependence on specific transcription factors. Infection of mice with the intracellular parasite Toxoplasma gondii is followed by a strong Th1-mediated immune response. Previous studies indicate that NK1.1 + cells contribute to the production of IFN-γ and TNF and cytotoxicity during acute T. gondii infection. Upon oral infection, the parasite infects intestinal enterocytes, and within the lamina propria, innate immune responses lead to initial parasite control although the infection disseminates widely and persists long-term in immune privileged sites despite adaptive immunity. Upon parasite entry into the small intestine, during the acute stage, ILC1 produce high levels of IFN-γ and TNF protecting barrier surfaces, thus essentially contributing to early parasite control. We will discuss here the role of innate lymphocytes during T. gondii infection in the context of the only recently appreciated diversity of ILC subsets. © 2018 John Wiley & Sons Ltd.
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Aryl Hydrocarbon Receptor Promotes RORγt+ ILCs and Controls Intestinal Immunity and Inflammation
Qiu, Ju; Zhou, Liang
2013-01-01
Unlike adaptive immune cells that require antigen recognition and functional maturation during infection, innate lymphoid cells (ILCs) usually respond to pathogens promptly and serve as the first line of defense in infectious diseases. RAR-related orphan receptors (RORγt)+ ILCs are one of the innate cell populations that have recently been intensively studied. During the fetal stage of development, RORγt+ ILCs (e.g., lymphoid tissue inducer-LTi cells) are required for lymphoid organogenesis. In adult mice, RORγt+ ILCs are abundantly present in the gut to exert immune defensive functions. Under certain circumstances, however, RORγt+ ILCs can be pathogenic and contribute to intestinal inflammation. Aryl hydrocarbon receptor (Ahr), a ligand-dependent transcriptional factor, is widely expressed by various immune and non-immune cells. In the gut, the ligand for Ahr can be derived/generated from diet, microflora, and/or host cells. Ahr has been shown to regulate different cell populations in the immune system including RORγt+ ILCs, T helper (Th)17/22 cells, γδT cells, regulatory T cells (Tregs), Tr1 cells, and antigen presenting cells (APCs). In this review, we will focus on the development and function of RORγt+ ILCs, and discuss the role of Ahr in intestinal immunity and inflammation in mice and in humans. Better understanding the function of Ahr in the gut is important for developing new therapeutic means to target Ahr in future treatment of infectious and autoimmune diseases. PMID:23975386
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Implications of the 750 GeV γγ Resonance as a Case Study for the International Linear Collider
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fujii, Keisuke; Grojean, Christophe; Peskin, Michael E.
If the γγ resonance at 750 GeV suggested by 2015 LHC data turns out to be a real effect, what are the implications for the physics case and upgrade path of the International Linear Collider? Whether or not the resonance is confirmed, this question provides an interesting case study testing the robustness of the ILC physics case. In this note, we address this question with two points: (1) Almost all models proposed for the new 750 GeV particle require additional new particles with electroweak couplings. The key elements of the 500 GeV ILC physics program - precision measurements of themore » Higgs boson, the top quark, and 4-fermion interactions - will powerfully discriminate among these models. This information will be important in conjunction with new LHC data, or alone, if the new particles accompanying the 750 GeV resonance are beyond the mass reach of the LHC. (2) Over a longer term, the energy upgrade of the ILC to 1 TeV already discussed in the ILC TDR will enable experiments in γγ and e +e - collisions to directly produce and study the 750 GeV particle from these unique initial states.« less
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Huang, Qingsong; Niu, Zhiguo; Tan, Jing; Yang, Jun; Liu, Yun; Ma, Haijun; Lee, Vincent W.S.; Sun, Shuming; Song, Xiangfeng; Guo, Minghao; Wang, Yiping
2015-01-01
IL-25 is an important immune regulator that can promote Th2 immune response-dependent immunity, inflammation, and tissue repair in asthma, intestinal infection, and autoimmune diseases. In this study, we examined the effects of IL-25 in renal ischemic/reperfusion injury (IRI). Treating IRI mice with IL-25 significantly improved renal function and reduced renal injury. Furthermore, IL-25 treatment increased the levels of IL-4, IL-5, and IL-13 in serum and kidney and promoted induction of alternatively activated (M2) macrophages in kidney. Notably, IL-25 treatment also increased the frequency of type 2 innate lymphoid cells (ILC2s) and multipotent progenitor type 2 (MPPtype2) cells in kidney. IL-25–responsive ILC2 and MPPtype2 cells produced greater amounts of Th2 cytokines that associated with the induction of M2 macrophages and suppression of classically activated (M1) macrophages in vitro. Finally, adoptive transfer of ILC2s or MPPtype2 cells not only reduced renal functional and histologic injury in IRI mice but also induced M2 macrophages in kidney. In conclusion, our data identify a mechanism whereby IL-25-elicited ILC2 and MPPtype2 cells regulate macrophage phenotype in kidney and prevent renal IRI. PMID:25556172
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Colonization and effector functions of innate lymphoid cells in mucosal tissues.
Kim, Myunghoo; Kim, Chang H
2016-10-01
Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
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Optimization of detectors for the ILC
NASA Astrophysics Data System (ADS)
Suehara, Taikan; ILD Group; SID Group
2016-04-01
International Linear Collider (ILC) is a next-generation e+e- linear collider to explore Higgs, Beyond-Standard-Models, top and electroweak particles with great precision. We are optimizing our two detectors, International Large Detector (ILD) and Silicon Detector (SiD) to maximize the physics reach expected in ILC with reasonable detector cost and good reliability. The optimization study on vertex detectors, main trackers and calorimeters is underway. We aim to conclude the optimization to establish final designs in a few years, to finish detector TDR and proposal in reply to expected ;green sign; of the ILC project.
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Interactions between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System
Symowski, Cornelia; Voehringer, David
2017-01-01
Type 2 innate lymphoid cells (ILC2s) are a major source of cytokines, which are also produced by Th2 cells and several cell types of the innate immune system. Work over the past few years indicates that ILC2s play a central role in regulating type 2 immune responses against allergens and helminths. ILC2s can interact with a variety of cells types of the innate and adaptive immune system by cell–cell contacts or by communication via soluble factors. In this review, we provide an overview about recent advances in our understanding how ILC2s orchestrate type 2 immune responses with focus on direct interactions between ILC2s and other cells of the immune system. PMID:29163497
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Interactions between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System.
Symowski, Cornelia; Voehringer, David
2017-01-01
Type 2 innate lymphoid cells (ILC2s) are a major source of cytokines, which are also produced by Th2 cells and several cell types of the innate immune system. Work over the past few years indicates that ILC2s play a central role in regulating type 2 immune responses against allergens and helminths. ILC2s can interact with a variety of cells types of the innate and adaptive immune system by cell-cell contacts or by communication via soluble factors. In this review, we provide an overview about recent advances in our understanding how ILC2s orchestrate type 2 immune responses with focus on direct interactions between ILC2s and other cells of the immune system.
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Innate lymphoid cells in autoimmunity and chronic inflammatory diseases.
Xiong, Tingting; Turner, Jan-Eric
2018-03-22
Abnormal activation of the innate immune system is a common feature of autoimmune and chronic inflammatory diseases. Since their identification as a separate family of leukocytes, innate lymphoid cells (ILCs) have emerged as important effector cells of the innate immune system. Alterations in ILC function and subtype distribution have been observed in a variety of immune-mediated diseases in humans and evidence from experimental models suggests a subtype specific role of ILCs in the pathophysiology of autoimmune inflammation. In this review, we discuss recent advances in the understanding of ILC biology in autoimmune and chronic inflammatory disorders, including multiple sclerosis, inflammatory bowel diseases, psoriasis, and rheumatic diseases, with a special focus on the potential of ILCs as therapeutic targets for the development of novel treatment strategies in humans.
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Control of pathogens and microbiota by innate lymphoid cells.
Cording, Sascha; Medvedovic, Jasna; Lecuyer, Emelyne; Aychek, Tegest; Eberl, Gérard
2018-05-28
Innate lymphoid cells (ILCs) are the innate counterpart of T cells. Upon infection or injury, ILCs react promptly to direct the developing immune response to the one most adapted to the threat facing the organism. Therefore, ILCs play an important role early in resistance to infection, but also to maintain homeostasis with the symbiotic microbiota following perturbations induced by diet and pathogens. Such roles of ILCs have been best characterized in the intestine and lung, mucosal sites that are exposed to the environment and are therefore colonized with diverse but specific types of microbes. Understanding the dialogue between pathogens, microbiota and ILCs may lead to new strategies to re-inforce immunity for prevention, vaccination and therapy. Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
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Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis
Mindt, Barbara C.; Fritz, Jörg H.; Duerr, Claudia U.
2018-01-01
Group 2 innate lymphoid cells (ILC2) represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung. PMID:29760695
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Sugita, Kazunari; Steer, Catherine A; Martinez-Gonzalez, Itziar; Altunbulakli, Can; Morita, Hideaki; Castro-Giner, Francesc; Kubo, Terufumi; Wawrzyniak, Paulina; Rückert, Beate; Sudo, Katsuko; Nakae, Susumu; Matsumoto, Kenji; O'Mahony, Liam; Akdis, Mübeccel; Takei, Fumio; Akdis, Cezmi A
2018-01-01
Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis; however, the influence of ILC2s on the bronchial epithelial barrier has not been investigated previously. We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic patients and healthy subjects and general innate lymphoid cell- and ILC2-deficient mice. Cocultures of human ILC2s and bronchial epithelial cells were used to determine transepithelial electrical resistance, paracellular flux, and TJ mRNA and protein expressions. The effect of ILC2s on TJs was examined by using a murine model of IL-33-induced airway inflammation in wild-type, recombination-activating gene 2 (Rag2) -/- , Rag2 -/- Il2rg -/- , and Rora sg/sg mice undergoing bone marrow transplantation to analyze the in vivo relevance of barrier disruption by ILC2s. ILC2s significantly impaired the epithelial barrier, as demonstrated by reduced transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran permeability in air-liquid interface cultures of human bronchial epithelial cells. This was in parallel to decreased mRNAs and disrupted protein expression of TJ proteins and was restored by neutralization of IL-13. Intranasal administration of recombinant IL-33 to wild-type and Rag2 -/- mice lacking T and B cells triggered TJ disruption, whereas Rag2 -/- Il2rg -/- and Rora sg/sg mice undergoing bone marrow transplantation that lack ILC2s did not show any barrier leakiness. Direct nasal administration of IL-13 was sufficient to induce deficiency in the TJ barrier in the bronchial epithelium of mice in vivo. These data highlight an essential mechanism in asthma pathogenesis by demonstrating that ILC2s are responsible for bronchial epithelial TJ barrier leakiness through IL-13. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Qiu, Ju; Zhou, Liang
2013-11-01
Unlike adaptive immune cells that require antigen recognition and functional maturation during infection, innate lymphoid cells (ILCs) usually respond to pathogens promptly and serve as the first line of defense in infectious diseases. RAR-related orphan receptor (RORγt)⁺ group 3 ILCs are one of the innate cell populations that have recently been intensively studied. During the fetal stage of development, RORγt⁺ group 3 ILCs (e.g., lymphoid tissue inducer cells) are required for lymphoid organogenesis. In adult mice, RORγt⁺ group 3 ILCs are abundantly present in the gut to exert immune defensive functions. Under certain circumstances, however, RORγt⁺ group 3 ILCs can be pathogenic and contribute to intestinal inflammation. Aryl hydrocarbon receptor (Ahr), a ligand-dependent transcriptional factor, is widely expressed by various immune and non-immune cells. In the gut, the ligand for Ahr can be derived/generated from diet, microflora, and/or host cells. Ahr has been shown to regulate different cell populations in the immune system including RORγt⁺ group 3 ILCs, T helper (Th)17/22 cells, γδT cells, regulatory T cells (Tregs), Tr1 cells, and antigen presenting cells. In this review, we will focus on the development and function of RORγt⁺ group 3 ILCs, and discuss the role of Ahr in intestinal immunity and inflammation in mice and in humans. A better understanding of the function of Ahr in the gut is important for developing new therapeutic means to target Ahr in future treatment of infectious and autoimmune diseases.
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USDA-ARS?s Scientific Manuscript database
Innate lymphoid cells (ILCs) play an important role in many immune processes, including control of infections, inflammation and tissue repair. To date little is known about the metabolism of ILCs under steady-state conditions and infection, and whether these cells can metabolically adapt in response...
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S1P dependent inter organ trafficking of group 2 innate lymphoid cells suppots host defense
USDA-ARS?s Scientific Manuscript database
Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a...
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AHR prevents human IL-1R1hi ILC3 differentiation to natural killer cells
Hughes, Tiffany; Briercheck, Edward L.; Freud, Aharon G.; Trotta, Rossana; McClory, Susan; Scoville, Steven D.; Keller, Karen; Deng, Youcai; Cole, Jordan; Harrison, Nicholas; Mao, Charlene; Zhang, Jianying; Benson, Don M.; Yu, Jianhua; Caligiuri, Michael A.
2014-01-01
SUMMARY Accumulating evidence indicates that human natural killer (NK) cells develop in secondary lymphoid tissue (SLT) through a so-called “stage 3” developmental intermediate minimally characterized by a CD34-CD117+CD94- immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC) types that includes interleukin-1 receptor (IL-1R1) positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here we show that antagonism of the aryl hydrocarbon receptor (AHR) or silencing of AHR gene expression promotes differentiation of tonsillar IL-22-producing IL-1R1hi human ILC3s to CD56brightCD94+ IFN-gamma-producing cytolytic mature NK cells expressing eomesodermin (EOMES) and T-Box Protein 21 (TBX21 or TBET). Hence, AHR is a transcription factor that prevents human IL-1R1hi ILC3s from differentiating into NK cells. PMID:24953655
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van de Ven, Robert A. H.; Tenhagen, Milou; Meuleman, Wouter; van Riel, Jeske J. G.; Schackmann, Ron C. J.; Derksen, Patrick W. B.
2015-01-01
E-cadherin inactivation underpins the progression of invasive lobular breast carcinoma (ILC). In ILC, p120-catenin (p120) translocates to the cytosol where it controls anchorage independence through the Rho-Rock signaling pathway, a key mechanism driving tumor growth and metastasis. We now demonstrate that anchorage-independent ILC cells show an increase in nuclear p120, which results in relief of transcriptional repression by Kaiso. To identify the Kaiso target genes that control anchorage independence we performed genome-wide mRNA profiling on anoikis-resistant mouse ILC cells, and identified 29 candidate target genes, including the established Kaiso target Wnt11. Our data indicate that anchorage-independent upregulation of Wnt11 in ILC cells is controlled by nuclear p120 through inhibition of Kaiso-mediated transcriptional repression. Finally, we show that Wnt11 promotes activation of RhoA, which causes ILC anoikis resistance. Our findings thereby establish a mechanistic link between E-cadherin loss and subsequent control of Rho-driven anoikis resistance through p120- and Kaiso-dependent expression of Wnt11. PMID:25713299
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Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury
Overall, Christopher C.
2017-01-01
The meningeal space is occupied by a diverse repertoire of immune cells. Central nervous system (CNS) injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation remains poorly understood. Here, we describe type 2 innate lymphocytes (ILC2s) as a novel cell type resident in the healthy meninges that are activated after CNS injury. ILC2s are present throughout the naive mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile. After spinal cord injury (SCI), meningeal ILC2s are activated in an IL-33–dependent manner, producing type 2 cytokines. Using RNAseq, we characterized the gene programs that underlie the ILC2 activation state. Finally, addition of wild-type lung-derived ILC2s into the meningeal space of IL-33R−/− animals partially improves recovery after SCI. These data characterize ILC2s as a novel meningeal cell type that responds to SCI and could lead to new therapeutic insights for neuroinflammatory conditions. PMID:27994070
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Crosstalk between Innate Lymphoid Cells and Other Immune Cells in the Tumor Microenvironment
Irshad, Sheeba; Gordon, Peter; Wong, Felix; Sheriff, Ibrahim; Tutt, Andrew; Ng, Tony
2016-01-01
Our knowledge and understanding of the tumor microenvironment (TME) have been recently expanded with the recognition of the important role of innate lymphoid cells (ILC). Three different groups of ILC have been described based on their ability to produce cytokines that mediate the interactions between innate and adaptive immune cells in a variety of immune responses in infection, allergy, and autoimmunity. However, recent evidence from experimental models and clinical studies has demonstrated that ILC contribute to the mechanisms that generate suppressive or tolerant environments that allow tumor regression or progression. Defining the complex network of interactions and crosstalk of ILC with other immune cells and understanding the specific contributions of each type of ILC leading to tumor development will allow the manipulation of their function and will be important to develop new interventions and therapeutic strategies. PMID:27882334
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Carbognin, Luisa; Sperduti, Isabella; Brunelli, Matteo; Marcolini, Lisa; Nortilli, Rolando; Pilotto, Sara; Zampiva, Ilaria; Merler, Sara; Fiorio, Elena; Filippi, Elisa; Manfrin, Erminia; Pellini, Francesca; Bonetti, Franco; Pollini, Giovanni Paolo; Tortora, Giampaolo; Bria, Emilio
2016-03-22
The aim of this analysis was to investigate the potential impact of Ki67 assay in a series of patients affected by early stage invasive lobular carcinoma (ILC) undergone surgery. Clinical-pathological data were correlated with disease-free and overall survival (DFS/OS). The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate appropriate cut-offs. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed to assess the interaction between 'pure' or 'mixed' histology ILC and Ki67. At a median follow-up of 67 months, 10-years DFS and OS of 405 patients were 67.8 and 79.8%, respectively. Standardized Log-Rank statistics identified 2 optimal cut-offs (6 and 21%); 10-years DFS and OS were 75.1, 66.5, and 30.2% (p = 0.01) and 84.3, 76.4 and 59% (p = 0.003), for patients with a Ki67 < 6%, between 6 and 21%, and >21%, respectively. Ki67 and lymph-node status were independent predictor for longer DFS and OS at the multivariate analysis, with radiotherapy (for DFS) and age (for OS). Ki67 highly replicated at the internal cross-validation analysis (DFS 85%, OS 100%). The STEPP analysis showed that DFS rate decreases as Ki67 increases and those patients with 'pure' ILC performed worse than 'mixed' histology. Despite the retrospective and exploratory nature of the study, Ki67 was able to significantly discriminate the prognosis of patients with ILC, and the effect was more pronounced for patients with 'pure' ILC.
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LCFIPlus: A framework for jet analysis in linear collider studies
NASA Astrophysics Data System (ADS)
Suehara, Taikan; Tanabe, Tomohiko
2016-02-01
We report on the progress in flavor identification tools developed for a future e+e- linear collider such as the International Linear Collider (ILC) and Compact Linear Collider (CLIC). Building on the work carried out by the LCFIVertex collaboration, we employ new strategies in vertex finding and jet finding, and introduce new discriminating variables for jet flavor identification. We present the performance of the new algorithms in the conditions simulated using a detector concept designed for the ILC. The algorithms have been successfully used in ILC physics simulation studies, such as those presented in the ILC Technical Design Report.
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37 CFR 1.58 - Chemical and mathematical formulae and tables.
Code of Federal Regulations, 2010 CFR
2010-07-01
...) type font or lettering style having capital letters which should be at least 0.422 cm. (0.166 inch) high (e.g., preferably Arial, Times Roman, or Courier with a font size of 12), but may be no smaller than 0.21 cm. (0.08 inch) high (e.g., a font size of 6). A space at least 0.64 cm. (1/4 inch) high...
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Thylstrup, Birgitte; Hesse, Morten
2016-06-01
Antisocial behavior is associated with low quality of life for the patient and with adverse effects on society and those close to the antisocial patient. However, most patients with antisocial behavior are not seen in treatment settings that focus on their personality but rather in criminal justice settings, substance-abuse treatment, and social welfare settings. This article describes the adaptation and implementation of a highly structured manualized treatment, Impulsive Lifestyle Counseling (ILC), based on the Lifestyle Issues program, a 10-week psychoeducation program studied in prison settings. ILC consists of four sessions over 4 weeks and a booster session 8 weeks later. The goal of treatment is described to patients as "to help people identify their impulsive thoughts and lifestyle leading to problems with drug use, other people, and the police." Two clinical examples and reflections on our experiences with the training and implementation of the ILC program are presented. © The Author(s) 2011.
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Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma?
Conlon, Niamh; Ross, Dara S; Howard, Jane; Catalano, Jeffrey P; Dickler, Maura N; Tan, Lee K
2015-01-01
Oncotype Dx Breast Cancer Assay is a 21-gene assay used in estrogen receptor (ER)-positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER-2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision-making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions. © 2015 Wiley Periodicals, Inc.
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Type 2 Innate Lymphoid Cells: Friends or Foes—Role in Airway Allergic Inflammation and Asthma
Pishdadian, Abbas; Varasteh, Abdol-Reza; Sankian, Mojtaba
2012-01-01
Innate-like lymphocytes (ILLs) and innate lymphoid cells (ILCs) are two newly characterized families of lymphocytes with limited and no rearranged antigen receptors, respectively. These soldiers provide a first line of defense against foreign insults by triggering a prompt innate immune response and bridging the gap of innate and adaptive immunity. Type 2 innate lymphoid cells (ILCs2) are newly identified members of the ILC family that play a key role in type 2 immune responses by prompt production of type 2 cytokines (especially IL-5 and IL-13) in response to antigen-induced IL-25/33 and by recruiting type 2 “immune franchise.” Regarding the two different roles of type 2 cytokines, helminth expulsion and type 2-related diseases, here we review the latest advances in ILC2 biology and examine the pivotal role of resident ILCs2 in allergen-specific airway inflammation and asthma. PMID:23209480
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Type 2 innate lymphoid cells: friends or foes-role in airway allergic inflammation and asthma.
Pishdadian, Abbas; Varasteh, Abdol-Reza; Sankian, Mojtaba
2012-01-01
Innate-like lymphocytes (ILLs) and innate lymphoid cells (ILCs) are two newly characterized families of lymphocytes with limited and no rearranged antigen receptors, respectively. These soldiers provide a first line of defense against foreign insults by triggering a prompt innate immune response and bridging the gap of innate and adaptive immunity. Type 2 innate lymphoid cells (ILCs2) are newly identified members of the ILC family that play a key role in type 2 immune responses by prompt production of type 2 cytokines (especially IL-5 and IL-13) in response to antigen-induced IL-25/33 and by recruiting type 2 "immune franchise." Regarding the two different roles of type 2 cytokines, helminth expulsion and type 2-related diseases, here we review the latest advances in ILC2 biology and examine the pivotal role of resident ILCs2 in allergen-specific airway inflammation and asthma.
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Role of Type 2 Innate Lymphoid Cells in Allergic Diseases.
Cosmi, Lorenzo; Liotta, Francesco; Maggi, Laura; Annunziato, Francesco
2017-09-11
The adaptive immune response orchestrated by type 2 T helper (Th2) lymphocytes, strictly cooperates with the innate response of group 2 innate lymphoid cells (ILC2), in the protection from helminths infection, as well as in the pathogenesis of allergic disease. The aim of this review is to explore the pathogenic role of ILC2 in different type 2-mediated disorders. Recent studies have shown that epithelial cell-derived cytokines and their responding cells, ILC2, play a pathogenic role in bronchial asthma, chronic rhinosinusitis, and atopic dermatitis. The growing evidences of the contribution of ILC2 in the induction and maintenance of allergic inflammation in such disease suggest the possibility to target them in therapy. Biological therapies blocking ILC2 activation or neutralizing their effector cytokines are currently under evaluation to be used in patients with type 2-dominated diseases.
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Beyond NK cells: the expanding universe of innate lymphoid cells.
Cella, Marina; Miller, Hannah; Song, Christina
2014-01-01
For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.
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Hatfield, Julianne K; Brown, Melissa A
2015-10-01
Innate lymphoid cells are immune cells that reside in tissues that interface with the external environment and contribute to the first line defense against pathogens. However, they also have roles in promoting chronic inflammation. Here we demonstrate that group 3 ILCs, (ILC3s - CD45+Lin-IL-7Rα+RORγt+), are normal residents of the meninges and exhibit disease-induced accumulation and activation in EAE. In addition to production of the pro-inflammatory cytokines IL-17 and GM-CSF, ILC3s constitutively express CD30L and OX40L, molecules required for memory T cell survival. We show that disease-induced trafficking of transferred wild type T cells to the meninges is impaired in ILC3-deficient Rorc-/- mice. Furthermore, lymphoid tissue inducer cells, a c-kit+ ILC3 subset that promotes ectopic lymphoid follicle development, a hallmark of many autoimmune diseases, are reduced in the meninges of EAE-resistant c-kit mutant Kit(W/Wv) mice. We propose that ILC3s sustain neuroinflammation by supporting T cell survival and reactivation in the meninges. Copyright © 2015 Elsevier Inc. All rights reserved.
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Innate lymphoid cells: the role in respiratory infections and lung tissue damage.
Głobińska, Anna; Kowalski, Marek L
2017-10-01
Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.
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Emgård, Johanna; Kammoun, Hana; García-Cassani, Bethania; Chesné, Julie; Parigi, Sara M; Jacob, Jean-Marie; Cheng, Hung-Wei; Evren, Elza; Das, Srustidhar; Czarnewski, Paulo; Sleiers, Natalie; Melo-Gonzalez, Felipe; Kvedaraite, Egle; Svensson, Mattias; Scandella, Elke; Hepworth, Matthew R; Huber, Samuel; Ludewig, Burkhard; Peduto, Lucie; Villablanca, Eduardo J; Veiga-Fernandes, Henrique; Pereira, João P; Flavell, Richard A; Willinger, Tim
2018-01-16
Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Arabic OCR: toward a complete system
NASA Astrophysics Data System (ADS)
El-Bialy, Ahmed M.; Kandil, Ahmed H.; Hashish, Mohamed; Yamany, Sameh M.
1999-12-01
Latin and Chinese OCR systems have been studied extensively in the literature. Yet little work was performed for Arabic character recognition. This is due to the technical challenges found in the Arabic text. Due to its cursive nature, a powerful and stable text segmentation is needed. Also; features capturing the characteristics of the rich Arabic character representation are needed to build the Arabic OCR. In this paper a novel segmentation technique which is font and size independent is introduced. This technique can segment the cursive written text line even if the line suffers from small skewness. The technique is not sensitive to the location of the centerline of the text line and can segment different font sizes and type (for different character sets) occurring on the same line. Features extraction is considered one of the most important phases of the text reading system. Ideally, the features extracted from a character image should capture the essential characteristics of this character that are independent of the font type and size. In such ideal case, the classifier stores a single prototype per character. However, it is practically challenging to find such ideal set of features. In this paper, a set of features that reflect the topological aspects of Arabia characters is proposed. These proposed features integrated with a topological matching technique introduce an Arabic text reading system that is semi Omni.
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Prediction of final error level in learning and repetitive control
NASA Astrophysics Data System (ADS)
Levoci, Peter A.
Repetitive control (RC) is a field that creates controllers to eliminate the effects of periodic disturbances on a feedback control system. The methods have applications in spacecraft problems, to isolate fine pointing equipment from periodic vibration disturbances such as slight imbalances in momentum wheels or cryogenic pumps. A closely related field of control design is iterative learning control (ILC) which aims to eliminate tracking error in a task that repeats, each time starting from the same initial condition. Experiments done on a robot at NASA Langley Research Center showed that the final error levels produced by different candidate repetitive and learning controllers can be very different, even when each controller is analytically proven to converge to zero error in the deterministic case. Real world plant and measurement noise and quantization noise (from analog to digital and digital to analog converters) in these control methods are acted on as if they were error sources that will repeat and should be cancelled, which implies that the algorithms amplify such errors. Methods are developed that predict the final error levels of general first order ILC, of higher order ILC including current cycle learning, and of general RC, in the presence of noise, using frequency response methods. The method involves much less computation than the corresponding time domain approach that involves large matrices. The time domain approach was previously developed for ILC and handles a certain class of ILC methods. Here methods are created to include zero-phase filtering that is very important in creating practical designs. Also, time domain methods are developed for higher order ILC and for repetitive control. Since RC and ILC must be implemented digitally, all of these methods predict final error levels at the sample times. It is shown here that RC can easily converge to small error levels between sample times, but that ILC in most applications will have large and diverging intersample error if in fact zero error is reached at the sample times. This is independent of the ILC law used, and is purely a property of the physical system. Methods are developed to address this issue.
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Optimization of Helium Vessel Design for ILC Cavities
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fratangelo, Enrico
2009-01-01
The ILC (International Linear Collider) is a proposed new major particle accelerator. It consists of two 20 km long linear accelerators colliding electrons and positrons at an energy exceeding 500 GeV, Achieving this collision energy while keeping reasonable accelerator dimensions requires the use of high electric field superconducting cavities as the main acceleration element. These cavities are operated at l.3 GHz inside an appropriate container (He vessel) at temperatures as low as 1.4 K using superfluid Helium as the refrigerating medium. The purpose of this thesis, in the context of the ILC R&D activities currently in progress at Fermilab (Fermimore » National Accelerator Laboratory), is the mechanical study of an ILC superconducting cavity and Helium vessel prototype. The main goals of these studies are the determination of the limiting working conditions of the whole He vessel assembly, the simulation of the manufacturing process of the cavity end-caps and the assessment of the Helium vessel's efficiency. In addition this thesis studies the requirements to certify the compliance with the ASME Code of the whole cavity/vessel assembly. Several Finite Elements Analyses were performed by the candidate himself in order to perform the studies listed above and described in detail in Chapters 4 through 8. ln particular the candidate has developed an improved procedure to obtain more accurate results with lower computational times. These procedures will be accurately described in the following chapters. After an introduction that briefly describes the Fennilab and in particular the Technical Division (where all the activities concerning with this thesis were developed), the first part of this thesis (Chapters 2 and 3) explains some of the main aspects of modem particle accelerators. Moreover it describes the most important particle accelerators working at the moment and the basic features of the ILC project. Chapter 4 describes all the activities that were done to certify the compliance of the Helium vessel and the cavity to the ASME code standard. After briefly recalling to the main contents of the the ASME Code (Sections II and Vlll - Division ll), the procedure used for finding all relevant stresses and comparing the obtained results with the maximum values allowed are explained. This part also includes the buckling verification of the cavity. In Chapter 5 the manufacturing process of the cavity end-caps, whose function is to link the Helium vessel with the cavity, is studied. The present configuration of the dies is described and the manufacturing process is simulated in order to explain the origin of some defects fol.llld on real parts. Finally a new design of the dies is proposed and the resulting deformed piece is compared with the design requirements. Chapter 6 describes a finite elements analysis to assess the efficiency and the stiffness of the Helium vessel. Furthermore the results of the optimization of the Helium vessel (in order to increase the value of the efficiency) are reported. The same stiffness analysis is used in Chapter 7 for the Blade-Tuner study. After a description of this tuner and of its function, the preliminary analyses done to confirm the results provided by the vendor are described and then its limiting load conditions are found. Chapter 8 shows a study of the resistance of all the welds present in between the cavity and the end-cap and between the end-caps and the He vessel for a smaller superconducting cavity operating at 3.9 GHz. Finally Chapter 9 briefly describes some R&D activities in progress at INFN (Section of Pisa) and Fermilab that could produce significant cost reductions of the Helium vessel design. All the finite elements analyses contained and described in this thesis made possible the certification of the whole superconducting cavity-Helium vessel assembly at Fermilab. Furthermore they gave several useful indications to the Fermilab staff to improve the performance of the Helium vessel by modifying some design parameters or refining the manufacturing processes.« less
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Circulating innate lymphoid cells are unchanged in response to DAC HYP therapy.
Gillard, Geoffrey O; Saenz, Steven A; Huss, David J; Fontenot, Jason D
2016-05-15
Innate lymphoid cells (ILCs) play an important role in immunity, inflammation, and tissue remodeling and their dysregulation is implicated in autoimmune and inflammatory disorders. We analyzed the impact of daclizumab, a humanized monoclonal anti-CD25 antibody, on circulating natural killer (NK) cells and ILCs in a cohort of multiple sclerosis patients. An increase in CD56(bright) NK cells and CD56(hi)CD16(intermediate) transitional NK cells was observed. No significant change in total ILCs or major ILC subpopulations was observed. These results refine our understanding of the impact of daclizumab on innate lymphoid cell populations. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
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Cryogenic performance of a conduction-cooling splittable quadrupole magnet for ILC cryomodules
NASA Astrophysics Data System (ADS)
Kimura, N.; Andreev, N.; Kashikhin, V. S.; Kerby, J.; Takahashi, M.; Tartaglia, M. A.; Tosaka, T.; Yamamoto, A.
2014-01-01
A conduction-cooled splittable superconducting quadrupole magnet was designed and fabricated at Fermilab for use in cryomodules of the International Linear Collider (ILC) type, in which the magnet was to be assembled around the beam tube to avoid contaminating the ultraclean superconducting radio frequency cavity volume. This quadrupole was first tested in a liquid helium bath environment at Fermilab, where its quench and magnetic properties were characterized. Because the device is to be cooled by conduction when installed in cryomodules, a separate test with a conduction-cooled configuration was planned at KEK and Fermilab. The magnet was converted to a conduction-cooled configuration by adding conduction-cooling passages made of high-purity aluminum. Efforts to convert and refabricate the magnet into a cryostat equipped with a double-stage pulse-tube-type cryocooler began in 2011, and a thermal performance test, including a magnet excitation test of up to 30 A, was conducted at KEK. In this test, the magnet with the conduction-cooled configuration was successfully cooled to 4 K within 190 h, with an acceptable heat load of less than 1 W at 4 K. It was also confirmed that the conduction-cooled splittable superconducting quadrupole magnet was practical for use in ILC-type cryomodules.
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Halim, Timotheus Y F; Rana, Batika M J; Walker, Jennifer A; Kerscher, Bernhard; Knolle, Martin D; Jolin, Helen E; Serrao, Eva M; Haim-Vilmovsky, Liora; Teichmann, Sarah A; Rodewald, Hans-Reimer; Botto, Marina; Vyse, Timothy J; Fallon, Padraic G; Li, Zhi; Withers, David R; McKenzie, Andrew N J
2018-06-19
The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7ra Cre/+ Tnfsf4 fl/fl mice). Moreover, Il7ra Cre/+ Tnfsf4 fl/fl mice failed to mount effective Th2 and Treg cell responses and corresponding adaptive type 2 pulmonary inflammation arising from Nippostrongylus brasiliensis infection or allergen exposure. Thus, the increased expression of OX40L in response to IL-33 acts as a licensing signal in the orchestration of tissue-specific adaptive type 2 immunity, without which this response fails to establish. Copyright © 2018 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.
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Radiation Requirements and Testing of Cryogenic Thermometers for the Ilc
NASA Astrophysics Data System (ADS)
Barnett, T.; Filippov, Yu. P.; Filippova, E. Yu.; Mokhov, N. V.; Nakao, N.; Klebaner, A. L.; Korenev, S. A.; Theilacker, J. C.; Trenikhina, J.; Vaziri, K.
2008-03-01
Large quantity of cryogenic temperature sensors will be used for operation of the International Linear Collider (ILC). Most of them will be subject to high radiation doses during the accelerator lifetime. Understanding of particle energy spectra, accumulated radiation dose in thermometers and its impact on performance are vital in establishing technical specification of cryogenic thermometry for the ILC. Realistic MARS15 computer simulations were performed to understand the ILC radiation environment. Simulation results were used to establish radiation dose requirements for commercially available cryogenic thermometers. Two types of thermometers, Cernox® and TVO, were calibrated prior to irradiation using different technique. The sensors were subjected then to up to 200 kGy electron beam irradiation with kinetic energy of 5 MeV, a representative of the situation at the ILC operation. A post-irradiation behavior of the sensors was studied. The paper describes the MARS15 model, simulation results, cryogenic test set-up, irradiation tests, and cryogenic test results.
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NASA Astrophysics Data System (ADS)
Yan, Fei; Tian, Fuli; Shi, Zhongke
2016-10-01
Urban traffic flows are inherently repeated on a daily or weekly basis. This repeatability can help improve the traffic conditions if it is used properly by the control system. In this paper, we propose a novel iterative learning control (ILC) strategy for traffic signals of urban road networks using the repeatability feature of traffic flow. To improve the control robustness, the ILC strategy is further integrated with an error feedback control law in a complementary manner. Theoretical analysis indicates that the ILC-based traffic signal control methods can guarantee the asymptotic learning convergence, despite the presence of modeling uncertainties and exogenous disturbances. Finally, the impacts of the ILC-based signal control strategies on the network macroscopic fundamental diagram (MFD) are examined. The results show that the proposed ILC-based control strategies can homogenously distribute the network accumulation by controlling the vehicle numbers in each link to the desired levels under different traffic demands, which can result in the network with high capacity and mobility.
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Type two innate lymphoid cells; the Janus cells in health and disease
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
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Epidermal Notch1 recruits RORγ(+) group 3 innate lymphoid cells to orchestrate normal skin repair.
Li, Zhi; Hodgkinson, Tom; Gothard, Elizabeth J; Boroumand, Soulmaz; Lamb, Rebecca; Cummins, Ian; Narang, Priyanka; Sawtell, Amy; Coles, Jenny; Leonov, German; Reboldi, Andrea; Buckley, Christopher D; Cupedo, Tom; Siebel, Christian; Bayat, Ardeshir; Coles, Mark C; Ambler, Carrie A
2016-04-21
Notch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal. Epidermal Notch induces recruitment of immune cell subsets including RORγ(+) ILC3s into wounded dermis; RORγ(+) ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for RORγ(+) ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNFα and the ILC3 recruitment chemokines CCL20 and CXCL13. TNFα, as a Notch1 effector, directs ILC3 localization and rates of wound healing. Altogether these findings suggest that Notch is a key stress/injury signal in skin epithelium driving innate immune cell recruitment and normal skin tissue repair.
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Evaluation of Calibration Laboratories Performance
NASA Astrophysics Data System (ADS)
Filipe, Eduarda
2011-12-01
One of the main goals of interlaboratory comparisons (ILCs) is the evaluation of the laboratories performance for the routine calibrations they perform for the clients. In the frame of Accreditation of Laboratories, the national accreditation boards (NABs) in collaboration with the national metrology institutes (NMIs) organize the ILCs needed to comply with the requirements of the international accreditation organizations. In order that an ILC is a reliable tool for a laboratory to validate its best measurement capability (BMC), it is needed that the NMI (reference laboratory) provides a better traveling standard—in terms of accuracy class or uncertainty—than the laboratories BMCs. Although this is the general situation, there are cases where the NABs ask the NMIs to evaluate the performance of the accredited laboratories when calibrating industrial measuring instruments. The aim of this article is to discuss the existing approaches for the evaluation of ILCs and propose a basis for the validation of the laboratories measurement capabilities. An example is drafted with the evaluation of the results of mercury-in-glass thermometers ILC with 12 participant laboratories.
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Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells
Rauber, Simon; Luber, Markus; Weber, Stefanie; Maul, Lisa; Soare, Alina; Wohlfahrt, Thomas; Lin, Neng-Yu; Dietel, Katharina; Bozec, Aline; Herrmann, Martin; Kaplan, Mark H.; Weigmann, Benno; Zaiss, Mario M.; Fearon, Ursula; Veale, Douglas J.; Canete, Juan D.; Distler, Oliver; Rivellese, Felice; Pitzalis, Costantino; Neurath, Markus F.; McKenzie, Andrew N.J.; Wirtz, Stefan; Schett, Georg; Distler, Jörg H.W.; Ramming, Andreas
2017-01-01
Inflammatory diseases such as arthritis are chronic conditions that fail to resolve spontaneously. While the cytokine and cellular pathways triggering arthritis are well defined, those responsible for the resolution of inflammation are incompletely characterized. Here we identified IL-9-producing type 2 innate lymphoid cells (ILC2s) as a molecular and cellular pathway that orchestrates the resolution of chronic inflammation. In mice, the absence of IL-9 impaired ILC2 proliferation, activation of regulatory T cells (Treg) and resulted in chronic arthritis with excessive cartilage destruction and bone loss. In contrast, treatment with IL-9 promoted ILC2-dependent Treg activation and effectively induced resolution of inflammation and protection of bone. Rheumatoid arthritis patients in remission demonstrated high numbers of IL-9+ ILC2s in the joints and in the circulation. Hence, fostering IL-9-mediated ILC2 activation may offer a novel therapeutic approach inducing resolution of inflammation rather than suppression of inflammatory responses. PMID:28714991
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Optical Wireless Communications
NASA Astrophysics Data System (ADS)
Arnon, Shlomi; Britz, David M.; Boucouvalas, Anthony C.; Kavehrad, Mohsen
2005-01-01
Call for Papers
Optical Wireless Communications
Submission Deadline: 1 February 2005Guest Editors: .showcase,.showcasetransportation{opacity:1}.content-list-widget .header-box .title{color:#fff }.content-list-widget .header-box{background-color:#0079C2;border-bottom:5px solid #00A4E4}ul.fa-blue-arrow a::before{font-family:FontAwesome;content:'\\f138';margin:0 5px 0 -15px;color:#0079C2;text-indent
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Shikhagaie, Medya Mara; Björklund, Åsa K; Mjösberg, Jenny; Erjefält, Jonas S; Cornelissen, Anne S; Ros, Xavier Romero; Bal, Suzanne M; Koning, Jasper J; Mebius, Reina E; Mori, Michiko; Bruchard, Melanie; Blom, Bianca; Spits, Hergen
2017-02-14
Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1 + group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1 + ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1 + ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1 - cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1 + ILC3s. NRP1 + ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
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Hsu, Wei-Chuan; Cheng, Chu-Nian; Lee, Te-Wei; Hwang, Jeng-Jong
2015-09-01
We aimed to construct epidermal growth factor receptor (EGFR)-targeting cetuximab-immunoliposomes (IL-C225) for targeted delivery of doxorubicin and rhenium-188 (Re-188) to EGFR(+) cancer cells. Synthesized IL-C225 was analyzed by dynamic light scattering, transmission electron microscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. Cell binding and internalization were examined using doxorubicin-loaded IL-C225 (DXR-IL-C225) with confocal microscopy. IL-C225 combined with doxorubicin and Re-188 ((188)Re-DXR-IL-C225) was synthesized, and the cytotoxic effects of (188)Re-DXR-IL-C225 were analyzed in EGFR(+) cancer cells using cell viability assays. IL-C225 bound to EGFR on A431 cancer cells and was rapidly internalized. Furthermore, IL-C225 localized within the tumor cells efficiently. (188)Re-DXR-IL-C225 exhibited outstanding cytotoxic effects against EGFR(+) cancer cells in vitro and showed superior cytotoxic effects compared to DXR-IL-C225 or (188)Re-IL-C225 alone. The new formulation of (188)Re-DXR-IL-C225 may be a potential theranostic vehicle for delivery of drugs in the treatment of EGFR-overexpressing human cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
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Luci, Carmelo; Bekri, Selma; Bihl, Franck; Pini, Jonathan; Bourdely, Pierre; Nouhen, Kelly; Malgogne, Angélique; Walzer, Thierry; Braud, Véronique M.; Anjuère, Fabienne
2015-01-01
Innate and adaptive immune cells work in concert to generate efficient protection at mucosal surface. Vaginal mucosa is an epithelial tissue that contains innate and adaptive immune effector cells. Our previous studies demonstrated that vaginal administration of Cholera toxin -based vaccines generate antigen-specific CD8 T cells through the stimulation of local dendritic cells (DC). Innate lymphoid cells (ILC) are a group of lymphocytes localized in epithelial tissues that have important immune functions against pathogens and in tissue homeostasis. Their contribution to vaccine-induced mucosal T cell responses is an important issue for the design of protective vaccines. We report here that the vaginal mucosa contains a heterogeneous population of NKp46+ ILC that includes conventional NK cells and ILC1-like cells. We show that vaginal NKp46+ ILC dampen vaccine-induced CD8 T cell responses generated after local immunization. Indeed, in vivo depletion of NKp46+ ILC with anti-NK1.1 antibody or NKG2D blockade increases the magnitude of vaginal OVA-specific CD8 T cells. Furthermore, such treatments also increase the number of DC in the vagina. NKG2D ligands being expressed by vaginal DC but not by CD8 T cells, these results support that NKp46+ ILC limit mucosal CD8 T cell responses indirectly through the NKG2D-dependent elimination of vaginal DC. Our data reveal an unappreciated role of NKp46+ ILC in the regulation of mucosal CD8 T cell responses. PMID:26630176
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Embedding Fonts in MetaPost Output
2016-04-19
by John Hobby ) based on Donald Knuth’s META- FONT [4] with high quality PostScript output. An outstanding feature of MetaPost is that typeset fonts in...output, the graphics are perfectly scalable to any arbitrary res- olution. John Hobby , its author, writes: “[MetaPost] is really a programming lan- guage...for generating graphics, especially fig- ures for TEX [5] and troff documents.” This quote by Hobby indicates that MetaPost figures are not only
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Ying, Xinyu; Su, Zhaoliang; Bie, Qingli; Zhang, Pan; Yang, Huijian; Wu, Yumin; Xu, Yunyun; Wu, Jing; Zhang, Mengying; Wang, Shengjun; Xu, Huaxi
2016-06-01
In recent years, T helper (Th) 9 cells have been demonstrated to be key mediators in immune responses in asthmatic lungs, and innate lymphoid cells 2 (ILC2s) have been described as a novel type of innate immunocyte with the ability to enhance immunoglobulin E (IgE) production. However, the interaction between ILC2s and Th9 cells in the pulmonary system of a mouse model of asthma remains to be elucidated. In the present study, the response state of lung tissue with regards to Th9 and ILC2s in a mouse model of asthma was investigated by detecting Th9‑ and ILC2‑associated cytokine receptors. The present study also investigated the association between the expression levels of the cytokine receptors in lung tissue samples and the IgE levels in sera samples from mouse models of asthma. Results from the present study demonstrated that the frequency of ILC2s and Th9 cells was significantly increased in the lung tissue samples, indicating that a Th2-type immune response had occurred. In addition, high mRNA expression levels of RAR‑related orphan receptor α, interleukin 1 receptor‑like 1, transcription factor PU.1 and interleukin (IL)‑9 were observed. Furthermore, IL‑5Rα, IL‑13Rα2 and high‑affinity IgE receptor were increased in mouse models of asthma, and a positive association was observed between the expression levels of ILC2‑ or Th9‑associated receptors in tissue samples and IgE levels in the sera. This indicated that ILC2s and Th9 were in a state of polarization and may promote each other in the lung tissue of mouse models of asthma, and that the lung tissue was responding to the two types of cells via increased expression of receptors.
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Immune Modules Shared by Innate Lymphoid Cells and T Cells
Robinette, Michelle L.; Colonna, Marco
2016-01-01
In recent years, innate lymphoid cells (ILCs) have emerged as innate correlates to T cells. The similarities between ILCs and T cells indicate that lymphocytes of fundamentally distinct lineages can share core “immune modules” that encompass transcriptional circuitry and effector functions, while utilizing non-redundant, complementary mechanisms of pattern recognition to enact these functions. We review modules currently recognized to be shared between ILCs and T cells. PMID:27817796
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Higgs boson production in the littlest Higgs model with T-parity at the ILC
NASA Astrophysics Data System (ADS)
Han, Jinzhong; Yang, Guang; Meng, Ming; Wang, Weijian; Li, Jingyun
2018-04-01
We investigate the Higgs boson production processes e+e‑→ ZH, e+e‑→ νν¯H, e+e‑→ tt¯H, e+e‑→ ZHH and e+e‑→ νν¯HH in the littlest Higgs model with T-parity (LHT) at the International Linear Collider (ILC). We calculate the LHT model predictions on the production rate of these processes at the ILC in the case of (un)polarized beams and the signal strengths of the production processes ZH and νν¯H with Higgs decaying to bb¯(gg,γγ). In the allowed parameter space, we find that the signal strengths μgg is most likely approach to the expected precision of the ILC.
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Baloch, A H; Khosa, A N; Bangulzai, N; Sadia, H; Ahmed, M; Khan, F; Jan, M; Tareen, M; Kakar, M H; Shuja, J; Naseeb, H K; Ahmad, J
2016-01-01
Invasive lobular carcinoma (ILC) is the second most common type of breast cancer accounting for 5%-15% of all the breast cancer cases. The present study was performed on 171 breast cancer patients from Balochistan registered in CENAR (Center for Nuclear Medicine and Radiotherapy), Quetta. Written consent was obtained from the patients. The history of the disease was taken from the patients, and the patients' enrollment files were retrieved. Of the 171 patients, 5 (2.96%) were diagnosed with ILC with tumor Grade II, and stage of the cancer reported was Grade III in all the 5 patients affected with ILC. ILC is the second most common type of breast cancer diagnosed with comparatively lower grade but almost reported infiltrating.
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Wei, Xin; Wang, Jiu-Ping; Hao, Chun-Qiu; Yang, Xiao-Fei; Wang, Lin-Xu; Huang, Chang-Xing; Bai, Xue-Fan; Lian, Jian-Qi; Zhang, Ye
2016-01-01
The mechanism of hepatitis B virus (HBV) induced liver inflammation is not fully elucidated. Notch signaling augmented interleukin (IL)-22 secretion in CD4+ T cells, and Notch-IL-22 axis fine-tuned inflammatory response. We previously demonstrated a proinflammatory role of IL-22 in HBV infection. Thus, in this study, we analyzed the role of Notch in development of IL-22-producing cells in HBV infection by inhibition of Notch signaling using γ-secretase inhibitor DAPT in both hydrodynamic induced HBV-infected mouse model and in peripheral blood cells isolated from patients with HBV infection. mRNA expressions of Notch1 and Notch2 were significantly increased in livers and CD4+ T cells upon HBV infection. Inhibition of Notch signaling in vivo leaded to the reduction in NKp46+ innate lymphoid cells 22 (ILC22) and lymphoid tissue inducer 4 (LTi4) cells in the liver. This process was accompanied by downregulating the expressions of IL-22 and related proinflammatory cytokines and chemokines in the liver, as well as blocking the recruitment of antigen-non-specific inflammatory cells into the liver and subsequent liver injury, but did not affect HBV antigens production and IL-22 secretion in the serum. Furthermore, IL-22 production in HBV non-specific cultured CD4+ T cells, but not HBV-specific CD4+ T cells, was reduced in response to in vitro inhibition of Notch signaling. In conclusion, Notch siganling appears to be an important mediator of the liver inflammation by modulating hepatic ILC22. The potential proinflammatory effect of Notch-mediated ILC22 may be significant for the development of new therapeutic approaches for treatment of hepatitis B. PMID:27800305
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A critical look at spatial scale choices in satellite-based aerosol indirect effect studies
NASA Astrophysics Data System (ADS)
Grandey, B. S.; Stier, P.
2010-06-01
Analysing satellite datasets over large regions may introduce spurious relationships between aerosol and cloud properties due to spatial variations in aerosol type, cloud regime and synoptic regime climatologies. Using MODerate resolution Imaging Spectroradiometer data, we calculate relationships between aerosol optical depth τa, derived liquid cloud droplet effective number concentration Ne and liquid cloud droplet effective radius re at different spatial scales. Generally, positive values of dlnNe dlnτa are found for ocean regions, whilst negative values occur for many land regions. The spatial distribution of dlnre dlnτa shows approximately the opposite pattern, with generally postive values for land regions and negative values for ocean regions. We find that for region sizes larger than 4°×4°, spurious spatial variations in retrieved cloud and aerosol properties can introduce widespread significant errors to calculations of dlnNe dlnτa and dlnre dlnτa . For regions on the scale of 60°×60°, these methodological errors may lead to an overestimate in global cloud albedo effect radiative forcing of order 80%.
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Cochez, Perrine M; Michiels, Camille; Hendrickx, Emilie; Van Belle, Astrid B; Lemaire, Muriel M; Dauguet, Nicolas; Warnier, Guy; de Heusch, Magali; Togbe, Dieudonnée; Ryffel, Bernhard; Coulie, Pierre G; Renauld, Jean-Christophe; Dumoutier, Laure
2016-06-01
IL-22 has a detrimental role in skin inflammatory processes, for example in psoriasis. As transcription factor, AhR controls the IL-22 production by several cell types (i.e. Th17 cells). Here, we analyzed the role of Ahr in IL-22 production by immune cells in the inflamed skin, using an imiquimod-induced psoriasis mouse model. Our results indicate that IL-22 is expressed in the ear of imiquimod-treated Ahr(-/-) mice but less than in wild-type mice. We then studied the role of AhR on three cell populations known to produce IL-22 in the skin: γδ T cells, Th17 cells, and ILC3, and a novel IL-22-producing cell type identified in this setting: CD4(-) CD8(-) TCRβ(+) T cells. We showed that AhR is required for IL-22 production by Th17, but not by the three other cell types, in the imiquimod-treated ears. Moreover, AhR has a role in the recruitment of γδ T cells, ILC3, and CD4(-) CD8(-) TCRβ(+) T cells into the inflamed skin or in their local proliferation. Taken together, AhR has a direct role in IL-22 production by Th17 cells in the mouse ear skin, but not by γδ T cells, CD4(-) CD8(-) TCRβ(+) T cells and ILCs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Verhoef, Philip A; Constantinides, Michael G; McDonald, Benjamin D; Urban, Joseph F; Sperling, Anne I; Bendelac, Albert
2016-02-01
The transcription factor promyelocytic leukemia zinc finger (PLZF) is transiently expressed during development of type 2 innate lymphoid cells (ILC2s) but is not present at the mature stage. We hypothesized that PLZF-deficient ILC2s have functional defects in the innate allergic response and represent a tool for studying innate immunity in a mouse with a functional adaptive immune response. We determined the consequences of PLZF deficiency on ILC2 function in response to innate and adaptive immune stimuli by using PLZF(-/-) mice and mixed wild-type:PLZF(-/-) bone marrow chimeras. PLZF(-/-) mice, wild-type littermates, or mixed bone marrow chimeras were treated with the protease allergen papain or the cytokines IL-25 and IL-33 or infected with the helminth Nippostrongylus brasiliensis to induce innate type 2 allergic responses. Mice were sensitized with intraperitoneal ovalbumin-alum, followed by intranasal challenge with ovalbumin alone, to induce adaptive TH2 responses. Lungs were analyzed for immune cell subsets, and alveolar lavage fluid was analyzed for ILC2-derived cytokines. In addition, ILC2s were stimulated ex vivo for their capacity to release type 2 cytokines. PLZF-deficient lung ILC2s exhibit a cell-intrinsic defect in the secretion of IL-5 and IL-13 in response to innate stimuli, resulting in defective recruitment of eosinophils and goblet cell hyperplasia. In contrast, the adaptive allergic inflammatory response to ovalbumin and alum was unimpaired. PLZF expression at the innate lymphoid cell precursor stage has a long-range effect on the functional properties of mature ILC2s and highlights the importance of these cells for innate allergic responses in otherwise immunocompetent mice. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.
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Derias, Mina; Subramanian, Ashok; Allan, Simon; Shah, Elizabeth; Teraifi, Hassan El; Howlett, David
2016-07-01
Invasive lobular carcinoma (ILC) accounts for 5-15% of breast cancers. In comparison to other types of breast cancer, ILC is more likely to be associated with multifocal and contralateral breast involvement as well as a tendency to a diffuse infiltrative growth pattern which can represent a diagnostic challenge. The National Institute of Clinical Excellence guidelines in 2009 recommended the use of magnetic resonance imaging (MRI) in the preoperative assessment of ILC. This study aims to assess compliance with the guidelines in two District General Hospitals and the utility of MRI in the investigation of ILC. All cases of ILC between 2011 and 2013 were retrospectively identified from the pathology database and their breast imaging findings, pathology report, and operative intervention were reviewed. A total of 126 patients were identified with ILC, of these 46 had MRI preoperatively (36.5%). MRI upgraded mammography/ultrasound diagnoses in 10 patients (21.7%). MRI showed multicentric unilateral disease in 17 patients (37.0%) occult on ultrasound/mammogram, with these patients undergoing mastectomy and 16/17 (94.1%) confirmed multifocality on pathology. MRI showed a contralateral lesion in 9 patients (19.6%), four (8.7%) of which were malignant and had bilateral surgery, and five (10.9%) were benign on further imaging/biopsy. MRI also downgraded three patients (6.5%) to unifocal disease with reported multifocal appearances on mammography/ultrasound, and these patients underwent breast-conserving surgery. MRI adds significant additional information to mammograms/ultrasound in ILC and should be undertaken in all such cases preoperatively assuming no contraindication. © 2016 Wiley Periodicals, Inc.
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Monticelli, Laurel A; Osborne, Lisa C; Noti, Mario; Tran, Sara V; Zaiss, Dietmar M W; Artis, David
2015-08-25
The barrier surfaces of the skin, lung, and intestine are constantly exposed to environmental stimuli that can result in inflammation and tissue damage. Interleukin (IL)-33-dependent group 2 innate lymphoid cells (ILC2s) are enriched at barrier surfaces and have been implicated in promoting inflammation; however, the mechanisms underlying the tissue-protective roles of IL-33 or ILC2s at surfaces such as the intestine remain poorly defined. Here we demonstrate that, following activation with IL-33, expression of the growth factor amphiregulin (AREG) is a dominant functional signature of gut-associated ILC2s. In the context of a murine model of intestinal damage and inflammation, the frequency and number of AREG-expressing ILC2s increases following intestinal injury and genetic disruption of the endogenous AREG-epidermal growth factor receptor (EGFR) pathway exacerbated disease. Administration of exogenous AREG limited intestinal inflammation and decreased disease severity in both lymphocyte-sufficient and lymphocyte-deficient mice, revealing a previously unrecognized innate immune mechanism of intestinal tissue protection. Furthermore, treatment with IL-33 or transfer of ILC2s ameliorated intestinal disease severity in an AREG-dependent manner. Collectively, these data reveal a critical feedback loop in which cytokine cues from damaged epithelia activate innate immune cells to express growth factors essential for ILC-dependent restoration of epithelial barrier function and maintenance of tissue homeostasis.
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Type two innate lymphoid cells: the Janus cells in health and disease.
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.
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Cheng, Hang; Jin, Chengyan; Wu, Jing; Zhu, Shan; Liu, Yong-Jun; Chen, Jingtao
2017-12-01
The lung is an important open organ and the primary site of respiration. Many life-threatening diseases develop in the lung, e.g., pneumonia, asthma, chronic obstructive pulmonary diseases (COPDs), pulmonary fibrosis, and lung cancer. In the lung, innate immunity serves as the frontline in both anti-irritant response and anti-tumor defense and is also critical for mucosal homeostasis; thus, it plays an important role in containing these pulmonary diseases. Innate lymphoid cells (ILCs), characterized by their strict tissue residence and distinct function in the mucosa, are attracting increased attention in innate immunity. Upon sensing the danger signals from damaged epithelium, ILCs activate, proliferate, and release numerous cytokines with specific local functions; they also participate in mucosal immune-surveillance, immune-regulation, and homeostasis. However, when their functions become uncontrolled, ILCs can enhance pathological states and induce diseases. In this review, we discuss the physiological and pathological functions of ILC subsets 1 to 3 in the lung, and how the pathogenic environment affects the function and plasticity of ILCs.
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Human innate lymphoid cells (ILCs) in filarial infections.
Bonne-Année, S; Nutman, T B
2018-02-01
Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
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Corrosion on Fatigue and Fatigue Crack Growth in Aircraft Structural Materials
1979-06-01
nmonth- of 1Q730 v,’ ilc th au!Ihor xas. a! !Lockhehed Rvye (anyon Adva.nce,1d tj;ion in(I Research Laboratory. Mr. Gary Gos’s andl Mr. WValter Fitze ti...frtaerltd o11 1~ a cuea o rnicr srruae. 150x.IILI’ r11da- o p sdo’ l-akddi pe.Fgrc ()id4()c hl’ micro,,ructura ’Setd ~ ila i l--n ig ilc to ~IiiCId...bart 16 iretorted increcascd fatigue 0 t C Id ’ L5 treg th fof t eiii I Ic iti:ci st to L)i poic ed lirfe r; irnod a Ipho -teta or f inef~t
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Anthropomorphic robot for recognition and drawing generalized object images
NASA Astrophysics Data System (ADS)
Ginzburg, Vera M.
1998-10-01
The process of recognition, for instance, understanding the text, written by different fonts, consists in the depriving of the individual attributes of the letters in the particular font. It is shown that such process, in Nature and technique, can be provided by the narrowing the spatial frequency of the object's image by its defocusing. In defocusing images remain only areas, so-called Informative Fragments (IFs), which all together form the generalized (stylized) image of many identical objects. It is shown that the variety of shapes of IFs is restricted and can be presented by `Geometrical alphabet'. The `letters' for this alphabet can be created using two basic `genetic' figures: a stripe and round spot. It is known from physiology that the special cells of visual cortex response to these particular figures. The prototype of such `genetic' alphabet has been made using Boolean algebra (Venn's diagrams). The algorithm for drawing the letter's (`genlet's') shape in this alphabet and generalized images of objects (for example, `sleeping cat'), are given. A scheme of an anthropomorphic robot is shown together with results of model computer experiment of the robot's action--`drawing' the generalized image.
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The GeantV project: Preparing the future of simulation
Amadio, G.; J. Apostolakis; Bandieramonte, M.; ...
2015-12-23
Detector simulation is consuming at least half of the HEP computing cycles, and even so, experiments have to take hard decisions on what to simulate, as their needs greatly surpass the availability of computing resources. New experiments still in the design phase such as FCC, CLIC and ILC as well as upgraded versions of the existing LHC detectors will push further the simulation requirements. Since the increase in computing resources is not likely to keep pace with our needs, it is therefore necessary to explore innovative ways of speeding up simulation in order to sustain the progress of High Energymore » Physics. The GeantV project aims at developing a high performance detector simulation system integrating fast and full simulation that can be ported on different computing architectures, including CPU accelerators. After more than two years of R&D the project has produced a prototype capable of transporting particles in complex geometries exploiting micro-parallelism, SIMD and multithreading. Portability is obtained via C++ template techniques that allow the development of machine- independent computational kernels. Furthermore, a set of tables derived from Geant4 for cross sections and final states provides a realistic shower development and, having been ported into a Geant4 physics list, can be used as a basis for a direct performance comparison.« less
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Immune modules shared by innate lymphoid cells and T cells.
Robinette, Michelle L; Colonna, Marco
2016-11-01
In recent years, innate lymphoid cells (ILCs) have emerged as innate correlates to T cells. The similarities between ILCs and T cells indicate that lymphocytes of fundamentally distinct lineages can share core "immune modules" that encompass transcriptional circuitry and effector functions while using nonredundant complementary mechanisms of pattern recognition to enact these functions. We review modules currently recognized to be shared between ILCs and T cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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A Descriptive Study of the DoD-Managed Freight Forwarder Concept.
1986-09-01
AFLC/PMPO AMSAC-OL/ 7 AFLC ILC/ AWST MTMCEA/ ITEL AFLC ILC/EC MTMC-ITX AFLC ILC/GB USN/OP-632B AF IT! LSM USN/SUP-07C DISAM/DIC USASAC-NCAD (OL/T) SAAC...commercial insurance coverage for the protection of all purchaser-owned FMS materiel while in custody of the freight forwarder. r . Process FMS customer...export for each shipment. r . Provide export boxing and marking if required. s. Carry out freight rate negotiations as required. t. Retrieve freight from
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Estudo espectral em raios-X duros de fontes do tipo Z com o HEXTE/RXTE
NASA Astrophysics Data System (ADS)
D'Amico, F.; Heindl, W. A.; Rothschild, R. E.
2003-08-01
Apresentam-se os resultados de um estudo espectral em raios-X de fontes do tipo Z. As fontes do tipo Z são binárias de raios-X de baixa massa (BXBM) com campo magnético intermediário (B~109G). Esta classe de fontes é composta por apenas 6 fontes Galácticas (a saber: ScoX-1, 9, 7, CygX-2, 5 e 0). A nossa análise se concentra na faixa de raios-X duros (E ~ 20keV), até cerca de 200keV, faixa ótima de operação do telescópio "High Energy X-ray Timing Experiment" (HEXTE), um dos três telescópios de raios-X à bordo do Rossi X-ray Timing Explorer (RXTE). Nossa motivação para tal estudo, uma busca de caudas em raios-X duros em fontes do tipo Z, foi o pouco conhecimento sobre a emissão nesta faixa de energia das referidas fontes quando comparadas, por exemplo, as fontes do tipo atoll (também BXBM). Apresentam-se a análise/redução de dados e explicita-se a maneira como o HEXTE mede o ru1do de fundo. Especial atenção é direcionada a este item devido a localização das fontes do tipo Z e também ao problema de contaminação por fontes próximas. Com exceção de ScoX-1, nenhuma cauda em raios-X duros foi encontrada para as outras fontes, a despeito de resultados de detecção dessas caudas em algumas fontes pelo satélite BeppoSAX. As interpretações deste resultado serão apresentadas. Do ponto de vista deste estudo, nós deduzimos que a produção de caudas de raios-X duros em fontes do tipo Z é um processo disparado quando, pelo menos, uma condição é satisfeita: o brilho da componente térmica do espectro precisa estar acima de um certo valor limiar de ~4´1036ergs-1.
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De Grove, Katrien C; Provoost, Sharen; Hendriks, Rudi W; McKenzie, Andrew N J; Seys, Leen J M; Kumar, Smitha; Maes, Tania; Brusselle, Guy G; Joos, Guy F
2017-01-01
Although the prominent role of T H 2 cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2s) can also contribute to orchestration of allergic responses. Several experimental and epidemiologic studies have provided evidence that allergen-induced airway responses can be further enhanced on exposure to environmental pollutants, such as diesel exhaust particles (DEPs). However, the components and pathways responsible remain incompletely known. We sought to investigate the relative contribution of ILC2 and adaptive T H 2 cell responses in a murine model of DEP-enhanced allergic airway inflammation. Wild-type, Gata-3 +/nlslacZ (Gata-3-haploinsufficient), RAR-related orphan receptor α (RORα) fl/fl IL7R Cre (ILC2-deficient), and recombination-activating gene (Rag) 2 -/- mice were challenged with saline, DEPs, or house dust mite (HDM) or DEP+HDM. Airway hyperresponsiveness, as well as inflammation, and intracellular cytokine expression in ILC2s and T H 2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed. Concomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, as characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2s and T H 2 cells, type 2 cytokine production, and airway hyperresponsiveness compared with sole DEPs or HDM. Reduced Gata-3 expression decreased the number of functional ILC2s and T H 2 cells in DEP+HDM-exposed mice, resulting in an impaired DEP-enhanced allergic airway inflammation. Interestingly, although the DEP-enhanced allergic inflammation was marginally reduced in ILC2-deficient mice that received combined DEP+HDM, it was abolished in DEP+HDM-exposed Rag2 -/- mice. These data indicate that dysregulation of ILC2s and T H 2 cells attenuates DEP-enhanced allergic airway inflammation. In addition, a crucial role for the adaptive immune system was shown on concomitant DEP+HDM exposure. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Banerjee, Jayeeta; Bhattacharyya, Moushum
2011-12-01
There is a rapid shifting of media: from printed paper to computer screens. This transition is modifying the process of how we read and understand text. The efficiency of reading is dependent on how ergonomically the visual information is presented. Font types and size characteristics have been shown to affect reading. A detailed investigation of the effect of the font type and size on reading on computer screens has been carried out by using subjective, objective and physiological evaluation methods on young adults. A group of young participants volunteered for this study. Two types of fonts were used: Serif fonts (Times New Roman, Georgia, Courier New) and Sans serif fonts (Verdana, Arial, Tahoma). All fonts were presented in 10, 12 and 14 point sizes. This study used a 6 X 3 (font type X size) design matrix. Participants read 18 passages of approximately the same length and reading level on a computer monitor. Reading time, ranking and overall mental workload were measured. Eye movements were recorded by a binocular eye movement recorder. Reading time was minimum for Courier New l4 point. The participants' ranking was highest and mental workload was least for Verdana 14 point. The pupil diameter, fixation duration and gaze duration were least for Courier New 14 point. The present study recommends using 14 point sized fonts for reading on computer screen. Courier New is recommended for fast reading while for on screen presentation Verdana is recommended. The outcome of this study will help as a guideline to all the PC users, software developers, web page designers and computer industry as a whole.
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NASA Astrophysics Data System (ADS)
Zadkov, Victor N.; Koroteev, Nikolai I.
1995-10-01
An experience of managing the continuing education and retraining programs at the International Laser Center (ILC) of Moscow State University is discussed. The offered programs are in a wide range of areas, namely laser physics and technology, laser biophysics and biomedicine, laser chemistry, and computers in laser physics. The attendees who are presumably scientists, engineers, technical managers, and graduate students can join these programs through the annual ILC term (6 months), individual training and research programs (up to a year), annual ILC Laser Graduate School, graduate study, and post-docs program, which are reviewed in the paper. A curriculum that includes basic and specialized courses is described in detail. A brief description of the ILC Laser Teaching and Computer Labs that support all the educational courses is given as well.
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Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.
Hoorweg, Kerim; Peters, Charlotte P; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M; Spits, Hergen; Cupedo, Tom
2012-01-01
Human RORC(+) lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC(+) innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC(+) innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44(+) IL-22 producing cells are present in tonsils while NKp44(-) IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44(+) ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44(+) ILC are the main ILC subset producing IL-22. NKp44(-) ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.
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NASA Astrophysics Data System (ADS)
Jain, S.
2017-03-01
The High Granularity Calorimeter (HGCAL) is the technology choice of the CMS collaboration for the endcap calorimetry upgrade planned to cope with the harsh radiation and pileup environment at the High Luminosity-LHC . The HGCAL is realized as a sampling calorimeter, including an electromagnetic compartment comprising 28 layers of silicon pad detectors with pad areas of 0.5-01. cm2 interspersed with absorbers made from tungsten and copper to form a highly compact and granular device. Prototype modules, based on hexagonal silicon pad sensors, with 128 channels, have been constructed and tested in beams at FNAL and at CERN. The modules include many of the features required for this challenging detector, including a PCB glued directly to the sensor, using through-hole wire-bonding for signal readout and 5 mm spacing between layers—including the front-end electronics and all services. Tests in 2016 have used an existing front-end chip —Skiroc2 (designed for the CALICE experiment for ILC). We present results from first tests of these modules both in the laboratory and with beams of electrons, pions and protons, including noise performance, calibration with mips and electron signals.
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Lapinski, Maria Knight; Randall, Liisa M; Peterson, Mark; Peterson, Amy; Klein, Katherine A
2009-09-01
This article reports the results of a small-scale quasi-experiment that tested the efficacy of the Prevention Options for Positives intervention. The experiment tested for the outcomes of group sessions combined with individual-level counseling (ILC) versus ILC-only for men who have sex with men who are HIV positive. Both arms of the intervention were based on behavior change theory and dealt specifically with communication outcomes. The results indicate that the group- and individual-level interventions combined have a greater impact on risk communication behaviors with main partners than did the ILC-only sessions. group-session/ILC participants were more likely to decide not to have sex if they were drunk or high, and more likely to tell their partner and ask their partner about HIV status than were participants in the ILC groups. Knowledge about HIV was relatively high, and there was little change across groups. The Prevention Options for Positives intervention influenced the relative importance of various referent groups, but normative beliefs were not affected. The implications of these findings for communication practice and research with HIV-positive men who have sex with men are addressed.
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Hirota, Keiji; Hashimoto, Motomu; Ito, Yoshinaga; Matsuura, Mayumi; Ito, Hiromu; Tanaka, Masao; Watanabe, Hitomi; Kondoh, Gen; Tanaka, Atsushi; Yasuda, Keiko; Kopf, Manfred; Potocnik, Alexandre J; Stockinger, Brigitta; Sakaguchi, Noriko; Sakaguchi, Shimon
2018-06-19
Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention. Copyright © 2018 Elsevier Inc. All rights reserved.
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Epigenomic Views of Innate Lymphoid Cells.
Sciumè, Giuseppe; Shih, Han-Yu; Mikami, Yohei; O'Shea, John J
2017-01-01
The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises other innate-like T lymphocytes. Beyond the recognition of specialized effector functionalities in diverse lymphocytes, features typical of T cells, such as plasticity and memory, are also relevant for innate lymphocytes. Herein, we review what we have learned in terms of the molecular mechanisms underlying these shared functions, focusing on insights provided by next generation sequencing technologies. We review data on the role of lineage-defining- and signal-dependent transcription factors (TFs). ILC regulomes emerge developmentally whereas the much of the open chromatin regions of T cells are generated acutely, in an activation-dependent manner. And yet, these regions of open chromatin in T cells and ILCs have remarkable overlaps, suggesting that though accessibility is acquired by distinct modes, the end result is that convergent signaling pathways may be involved. Although much is left to be learned, substantial progress has been made in understanding how TFs and epigenomic status contribute to ILC biology in terms of differentiation, specification, and plasticity.
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Innate lymphoid cells, precursors and plasticity.
Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas
2016-11-01
Innate lymphoid cells (ILC) have only recently been recognized as a separate entity of the lymphoid lineage. Their subpopulations share common characteristics in terms of early development and major transcriptional circuitry with their related cousins of the T cell world. It is currently hypothesized that ILCs constitute an evolutionary older version of the lymphoid immune system. They are found at all primary entry points for pathogens such as mucosal surfaces of the lung and gastrointestinal system, the skin and the liver, which is the central contact point for pathogens that breach the intestinal barrier and enter the circulation. There, ILC contribute to the first line defense as well as to organ homeostasis. However, ILC are not only involved in classical defense tasks, but also contribute to the organogenesis of lymphoid organs as well as tissue remodeling and even stem cell regeneration. ILC may, therefore, implement different functions according to their emergence in ontogeny, their development and their final tissue location. We will review here their early development from precursors of the fetal liver and the adult bone marrow as well as their late plasticity in adaptation to their environment. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
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Epigenomic Views of Innate Lymphoid Cells
Sciumè, Giuseppe; Shih, Han-Yu; Mikami, Yohei; O’Shea, John J.
2017-01-01
The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises other innate-like T lymphocytes. Beyond the recognition of specialized effector functionalities in diverse lymphocytes, features typical of T cells, such as plasticity and memory, are also relevant for innate lymphocytes. Herein, we review what we have learned in terms of the molecular mechanisms underlying these shared functions, focusing on insights provided by next generation sequencing technologies. We review data on the role of lineage-defining- and signal-dependent transcription factors (TFs). ILC regulomes emerge developmentally whereas the much of the open chromatin regions of T cells are generated acutely, in an activation-dependent manner. And yet, these regions of open chromatin in T cells and ILCs have remarkable overlaps, suggesting that though accessibility is acquired by distinct modes, the end result is that convergent signaling pathways may be involved. Although much is left to be learned, substantial progress has been made in understanding how TFs and epigenomic status contribute to ILC biology in terms of differentiation, specification, and plasticity. PMID:29250060
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bhattacharyya, Sampriti; Pilipenko, Roman; /Fermilab
2010-01-01
Superconducting accelerators, such as the International Linear Collider (ILC), rely on very high Q accelerating cavities to achieve high electric fields at low RF power. Such cavities have very narrow resonances: a few kHz with a 1.3GHz resonance frequency for the ILC. Several mechanical factors cause tune shifts much larger than this: pressure variations in the liquid helium bath; microphonics from pumps and other mechanical devices; and for a pulsed machine such as the ILC, Lorentz force detuning (pressure from the contained RF field). Simple passive stiffening is limited by many manufacturing and material considerations. Therefore, active tuning using piezomore » actuators is needed. Here we study a supply for their operation. Since commercial power amplifiers are expensive, we analyzed the characteristics of four power amplifiers: (iPZD) built by Istituto Nazionale di Fisica Nucleare (Sezione di Pisa); and a DC-DC converter power supply built in Fermilab (Piezo Master); and two commercial amplifiers, Piezosystem jena and Piezomechanik. This paper presents an analysis and characterization of these amplifiers to understand the cost benefit and reliability when using in a large scale, pulsed beam accelerator like the ILC.« less
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Machine-related backgrounds in the SiD detector at ILC
NASA Astrophysics Data System (ADS)
Denisov, D. S.; Mokhov, N. V.; Striganov, S. I.; Kostin, M. A.; Tropin, I. S.
2006-12-01
With a multi-stage collimation system and magnetic iron spoilers in the tunnel, the background particle fluxes on the ILC detector can be substantially reduced. At the same time, beam-halo interactions with collimators and protective masks in the beam delivery system create fluxes of muons and other secondary particles which can still exceed the tolerable levels for some of the ILC sub-detectors. Results of modeling of such backgrounds in comparison to those from the e+e- interactions are presented in this paper for the SiD detector.
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Cooperative Security in Northeast Asia. A China-Japan-South Korea Coalition Approach
1990-01-01
14)1) cSidllishl~ilg a sinIIdI4.i lis15 o I S treg (ional sccuh ii Of , orts. Of) licccss’i1 . scYcrdI I I(l IWtV \\ "ItIg"t CalV(Iiigi CM-t iaua tics...hoiliogtimi A -11 1)jiit(11]-(.( ( dl 0III 1Kmi (2 vI rl cnrl(111 ii(12 Oii~ f th an IiU 11(h2ld tid(2. I ilc - historic111es kt~Ii .ts he~ MSiiiitC...See- ietiarvN oF[ State \\( Ilcs (tIl (Iili 1101 Hiclittio the Korean P~eninisula inl (ItfIiniti ’s g’lobal sceur i initere’sts, ledl to the Soviet- land
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Cavity BPM system tests for the ILC energy spectrometer
NASA Astrophysics Data System (ADS)
Slater, M.; Adolphsen, C.; Arnold, R.; Boogert, S.; Boorman, G.; Gournaris, F.; Hildreth, M.; Hlaing, C.; Jackson, F.; Khainovski, O.; Kolomensky, Yu. G.; Lyapin, A.; Maiheu, B.; McCormick, D.; Miller, D. J.; Orimoto, T. J.; Szalata, Z.; Thomson, M.; Ward, D.; Wing, M.; Woods, M.
2008-07-01
The main physics programme of the International Linear Collider (ILC) requires a measurement of the beam energy at the interaction point with an accuracy of 10-4 or better. To achieve this goal a magnetic spectrometer using high resolution beam position monitors (BPMs) has been proposed. This paper reports on the cavity BPM system that was deployed to test this proposal. We demonstrate sub-micron resolution and micron level stability over 20 h for a 1 m long BPM triplet. We find micron-level stability over 1 h for 3 BPM stations distributed over a 30 m long baseline. The understanding of the behaviour and response of the BPMs gained from this work has allowed full spectrometer tests to be carried out.
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MERCURY REMOVAL FROM STACK GAS BY AQUEOUS SCRUBBING
Fundamental results will be obtained on the reaction kinetics in mass transfer boundary layers for the following systems:
- Hg(g)/Cl2(g)/SO2(g)/sulfite
Hg(g)/ClO2(g)/SO2... -
Marmor, Schelomo; Hui, Jane Yuet Ching; Huang, Jing Li; Kizy, Scott; Beckwith, Heather; Blaes, Anne H; Rueth, Natasha M; Tuttle, Todd M
2017-08-15
Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC. Women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 1 (HER2) -negative, stage I/II IDC and ILC who received endocrine therapy were identified from the 2000 to 2014 California Cancer Registry. Patient, tumor, and treatment characteristics were collected. Ten-year overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. In total, 32,997 women with IDC and 4638 with ILC were identified. The receipt of chemotherapy significantly decreased during the study for both subtypes. For patients with IDC, the 10-year OS rate was 95% among those who received endocrine therapy alone versus 93% (P < .01) among those who received endocrine therapy plus chemotherapy. For patients with ILC, the 10-year OS rate was 94% among those who received endocrine therapy alone versus 92% (P < .01) among those who received endocrine therapy plus chemotherapy. After adjusting for patient and treatment factors, adjuvant chemotherapy was significantly associated with a decreased 10-year hazard of death for patients with IDC (hazard ratio, 0.83; 95% confidence interval, 0.74-0.92). In contrast, adjuvant chemotherapy was not independently associated with the adjusted 10-year hazard of death for patients with ILC (hazard ratio, 1.14; 95% confidence interval, 0.90-1.46). Adjuvant chemotherapy was not associated with improved OS for patients with ER-positive, HER2-negative, stage I/II ILC. Avoidance of ineffective chemotherapy will markedly reduce the adverse effects and economic burden of breast cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society. © 2017 American Cancer Society.
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A critical look at spatial scale choices in satellite-based aerosol indirect effect studies
NASA Astrophysics Data System (ADS)
Grandey, B. S.; Stier, P.
2010-12-01
Analysing satellite datasets over large regions may introduce spurious relationships between aerosol and cloud properties due to spatial variations in aerosol type, cloud regime and synoptic regime climatologies. Using MODerate resolution Imaging Spectroradiometer data, we calculate relationships between aerosol optical depth τa derived liquid cloud droplet effective number concentration Ne and liquid cloud droplet effective radius re at different spatial scales. Generally, positive values of dlnNedlnτa are found for ocean regions, whilst negative values occur for many land regions. The spatial distribution of dlnredlnτa shows approximately the opposite pattern, with generally postive values for land regions and negative values for ocean regions. We find that for region sizes larger than 4° × 4°, spurious spatial variations in retrieved cloud and aerosol properties can introduce widespread significant errors to calculations of dlnNedlnτa and dlnredlnτa. For regions on the scale of 60° × 60°, these methodological errors may lead to an overestimate in global cloud albedo effect radiative forcing of order 80% relative to that calculated for regions on the scale of 1° × 1°.
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Belief Systems and Language Understanding
1975-01-01
Sedlak (1074), Searle (1060), Gtrawson (196U), and Wittgenstein (1958). [4] (1973), Charniak (1072), ilcCarthy and Hayes (1969), HcDermott (107...in Speech Acts", Philosophical Review 73, ^39-460. Wittgenstein , Ludwig 1958 Philosophical Investigations ( New York: The Macmillan Co.) (Tr
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ari Palczewski, Rongli Geng, Grigory Eremeev
2011-07-01
We designed and built two high resolution (0.6-0.55mm special resolution [1.1-1.2mm separation]) thermometry arrays prototypes out of the Allen Bradley 90-120 ohm 1/8 watt resistor to measure surface temperature profiles on SRF cavities. One array was designed to be physically flexible and conform to any location on a SRF cavity; the other was modeled after the common G-10/stycast 2850 thermometer and designed to fit on the equator of an ILC (Tesla 1.3GHz) SRF cavity. We will discuss the advantages and disadvantages of each array and their construction. In addition we will present a case study of the arrays performance onmore » a real SRF cavity TB9NR001. TB9NR001 presented a unique opportunity to test the performance of each array as it contained a dual (4mm separation) cat eye defect which conventional methods such as OST (Oscillating Superleak second-sound Transducers) and full coverage thermometry mapping were unable to distinguish between. We will discuss the new arrays ability to distinguish between the two defects and their preheating performance.« less
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Performance of a reentrant cavity beam position monitor
NASA Astrophysics Data System (ADS)
Simon, Claire; Luong, Michel; Chel, Stéphane; Napoly, Olivier; Novo, Jorge; Roudier, Dominique; Rouvière, Nelly; Baboi, Nicoleta; Mildner, Nils; Nölle, Dirk
2008-08-01
The beam-based alignment and feedback systems, essential operations for the future colliders, require high resolution beam position monitors (BPMs). In the framework of the European CARE/SRF program, a reentrant cavity BPM with its associated electronics was developed by the CEA/DSM/Irfu in collaboration with DESY. The design, the fabrication, and the beam test of this monitor are detailed within this paper. This BPM is designed to be inserted in a cryomodule, work at cryogenic temperature in a clean environment. It has achieved a resolution better than 10μm and has the possibility to perform bunch to bunch measurements for the x-ray free electron laser (X-FEL) and the International Linear Collider (ILC). Its other features are a small size of the rf cavity, a large aperture (78 mm), and an excellent linearity. A first prototype of a reentrant cavity BPM was installed in the free electron laser in Hamburg (FLASH), at Deutsches Elektronen-Synchrotron (DESY) and demonstrated its operation at cryogenic temperature inside a cryomodule. The second, installed, also, in the FLASH linac to be tested with beam, measured a resolution of approximately 4μm over a dynamic range ±5mm in single bunch.
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Ayala, Guillermo; Díez, Fernando; Gassó, María T; Jones, Brian E; Martín-Portugués, Rafael; Ramiro-Aparicio, Juan
2016-04-30
The internal lubricant content (ILC) of inhalation grade HPMC capsules is a key factor to ensure good powder release when the patient inhales a medicine from a dry powder inhaler (DPI). Powder release from capsules has been shown to be influenced by the ILC. The characteristics used to measure this are the emitted dose, fine particle fraction and mass median aerodynamic diameter. In addition the ILC level is critical for capsule shell manufacture because it is an essential part of the process that cannot work without it. An experiment has been applied to the manufacture of inhalation capsules with the required ILC. A full factorial model was used to identify the controlling factors and from this a linear model has been proposed to improve control of the process. Copyright © 2016 Elsevier B.V. All rights reserved.
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P { font-size : 10px; font-weight : normal; font-family : helvetica, verdana, arial; color : #000000; ; line-height: 11px} .title { font-size : 12px; font-weight : bold; font-family : helvetica
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The Development of Adult Innate Lymphoid Cells
Yang, Qi; Bhandoola, Avinash
2016-01-01
Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally-distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595
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NASA Astrophysics Data System (ADS)
Ordonez, Robert F.; Mittemeyer, Bernhard T.; Aronoff, David R.; de Riese, Werner T. W.
2003-06-01
The use of minimally invasive treatments for benign prostatic hyperplasia (BPH) have been introduced into the medical community. Over the last decade several minimally invasive treatment techniques have been approved for use. In particular, interstitial laser coagulation (ILC) has shown pomise as an alternative to the current gold standard, transurethral resection of prostate (TURP). Studies show ILC to have equal efficacy as TURP while causing less side effects. Future technical advances as well as increased physician experience with ILC could lead to the replacement of TURP as the gold standard in trestment of BPH.
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Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications.
Kortekaas Krohn, I; Shikhagaie, M M; Golebski, K; Bernink, J H; Breynaert, C; Creyns, B; Diamant, Z; Fokkens, W J; Gevaert, P; Hellings, P; Hendriks, R W; Klimek, L; Mjösberg, J; Morita, H; Ogg, G S; O'Mahony, L; Schwarze, J; Seys, S F; Shamji, M H; Bal, S M
2018-04-01
Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
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Feng, Zhao; Ling, Jie; Ming, Min; Xiao, Xiao-Hui
2017-08-01
For precision motion, high-bandwidth and flexible tracking are the two important issues for significant performance improvement. Iterative learning control (ILC) is an effective feedforward control method only for systems that operate strictly repetitively. Although projection ILC can track varying references, the performance is still limited by the fixed-bandwidth Q-filter, especially for triangular waves tracking commonly used in a piezo nanopositioner. In this paper, a wavelet transform-based linear time-varying (LTV) Q-filter design for projection ILC is proposed to compensate high-frequency errors and improve the ability to tracking varying references simultaneously. The LVT Q-filter is designed based on the modulus maximum of wavelet detail coefficients calculated by wavelet transform to determine the high-frequency locations of each iteration with the advantages of avoiding cross-terms and segmenting manually. The proposed approach was verified on a piezo nanopositioner. Experimental results indicate that the proposed approach can locate the high-frequency regions accurately and achieve the best performance under varying references compared with traditional frequency-domain and projection ILC with a fixed-bandwidth Q-filter, which validates that through implementing the LTV filter on projection ILC, high-bandwidth and flexible tracking can be achieved simultaneously by the proposed approach.
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Lo, Bernard C; Gold, Matthew J; Hughes, Michael R; Antignano, Frann; Valdez, Yanet; Zaph, Colby; Harder, Kenneth W; McNagny, Kelly M
2016-09-02
Fibrosis is the result of dysregulated tissue regeneration and is characterized by excessive accumulation of matrix proteins that become detrimental to tissue function. In Crohn's disease, this manifests itself as recurrent gastrointestinal strictures for which there is no effective therapy beyond surgical intervention. Using a model of infection-induced chronic gut inflammation, we show that Rora -deficient mice are protected from fibrosis; infected intestinal tissues display diminished pathology, attenuated collagen deposition and reduced fibroblast accumulation. Although Rora is best known for its role in ILC2 development, we find that Salmonella -induced fibrosis is independent of eosinophils, STAT6 signaling and Th2 cytokine production arguing that this process is largely ILC2-independent. Instead, we observe reduced levels of ILC3- and T cell-derived IL-17A and IL-22 in infected gut tissues. Furthermore, using Rora sg/sg / Rag1 -/- bone marrow chimeric mice, we show that restoring ILC function is sufficient to re-establish IL-17A and IL-22 production and a profibrotic phenotype. Our results show that RORα-dependent ILC3 functions are pivotal in mediating gut fibrosis and they offer an avenue for therapeutic intervention in Crohn's-like diseases.
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Governance of the International Linear Collider Project
DOE Office of Scientific and Technical Information (OSTI.GOV)
Foster, B.; /Oxford U.; Barish, B.
Governance models for the International Linear Collider Project are examined in the light of experience from similar international projects around the world. Recommendations for one path which could be followed to realize the ILC successfully are outlined. The International Linear Collider (ILC) is a unique endeavour in particle physics; fully international from the outset, it has no 'host laboratory' to provide infrastructure and support. The realization of this project therefore presents unique challenges, in scientific, technical and political arenas. This document outlines the main questions that need to be answered if the ILC is to become a reality. It describesmore » the methodology used to harness the wisdom displayed and lessons learned from current and previous large international projects. From this basis, it suggests both general principles and outlines a specific model to realize the ILC. It recognizes that there is no unique model for such a laboratory and that there are often several solutions to a particular problem. Nevertheless it proposes concrete solutions that the authors believe are currently the best choices in order to stimulate discussion and catalyze proposals as to how to bring the ILC project to fruition. The ILC Laboratory would be set up by international treaty and be governed by a strong Council to whom a Director General and an associated Directorate would report. Council would empower the Director General to give strong management to the project. It would take its decisions in a timely manner, giving appropriate weight to the financial contributions of the member states. The ILC Laboratory would be set up for a fixed term, capable of extension by agreement of all the partners. The construction of the machine would be based on a Work Breakdown Structure and value engineering and would have a common cash fund sufficiently large to allow the management flexibility to optimize the project's construction. Appropriate contingency, clearly apportioned at both a national and global level, is essential if the project is to be realised. Finally, models for running costs and decommissioning at the conclusion of the ILC project are proposed. This document represents an interim report of the bodies and individuals studying these questions inside the structure set up and supervised by the International Committee for Future Accelerators (ICFA). It represents a request for comment to the international community in all relevant disciplines, scientific, technical and most importantly, political. Many areas require further study and some, in particular the site selection process, have not yet progressed sufficiently to be addressed in detail in this document. Discussion raised by this document will be vital in framing the final proposals due to be published in 2012 in the Technical Design Report being prepared by the Global Design Effort of the ILC.« less
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March 29, 2005
FACT SHEET: 12 CFR 740.4 - Requirements for the official sign.
Code of Federal Regulations, 2010 CFR
2010-01-01
... and appearing on NCUA's official website, or alter by hand or otherwise the official sign depicted in... directly.” This sign must be similar to the official sign in terms of design, color, and font. (2) A teller... official sign in terms of design, color, and font. (3) A teller in a branch of a nonfederally insured...
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Changing concentration, lifetime and climate forcing of atmospheric methane
NASA Astrophysics Data System (ADS)
Lelieveld, Jos; Crutzen, Paul J.; Dentener, Frank J.
1998-04-01
Previous studies on ice core analyses and recent in situ measurements have shown that CH4 has increased from about 0.75 1.73μmol/mol during the past 150years. Here, we review sources and sink estimates and we present global 3D model calculations, showing that the main features of the global CH4 distribution are well represented. The model has been used to derive the total CH4 emission source, being about 600 Tg yr-1. Based on published results of isotope measurements the total contribution of fossil fuel related CH4 emissions has been estimated to be about 110 Tg yr-1. However, the individual coal, natural gas and oil associated CH4 emissions can not be accurately quantified. In particular natural gas and oil associated emissions remain speculative. Since the total anthropogenic CH4 source is about 410 Tg yr-1 (
70% of the total source) and the mean recent atmospheric CH4 increase is 20 Tg yr-1 an anthropogenic source reduction of 5% could stabilize the atmospheric CH4 level. We have calculated the indirect chemical effects of increasing CH4 on climate forcing on the basis of global 3D chemistry-transport and radiative transfer calculations. These indicate an enhancement of the direct radiative effect by about 30%, in agreement with previous work. The contribution of CH4 (direct and indirect effects) to climate forcing during the past 150years is 0.57W m
2 (direct 0.44W m2, indirect 0.13 W m2). This is about 35% of the climate forcing by CO2 (1.6W m2) and about 22% of the forcing by all long-lived greenhouse gases (2.6 W m2). Scenario calculations (IPCC-IS92a) indicate that the CH4 lifetime in the atmosphere increased by about 25 30%during the past 150years to a current value of 7.9years. Future lifetime changes are expected to be much smaller, about 6%, mostly due to the expected increase of tropospheric O3 (→OH) in the tropics. The global mean concentration of CH4 may increase to about 2.55μmol/mol, its lifetime is expected to increase to 8.4years in the year 2050. Further, we have calculated a CH4 global warming potential (GWP) of 21 (kgCH4/kgCO2) over a time horizon of 100years, in agreement with IPCC (1996). Scenario calculations indicate that the importance of the climate forcing by CH4 (including indirect effects) relative to that of CO2 will decrease in future; currently this is about 35%, while this is expected to decrease to about 15% in the year 2050. -
Cavity BPM System Tests for the ILC Spectrometer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Slater, M.
2007-12-21
The main physics program of the International Linear Collider (ILC) requires a measurement of the beam energy at the interaction point with an accuracy of 10{sup -4} or better. To achieve this goal a magnetic spectrometer using high resolution beam position monitors (BPMs) has been proposed. This paper reports on the cavity BPM system that was deployed to test this proposal. We demonstrate sub-micron resolution and micron level stability over 20 hours for a 1 m long BPM triplet. We find micron-level stability over 1 hour for 3 BPM stations distributed over a 30 m long baseline. The understanding ofmore » the behavior and response of the BPMs gained from this work has allowed full spectrometer tests to be carried out.« less
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Electrochemical Properties of LaNi(sub 5-x)Ge(sub x) Alloys in Ni-MH Batteries
NASA Technical Reports Server (NTRS)
Bowman, R. C., Jr.; Witham, C.
1997-01-01
Electrochemical studies were performed on LaNi(sub 5-x)Ge(sub x) metal hydride alloys with 0 <= x <= 0.5. We carried out single-electrode studies to understand the effects of the Ge substituent on the hydrogen absorption characteristics, the electrochemical capacity, and the electrochemical kinetics of hydrogen absorption and desorption.
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Impact of Strain Elastography on BI-RADS classification in small invasive lobular carcinoma.
Chiorean, Angelica Rita; Szep, Mădălina Brîndușa; Feier, Diana Sorina; Duma, Magdalena; Chiorean, Marco Andrei; Strilciuc, Ștefan
2018-05-02
The purpose of this study was to determine the impact of strain elastography (SE) on the Breast Imaging Reporting Data System (BI-RADS) classification depending on invasive lobular carcinoma (ILC) lesion size. We performed a retrospective analysis on a sample of 152 female subjects examined between January 2010 - January 2017. SE was performed on all patients and ILC was subsequently diagnosed by surgical or ultrasound-guided biopsy. BI-RADS 1, 2, 6 and Tsukuba BGR cases were omitted. BI-RADS scores were recorded before and after the use of SE. The differences between scores were compared to the ILC tumor size using nonparametric tests and logistic binary regression. We controlled for age, focality, clinical assessment, heredo-collateral antecedents, B-mode and Doppler ultrasound examination. An ROC curve was used to identify the optimal cut-off point for size in relationship to BI-RADS classificationdifference using Youden's index. The histological subtypes of ILC lesions (n=180) included in the sample were luminal A (70%, n=126), luminal B (27.78%, n=50), triple negative (1.67%, n=3) and HER2+ (0.56%, n=1). The BI-RADS classification was higher when SE was performed (Z=- 6.629, p<0.000). The ROC curve identified a cut-off point of 13 mm for size in relationship to BI-RADS classification difference (J=0.670, p<0.000). Small ILC tumors were 17.92% more likely to influence BI-RADS classification (p<0.000). SE offers enhanced BI-RADS classification in small ILC tumors (<13 mm). Sonoelastography brings added value to B-mode breast ultrasound as an adjacent to mammography in breast cancer screening.
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Goverse, Gera; Labao-Almeida, Carlos; Ferreira, Manuela; Molenaar, Rosalie; Wahlen, Sigrid; Konijn, Tanja; Koning, Jasper; Veiga-Fernandes, Henrique; Mebius, Reina E
2016-06-15
Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR(-) and NCR(+) ILC3 subsets in the small intestine of mice raised on a vitamin A-deficient diet. Additionally, the percentages of IL-22-producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR(-) ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A-deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid-related orphan receptor γt-Cre × RARα-DN mice had reduced numbers of NCR(-) and NCR(+) ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid-related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines. Copyright © 2016 by The American Association of Immunologists, Inc.
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Zhao, Di; Cai, Chenwen; Zheng, Qing; Jin, Shuang; Song, Dongjuan; Shen, Jun; Ran, Zhihua
2017-01-29
The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage. This study aimed to investigate whether antibiotics could interfere with ILCs-dependent tissue repair. Dextran sodium sulfate (DSS)-induced colitis was established in mice pre-treated with reagent of different antibiotic spectrum. Both morphological and molecular markers of tissue repair after DSS cessation were detected. ILCs population and function status were also recorded. Further attention was paid to the response of dendritic cells after antibiotics treatment, which were claimed to regulate colonic ILC3s in an IL-23 dependent way. Using of vancomycin resulted in delayed tissue repairing after experimental colitis. Both colonic IL-22/pSTAT3 axis and ILC3 population were found decreased in this situation. Vancomycin treatment diminished the upstream IL-23 and producer dendritic cell population. The reduced dendritic cell number may due to inadequate chemokines and colony-stimulating factors supply. Presence of vancomycin-sensitive microbiota is required for the maturation of ILC3-activating dendritic cells hence maintain the sufficient IL-22/pSTAT3 level in the colon during tissue healing. Manipulation of colonic microbiota may help achieve colonic mucosal healing post inflammation and injury. Copyright © 2016. Published by Elsevier Inc.
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Gpr109a Limits Microbiota-Induced IL-23 Production To Constrain ILC3-Mediated Colonic Inflammation.
Bhatt, Brinda; Zeng, Peng; Zhu, Huabin; Sivaprakasam, Sathish; Li, Siyi; Xiao, Haiyan; Dong, Lixin; Shiao, Pamela; Kolhe, Ravindra; Patel, Nikhil; Li, Honglin; Levy-Bercowski, Daniel; Ganapathy, Vadivel; Singh, Nagendra
2018-04-15
A set of coordinated interactions between gut microbiota and the immune cells surveilling the intestine play a key role in shaping local immune responses and intestinal health. Gpr109a is a G protein-coupled receptor expressed at a very high level on innate immune cells and previously shown to play a key role in the induction of colonic regulatory T cells. In this study, we show that Gpr109a -/- Rag1 -/- mice exhibit spontaneous rectal prolapse and colonic inflammation, characterized by the presence of an elevated number of IL-17-producing Rorγt + innate lymphoid cells (ILCs; ILC3). Genetic deletion of Rorγt alleviated the spontaneous colonic inflammation in Gpr109a -/- Rag1 -/- mice. Gpr109a-deficient colonic dendritic cells produce higher amounts of IL-23 and thereby promote ILC3. Moreover, the depletion of gut microbiota by antibiotics treatment decreased IL-23 production, ILC3, and colonic inflammation in Gpr109a -/- Rag1 -/- mice. The ceca of Gpr109a -/- Rag1 -/- mice showed significantly increased colonization by members of Bacteroidaceae , Porphyromonadaceae , Prevotellaceae, Streptococcaceae , Christensenellaceae , and Mogibacteriaceae , as well as IBD-associated microbiota such as Enterobacteriaceae and Mycoplasmataceae , compared with Rag1 -/- mice, housed in a facility positive for Helicobacter and murine norovirus. Niacin, a Gpr109a agonist, suppressed both IL-23 production by colonic DCs and ILC3 number in a Gpr109a-dependent manner. Collectively, our data present a model suggesting that targeting Gpr109a will be potentially beneficial in the suppression of IL-23-mediated immunopathologies. Copyright © 2018 by The American Association of Immunologists, Inc.
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Chudasama, Y; Robbins, Trevor W
2003-09-24
To examine possible heterogeneity of function within the ventral regions of the rodent frontal cortex, the present study compared the effects of excitotoxic lesions of the orbitofrontal cortex (OFC) and the infralimbic cortex (ILC) on pavlovian autoshaping and discrimination reversal learning. During the pavlovian autoshaping task, in which rats learn to approach a stimulus predictive of reward [conditional stimulus (CS+)], only the OFC group failed to acquire discriminated approach but was unimpaired when preoperatively trained. In the visual discrimination learning and reversal task, rats were initially required to discriminate a stimulus positively associated with reward. There was no effect of either OFC or ILC lesions on discrimination learning. When the stimulus-reward contingencies were reversed, both groups of animals committed more errors, but only the OFC-lesioned animals were unable to suppress the previously rewarded stimulus-reward association, committing more "stimulus perseverative" errors. In contrast, the ILC group showed a pattern of errors that was more attributable to "learning" than perseveration. These findings suggest two types of dissociation between the effects of OFC and ILC lesions: (1) OFC lesions impaired the learning processes implicated in pavlovian autoshaping but not instrumental simultaneous discrimination learning, whereas ILC lesions were unimpaired at autoshaping and their reversal learning deficit did not reflect perseveration, and (2) OFC lesions induced perseverative responding in reversal learning but did not disinhibit responses to pavlovian CS-. In contrast, the ILC lesion had no effect on response inhibitory control in either of these settings. The findings are discussed in the context of dissociable executive functions in ventral sectors of the rat prefrontal cortex.
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IL233, A Novel IL-2 and IL-33 Hybrid Cytokine, Ameliorates Renal Injury.
Stremska, Marta E; Jose, Sheethal; Sabapathy, Vikram; Huang, Liping; Bajwa, Amandeep; Kinsey, Gilbert R; Sharma, Poonam R; Mohammad, Saleh; Rosin, Diane L; Okusa, Mark D; Sharma, Rahul
2017-09-01
CD4 + Foxp3 + regulatory T cells (Tregs) protect the kidney during AKI. We previously found that IL-2, which is critical for Treg homeostasis, upregulates the IL-33 receptor (ST2) on CD4 + T cells, thus we hypothesized that IL-2 and IL-33 cooperate to enhance Treg function. We found that a major subset of Tregs in mice express ST2, and coinjection of IL-2 and IL-33 increased the number of Tregs in lymphoid organs and protected mice from ischemia-reperfusion injury (IRI) more efficiently than either cytokine alone. Accordingly, we generated a novel hybrid cytokine (IL233) bearing the activities of IL-2 and IL-33 for efficient targeting to Tregs. IL233 treatment increased the number of Tregs in blood and spleen and prevented IRI more efficiently than a mixture of IL-2 and IL-33. Injection of IL233 also increased the numbers of Tregs in renal compartments. Moreover, IL233-treated mice had fewer splenic Tregs and more Tregs in kidneys after IRI. In vitro , splenic Tregs from IL233-treated mice suppressed CD4 + T cell proliferation better than Tregs from saline-treated controls. IL233 treatment also improved the ability of isolated Tregs to inhibit IRI in adoptive transfer experiments and protected mice from cisplatin- and doxorubicin-induced nephrotoxic injury. Finally, treatment with IL233 increased the proportion of ST2-bearing innate lymphoid cells (ILC2) in blood and kidneys, and adoptive transfer of ILC2 also protected mice from IRI. Thus, the novel IL233 hybrid cytokine, which utilizes the cooperation of IL-2 and IL-33 to enhance Treg- and ILC2-mediated protection from AKI, bears strong therapeutic potential. Copyright © 2017 by the American Society of Nephrology.
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Scenario analysis of energy-based low-carbon development in China.
Zhou, Yun; Hao, Fanghua; Meng, Wei; Fu, Jiafeng
2014-08-01
China's increasing energy consumption and coal-dominant energy structure have contributed not only to severe environmental pollution, but also to global climate change. This article begins with a brief review of China's primary energy use and associated environmental problems and health risks. To analyze the potential of China's transition to low-carbon development, three scenarios are constructed to simulate energy demand and CO₂ emission trends in China up to 2050 by using the Long-range Energy Alternatives Planning System (LEAP) model. Simulation results show that with the assumption of an average annual Gross Domestic Product (GDP) growth rate of 6.45%, total primary energy demand is expected to increase by 63.4%, 48.8% and 12.2% under the Business as Usual (BaU), Carbon Reduction (CR) and Integrated Low Carbon Economy (ILCE) scenarios in 2050 from the 2009 levels. Total energy-related CO₂ emissions will increase from 6.7 billiontons in 2009 to 9.5, 11, 11.6 and 11.2 billiontons; 8.2, 9.2, 9.6 and 9 billiontons; 7.1, 7.4, 7.2 and 6.4 billiontons in 2020, 2030, 2040 and 2050 under the BaU, CR and ILCE scenarios, respectively. Total CO₂ emission will drop by 19.6% and 42.9% under the CR and ILCE scenarios in 2050, compared with the BaU scenario. To realize a substantial cut in energy consumption and carbon emissions, China needs to make a long-term low-carbon development strategy targeting further improvement of energy efficiency, optimization of energy structure, deployment of clean coal technology and use of market-based economic instruments like energy/carbon taxation. Copyright © 2014. Published by Elsevier B.V.
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Besnard, Anne-Gaelle; Guabiraba, Rodrigo; Niedbala, Wanda; Palomo, Jennifer; Reverchon, Flora; Shaw, Tovah N; Couper, Kevin N; Ryffel, Bernhard; Liew, Foo Y
2015-02-01
Cerebral malaria (CM) is a complex parasitic disease caused by Plasmodium sp. Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to the development of cerebral pathology. Using the blood-stage PbA (Plasmodium berghei ANKA) model of infection, we show here that administration of the pro-Th2 cytokine, IL-33, prevents the development of experimental cerebral malaria (ECM) in C57BL/6 mice and reduces the production of inflammatory mediators IFN-γ, IL-12 and TNF-α. IL-33 drives the expansion of type-2 innate lymphoid cells (ILC2) that produce Type-2 cytokines (IL-4, IL-5 and IL-13), leading to the polarization of the anti-inflammatory M2 macrophages, which in turn expand Foxp3 regulatory T cells (Tregs). PbA-infected mice adoptively transferred with ILC2 have elevated frequency of M2 and Tregs and are protected from ECM. Importantly, IL-33-treated mice deleted of Tregs (DEREG mice) are no longer able to resist ECM. Our data therefore provide evidence that IL-33 can prevent the development of ECM by orchestrating a protective immune response via ILC2, M2 macrophages and Tregs.
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Besnard, Anne-Gaelle; Guabiraba, Rodrigo; Niedbala, Wanda; Palomo, Jennifer; Reverchon, Flora; Shaw, Tovah N.; Couper, Kevin N.; Ryffel, Bernhard; Liew, Foo Y.
2015-01-01
Cerebral malaria (CM) is a complex parasitic disease caused by Plasmodium sp. Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to the development of cerebral pathology. Using the blood-stage PbA (Plasmodium berghei ANKA) model of infection, we show here that administration of the pro-Th2 cytokine, IL-33, prevents the development of experimental cerebral malaria (ECM) in C57BL/6 mice and reduces the production of inflammatory mediators IFN-γ, IL-12 and TNF-α. IL-33 drives the expansion of type-2 innate lymphoid cells (ILC2) that produce Type-2 cytokines (IL-4, IL-5 and IL-13), leading to the polarization of the anti-inflammatory M2 macrophages, which in turn expand Foxp3 regulatory T cells (Tregs). PbA-infected mice adoptively transferred with ILC2 have elevated frequency of M2 and Tregs and are protected from ECM. Importantly, IL-33-treated mice deleted of Tregs (DEREG mice) are no longer able to resist ECM. Our data therefore provide evidence that IL-33 can prevent the development of ECM by orchestrating a protective immune response via ILC2, M2 macrophages and Tregs. PMID:25659095
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Raykova, Ana; Carrega, Paolo; Lehmann, Frank M; Ivanek, Robert; Landtwing, Vanessa; Quast, Isaak; Lünemann, Jan D; Finke, Daniela; Ferlazzo, Guido; Chijioke, Obinna; Münz, Christian
2017-12-26
Type 3 innate lymphoid cells (ILC3s) fulfill protective functions at mucosal surfaces via cytokine production. Although their plasticity to become ILC1s, the innate counterparts of type 1 helper T cells, has been described previously, we report that they can differentiate into cytotoxic lymphocytes with many characteristics of early differentiated natural killer (NK) cells. This transition is promoted by the proinflammatory cytokines interleukin 12 (IL-12) and IL-15, and correlates with expression of the master transcription factor of cytotoxicity, eomesodermin (Eomes). As revealed by transcriptome analysis and flow cytometric profiling, differentiated ILC3s express CD94, NKG2A, NKG2C, CD56, and CD16 among other NK-cell receptors, and possess all components of the cytotoxic machinery. These characteristics allow them to recognize and kill leukemic cells with perforin and granzymes. Therefore, ILC3s can be harnessed for cytotoxic responses via differentiation under the influence of proinflammatory cytokines.
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NASA Astrophysics Data System (ADS)
Cai, Zhonglun; Chen, Peng; Angland, David; Zhang, Xin
2014-03-01
A novel iterative learning control (ILC) algorithm was developed and applied to an active flow control problem. The technique uses pulsed air jets to delay flow separation on a two-element high-lift wing. The ILC algorithm uses position-based pressure measurements to update the actuation. The method was experimentally tested on a wing model in a 0.9 m × 0.6 m low-speed wind tunnel at the University of Southampton. Compressed air and fast switching solenoid valves were used as actuators to excite the flow, and the pressure distribution around the chord of the wing was measured as a feedback control signal for the ILC controller. Experimental results showed that the actuation was able to delay the separation and increase the lift by approximately 10%-15%. By using the ILC algorithm, the controller was able to find the optimum control input and maintain the improvement despite sudden changes of the separation position.
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Back to the drawing board: Understanding the complexity of hepatic innate lymphoid cells.
Marotel, Marie; Hasan, Uzma; Viel, Sébastien; Marçais, Antoine; Walzer, Thierry
2016-09-01
Recent studies of immune populations in nonlymphoid organs have highlighted the great diversity of the innate lymphoid system. It has also become apparent that mouse and human innate lymphoid cells (ILCs) have distinct phenotypes and properties. In this issue of the European Journal of Immunology, Harmon et al. [Eur. J. Immunol. 2016. 46: 2111-2120] characterized human hepatic NK-cell subsets. The authors report that hepatic CD56(bright) NK cells resemble mouse liver ILC1s in that they express CXCR6 and have an immature phenotype. However, unlike mouse ILC1s, they express high levels of Eomes and low levels of T-bet, and upon stimulation with tumor cells, secrete low amounts of cytokines. These unexpected findings further support the differences between human and mouse immune populations and prompt the study of the role of hepatic ILC subsets in immune responses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.
Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom
2015-11-01
Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. Copyright © 2015 by The American Association of Immunologists, Inc.
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Engineering challenges for detectors at the ILC
Oriunno, Marco
2016-05-31
Over the last years two proposals for experiments at the ILC have been developed, ILD and SID. Extensive R&D has been carried out around the world to develop the needed technologies. Furthermore a first round of engineering studies was made as part of the ILC TDR to understand the integration of these different sub-systems into coherent and integrated detector concepts. Among the key challenges for the sub detectors are the extreme low mass/low power requirements or the extreme channel densities needed in particle flow based detectors. Throughout these studies special care was taken to ensure that the engineering models andmore » the simulation models, used in studies of the physics capabilities of the detectors, stay synchronized. In the near future, the models will need to be evolved to take the special requirements of the potential ILC site in Japan into account. Furthermore, the state of the integration of the detectors, and the future directions, will be discussed.« less
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Zanini, Cristina; Bruno, Stefania; Mandili, Giorgia; Baci, Denisa; Cerutti, Francesco; Cenacchi, Giovanna; Izzi, Leo; Camussi, Giovanni; Forni, Marco
2011-01-01
Background Regarding regenerative medicine for diabetes, accessible sources of Mesenchymal Stem Cells (MSCs) for induction of insular beta cell differentiation may be as important as mastering the differentiation process itself. Methodology/Principal Findings In the present work, stem cells from pancreatic islets (human islet-mesenchymal stem cells, HI-MSCs) and from human bone marrow (bone marrow mesenchymal stem cells, BM-MSCs) were cultured in custom-made serum-free medium, using suitable conditions in order to induce differentiation into Islet-like Cells (ILCs). HI-MSCs and BM-MSCs were positive for the MSC markers CD105, CD73, CD90, CD29. Following this induction, HI-MSC and BM-MSC formed evident islet-like structures in the culture flasks. To investigate functional modifications after induction to ILCs, ultrastructural analysis and immunofluorescence were performed. PDX1 (pancreatic duodenal homeobox gene-1), insulin, C peptide and Glut-2 were detected in HI-ILCs whereas BM-ILCs only expressed Glut-2 and insulin. Insulin was also detected in the culture medium following glucose stimulation, confirming an initial differentiation that resulted in glucose-sensitive endocrine secretion. In order to identify proteins that were modified following differentiation from basal MSC (HI-MSCs and BM-MSCs) to their HI-ILCs and BM-ILCs counterparts, proteomic analysis was performed. Three new proteins (APOA1, ATL2 and SODM) were present in both ILC types, while other detected proteins were verified to be unique to the single individual differentiated cells lines. Hierarchical analysis underscored the limited similarities between HI-MSCs and BM-MSCs after induction of differentiation, and the persistence of relevant differences related to cells of different origin. Conclusions/Significance Proteomic analysis highlighted differences in the MSCs according to site of origin, reflecting spontaneous differentiation and commitment. A more detailed understanding of protein assets may provide insights required to master the differentiation process of HI-MSCs to functional beta cells based only upon culture conditioning. These findings may open new strategies for the clinical use of BM-MSCs in diabetes. PMID:22194812
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The International Linear Collider
NASA Astrophysics Data System (ADS)
List, Benno
2014-04-01
The International Linear Collider (ILC) is a proposed e+e- linear collider with a centre-of-mass energy of 200-500 GeV, based on superconducting RF cavities. The ILC would be an ideal machine for precision studies of a light Higgs boson and the top quark, and would have a discovery potential for new particles that is complementary to that of LHC. The clean experimental conditions would allow the operation of detectors with extremely good performance; two such detectors, ILD and SiD, are currently being designed. Both make use of novel concepts for tracking and calorimetry. The Japanese High Energy Physics community has recently recommended to build the ILC in Japan.
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Lo, Bernard C; Gold, Matthew J; Hughes, Michael R; Antignano, Frann; Valdez, Yanet; Zaph, Colby; Harder, Kenneth W; McNagny, Kelly M
2016-09-02
Fibrosis is the result of dysregulated tissue regeneration and is characterized by excessive accumulation of matrix proteins that become detrimental to tissue function. In Crohn's disease, this manifests itself as recurrent gastrointestinal strictures for which there is no effective therapy beyond surgical intervention. Using a model of infection-induced chronic gut inflammation, we show that Rora -deficient mice are protected from fibrosis; infected intestinal tissues display diminished pathology, attenuated collagen deposition, and reduced fibroblast accumulation. Although Rora is best known for its role in group 2 innate lymphoid cell (ILC2) development, we find that Salmonella -induced fibrosis is independent of eosinophils, signal transducer and activator of transcription 6 signaling, and T helper 2 cytokine production, arguing that this process is largely ILC2-independent. Instead, we observe reduced levels of ILC3- and T cell-derived interleukin-17A (IL-17A) and IL-22 in infected gut tissues. Furthermore, using Rora sg/sg / Rag1 -/- bone marrow chimeric mice, we show that restoring ILC function is sufficient to reestablish IL-17A and IL-22 production and a profibrotic phenotype. Our results show that RORα (retinoic acid receptor-related orphan receptor α)-dependent ILC3 functions are pivotal in mediating gut fibrosis, and they offer an avenue for therapeutic intervention in Crohn's-like diseases. Copyright © 2016, American Association for the Advancement of Science.
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Industrialization of Superconducting RF Accelerator Technology
NASA Astrophysics Data System (ADS)
Peiniger, Michael; Pekeler, Michael; Vogel, Hanspeter
2012-01-01
Superconducting RF (SRF) accelerator technology has basically existed for 50 years. It took about 20 years to conduct basic R&D and prototyping at universities and international institutes before the first superconducting accelerators were built, with industry supplying complete accelerator cavities. In parallel, the design of large scale accelerators using SRF was done worldwide. In order to build those accelerators, industry has been involved for 30 years in building the required cavities and/or accelerator modules in time and budget. To enable industry to supply these high tech components, technology transfer was made from the laboratories in the following three regions: the Americas, Asia and Europe. As will be shown, the manufacture of the SRF cavities is normally accomplished in industry whereas the cavity testing and module assembly are not performed in industry in most cases, yet. The story of industrialization is so far a story of customized projects. Therefore a real SRF accelerator product is not yet available in this market. License agreements and technology transfer between leading SRF laboratories and industry is a powerful tool for enabling industry to manufacture SRF components or turnkey superconducting accelerator modules for other laboratories and users with few or no capabilities in SRF technology. Despite all this, the SRF accelerator market today is still a small market. The manufacture and preparation of the components require a range of specialized knowledge, as well as complex and expensive manufacturing installations like for high precision machining, electron beam welding, chemical surface preparation and class ISO4 clean room assembly. Today, the involved industry in the US and Europe comprises medium-sized companies. In Japan, some big enterprises are involved. So far, roughly 2500 SRF cavities have been built by or ordered from industry worldwide. Another substantial step might come from the International Linear Collider (ILC) project currently being designed by the international collaboration GDE (`global design effort'). If the ILC will be built, about 18,000 SRF cavities need to be manufactured worldwide within about five years. The industrialization of SRF accelerator technology is analyzed and reviewed in this article in view of the main accelerator projects of the last two to three decades.
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ERIC Educational Resources Information Center
Research Exchange, 2001
2001-01-01
These three newsletters focus on advances and challenges in disability research. The first issue focuses on the results of a survey that investigated how many consumers with disabilities had a computer available in their home and their Internet use. The study involved administrators of Independent Living Centers (ILC) and ILC consumers. Findings…
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Status Of the ILC Main Linac Design
DOE Office of Scientific and Technical Information (OSTI.GOV)
Saini, Arun; Kapin, Valery; Solyak, Nikolay
2017-05-01
International Linear collider (ILC) is a proposed accelerator facility which is primarily based on two 11-km long superconducting main linacs. In this paper we present recent updates on the main linac design and discuss changes made in order to meet specification outlined in the technical design report (TDR).
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48 CFR 28.204-3 - Irrevocable letter of credit (ILC).
Code of Federal Regulations, 2010 CFR
2010-10-01
... no document other than a written demand and the ILC (and letter of confirmation, if any), expire only... by another acceptable financial institution that had letter of credit business of at least $25... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Irrevocable letter of...
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New Pyrazolium Salts as a Support for Ionic Liquid Crystals and Ionic Conductors
Pastor, María Jesús; Sánchez, Ignacio; Schmidt, Rainer; Cano, Mercedes
2018-01-01
Ionic liquid crystals (ILCs) are a class of materials that combine the properties of liquid crystals (LCs) and ionic liquids (ILs). This type of materials is directed towards properties such as conductivity in ordered systems at different temperatures. In this work, we synthesize five new families of ILCs containing symmetrical and unsymmetrical substituted pyrazolium cations, with different alkyl long-chains, and anions such as Cl−, BF4−, ReO4−, p-CH3-6H4SO3− (PTS) and CF3SO3− (OTf). We study their thermal behavior by polarized light optical microscopy (POM) and differential scanning calorimetry (DSC). All of them, except those with OTf as counteranion, show thermotropic mesomorphism. The observations by POM reveal textures of lamellar mesophases. Those agree with the arrangement observed in the X-ray crystal structure of [H2pzR(4),R(4)][ReO4]. The nature of the mesophases is also confirmed by variable temperature powder X-ray diffraction. On the other hand, the study of the dielectric properties at variable temperature in mesomorphic (Cl− and BF4−) and non-mesomorphic (OTf) salts indicates that the supramolecular arrangement of the mesophase favors a greater ionic mobility and therefore ionic conductivity. PMID:29614030
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Kong, Yong-Ku; Lee, Inseok; Jung, Myung-Chul; Song, Young-Woong
2011-05-01
This study evaluated the effects of age (20s and 60s), viewing distance (50 cm, 200 cm), display type (paper, monitor), font type (Gothic, Ming), colour contrast (black letters on white background, white letters on black background) and number of syllables (one, two) on the legibility of Korean characters by using the four legibility measures (minimum letter size for 100% correctness, maximum letter size for 0% correctness, minimum letter size for the least discomfort and maximum letter size for the most discomfort). Ten subjects in each age group read the four letters presented on a slide (letter size varied from 80 pt to 2 pt). Subjects also subjectively rated the reading discomfort of the letters on a 4-point scale (1 = no discomfort, 4 = most discomfort). According to the ANOVA procedure, age, viewing distance and font type significantly affected the four dependent variables (p < 0.05), while the main effect of colour contrast was not statistically significant for any measures. Two-syllable letters had smaller letters than one-syllable letters in the two correctness measures. The younger group could see letter sizes two times smaller than the old group could and the viewing distance of 50 cm showed letters about three times smaller than those at a 200 cm viewing distance. The Gothic fonts were smaller than the Ming fonts. Monitors were smaller than paper for correctness and maximum letter size for the most discomfort. From a comparison of the results for correctness and discomfort, people generally preferred larger letter sizes to those that they could read. The findings of this study may provide basic information for setting a global standard of letter size or font type to improve the legibility of characters written in Korean. STATEMENT OF RELEVANCE: Results obtained in this study will provide basic information and guidelines for setting standards of letter size and font type to improve the legibility of characters written in Korean. Also, the results might offer useful information for people who are working on design of visual displays.
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Discriminating leptonic Yukawa interactions with doubly charged scalar at the ILC
NASA Astrophysics Data System (ADS)
Nomura, Takaaki; Okada, Hiroshi; Yokoya, Hiroshi
2018-04-01
We explore discrimination of two types of leptonic Yukawa interactions associated with Higgs triplet, LbarLc ΔLL, and with SU (2) singlet doubly charged scalar, ebarRc k++eR. These interactions can be distinguished by measuring the effects of doubly charged scalar boson exchange in the e+e- →ℓ+ℓ- processes at polarized electron-positron colliders. We study a forward-backward asymmetry of scattering angular distribution to estimate the sensitivity for these effects at the ILC. In addition, we investigate prospects of upper bounds on the Yukawa couplings by combining the constraints of lepton flavor violation processes and the e+e- →ℓ+ℓ- processes at the LEP and the ILC.
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Cooper, Megan A; Fehniger, Todd A; Colonna, Marco
2017-12-18
Studies over the last decade have decisively shown that innate immune natural killer (NK) cells exhibit enhanced long-lasting functional responses following a single activation event. With the increased recognition of memory and memory-like properties of NK cells, questions have arisen with regard to their ability to effectively mediate vaccination responses in humans. Moreover, recently discovered innate lymphoid cells (ILCs) could also potentially exhibit memory-like functions. Here, we review different forms of NK cell memory, and speculate about the ability of these cells and ILCs to meaningfully contribute to vaccination responses. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.
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The Next Linear Collider Program
posted to the new SLAC ILC web site http://www-project.slac.stanford.edu/ilc/. Also, see the new site for . The NLC web site will remain accessible as an archive of important work done on the many systems | Navbar || || Documentation | NLC Playpen | Web Comments & Suggestions | Desktop Trouble Call | LC
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Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian; Jin, Yi; Turner, Jacob; Moore, Amanda J; Saito, Rintaro; Yoshida, Kenichi; Ogawa, Seishi; Rodewald, Hans-Reimer; Lin, Yin C; Kawamoto, Hiroshi; Murre, Cornelis
2017-05-16
Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.
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Stires, Hillary; Heckler, Mary M; Fu, Xiaoyong; Li, Zhao; Grasso, Catherine S; Quist, Michael J; Lewis, Joseph A; Klimach, Uwe; Zwart, Alan; Mahajan, Akanksha; Győrffy, Balázs; Cavalli, Luciane R; Riggins, Rebecca B
2018-08-15
Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
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Dudakov, Jarrod A; Mertelsmann, Anna M; O'Connor, Margaret H; Jenq, Robert R; Velardi, Enrico; Young, Lauren F; Smith, Odette M; Boyd, Richard L; van den Brink, Marcel R M; Hanash, Alan M
2017-08-17
Graft-versus-host disease (GVHD) and posttransplant immunodeficiency are frequently related complications of allogeneic hematopoietic transplantation. Alloreactive donor T cells can damage thymic epithelium, thus limiting new T-cell development. Although the thymus has a remarkable capacity to regenerate after injury, endogenous thymic regeneration is impaired in GVHD. The mechanisms leading to this regenerative failure are largely unknown. Here we demonstrate in experimental mouse models that GVHD results in depletion of intrathymic group 3 innate lymphoid cells (ILC3s) necessary for thymic regeneration. Loss of thymic ILC3s resulted in deficiency of intrathymic interleukin-22 (IL-22) compared with transplant recipients without GVHD, thereby inhibiting IL-22-mediated protection of thymic epithelial cells (TECs) and impairing recovery of thymopoiesis. Conversely, abrogating IL-21 receptor signaling in donor T cells and inhibiting the elimination of thymic ILCs improved thymopoiesis in an IL-22-dependent fashion. We found that the thymopoietic impairment in GVHD associated with loss of ILCs could be improved by restoration of IL-22 signaling. Despite uninhibited alloreactivity, exogenous IL-22 administration posttransplant resulted in increased recovery of thymopoiesis and development of new thymus-derived peripheral T cells. Our study highlights the role of innate immune function in thymic regeneration and restoration of adaptive immunity posttransplant. Manipulation of the ILC-IL-22-TEC axis may be useful for augmenting immune reconstitution after clinical hematopoietic transplantation and other settings of T-cell deficiency. © 2017 by The American Society of Hematology.
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Fast calculation of the `ILC norm' in iterative learning control
NASA Astrophysics Data System (ADS)
Rice, Justin K.; van Wingerden, Jan-Willem
2013-06-01
In this paper, we discuss and demonstrate a method for the exploitation of matrix structure in computations for iterative learning control (ILC). In Barton, Bristow, and Alleyne [International Journal of Control, 83(2), 1-8 (2010)], a special insight into the structure of the lifted convolution matrices involved in ILC is used along with a modified Lanczos method to achieve very fast computational bounds on the learning convergence, by calculating the 'ILC norm' in ? computational complexity. In this paper, we show how their method is equivalent to a special instance of the sequentially semi-separable (SSS) matrix arithmetic, and thus can be extended to many other computations in ILC, and specialised in some cases to even faster methods. Our SSS-based methodology will be demonstrated on two examples: a linear time-varying example resulting in the same ? complexity as in Barton et al., and a linear time-invariant example where our approach reduces the computational complexity to ?, thus decreasing the computation time, for an example, from the literature by a factor of almost 100. This improvement is achieved by transforming the norm computation via a linear matrix inequality into a check of positive definiteness - which allows us to further exploit the almost-Toeplitz properties of the matrix, and additionally provides explicit upper and lower bounds on the norm of the matrix, instead of the indirect Ritz estimate. These methods are now implemented in a MATLAB toolbox, freely available on the Internet.
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IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells.
Hashiguchi, Masaaki; Kashiwakura, Yuji; Kojima, Hidefumi; Kobayashi, Ayano; Kanno, Yumiko; Kobata, Tetsuji
2015-03-01
Eosinophils are multifunctional leukocytes involved in allergic reactions as well as adipose tissue regulation. IL-5 is required for eosinophil survival; however, the in vivo mechanisms of eosinophil regulation are not fully understood. A tg mouse model with il5 promoter-driven EGFP expression was established for detecting the IL-5-producing cells in vivo. Il5-egfp tg mice expressed high levels of EGFP in gonadal adipose tissue (GAT) cells. EGFP(+) cells in GAT were mainly group 2 innate lymphoid cells (ILCs). IL-33 preferentially expanded EGFP(+) cells and eosinophils in GAT in vivo. EGFP(+) ILCs were found to upregulate prg2 mRNA expression in GAT eosinophils. These results demonstrate that ILCs activate eosinophils in GAT. The blockage of IL-33Rα, on the other hand, did not impair EGFP(+) ILC numbers but did impair eosinophil numbers in vivo. GAT eosinophils expressed IL-33Rα and IL-33 expanded eosinophil numbers in CD90(+) cell-depleted mice. IL-33 was further observed to induce the expression of retnla and epx mRNA in eosinophils. These findings demonstrate that IL-33 directly activates eosinophils in GAT, and together with our other findings described above, our findings show that IL-33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC-mediated pathway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Cao, M; Zhang, J B; Dong, D D; Mou, Y; Li, K; Fang, J; Wang, Z Y; Chen, C; Zhao, J; Yie, S M
2015-10-16
Cells isolated from human first trimester umbilical cord perivascular layer (hFTM-PV) tissues display the pluripotent characteristics of stem cells. In this study, we examined whether hFTM-PV cells can differentiate into islet-like clusters (ILCs) in vitro, and whether transplantation of the hFTM-PV cells with and without differentiation in vitro can alleviate diabetes in nude mice. The hFTM-PV cells were differentiated into ILCs in vitro through a simple stepwise culture protocol. To examine the in vivo effects of the cells, the hFTM-PV cells with and without differentiation in vitro were transplanted into the abdominal cavity of nude mice with streptozotocin (STZ)-induced diabetes. Blood glucose levels, body weight, and the survival probability of the diabetic nude mice were then statistically analyzed. The hFTM-PV cells were successfully induced into ILCs that could release insulin in response to elevated concentrations of glucose in vitro. In transplantation experiments, we observed that mice transplanted with the undifferentiated hFTM-PV cells, embryonic body-like cell aggregations, or ILCs all demonstrated normalized hyperglycemia and showed improved survival rate compared with those without cell transplantation. The hFTM-PV cells have the ability to differentiate into ILCs in vitro and transplantations of undifferentiated and differentiated cells can alleviate STZ-induced diabetes in nude mice. This may offer a potential cell source for stem cell-based therapy for treating diabetes in the future.
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Optimization of the beam crossing angle at the ILC for e+e‑ and γ γ collisions
NASA Astrophysics Data System (ADS)
Telnov, V. I.
2018-03-01
At this time, the design of the International Linear Collider (ILC) is optimized for e+e‑ collisions; the photon collider (γ γ and >=) is considered as an option. Unexpected discoveries, such as the diphoton excess digamma(750) seen at the LHC, could strongly motivate the construction of a photon collider. In order to enable the γ γ collision option, the ILC design should be compatible with it from the very beginning. In this paper, we discuss the problem of the beam crossing angle. In the ILC technical design [1], this angle is 14 mrad, which is just enough to provide enough space for the final quadrupoles and outgoing beams. For γ γ collisions, the crossing angle must be larger because the low-energy electrons that result from multiple Compton scattering get large disruption angles in collisions with the opposing electron beam and some deflection in the solenoidal detector field. For a 2E0=500 GeV collider, the required crossing angle is about 25 mrad. In this paper, we consider the factors that determine the crossing angle as well as its minimum permissible value that does not yet cause a considerable reduction of the γ γ luminosity. It is shown that the best solution is to increase the laser wavelength from the current 1 μm (which is optimal for 2E0=500 GeV) to 2 μm as this makes possible achieving high γ γ luminosities at a crossing angle of 20 mrad, which is also quite comfortable for e+e‑ collisions, does not cause any degradation of the e+e‑ luminosity and opens the possibility for a more energetic future collider in the same tunnel (e.g., CLIC). Moreover, the 2 μm wavelength is optimal for a 2E0 = 1 TeV collider, e.g., a possible ILC energy upgrade. Please consider this paper an appeal to increase the ILC crossing angle from 14 to 20 mrad.
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Using Scribe to Select Fonts on the Penguin.
1984-02-01
indicates several things about that font. The first segment of the name (for example, Helvetica or TimesRoman) may indicate its shape and form. The number...nesting mi0me Penguins wre classified in the phylum Chordat &. subohylum Vefletwa. ciMs Ayes, order Spheniciformee. family Sphenclae. *4xtiracted fromt...somtimes great distances--each fall to their nesting sites. Penguins are classified In thes phylum Chordate , subphylum Vertebrate, class Ave$, order
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Dyslexie font does not benefit reading in children with or without dyslexia.
Kuster, Sanne M; van Weerdenburg, Marjolijn; Gompel, Marjolein; Bosman, Anna M T
2018-04-01
In two experiments, the claim was tested that the font "Dyslexie", specifically designed for people with dyslexia, eases reading performance of children with (and without) dyslexia. Three questions were investigated. (1) Does the Dyslexie font lead to faster and/or more accurate reading? (2) Do children have a preference for the Dyslexie font? And, (3) is font preference related to reading performance? In Experiment 1, children with dyslexia (n = 170) did not read text written in Dyslexie font faster or more accurately than in Arial font. The majority preferred reading in Arial and preference was not related to reading performance. In Experiment 2, children with (n = 102) and without dyslexia (n = 45) read word lists in three different font types (Dyslexie, Arial, Times New Roman). Words written in Dyslexie font were not read faster or more accurately. Moreover, participants showed a preference for the fonts Arial and Times New Roman rather than Dyslexie, and again, preference was not related to reading performance. These experiments clearly justify the conclusion that the Dyslexie font neither benefits nor impedes the reading process of children with and without dyslexia.
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Mills, Matthew N; Yang, George Q; Oliver, Daniel E; Liveringhouse, Casey L; Ahmed, Kamran A; Orman, Amber G; Laronga, Christine; Hoover, Susan J; Khakpour, Nazanin; Costa, Ricardo L B; Diaz, Roberto
2018-06-02
Triple negative breast cancer (TNBC) is an aggressive disease, but recent studies have identified heterogeneity in patient outcomes. However, the utility of histologic subtyping in TNBC has not yet been well-characterised. This study utilises data from the National Cancer Center Database (NCDB) to complete the largest series to date investigating the prognostic importance of histology within TNBC. A total of 729,920 patients (pts) with invasive ductal carcinoma (IDC), metaplastic breast carcinoma (MBC), medullary breast carcinoma (MedBC), adenoid cystic carcinoma (ACC), invasive lobular carcinoma (ILC) or apocrine breast carcinoma (ABC) treated between 2004 and 2012 were identified in the NCDB. Of these, 89,222 pts with TNBC that received surgery were analysed. Kaplan-Meier analysis, log-rank testing and multivariate Cox proportional hazards regression were utilised with overall survival (OS) as the primary outcome. MBC (74.1%), MedBC (60.6%), ACC (75.7%), ABC (50.1%) and ILC (1.8%) had significantly different proportions of triple negativity when compared to IDC (14.0%, p < 0.001). TNBC predicted an inferior OS in IDC (p < 0.001) and ILC (p < 0.001). Lumpectomy and radiation (RT) were more common in MedBC (51.7%) and ACC (51.5%) and less common in MBC (33.1%) and ILC (25.4%), when compared to IDC (42.5%, p < 0.001). TNBC patients with MBC (HR 1.39, p < 0.001), MedBC (HR 0.42, p < 0.001) and ACC (HR 0.32, p = 0.003) differed significantly in OS when compared to IDC. Our results indicate that histologic heterogeneity in TNBC significantly informs patient outcomes and thus, has the potential to aid in the development of optimum personalised treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.
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The Independent Living Movement in Asia: Solidarity from Japan
ERIC Educational Resources Information Center
Hayashi, Reiko; Okuhira, Masako
2008-01-01
Independent living movements of disabled people are emerging in Asian countries, supported by independent living centres (ILCs) in Japan. A study was conducted in Japan to explore the impact of the training program offered by Japanese ILCs to disabled people from other Asian countries. A sample of 35 people was selected by a snowballing method.…
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Lymphoid microenvironments and innate lymphoid cells in the gut.
Pearson, Claire; Uhlig, Holm H; Powrie, Fiona
2012-06-01
Gut-associated lymphoid tissue (GALT) is a sensor region for luminal content and plays an important role in lymphoid maturation, activation and differentiation. It comprises isolated and aggregated lymphoid follicles, cryptopatches (CPs) and tertiary lymphoid tissue. Innate lymphoid cells (ILCs) play a central role within GALT. Prenatal GALT development is dependent on ILC lymphoid-inducer function. Postnatally, these cells rapidly respond to commensal and pathogenic intestinal bacteria, parasites and food components by polarized cytokine production [such as interleukin (IL)-22, IL-17 or IL-13] and further contribute to GALT formation and function. Here, we discuss how ILCs shape lymphoid intestinal microenvironments and act as amplifier cells for innate and adaptive immune responses. Copyright © 2012. Published by Elsevier Ltd.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Woohyun; Katipamula, Srinivas; Lutes, Robert G.
This report describes how the intelligent load control (ILC) algorithm can be implemented to achieve peak demand reduction while minimizing impacts on occupant comfort. The algorithm was designed to minimize the additional sensors and minimum configuration requirements to enable a scalable and cost-effective implementation for both large and small-/medium-sized commercial buildings. The ILC algorithm uses an analytic hierarchy process (AHP) to dynamically prioritize the available curtailable loads based on both quantitative (deviation of zone conditions from set point) and qualitative rules (types of zone). Although the ILC algorithm described in this report was highly tailored to work with rooftop units,more » it can be generalized for application to other building loads such as variable-air-volume (VAV) boxes and lighting systems.« less
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Majorana neutrino signals at Belle-II and ILC
NASA Astrophysics Data System (ADS)
Yue, Chong-Xing; Guo, Yu-Chen; Zhao, Zhen-Hua
2017-12-01
For some theoretical and experimental considerations, the relatively light Majorana neutrinos at the GeV scale have been attracting some interest. In this article we consider a scenario with only one Majorana neutrino N, negligible mixing with the active neutrinos νL, where the Majorana neutrino interactions could be described in a model independent approach based on an effective theory. Under such a framework, we particularly study the feasibility of observing the N with mass in the range 0-30 GeV via the process e+e- → νN → γ + E̸ in the future Belle-II and ILC experiments. The results show that it is unpromising for Belle-II to observe the signal, while ILC may easily make a discovery for the Majorana neutrino.
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Manufacturing Methods and Technology Project Summary Reports.
1983-12-01
25 .4B 1.4 MICROCOPY RESOLUTION TEST CHART NATIONAL @u9(Au OF STANDAROS , 6 ’A % . a us$ARMY ,$. ’ AREA00S D 0- ilC’ , ATIh FO WWFC RN 7 i rI 444 . 4 ...NUMBER 4 . TITLE (end Subtitle) TYPE OF REPORT & PERIOD COVERED MA NU FACTURING MTOSADTECHNOLOGY PROJECT SUMMARY REPORTS Semi-Annual - Jul - Dec 1983 6 ...material. 4 . Improve substrate attachment. S5. Optimize pin swaging and soldering. 6 . Design a hybrid cover for the current uncased circuit. The
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Pb1-xMnxTe Crystals as a New Thermoelectric Material
NASA Astrophysics Data System (ADS)
Osinniy, V.; Jędrzejczak, A.; Domuchowski, W.; Dybko, K.; Witkowska, B.; Story, T.
2006-11-01
We studied experimentally thermoelectric properties of p-type bulk crystals of Pb1-xMnxTe and Pb1-x-yAgyMnxTe (0≤ x≤ 0.083 and y≤0.017) at room and liquid nitrogen temperatures. Model calculations of the thermoelectric figure of merit parameter (Z) involved the analysis of carrier concentration, carrier mobility, density of states as well as electronic and lattice contributions to the thermal conductivity of PbMnTe. In the analysis we took into account the main effect of Mn concentration on the band structure parameters of PbMnTe, i.e. the increase of the energy gap. The analysis of electrical, thermoelectric, and thermal properties of Pb1-xMnxTe crystals showed that, at room temperature, the maximum values of the parameter Z occur in crystals with Mn content 0.05≤ x≤0.07 and are comparable with a maximal value of Z observed in PbTe. At T=400 K the increase in the parameter Z by 10% is expected in Pb1-xMnxTe crystal (as compared to PbTe) for a very high concentration of holes of about p=5×1019 cm-3. The experimental data correctly reproduce the theoretical Z(p) dependence.
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Sugita, Jobu; Asada, Yosuke; Ishida, Waka; Iwamoto, Satoshi; Sudo, Katsuko; Suto, Hajime; Matsunaga, Toru; Fukuda, Ken; Fukushima, Atsuki; Yokoi, Norihiko; Ohno, Tatsukuni; Azuma, Miyuki; Ebihara, Nobuyuki; Saito, Hirohisa; Kubo, Masato; Nakae, Susumu
2017-01-01
Abstract Introduction Pathological changes of severe chronic allergic conjunctivitis are driven not only via acquired immunity but also via innate immunity. Type 2 immune response‐initiating cytokines may play some roles as innate immunity‐dependent components of the ocular surface inflammation. To investigate the involvement of type 2 immune response‐initiating cytokines in innate immunity‐dependent, papain‐induced conjunctival inflammation model using IL‐25‐, IL‐33‐, and TSLP receptor (TSLPR)‐knockout (KO) mice with reference to basophils and ILC2. Methods Papain‐soaked contact lenses (papain‐CLs) were installed in the conjunctival sacs of C57BL/6‐IL‐25 KO, IL‐33 KO, TSLPR KO, Rag2 KO, Bas‐TRECK, and wild‐type mice and their eyes were sampled at day 5. The eosinophil and basophil infiltration in papain‐CL model was evaluated histologically and cytokine expression was examined. To clarify the roles of basophils and ILC2, basophil/ILC2‐depletion experiments were carried out. Results Papain‐induced conjunctival inflammation exhibited eosinophil infiltration and upregulation of Th2 cytokine expression. Reduction of eosinophil and basophil infiltration and attenuated Th2 cytokine expression were observed in the papain‐CL model using IL‐33 KO and TSLPR KO mice. Depletion of basophils or ILC2s in the conjunctivae of the papain‐CL model reduced eosinophil infiltration. Conclusions Innate immunity‐driven type 2 immune responses of the ocular surface are dependent on IL‐33, TSLP, basophils, and ILC2. These components may be possible therapeutic targets for refractory allergic keratoconjunctivitis. PMID:28730605
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The Next Linear Collider Program
posted to the new SLAC ILC web site http://www-project.slac.stanford.edu/ilc/. Also, see the new site for . The NLC web site will remain accessible as an archive of important work done on the many systems to be complete by the end of the calendar year. NLC Website Search: Entire SLAC Web | Help Phonebook
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NASA Astrophysics Data System (ADS)
Maczewski, Lukasz
2010-05-01
The International Linear Collider (ILC) is a project of an electron-positron (e+e-) linear collider with the centre-of-mass energy of 200-500 GeV. Monolithic Active Pixel Sensors (MAPS) are one of the proposed silicon pixel detector concepts for the ILC vertex detector (VTX). Basic characteristics of two MAPS pixel matrices MIMOSA-5 (17 μm pixel pitch) and MIMOSA-18 (10 μm pixel pitch) are studied and compared (pedestals, noises, calibration of the ADC-to-electron conversion gain, detector efficiency and charge collection properties). The e+e- collisions at the ILC will be accompanied by intense beamsstrahlung background of electrons and positrons hitting inner planes of the vertex detector. Tracks of this origin leave elongated clusters contrary to those of secondary hadrons. Cluster characteristics and orientation with respect to the pixels netting are studied for perpendicular and inclined tracks. Elongation and precision of determining the cluster orientation as a function of the angle of incidence were measured. A simple model of signal formation (based on charge diffusion) is proposed and tested using the collected data.
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Flavorful Z‧ signatures at LHC and ILC
NASA Astrophysics Data System (ADS)
Chen, Shao-Long; Okada, Nobuchika
2008-10-01
There are lots of new physics models which predict an extra neutral gauge boson, referred as Z‧-boson. In a certain class of these new physics models, the Z‧-boson has flavor-dependent couplings with the fermions in the Standard Model (SM). Based on a simple model in which couplings of the SM fermions in the third generation with the Z‧-boson are different from those of the corresponding fermions in the first two generations, we study the signatures of Z‧-boson at the Large Hadron Collider (LHC) and the International Linear Collider (ILC). We show that at the LHC, the Z‧-boson with mass around 1 TeV can be produced through the Drell-Yan processes and its dilepton decay modes provide us clean signatures not only for the resonant production of Z‧-boson but also for flavor-dependences of the production cross sections. We also study fermion pair productions at the ILC involving the virtual Z‧-boson exchange. Even though the center-of-energy of the ILC is much lower than a Z‧-boson mass, the angular distributions and the forward-backward asymmetries of fermion pair productions show not only sizable deviations from the SM predictions but also significant flavor-dependences.
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NASA Astrophysics Data System (ADS)
Li, Zhifu; Hu, Yueming; Li, Di
2016-08-01
For a class of linear discrete-time uncertain systems, a feedback feed-forward iterative learning control (ILC) scheme is proposed, which is comprised of an iterative learning controller and two current iteration feedback controllers. The iterative learning controller is used to improve the performance along the iteration direction and the feedback controllers are used to improve the performance along the time direction. First of all, the uncertain feedback feed-forward ILC system is presented by an uncertain two-dimensional Roesser model system. Then, two robust control schemes are proposed. One can ensure that the feedback feed-forward ILC system is bounded-input bounded-output stable along time direction, and the other can ensure that the feedback feed-forward ILC system is asymptotically stable along time direction. Both schemes can guarantee the system is robust monotonically convergent along the iteration direction. Third, the robust convergent sufficient conditions are given, which contains a linear matrix inequality (LMI). Moreover, the LMI can be used to determine the gain matrix of the feedback feed-forward iterative learning controller. Finally, the simulation results are presented to demonstrate the effectiveness of the proposed schemes.
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Control of Innate and Adaptive Lymphocytes by the RAR-Retinoic Acid Axis.
Kim, Chang H
2018-02-01
Lymphocytes, such as T cells, B cells, and innate lymphoid cells (ILCs), play central roles in regulating immune responses. Retinoic acids (RAs) are vitamin A metabolites, produced and metabolized by certain tissue cells and myeloid cells in a tissue-specific manner. It has been established that RAs induce gut-homing receptors on T cells, B cells, and ILCs. A mounting body of evidence indicates that RAs exert far-reaching effects on functional differentiation and fate of these lymphocytes. For example, RAs promote effector T cell maintenance, generation of induced gut-homing regulatory and effector T cell subsets, antibody production by B cells, and functional maturation of ILCs. Key functions of RAs in regulating major groups of innate and adaptive lymphocytes are highlighted in this article.
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Design study of an optical cavity for a future photon collider at ILC
NASA Astrophysics Data System (ADS)
Klemz, G.; Mönig, K.; Will, I.
2006-08-01
Hard photons well above 100 GeV have to be generated in a future photon collider which essentially will be based on the infrastructure of the planned International Linear Collider (ILC). The energy of near-infrared laser photons will be boosted by Compton backscattering against a high-energy relativistic electron beam. For high effectiveness, a very powerful laser system is required that exceeds today's state-of-the-art capabilities. In this paper a design of an auxiliary passive cavity is discussed that resonantly enhances the peak-power of the laser. The properties and prospects of such a cavity are addressed on the basis of the specifications for the European TeV Energy Superconducting Linear Accelerator (TESLA) proposal. Those of the ILC are expected to be similar.
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Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis.
Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Spencer, Sean P; Belkaid, Yasmine; Merad, Miriam
2014-03-28
The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (T(reg)) numbers and impaired oral tolerance. We observed that RORγt(+) innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1β. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine.
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Innate Lymphoid Cells: A Promising New Regulator in Fibrotic Diseases.
Zhang, Yi; Tang, Jun; Tian, Zhiqiang; van Velkinburgh, Jennifer C; Song, Jianxun; Wu, Yuzhang; Ni, Bing
2016-09-02
Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity. Moreover, recent research has implicated ILCs as potential contributing factors to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary fibrosis. Here, we will summarize and discuss the key roles of ILCs and their related factors in fibrotic diseases and their potential for translation to the clinic.
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Exploration of very high gradient cavities
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eremeev, Grigory
2011-07-01
Several of the 9-cell ILC cavities processed at Jlab within ongoing ILC R&D program have shown interesting behavior at high fields, such as mode mixing and sudden field emission turn-on during quench. Equipped with thermometry and oscillating superleak transducer (OST) system for quench detection, we couple our RF measurements with local dissipation measurements. In this contribution we report on our findings with high gradient SRF cavities.
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Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency.
Cols, Montserrat; Rahman, Adeeb; Maglione, Paul J; Garcia-Carmona, Yolanda; Simchoni, Noa; Ko, Huai-Bin M; Radigan, Lin; Cerutti, Andrea; Blankenship, Derek; Pascual, Virginia; Cunningham-Rundles, Charlotte
2016-04-01
Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality. Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature. Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues. The linage-negative, CD127(+), CD161(+) lymphoid population containing T-box transcription factor, retinoic acid-related orphan receptor (ROR) γt, IFN-γ, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and RORγt and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN-γ(+)RORγt(+)CD3(-) cells were identified, suggesting a role in these mucosal inflammatory states. An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Chang, Yuna; Kang, Sung-Yoon; Kim, Jihyun; Kang, Hye-Ryun; Kim, Hye Young
2017-10-01
Hyper-IgE syndrome (HIES) is a very rare primary immune deficiency characterized by elevated serum IgE levels, recurrent bacterial infections, chronic dermatitis, and connective tissue abnormalities. Autosomal dominant (AD) HIES involves a mutation in signal transducer and activator of transcription 3 (STAT3) that leads to an impaired T H 17 response. STAT3 signaling is also involved in the function of RORγt + type 3 innate lymphoid cells (ILC3s) and RORγt + T H 17 cells. The aim of this study was to investigate the role of innate immune cells such as innate lymphoid cells (ILCs), granulocytes, and monocytes in a patient with HIES. Peripheral blood mononuclear cells (PBMCs) from a patient with HIES and three age-matched healthy controls were obtained for the analysis of the innate and adaptive immune cells. The frequencies of ILCs in PBMCs were lower in the patient with HIES than in the controls. Moreover, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A produced by ILC3s in PBMCs were lower in the patient with HIES than the controls. Compared with the controls, classical monocytes (CD14 + CD16 low ), which have a high antimicrobial capability, were also lower in the patient with HIES, while non-classical monocytes (CD14 low CD16 + ) as well as intermediate monocytes (CD14 + CD16 intermediate ) were higher. Taken together, these results indicate that the impaired immune defense against pathogenic microbes in the patient with HIES might be partially explained by functional defects in ILC3s and inflammatory monocytes.
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Probing Higgs-radion mixing in warped models through complementary searches at the LHC and the ILC
NASA Astrophysics Data System (ADS)
Frank, Mariana; Huitu, Katri; Maitra, Ushoshi; Patra, Monalisa
2016-09-01
We consider the Higgs-radion mixing in the context of warped space extradimensional models with custodial symmetry and investigate the prospects of detecting the mixed radion. Custodial symmetries allow the Kaluza-Klein excitations to be lighter and protect Z b b ¯ to be in agreement with experimental constraints. We perform a complementary study of discovery reaches of the Higgs-radion mixed state at the 13 and 14 TeV LHC and at the 500 and 1000 GeV International Linear Collider (ILC). We carry out a comprehensive analysis of the most significant production and decay modes of the mixed radion in the 80 GeV-1 TeV mass range and indicate the parameter space that can be probed at the LHC and the ILC. There exists a region of the parameter space which can be probed, at the LHC, through the diphoton channel even for a relatively low luminosity of 50 fb-1 . The reach of the four-lepton final state in probing the parameter space is also studied in the context of 14 TeV LHC, for a luminosity of 1000 fb-1 . At the ILC, with an integrated luminosity of 500 fb-1 , we analyze the Z -radion associated production and the W W fusion production, followed by the radion decay into b b ¯ and W+W-. The W W fusion production is favored over the Z -radion associated channel in probing regions of the parameter space beyond the LHC reach. The complementary study at the LHC and the ILC is useful both for the discovery of the radion and the understanding of its mixing sector.
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2010-03-16
Exceeded at ERP Soil and Groundwater Sites 86 A-2a. Identification of IRIS Chemicals of Interest on the ATSDR CERCLA Priority List of Hazardous...the Number (Bold Font) of Air Force ERP Samples in Which They Were Detected 317 A-4d. Air Force ERP Soil Samples: IRIS Chemicals of Interest...Ranked by the Number (Bold Font) of Air Force ERP Soil Samples in Which They Were Detected 333 A-4e. Air Force ERP Groundwater Samples: IRIS Chemicals of
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European X-Ray Free Electron Laser (EXFEL): local implications
NASA Astrophysics Data System (ADS)
Romaniuk, Ryszard S.
2013-10-01
European X-Ray FEL - free electron laser is under construction in DESY Hamburg. It is scheduled to be operational at 2015/16 at a cost more than 1 billion Euro. The laser uses SASE method to generate x-ray light. It is propelled by an electron linac of 17,5GeV energy and more than 2km in length. The linac uses superconducting SRF TESLA technology working at 1,3 GHz in frequency. The prototype of EXFEL is FLASH Laser (200 m in length), where the "proof of principle" was checked, and from the technologies were transferred to the bigger machine. The project was stared in the nineties by building a TTF Laboratory -Tesla Test Facility. The EXFEL laser is a child of a much bigger teraelectronovolt collider project TESLA (now abandoned in Germany but undertaken by international community in a form the ILC). A number of experts and young researchers from Poland participate in the design, construction and research of the FLASH and EXFEL lasers.
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DEPFET detectors for future electron-positron colliders
NASA Astrophysics Data System (ADS)
Marinas, C.
2015-11-01
The DEPFET Collaboration develops highly granular, ultra-thin pixel detectors for outstanding vertex reconstruction at future electron-positron collider experiments. A DEPFET sensor, by the integration of a field effect transistor on a fully depleted silicon bulk, provides simultaneous position sensitive detector capabilities and in pixel amplification. The characterization of the latest DEPFET prototypes has proven that a adequate signal-to-noise ratio and excellent single point resolution can be achieved for a sensor thickness of 50 micrometers. The close to final auxiliary ASICs have been produced and found to operate a DEPFET pixel detector of the latest generation with the required read-out speed. A complete detector concept is being developed for the Belle II experiment at the new Japanese super flavor factory. DEPFET is not only the technology of choice for the Belle II vertex detector, but also a prime candidate for the ILC. Therefore, in this contribution, the status of DEPFET R&D project is reviewed in the light of the requirements of the vertex detector at a future electron-positron collider.
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Development of semiconductor tracking: The future linear collider case
NASA Astrophysics Data System (ADS)
Savoy-Navarro, Aurore
2011-04-01
An active R&D on silicon tracking for the linear collider, SiLC, is pursued since several years to develop the new generation of large area silicon trackers for the future linear collider(s). The R&D objectives on new sensors, new front end processing of the signal, and the related mechanical and integration challenges for building such large detectors within the proposed detector concepts are described. Synergies and differences with the LHC construction and upgrades are explained. The differences between the linear collider projects, namely the international linear collider, ILC, and the compact linear collider, CLIC, are discussed as well. Two final objectives are presented for the construction of this important sub-detector for the future linear collider experiments: a relatively short term design based on micro-strips combined or not with a gaseous central tracker and a longer term design based on an all-pixel tracker.The R&D objectives on sensors include single sided micro-strips as baseline for the shorter term with the strips from large wafers (at least 6 in), 200 μm thick, 50 μm pitch and the edgeless and alignment friendly options. This work is conducted by SiLC in collaboration with three technical research centers in Italy, Finland, and Spain and HPK. SiLC is studied as well, using advanced Si sensor technologies for higher granularity trackers especially short strips and pixels all based on 3D technology. New Deep Sub-Micron CMOS mix mode (analog and digital) FE and readout electronics are developed to fully process the detector signals currently adapted to the ILC cycle. It is a high-level processing and a fully programmable ASIC; highly fault tolerant. In its latest version, handling 128 channels will equip these next coming years larger size silicon tracking prototypes at test beams. Connection of the FEE chip on the silicon detector especially in the strip case is a major issue. Very preliminary results with inline pitch adapter based on wiring were just achieved. Bump-bonding or 3D vertical interconnect is the other SiLC R&D objective. The goal is to simplify the overall architecture and decrease the material budget of these devices. Three tracking concepts are briefly discussed, two of which are part of the ILC Letter of Intent of the ILD and SiD detector concepts. These last years, SiLC successfully performed beam tests to experience and test these R&D lines.
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Data-Driven Based Asynchronous Motor Control for Printing Servo Systems
NASA Astrophysics Data System (ADS)
Bian, Min; Guo, Qingyun
Modern digital printing equipment aims to the environmental-friendly industry with high dynamic performances and control precision and low vibration and abrasion. High performance motion control system of printing servo systems was required. Control system of asynchronous motor based on data acquisition was proposed. Iterative learning control (ILC) algorithm was studied. PID control was widely used in the motion control. However, it was sensitive to the disturbances and model parameters variation. The ILC applied the history error data and present control signals to approximate the control signal directly in order to fully track the expect trajectory without the system models and structures. The motor control algorithm based on the ILC and PID was constructed and simulation results were given. The results show that data-driven control method is effective dealing with bounded disturbances for the motion control of printing servo systems.
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Air Force Geophysics Laboratory Aerodynamically Shaped Tethered Balloon. 45,000 Cubic Feet.
1980-12-01
21 ~i ag 1 -- - - - - ’U - .~ zw ’U - - .~ -- ~ - ~-4 a~ - ~ N. ’U 1 N. - - - ~ - - ~- >- - ~J-’~ - -4-4 ~4 Cf -4 N N~’ N -, N. N.-~N.N.- N. ~ ~ ~ N N...extent that the physical parafmters will change, thus requiring vendor formulation selection. The above polymers plus others such as Teflon, Saran and EPDM ...Lnating Between Plies L utYi1 rubber i,, recommended by ILC Dover, instead of neoprene, for the middle 1,1vor of two ply biased laminated
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NASA Astrophysics Data System (ADS)
Abubaker, A. A.; Lu, J.
2012-05-01
More and more, interest in the way data is displayed on screen has increased, especially with the increase in the number of people using e-text for learning purposes. So, this requires more focus on factors that affect screen legibility. Text display factors, such as font size, line length and font type, have an impact on reading online. Two font types [Arabic Traditional and Simplified Arabic] in four different sizes [10, 14, 16 and 18] are measured using Arabic text. On-line processes were measured using reading-aloud technique. Accuracy of reading was also measured by the average of errors that students made when reading the text, while reading speed was tested by the time it took students to read the text. However, results indicated that Arabic text in font size 10 is not readable to students aged 10 to 12. On the other hand, font sizes sixteen and eighteen are more readable than any smaller-sized font, the averages of error size 18 improve in all font types, while age has a significant impact on reading speed. Simplified Arabic font is reported as readable to students aged 10-12, especially in sizes 14 and 18.
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ERIC Educational Resources Information Center
Smith, Anita; Helms, Jenifer V.; St. John, Mark
2007-01-01
Inverness Research Associates served as external evaluators for the Center for Informal Learning and Schools (CILS) from its inception in 2002 as a National Science Foundation (NSF)-funded Center for Learning and Teaching. One of the programs that CILS developed was the Informal Learning Certificate (ILC) for informal science educators (mostly…
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Mukai, Kaori; Karasuyama, Hajime; Kabashima, Kenji; Kubo, Masato; Galli, Stephen J
2017-05-01
There is evidence that mast cells, basophils, and IgE can contribute to immune responses to parasites; however, the relative levels of importance of these effector elements in parasite immunity are not fully understood. Previous work in Il3 -deficient and c- kit mutant Kit W / W-v mice indicated that interleukin-3 and c-Kit contribute to expulsion of the intestinal nematode Strongyloides venezuelensis during primary infection. Our findings in mast cell-deficient Kit W-sh / W-sh mice and two types of mast cell-deficient mice that have normal c- kit ("Hello Kit ty" and MasTRECK mice) confirmed prior work in Kit W / W-v mice that suggested that mast cells play an important role in S. venezuelensis egg clearance in primary infections. We also assessed a possible contribution of basophils in immune responses to S. venezuelensis By immunohistochemistry, we found that numbers of basophils and mast cells were markedly increased in the jejunal mucosa during primary infections with S. venezuelensis Studies in basophil-deficient Mcpt8 DTR mice revealed a small but significant contribution of basophils to S. venezuelensis egg clearance in primary infections. Studies in mice deficient in various components of immune responses showed that CD4 + T cells and ILC2 cells, IgG, FcRγ, and, to a lesser extent, IgE and FcεRI contribute to effective immunity in primary S. venezuelensis infections. These findings support the conclusion that the hierarchy of importance of immune effector mechanisms in primary S. venezuelensis infection is as follows: CD4 + T cells/ILC2 cells, IgG, and FcRγ>mast cells>IgE and FcεRI>basophils. In contrast, in secondary S. venezuelensis infection, our evidence indicates that the presence of CD4 + T cells is of critical importance but mast cells, antibodies, and basophils have few or no nonredundant roles. Copyright © 2017 American Society for Microbiology.
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17 CFR 232.308 - Type size and font; legibility.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Type size and font; legibility. 232.308 Section 232.308 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... § 232.308 Type size and font; legibility. Provisions relating to type size, font and other legibility...
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How Much Do Metamemory Beliefs Contribute to the Font-Size Effect in Judgments of Learning?
Hu, Xiao; Li, Tongtong; Zheng, Jun; Su, Ningxin; Liu, Zhaomin; Luo, Liang
2015-01-01
Evidence shows that the font size of study items significantly influences judgments of learning (JOLs) and that people’s JOLs are generally higher for larger words than for smaller words. Previous studies have suggested that font size influences JOLs in a belief-based way. However, few studies have directly examined how much people’s beliefs contribute to the font-size effect in JOLs. This study investigated the degree to which font size influenced JOLs in a belief-based way. In Experiment 1, one group of participants (learners) studied words with different font sizes and made JOLs, whereas another group of participants (observers) viewed the learners' study phase and made JOLs for the learners. In Experiment 2, participants made both JOLs and belief-based recall predictions for large and small words. Our results suggest that metamemory beliefs play an important role in the font-size effect in JOLs. PMID:26556478
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Writing and reading training effects on font type and size preferences by students with low vision.
Atasavun Uysal, Songül; Düger, Tülin
2012-06-01
The effect of writing and reading training on preferred font type and size in low-vision students was evaluated in 35 children. An ophthalmologist confirmed low vision according to ICD-10-CM. Children identified the font type and size they could best read. The writing subtest of the Jebsen-Taylor Hand Function Test, read in 1 min., and legibility as measured by the number of readable written letters were used in evaluating the children. A writing and reading treatment program was conducted, beginning with the child's preferred font type and size, for 3 months, 2 days per week, for 45 min. per day at the child's school. Before treatment, the most preferred font type was Verdana; after treatment, the preferred font type and size changed. Students had gained reading and writing speed after training, but their writing legibility was not significantly better. Training might affect the preferred font type and size of students with low vision. Surprisingly, serif and sans-serif fonts were preferred about equally after treatment.
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Font generation of personal handwritten Chinese characters
NASA Astrophysics Data System (ADS)
Lin, Jeng-Wei; Wang, Chih-Yin; Ting, Chao-Lung; Chang, Ray-I.
2014-01-01
Today, digital multimedia messages have drawn more and more attention due to the great achievement of computer and network techniques. Nevertheless, text is still the most popular media for people to communicate with others. Many fonts have been developed so that product designers can choose unique fonts to demonstrate their idea gracefully. It is commonly believed that handwritings can reflect one's personality, emotion, feeling, education level, and so on. This is especially true in Chinese calligraphy. However, it is not easy for ordinary users to customize a font of their personal handwritings. In this study, we performed a process reengineering in font generation. We present a new method to create font in a batch mode. Rather than to create glyphs of characters one by one according to their codepoints, people create glyphs incrementally in an on-demand manner. A Java Implementation is developed to read a document image of user handwritten Chinese characters, and make a vector font of these handwritten Chinese characters. Preliminary experiment result shows that the proposed method can help ordinary users create their personal handwritten fonts easily and quickly.
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Computer Center Reference Manual
1988-06-20
Compiler options, separated by colons (default: A-:B?-:BREG-8:BT-:C-:D+:H2:A H+24:L+:O+:P-:+:RV-:S4:S+4:A ST-:T+: TREG -8:U-:V+:A-:Z+) CPU- - Cray to execute...4 a 0~ 0 -. C 6 0 _ .0’ 63 r C 6 0 C .. 60 0 6 .- 6 ILC A L U 00 00 IL C 6 1 6j 0 1.- U 0 E L 14. E Lc C0 a 60. LL 1 0’. . - 66 6 0 DL C 6 a 4
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Danna, Jérémy; Massendari, Delphine; Furnari, Benjamin; Ducrot, Stéphanie
2018-06-13
Two eye-movement experiments were conducted to examine the effects of font type on the recognition of words presented in central vision, using a variable-viewing-position technique. Two main questions were addressed: (1) Is the optimal viewing position (OVP) for word recognition modulated by font type? (2) Is the cursive font more appropriate than the printed font in word recognition in children who exclusively write using a cursive script? In order to disentangle the role of perceptual difficulty associated with the cursive font and the impact of writing habits, we tested French adults (Experiment 1) and second-grade French children, the latter having exclusively learned to write in cursive (Experiment 2). Results revealed that the printed font is more appropriate than the cursive for recognizing words in both adults and children: adults were slightly less accurate in cursive than in printed stimuli recognition and children were slower to identify cursive stimuli than printed stimuli. Eye-movement measures also revealed that the OVP curves were flattened in cursive font in both adults and children. We concluded that the perceptual difficulty of the cursive font degrades word recognition by impacting the OVP stability. Copyright © 2018 Elsevier B.V. All rights reserved.
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Understanding Collagen Organization in Breast Tumors to Predict and Prevent Metastasis
2012-09-01
metastasis. Specific Aim 2. Determine the role of Th1, Th2, and Tregs in governing collagen ordering in tumors, and their mechanism of action. (Months...surrounding tissue by penetrating through the basement membrane of the duct. Invasive Lobular Carcinoma ( ILC ) is the invasive growth of cancer...not as a predecessor to ILC , but rather a benign growth of abnormal cells that are commonly undetectable by mammograms but if detected (usually in
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Searching for the doubly charged scalars in the Georgi-Machacek model via γγ collisions at the ILC
NASA Astrophysics Data System (ADS)
Cao, Jun; Li, Yu-Qi; Liu, Yao-Bei
2018-04-01
The Georgi-Machacek (GM) model predicts the existence of the doubly-charged scalars H5±±, which can be seen the typical particles in this model and their diboson decay channels are one of the most promising ways to discover such new doubly-charged scalars. Based on the constraints of the latest combined ATLAS and CMS Higgs boson diphoton signal strength data at 2σ confidence level, we focus on the study of the triple scalar production in γγ collisions at the future International Linear collider (ILC): γγ → hH5++H 5‑‑, where the production cross-sections are very sensitive to the triple scalar coupling parameter ghHH. Considering the typical same-sign diboson decay modes for the doubly-charged scalars, the possible final signals might be detected via this process at the future ILC experiments.
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Model identification of new heavy Z‧ bosons at ILC with polarized beams
NASA Astrophysics Data System (ADS)
Pankov, A. A.; Tsytrinov, A. V.
2017-12-01
Extra neutral gauge bosons, Z‧s, are predicted by many theoretical scenarios of physics beyond the Standard Model, and intensive searches for their signatures will be performed at present and future high energy colliders. It is quite possible that Z‧s are heavy enough to lie beyond the discovery reach expected at the CERN Large Hadron Collider LHC, in which case only indirect signatures of Z‧ exchanges may occur at future colliders, through deviations of the measured cross sections from the Standard Model predictions. We here discuss in this context the expected sensitivity to Z‧ parameters of fermion-pair production cross sections at the planned International Linear Collider (ILC), especially as regards the potential of distinguishing different Z‧ models once such deviations are observed. Specifically, we evaluate the discovery and identification reaches on Z‧ gauge bosons pertinent to the E 6, LR, ALR, and SSM classes of models at the ILC.
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A Special Font for People with Dyslexia: Does it Work and, if so, why?
Marinus, Eva; Mostard, Michelle; Segers, Eliane; Schubert, Teresa M; Madelaine, Alison; Wheldall, Kevin
2016-08-01
In 2008 Christian Boer, a Dutch artist, developed a special font ("Dyslexie") to facilitate reading in children and adults with dyslexia. The font has received a lot of media attention worldwide (e.g., TheGuardian.com, Slate.com, TheAtlantic.com, USA Today, and io9.com). Interestingly, there is barely any empirical evidence for the efficacy of Dyslexie. This study aims to examine if Dyslexie is indeed more effective than a commonly used sans serif font (Arial) and, if so, whether this can be explained by its relatively large spacing settings. Participants were 39 low-progress readers who were learning to read in English. They were asked to read four different texts in four different font conditions that were all matched on letter display size (i.e., x-height), but differed in the degree to which they were matched for spacing settings. Results showed that low-progress readers performed better (i.e., read 7% more words per minute) in Dyslexie font than in standardly spaced Arial font. However, when within-word spacing and between-word spacing of Arial font was matched to that of Dyslexie font, the difference in reading speed was no longer significant. We concluded that the efficacy of Dyslexie font is not because of its specially designed letter shapes, but because of its particular spacing settings. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
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New Pyrazolium Salts as a Support for Ionic Liquid Crystals and Ionic Conductors.
Pastor, María Jesús; Sánchez, Ignacio; Campo, José A; Schmidt, Rainer; Cano, Mercedes
2018-04-03
Ionic liquid crystals (ILCs) are a class of materials that combine the properties of liquid crystals (LCs) and ionic liquids (ILs). This type of materials is directed towards properties such as conductivity in ordered systems at different temperatures. In this work, we synthesize five new families of ILCs containing symmetrical and unsymmetrical substituted pyrazolium cations, with different alkyl long-chains, and anions such as Cl - , BF₄ - , ReO₄ - , p -CH₃-₆H₄SO₃ - (PTS) and CF₃SO₃ - (OTf). We study their thermal behavior by polarized light optical microscopy (POM) and differential scanning calorimetry (DSC). All of them, except those with OTf as counteranion, show thermotropic mesomorphism. The observations by POM reveal textures of lamellar mesophases. Those agree with the arrangement observed in the X-ray crystal structure of [H₂pz R(4),R(4) ][ReO₄]. The nature of the mesophases is also confirmed by variable temperature powder X-ray diffraction. On the other hand, the study of the dielectric properties at variable temperature in mesomorphic (Cl - and BF₄ - ) and non-mesomorphic (OTf) salts indicates that the supramolecular arrangement of the mesophase favors a greater ionic mobility and therefore ionic conductivity.
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An Analysis of Water-to-Air Heat Pump Systems for Use in Government Facilities.
1980-09-01
factories , businesses, and homes could have a significant impact on total energy con- sumption. Various methods to reduce energy consumption include...MODEL GROUND WATER HEAT PUMP 95 ECOsOioIC: EVALUATION OF 4E i Il/C 0"C". 5InULATI -’ (S 4.’V;F, TEAx3 EC3OO, tC ANALISIS -ARlE7ERS E’NNtNG Yf. OF S:h
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NASA Astrophysics Data System (ADS)
Zhang, Meng; Huang, Zhongjia; Wang, Xiao; Zhang, Hongyu; Li, Taohai; Wu, Zhaolong; Luo, Youhua; Cao, Wei
2016-01-01
The inorganic layered crystal (ILC) MoS2 in low dimensions is considered as one of the most promising and efficient semiconductors. To enable the magnetism and keep intrinsic crystal structures, we carried out a first-principles study of the magnetic and semiconductive monolayer MoS2 adsorbed with the Mnn (n = 1-4) clusters, and bilayer MoS2 intercalated with the same clusters. Geometric optimizations of the Mnn@MoS2 systems show the complexes prefer to have Mnn@MoS2(M) pizza and Mnn@MoS2(B) sandwich forms in the mono- and bi-layered cases, respectively. Introductions of the clusters will enhance complex stabilities, while bonds and charge transfers are found between external Mn clusters and the S atoms in the hosts. The pizzas have medium magnetic moments of 3, 6, 9, 4 μB and sandwiches of 3, 2, 3, 2 μB following the manganese numbers. The pizzas and sandwiches are semiconductors, but with narrower bandgaps compared to their corresponding pristine hosts. Direct bandgaps were found in the Mnn@MoS2(M) (n = 1,4) pizzas, and excitingly in the Mn1@MoS2(B) sandwich. Combining functional clusters to the layered hosts, the present work shows a novel material manipulation strategy to boost semiconductive ILCs applications in magnetics.
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Brasseit, Jennifer; Kwong Chung, Cheong K C; Noti, Mario; Zysset, Daniel; Hoheisel-Dickgreber, Nina; Genitsch, Vera; Corazza, Nadia; Mueller, Christoph
2018-01-01
Aberrant interferon gamma (IFNγ) expression is associated with the pathogenesis of numerous autoimmune- and inflammatory disorders, including inflammatory bowel diseases (IBD). However, the requirement of IFNγ for the pathogenesis of chronic intestinal inflammation remains controversial. The aim of this study was thus to investigate the role of IFNγ in experimental mouse models of innate and adaptive immune cell-mediated intestinal inflammation using genetically and microbiota-stabilized hosts. While we find that IFNγ drives acute intestinal inflammation in the anti-CD40 colitis model in an innate lymphoid cell (ILC)-dependent manner, IFNγ secreted by both transferred CD4 T cells and/or cells of the lymphopenic Rag1 -/- recipient mice was dispensable for CD4 T cell-mediated colitis. In the absence of IFNγ, intestinal inflammation in CD4 T cell recipient mice was associated with enhanced IL17 responses; consequently, targeting IL17 signaling in IFNγ-deficient mice reduced T cell-mediated colitis. Intriguingly, in contrast to the anti-CD40 model of colitis, depletion of ILC in the Rag1 -/- recipients of colitogenic CD4 T cells did not prevent induction of colonic inflammation. Together, our findings demonstrate that IFNγ represents an essential, or a redundant, pro-inflammatory cytokine for the induction of intestinal inflammation, depending on the experimental mouse model used and on the nature of the critical disease inducing immune cell populations involved.
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Dyslexia and Fonts: Is a Specific Font Useful?
Bachmann, Christina; Mengheri, Lauro
2018-01-01
Nowadays, several books published in different fonts advertised as being particularly suitable for dyslexics are available on the market. Our research aimed to assess the significance of a specific reading font especially designed for dyslexia, called EasyReading™. The performances of good readers and dyslexics were compared. Fourth grade primary school students (533 students in total) were assessed based on reading tasks presented with two different layouts: the popular Times New Roman and EasyReading™, in order to investigate whether children’s performances were influenced by the fonts used. The results of the study were both statistically and clinically significant, proving that EasyReading™ can be considered a compensating tool for readers with dyslexia, and a simplifying font for all categories of readers. PMID:29757944
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International Workshop on Linear Colliders 2010
Lebrun, Ph.
2018-06-20
IWLC2010 International Workshop on Linear Colliders 2010ECFA-CLIC-ILC joint meeting: Monday 18 October - Friday 22 October 2010Venue: CERN and CICG (International Conference Centre Geneva, Switzerland). This year, the International Workshop on Linear Colliders organized by the European Committee for Future Accelerators (ECFA) will study the physics, detectors and accelerator complex of a linear collider covering both CLIC and ILC options. Contact Workshop Secretariat  IWLC2010 is hosted by CERN.
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International Workshop on Linear Colliders 2010
Yamada, Sakue
2018-05-24
IWLC2010 International Workshop on Linear Colliders 2010ECFA-CLIC-ILC joint meeting: Monday 18 October - Friday 22 October 2010Venue: CERN and CICG (International Conference Centre Geneva, Switzerland) This year, the International Workshop on Linear Colliders organized by the European Committee for Future Accelerators (ECFA) will study the physics, detectors and accelerator complex of a linear collider covering both CLIC and ILC options. Contact Workshop Secretariat  IWLC2010 is hosted by CERN
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Complement and Immunoregulation in Tissue Injury
2014-10-01
and neutrophil infiltration represent the initiating events in this process (9). Recently, the role of different T cell subsets ( Tregs , Th17) and B...first tested the hypothesis that ILCs , which rapidly release IL-17A in response to epithelial injury, are the relevant source of IL- 17A in small...intestinal IRI. To address this question we took advantage of the Rag2-/-γc-/- mouse, which lacks ILCs because it is deficient in IL-7 signaling, which
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Longitudinal Beam Diagnostics for the ILC Injectors and Bunch Compressors
DOE Office of Scientific and Technical Information (OSTI.GOV)
Piot, Philippe; Bracke, Adam; Demir, Veysel
2010-12-01
We present a diagnostics suite and analyze techniques for setting up the longitudinal beam dynamics in ILC e⁻ injectors and e⁺ and e⁻ bunch compressors. Techniques to measure the first order moments and recover the first order longitudinal transfer map of the injector's intricate bunching scheme are presented. Coherent transition radiation diagnostics needed to measure and monitor the bunch length downstream of the ~5 GeV bunch compressor are investigated using a vector diffraction model.
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Anbalagan, M; Yashwanth, R; Jagannadha Rao, A
2004-04-30
Postnatal Leydig cell development in rat involves an initial phase of proliferation of progenitor Leydig cells (PLCs) and subsequent differentiation of these cells into immature Leydig cells (ILCs) and adult Leydig cells (ALCs). With an objective to identify the molecular changes associated with Leydig cell differentiation, the mRNA population in PLCs and ILCs were analyzed by the technique of differential display reverse transcription polymerase chain reaction (DD-RT-PCR). Results revealed differential expression of several transcripts in PLCs and ILCs. Of the several differentially expressed transcripts, the expression of transcripts corresponding to collagen IV alpha6 (Col IV alpha6) and ribosomal protein L 41 (RpL41) decreased during the differentiation of PLC to ILC. Also there was an increase in the expression of transcripts encoding enzymes such as microsomal glutathione-S-transferase (mGST 1) and 7-dehydrocholesterol reductase (7-DHCR) during this process. While Col IV alpha6 and RpL41 are known to be involved in cellular proliferation, mGST 1 and 7-DHCR are essential for normal Leydig cell steroidogenesis. A detailed study on 7-DHCR expression in Leydig cells revealed that this enzyme plays a crucial role in steroidogenesis. Interestingly expression of this enzyme is not under acute regulation by Luteinizing hormone (LH). Copyright 2004 Elsevier Ireland Ltd.
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NASA Astrophysics Data System (ADS)
Angelescu, Andrei; Moreau, Grégory; Richard, François
2017-07-01
The radion scalar field might be the lightest new particle predicted by extradimensional extensions of the standard model. It could thus lead to the first signatures of new physics at the LHC collider. We perform a complete study of the radion production in association with the Z gauge boson in the custodially protected warped model with a brane-localized Higgs boson addressing the gauge hierarchy problem. Radion-Higgs mixing effects are present. Such a radion production receives possibly resonant contributions from the Kaluza-Klein excitations of the Z boson as well as the extra neutral gauge boson (Z'). All the exchange and mixing effects induced by those heavy bosons are taken into account in the radion coupling and rate calculations. The investigation of the considered radion production at the LHC allows us to be sensitive to some parts of the parameter space but only the ILC program at high luminosity would cover most of the theoretically allowed parameter space via the studied reaction. Complementary tests of the same theoretical parameters can be realized through the high accuracy measurements of the Higgs couplings at the ILC. The generic sensitivity limits on the rates discussed for the LHC and ILC potential reach can be applied to the searches for other (light) exotic scalar bosons.
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Lechuga, Julia; Galletly, Carol L; Broaddus, Michelle R; Dickson-Gomez, Julia B; Glasman, Laura R; McAuliffe, Timothy L; Vega, Miriam Y; LeGrand, Sarah; Mena, Carla A; Barlow, Morgan L; Valera, Erik; Montenegro, Judith I
2017-11-08
To develop, pilot test, and conduct psychometric analyses of an innovative scale measuring the influence of perceived immigration laws on Latino migrants' HIV-testing behavior. The Immigration Law Concerns Scale (ILCS) was developed in three phases: Phase 1 involved a review of law and literature, generation of scale items, consultation with project advisors, and subsequent revision of the scale. Phase 2 involved systematic translation- back translation and consensus-based editorial processes conducted by members of a bilingual and multi-national study team. In Phase 3, 339 sexually active, HIV-negative Spanish-speaking, non-citizen Latino migrant adults (both documented and undocumented) completed the scale via audio computer-assisted self-interview. The psychometric properties of the scale were tested with exploratory factor analysis and estimates of reliability coefficients were generated. Bivariate correlations were conducted to test the discriminant and predictive validity of identified factors. Exploratory factor analysis revealed a three-factor, 17-item scale. subscale reliability ranged from 0.72 to 0.79. There were significant associations between the ILCS and the HIV-testing behaviors of participants. Results of the pilot test and psychometric analysis of the ILCS are promising. The scale is reliable and significantly associated with the HIV-testing behaviors of participants. Subscales related to unwanted government attention and concerns about meeting moral character requirements should be refined.
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A Project to Design and Build the Magnets for a New Test Beamline, the ATF2, at KEK
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spencer, Cherrill M.; /slac; Sugahara, Ryuhei
2011-02-07
In order to achieve the high luminosity required at the proposed International Linear Collider (ILC), it is critical to focus the beams to nanometer size with the ILC Beam Delivery System, and to maintain the beams collisions with a nanometer-scale stability. To establish the technologies associated with this ultra-high precision beam handling, a special beamline has been designed and built as an extension of the existing extraction beamline of the Accelerator Test Facility at KEK, Japan. The ATF provides an adequate ultra-low emittance electron beam that is comparable to the ILC requirements; the ATF2 mimics the ILC final focus systemmore » to create a tightly focused, stable beam. There are 37 magnets in the ATF2, 29 quadrupoles, 5 sextupoles and 3 bends. These magnets had to be acquired in a short time and at minimum cost, which led to various acquisition strategies; but nevertheless they had to meet strict requirements on integrated strength, physical dimensions, compatibility with existing magnet movers and beam position monitors, mechanical stability and field stability and quality. This paper will describe how 2 styles of quadrupoles, 2 styles of sextupoles, one dipole style and their supports were designed, fabricated, refurbished or modified, measured and aligned by a small team of engineers from 3 continents.« less
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The embodiment of beauty: Evidence from viewing Chinese concrete words and pictographs.
Zhang, Wei; He, Xianyou; Zhao, Xueru; Lai, Siyan; Lai, Shuxian; Situ, Suiyan
2018-02-01
How is beauty embodied? According to the viewpoint of embodied cognition, the aesthetic processing of words or pictographs has roots in their referential archetypes. Four experiments tested whether the beauty of referential archetypes was routinely activated during the explicit and implicit aesthetic evaluations of the font structures of concrete Chinese words and pictographs in congruent or incongruent font colour. Results showed font structures of simplified Chinese words and pictographs were judged to be more beautiful when they referred to beautiful archetypes; and this pattern was reversed when they referred to ugly archetypes. Moreover, judgement was facilitated when font colour was congruent for Chinese words and pictographs referred to beautiful archetypes. For those referred to ugly archetypes, judgement was inhibited in congruent font colour but facilitated in incongruent font colour, suggesting aesthetic perceptions of the font structures of Chinese words and pictographs were derived from their referential natural objects. The spontaneous generation hypothesis of beauty is proposed to account for these findings. © 2016 International Union of Psychological Science.
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Botanical Dietary Supplements: Background Information
Skip navigation links U.S. Department of Health & Human Services HHS.gov National Institutes of Health NIH.gov Font Size Decrease Font Size Increase Font Size Strengthening Knowledge and Understanding of ...
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... Home / About Addiction / Alcohol / Alcohol Energy Drinks Alcohol Energy Drinks Read 34001 times font size decrease font size increase font size Print Email Alcohol energy drinks (AEDs) or Caffeinated alcoholic beverages (CABs) are ...
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Lefrançais, Emma; Duval, Anais; Mirey, Emilie; Roga, Stéphane; Espinosa, Eric; Cayrol, Corinne; Girard, Jean-Philippe
2014-01-01
Interleukin-33 (IL-33) is an alarmin cytokine from the IL-1 family. IL-33 activates many immune cell types expressing the interleukin 1 receptor-like 1 (IL1RL1) receptor ST2, including group-2 innate lymphoid cells (ILC2s, natural helper cells, nuocytes), the major producers of IL-5 and IL-13 during type-2 innate immune responses and allergic airway inflammation. IL-33 is likely to play a critical role in asthma because the IL33 and ST2/IL1RL1 genes have been reproducibly identified as major susceptibility loci in large-scale genome-wide association studies. A better understanding of the mechanisms regulating IL-33 activity is thus urgently needed. Here, we investigated the role of mast cells, critical effector cells in allergic disorders, known to interact with ILC2s in vivo. We found that serine proteases secreted by activated mast cells (chymase and tryptase) generate mature forms of IL-33 with potent activity on ILC2s. The major forms produced by mast cell proteases, IL-3395–270, IL-33107–270, and IL-33109–270, were 30-fold more potent than full-length human IL-331–270 for activation of ILC2s ex vivo. They induced a strong expansion of ILC2s and eosinophils in vivo, associated with elevated concentrations of IL-5 and IL-13. Murine IL-33 is also cleaved by mast cell tryptase, and a tryptase inhibitor reduced IL-33–dependent allergic airway inflammation in vivo. Our study identifies the central cleavage/activation domain of IL-33 (amino acids 66–111) as an important functional domain of the protein and suggests that interference with IL-33 cleavage and activation by mast cell and other inflammatory proteases could be useful to reduce IL-33–mediated responses in allergic asthma and other inflammatory diseases. PMID:25313073
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Toki, Shinji; Goleniewska, Kasia; Reiss, Sara; Zhou, Weisong; Newcomb, Dawn C; Bloodworth, Melissa H; Stier, Matthew T; Boyd, Kelli L; Polosukhin, Vasiliy V; Subramaniam, Sriram; Peebles, R Stokes
2016-01-01
Background Group 2 innate lymphoid cells (ILC2) are an important source of the type 2 cytokines interleukin (IL)-5 and IL-13 that are critical to the allergic airway phenotype. Previous studies reported that histone deacetylase (HDAC) inhibition by trichostatin A (TSA) downregulated adaptive allergic immune responses; however, the effect of HDAC inhibition on the early innate allergic immune response is unknown. Therefore, we investigated the effect of TSA on innate airway inflammation mediated by ILC2 activation. Methods BALB/c mice were challenged intranasally with Alternaria extract, exogenous recombinant mouse IL-33 (rmIL-33) or the respective vehicles for four consecutive days following TSA or vehicle treatment. Bronchoalveolar lavage (BAL) fluids and lungs were harvested 24 h after the last challenge. Results We found that TSA treatment significantly decreased the number of ILC2 expressing IL-5 and IL-13 in the lungs challenged with Alternaria extract or rmIL-33 compared with vehicle treatment (p<0.05). TSA treatment significantly decreased protein expression of IL-5, IL-13, CCL11 and CCL24 in the lung homogenates from Alternaria extract-challenged mice or rmIL-33-challenged mice compared with vehicle treatment (p<0.05). Further, TSA treatment significantly decreased the number of perivascular eosinophils and mucus production in the large airways that are critical components of the asthma phenotype (p<0.05). TSA did not change early IL-33 release in the BAL fluids; however, TSA decreased lung IL-33 expression from epithelial cells 24 h after last Alternaria extract challenge compared with vehicle treatment (p<0.05). Conclusions These results reveal that TSA reduces allergen-induced ILC2 activation and the early innate immune responses to an inhaled protease-containing aeroallergen. PMID:27071418
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Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J
2015-09-01
The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.
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Application Reuse Library for Software, Requirements, and Guidelines
NASA Technical Reports Server (NTRS)
Malin, Jane T.; Thronesbery, Carroll
1994-01-01
Better designs are needed for expert systems and other operations automation software, for more reliable, usable and effective human support. A prototype computer-aided Application Reuse Library shows feasibility of supporting concurrent development and improvement of advanced software by users, analysts, software developers, and human-computer interaction experts. Such a library expedites development of quality software, by providing working, documented examples, which support understanding, modification and reuse of requirements as well as code. It explicitly documents and implicitly embodies design guidelines, standards and conventions. The Application Reuse Library provides application modules with Demo-and-Tester elements. Developers and users can evaluate applicability of a library module and test modifications, by running it interactively. Sub-modules provide application code and displays and controls. The library supports software modification and reuse, by providing alternative versions of application and display functionality. Information about human support and display requirements is provided, so that modifications will conform to guidelines. The library supports entry of new application modules from developers throughout an organization. Example library modules include a timer, some buttons and special fonts, and a real-time data interface program. The library prototype is implemented in the object-oriented G2 environment for developing real-time expert systems.
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Development and Test of Robotically Assisted Extravehicular Activity Gloves
NASA Technical Reports Server (NTRS)
Rogers, Jonathan M.; Peters, Benjamin J.; Laske, Evan A.; McBryan, Emily R.
2017-01-01
Over the past two years, the High Performance EVA Glove (HPEG) project under NASA's Space Technology Mission Directorate (STMD) funded an effort to develop an electromechanically-assisted space suit glove. The project was a collaboration between the Johnson Space Center's Software, Robotics, and Simulation Division and the Crew and Thermal Systems division. The project sought to combine finger actuator technology developed for Robonaut 2 with the softgoods from the ILC Phase VI EVA glove. The Space Suit RoboGlove (SSRG) uses a system of three linear actuators to pull synthetic tendons attached to the glove's fingers to augment flexion of the user's fingers. To detect the user's inputs, the system utilizes a combination of string potentiometers along the back of the fingers and force sensitive resistors integrated into the fingertips of the glove cover layer. This paper discusses the development process from initial concepts through two major phases of prototypes, and the results of initial human testing. Initial work on the project focused on creating a functioning proof of concept, designing the softgoods integration, and demonstrating augmented grip strength with the actuators. The second year of the project focused on upgrading the actuators, sensors, and software with the overall goal of creating a system that moves with the user's fingers in order to reduce fatigue associated with the operation of a pressurized glove system. This paper also discusses considerations for a flight system based on this prototype development and address where further work is required to mature the technology.
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Progress in Multi-Dimensional Upwind Differencing
1992-09-01
Fligure 4a a shiock less t raii~so ilc soliit ion is reached from Ii itial val ies conitaining 1shiocks anid S sonic poinits: agarin. thle residiial...8217 j~ vi are chu i.ewil thtii( lealst alliilied \\wit the conivectiloll direct nwi. in1 .3 tlimeIros alj’uled. (hiul *IS a treg h11f,1r p( ir~to1to .3
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Enhancements to the Economic Impact Forecast System (EIFS).
1984-04-01
IU U .. A ILC.. Meww 4 """ Economia c. .- brmodc ’ The economic submodel is appropriately classified as an export base model that jointly determines...9 yes 3 Washington - 1963 State of Washington 27 no 4 Utah - 1963 State of Utah 39 yes 5 New Mexico - 1960 State of New Mexico 42 yes 6 Kansas - 1965... Mexico .311 .627 -.017 .360 .635 (13.266) (1.381) (8.507) Kansas .556 427 -.022 .616 .433 (11.270) (.854) (7156) Clinton .229 .681 -.005 .247 .677
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ATCA for Machines-- Advanced Telecommunications Computing Architecture
DOE Office of Scientific and Technical Information (OSTI.GOV)
Larsen, R.S.; /SLAC
2008-04-22
The Advanced Telecommunications Computing Architecture is a new industry open standard for electronics instrument modules and shelves being evaluated for the International Linear Collider (ILC). It is the first industrial standard designed for High Availability (HA). ILC availability simulations have shown clearly that the capabilities of ATCA are needed in order to achieve acceptable integrated luminosity. The ATCA architecture looks attractive for beam instruments and detector applications as well. This paper provides an overview of ongoing R&D including application of HA principles to power electronics systems.
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Role of Cathepsin C During Breast Cancer Metastasis
2011-09-01
carcinomas ( ILC ) – mostly histological grade two or three – were obtained from patients with no prior exposure to CTX (CTX-naïve) at the time of primary...invasive lobular carcinomas ( ILC ) mostly histological grade two or three were obtained from patients with no prior exposure to CTX (CTX naïve) at the time...intratumoral Tregs for chemotherapy in patients with early breast cancer. Clin Cancer Res 16:1272–1280. 46. Macchetti AH, et al. (2006) Tumor
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Producing good font attribute determination using error-prone information
NASA Astrophysics Data System (ADS)
Cooperman, Robert
1997-04-01
A method to provide estimates of font attributes in an OCR system, using detectors of individual attributes that are error-prone. For an OCR system to preserve the appearance of a scanned document, it needs accurate detection of font attributes. However, OCR environments have noise and other sources of errors, tending to make font attribute detection unreliable. Certain assumptions about font use can greatly enhance accuracy. Attributes such as boldness and italics are more likely to change between neighboring words, while attributes such as serifness are less likely to change within the same paragraph. Furthermore, the document as a whole, tends to have a limited number of sets of font attributes. These assumptions allow a better use of context than the raw data, or what would be achieved by simpler methods that would oversmooth the data.
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ERIC Educational Resources Information Center
Lv, Caixia; Wang, Quanhong
2012-01-01
Event-related brain potentials (ERPs) were recorded during a Chinese character decision task to examine whether N400 amplitude is modulated by stimulus font. Results revealed large negative-going ERPs in an N400 time window of 300-500 ms to stimuli presented in degraded Xing Kai Ti (XKT) font compared with more intact Song Ti (ST) font regardless…
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Bernard, Jean-Baptiste; Aguilar, Carlos; Castet, Eric
2016-01-01
Reading speed is dramatically reduced when readers cannot use their central vision. This is because low visual acuity and crowding negatively impact letter recognition in the periphery. In this study, we designed a new font (referred to as the Eido font) in order to reduce inter-letter similarity and consequently to increase peripheral letter recognition performance. We tested this font by running five experiments that compared the Eido font with the standard Courier font. Letter spacing and x-height were identical for the two monospaced fonts. Six normally-sighted subjects used exclusively their peripheral vision to run two aloud reading tasks (with eye movements), a letter recognition task (without eye movements), a word recognition task (without eye movements) and a lexical decision task. Results show that reading speed was not significantly different between the Eido and the Courier font when subjects had to read single sentences with a round simulated gaze-contingent central scotoma (10° diameter). In contrast, Eido significantly decreased perceptual errors in peripheral crowded letter recognition (-30% errors on average for letters briefly presented at 6° eccentricity) and in peripheral word recognition (-32% errors on average for words briefly presented at 6° eccentricity). PMID:27074013
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Bernard, Jean-Baptiste; Aguilar, Carlos; Castet, Eric
2016-01-01
Reading speed is dramatically reduced when readers cannot use their central vision. This is because low visual acuity and crowding negatively impact letter recognition in the periphery. In this study, we designed a new font (referred to as the Eido font) in order to reduce inter-letter similarity and consequently to increase peripheral letter recognition performance. We tested this font by running five experiments that compared the Eido font with the standard Courier font. Letter spacing and x-height were identical for the two monospaced fonts. Six normally-sighted subjects used exclusively their peripheral vision to run two aloud reading tasks (with eye movements), a letter recognition task (without eye movements), a word recognition task (without eye movements) and a lexical decision task. Results show that reading speed was not significantly different between the Eido and the Courier font when subjects had to read single sentences with a round simulated gaze-contingent central scotoma (10° diameter). In contrast, Eido significantly decreased perceptual errors in peripheral crowded letter recognition (-30% errors on average for letters briefly presented at 6° eccentricity) and in peripheral word recognition (-32% errors on average for words briefly presented at 6° eccentricity).
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Disfluent fonts don't help people solve math problems.
Meyer, Andrew; Frederick, Shane; Burnham, Terence C; Guevara Pinto, Juan D; Boyer, Ty W; Ball, Linden J; Pennycook, Gordon; Ackerman, Rakefet; Thompson, Valerie A; Schuldt, Jonathon P
2015-04-01
Prior research suggests that reducing font clarity can cause people to consider printed information more carefully. The most famous demonstration showed that participants were more likely to solve counterintuitive math problems when they were printed in hard-to-read font. However, after pooling data from that experiment with 16 attempts to replicate it, we find no effect on solution rates. We examine potential moderating variables, including cognitive ability, presentation format, and experimental setting, but we find no evidence of a disfluent font benefit under any conditions. More generally, though disfluent fonts slightly increase response times, we find little evidence that they activate analytic reasoning. (c) 2015 APA, all rights reserved).
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Progress in recognizing typeset mathematics
NASA Astrophysics Data System (ADS)
Fateman, Richard J.; Tokuyasu, Taku A.
1996-03-01
Printed mathematics has a number of features which distinguish it from conventional text. These include structure in two dimensions (fractions, exponents, limits), frequent font changes, symbols with variable shape (quotient bars), and substantially differing notational conventions from source to source. When compounded with more generic problems such as noise and merged or broken characters, printed mathematics offers a challenging arena for recognition. Our project was initially driven by the goal of scanning and parsing some 5,000 pages of elaborate mathematics (tables of definite integrals). While our prototype system demonstrates success on translating noise-free typeset equations into Lisp expressions appropriate for further processing, a more semantic top-down approach appears necessary for higher levels of performance. Such an approach may benefit the incorporation of these programs into a more general document processing viewpoint. We intend to release to the public our somewhat refined prototypes as utility programs in the hope that they will be of general use in the construction of custom OCR packages. These utilities are quite fast even as originally prototyped in Lisp, where they may be of particular interest to those working on 'intelligent' optical processing. Some routines have been re-written in C++ as well. Additional programs providing formula recognition and parsing also form a part of this system. It is important however to realize that distinct conflicting grammars are needed to cover variations in contemporary and historical typesetting, and thus a single simple solution is not possible.
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Probing top-Z dipole moments at the LHC and ILC
Röntsch, Raoul; Schulze, Markus
2015-08-11
We investigate the weak electric and magnetic dipole moments of top quark-Z boson interactions at the Large Hadron Collider (LHC) and the International Linear Collider (ILC). Their vanishingly small magnitude in the Standard Model makes these couplings ideal for probing New Physics interactions and for exploring the role of top quarks in electroweak symmetry breaking. In our analysis, we consider the production of two top quarks in association with a Z boson at the LHC, and top quark pairs mediated by neutral gauge bosons at the ILC. These processes yield direct sensitivity to top quark-Z boson interactions and complement indirectmore » constraints from electroweak precision data. Our computation is accurate to next-to-leading order in QCD, we include the full decay chain of top quarks and the Z boson, and account for theoretical uncertainties in our constraints. Furthermore, we find that LHC experiments will soon be able to probe weak dipole moments for the first time.« less
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Neutralino pair production at the photon-photon collider for the τ̃-coannihilation scenario
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sonmez, Nasuf, E-mail: nsonmez@cern.ch
Supersymmetry (SUSY) is a theory which gives an explanation for the strong and electroweak interactions from the grand unification scale down to the weak scale. The search for supersymmetric particles still continues at full speed at the LHC without success. The main task at the ILC is complementing the LHC result and also search for new physics. In this study, the neutralino pair production via photon-photon collision is studied for the t̃-coannihilation scenario in the context of MSSM at the ILC. In the calculation, all the possible one loop diagrams are taken into account for the photon-photon interaction. We presentmore » the production cross section and distribution of various observables for the lightest and next-to-lightest neutralino pairs for benchmark models which are specifically presented in the light of LHC8 data analysis, employing these benchmark models for neutralino pair production could show the potential of the ILC concerning the dark matter searches in supersymmetry.« less
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The effect of a specialized dyslexia font, OpenDyslexic, on reading rate and accuracy.
Wery, Jessica J; Diliberto, Jennifer A
2017-07-01
A single-subject alternating treatment design was used to investigate the extent to which a specialized dyslexia font, OpenDyslexic, impacted reading rate or accuracy compared to two commonly used fonts when used with elementary students identified as having dyslexia. OpenDyslexic was compared to Arial and Times New Roman in three reading tasks: (a) letter naming, (b) word reading, and (c) nonsense word reading. Data were analyzed through visual analysis and improvement rate difference, a nonparametric measure of nonoverlap for comparing treatments. Results from this alternating treatment experiment show no improvement in reading rate or accuracy for individual students with dyslexia, as well as the group as a whole. While some students commented that the font was "new" or "different", none of the participants reported preferring to read material presented in that font. These results indicate there may be no benefit for translating print materials to this font.
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Pastor, María Jesús; Cuerva, Cristián; Campo, José A.; Schmidt, Rainer; Torres, María Rosario; Cano, Mercedes
2016-01-01
Ionic liquid crystals (ILCs) allow the combination of the high ionic conductivity of ionic liquids (ILs) with the supramolecular organization of liquid crystals (LCs). ILCs salts were obtained by the assembly of long-chained diketonylpyridinium cations of the type [HOOR(n)pyH]+ and BF4−, ReO4−, NO3−, CF3SO3−, CuCl42− counter-ions. We have studied the thermal behavior of five series of compounds by differential scanning calorimetry (DSC) and hot stage polarized light optical microscopy (POM). All materials show thermotropic mesomorphism as well as crystalline polymorphism. X-ray diffraction of the [HOOR(12)pyH][ReO4] crystal reveals a layered structure with alternating polar and apolar sublayers. The mesophases also exhibit a lamellar arrangement detected by variable temperature powder X-ray diffraction. The CuCl42− salts exhibit the best LC properties followed by the ReO4− ones due to low melting temperature and wide range of existence. The conductivity was probed for the mesophases in one species each from the ReO4−, and CuCl42− families, and for the solid phase in one of the non-mesomorphic Cl− salts. The highest ionic conductivity was found for the smectic mesophase of the ReO4− containing salt, whereas the solid phases of all salts were dominated by electronic contributions. The ionic conductivity may be favored by the mesophase lamellar structure. PMID:28773485
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Derksen, Patrick W B; Braumuller, Tanya M; van der Burg, Eline; Hornsveld, Marten; Mesman, Elly; Wesseling, Jelle; Krimpenfort, Paul; Jonkers, Jos
2011-05-01
Breast cancer is the most common malignancy in women of the Western world. Even though a large percentage of breast cancer patients show pathological complete remission after standard treatment regimes, approximately 30-40% are non-responsive and ultimately develop metastatic disease. To generate a good preclinical model of invasive breast cancer, we have taken a tissue-specific approach to somatically inactivate p53 and E-cadherin, the cardinal cell-cell adhesion receptor that is strongly associated with tumor invasiveness. In breast cancer, E-cadherin is found mutated or otherwise functionally silenced in invasive lobular carcinoma (ILC), which accounts for 10-15% of all breast cancers. We show that mammary-specific stochastic inactivation of conditional E-cadherin and p53 results in impaired mammary gland function during pregnancy through the induction of anoikis resistance of mammary epithelium, resulting in loss of epithelial organization and a dysfunctional mammary gland. Moreover, combined inactivation of E-cadherin and p53 induced lactation-independent development of invasive and metastatic mammary carcinomas, which showed strong resemblance to human pleomorphic ILC. Dissemination patterns of mouse ILC mimic the human malignancy, showing metastasis to the gastrointestinal tract, peritoneum, lung, lymph nodes and bone. Our results confirm that loss of E-cadherin contributes to both mammary tumor initiation and metastasis, and establish a preclinical mouse model of human ILC that can be used for the development of novel intervention strategies to treat invasive breast cancer.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Yan, J.; Watanuki, S.; Fujii, K.
This paper presents a full simulation study of the measurement of the production cross section(ZH) of the Higgsstrahlung process e+e- ZH and the Higgs boson mass (MH) at the International Linear Collider (ILC), using events in which a Higgs boson recoils against a Z boson decaying into a pair of muons or electrons. The analysis is carried out for three center-of-mass energiesps =250, 350, and 500 GeV, and two beam polarizations e L e+ R and e Re+L , for which the polarizationsof e and e+ are Pe-; Pe+ =(-80%, +30%) and (+80%, -30%), respectively. Assuming an integrated luminosity ofmore » 250 fb1 for each beam polarization at ps = 250 GeV, where the best lepton momentum resolution is obtainable, ZH and MH can be determined with a precision of 2.5%and 37 MeV for e L e+R and 2.9% and 41 MeV for e-Re+L , respectively. Regarding a 20 year ILC physics program, the expected precisions for the HZZ coupling and MH are estimated to be 0.4% and 14MeV, respectively. The event selection is designed to optimize the precisions of ZH and MH while minimizing the bias on the measured ZH due to discrepancy in signal efficiencies among Higgs decay modes. For the first time, model independence has been demonstrated to a sub-percent level for the ZH measurement at each of the three center-of-mass energies. The results presented show the impact of center-of-mass energy and beam polarization on the evaluated precisons and serve as« less
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Constraints from triple gauge couplings on vectorlike leptons
Bertuzzo, Enrico; Machado, Pedro A. N.; Perez-Gonzalez, Yuber F.; ...
2017-08-30
Here, we study the contributions of colorless vectorlike fermions to the triple gauge couplings W +W -γ and W +W -Z 0. We consider models in which their coupling to the Standard Model Higgs boson is allowed or forbidden by quantum numbers. We assess the sensitivity of the future accelerators FCC-ee, ILC, and CLIC to the parameters of these models, assuming they will be able to constrain the anomalous triple gauge couplings with precision δ κV~O(10 -4), V = γ,Z 0. We show that the combination of measurements at different center-of-mass energies helps to improve the sensitivity to the contributionmore » of vectorlike fermions, in particular when they couple to the Higgs. In fact, the measurements at the FCC-ee and, especially, the ILC and the CLIC, may turn the triple gauge couplings into a new set of precision parameters able to constrain the models better than the oblique parameters or the H → γγ decay, even assuming the considerable improvement of the latter measurements achievable at the new machines.« less
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Constraints from triple gauge couplings on vectorlike leptons
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bertuzzo, Enrico; Machado, Pedro A. N.; Perez-Gonzalez, Yuber F.
Here, we study the contributions of colorless vectorlike fermions to the triple gauge couplings W +W -γ and W +W -Z 0. We consider models in which their coupling to the Standard Model Higgs boson is allowed or forbidden by quantum numbers. We assess the sensitivity of the future accelerators FCC-ee, ILC, and CLIC to the parameters of these models, assuming they will be able to constrain the anomalous triple gauge couplings with precision δ κV~O(10 -4), V = γ,Z 0. We show that the combination of measurements at different center-of-mass energies helps to improve the sensitivity to the contributionmore » of vectorlike fermions, in particular when they couple to the Higgs. In fact, the measurements at the FCC-ee and, especially, the ILC and the CLIC, may turn the triple gauge couplings into a new set of precision parameters able to constrain the models better than the oblique parameters or the H → γγ decay, even assuming the considerable improvement of the latter measurements achievable at the new machines.« less
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DEPFET pixel detector for future e-e+ experiments
NASA Astrophysics Data System (ADS)
Boronat, M.; DEPFET Collaboration
2016-04-01
The DEPFET Collaboration develops highly granular, ultra-thin pixel detectors for outstanding vertex reconstruction at future e+e- collider experiments. A DEPFET sensor provides, simultaneously, position sensitive detector capabilities and in-pixel amplification by the integration of a field effect transistor on a fully depleted silicon bulk. The characterization of the latest DEPFET prototypes has proven that a comfortable signal to noise ratio and excellent single point resolution can be achieved for a sensor thickness of 50 μm. A complete detector concept is being developed for the Belle II experiment at the new Japanese super flavor factory. The close to Belle related final auxiliary ASICs have been produced and found to operate a DEPFET pixel detector of the latest generation with the Belle II required read-out speed. DEPFET is not only the technology of choice for the Belle II vertex detector, but also a solid candidate for the International Linear Collider (ILC). Therefore, in this paper, the status of DEPFET R&D project is reviewed in the light of the requirements of the vertex detector at a future e+e- collider.
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Sendo, Sho; Saegusa, Jun; Okano, Takaichi; Takahashi, Soshi; Akashi, Kengo; Morinobu, Akio
2017-12-01
SKG mice develop interstitial lung disease (ILD) resembling rheumatoid arthritis-associated ILD in humans. The aim of this study was to clarify the mechanism underlying the lung pathology by analyzing lung-infiltrating cells in SKG mice with ILD. We assessed the severity of zymosan A (ZyA)-induced ILD in SKG mice histologically, and we examined lung-infiltrating cells by flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (MDSCs) were cultured in vitro with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4. The proliferation of 5,6-carboxyfluorescein diacetate N-succinimidyl ester-labeled naive T cells cocultured with isolated CD11b+Gr-1 dim cells and MDSCs was evaluated by flow cytometry. CD11b+Gr-1 dim cells were adoptively transferred to ZyA-treated SKG mice. MDSCs, Th17 cells, and group 1 and 3 innate lymphoid cells (ILC1s and ILC3s) were increased in the lungs; the proportion of these cells varied with ILD severity. In this process, we found that a unique cell population, CD11b+Gr-1 dim cells, was expanded in the severely inflamed lungs. Approximately half of the CD11b+Gr-1 dim cells expressed CD11c. CD11b+Gr-1 dim cells were induced from monocytic MDSCs with GM-CSF in vitro and were considered tolerogenic because they suppressed T cell proliferation. These CD11b+Gr-1 dim cells have never been described previously, and we termed them CD11b+Gr-1 dim tolerogenic dendritic cell (DC)-like cells. Th17 cells, ILC1s, and ILC3s in the inflamed lung produced GM-CSF, which may have expanded CD11b+Gr-1 dim tolerogenic DC-like cells in vivo. Furthermore, adoptive transfer of CD11b+Gr-1 dim tolerogenic DC-like cells significantly suppressed progression of ILD in SKG mice. We identified unique suppressive myeloid cells that were differentiated from monocytic MDSCs in SKG mice with ILD, and we termed them CD11b+Gr-1 dim tolerogenic DC-like cells. © 2017, American College of Rheumatology.
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NASA Astrophysics Data System (ADS)
Goto, Masaru
d-Serine is an endogenous coagonist for the N-methyl-d-aspartate receptor and is involved in excitatory neurotransmission in the brain. Mammalian pyridoxal 5’-phosphate-dependent serine racemase, which is localized in the mammalian brain, catalyzes the racemization of l-serine to yield d-serine and vice versa. We have determined the structures of three forms of the mammalian enzyme homolog from Schizosaccharomyces pombe. Lys57 and Ser82 located on the protein and solvent sides, respectively, with respect to the cofactor plane, are acid-base catalysts that shuttle protons to the substrate. The modified enzyme, which has a unique lysino-d-alanyl residue at the active site, also binds the substrate serine in the active site, suggesting that the lysino-d-alanyl residue acts as a catalytic base in the same manner as Lys57 of the wild type enzyme.
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A Laser Cavity for a Future Photon Collider at ILC
NASA Astrophysics Data System (ADS)
Klemz, G.; Moenig, K.
2006-04-01
Within a future photon-collider based on the infrastructure of ILC the energy of near-infrared laser photons will be boosted by Compton backscattering on a high energy electron beam to well above 100 GeV. By reason of luminosity, an extremely powerful lasersystem is required that will exceed today's state-of-the-art capabilities. An auxiliary cavity for resonantly enhancing the optical peak-power can relax demands on the power output of the laser. In this paper a possible design and the static aspects of a passive cavity are discussed.
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Bibliography on Cold Regions Science and Technology. Volume 36, Part 1, 1982.
1982-09-01
western MeNlurdo Sound. and the fact that thewe areas are truly rainless, many features Barrett, P I, ct al. .- lcr st fi p h ilc l I ,i,, . iss i and...beneath structures. Engi- 1981. Nir Mr. P 42 IlC Ressea equipment. ge rittund- leeriim utlmcog. Ertiten rick temperature. Snon Riesal’. A, \\. depth...i Jarri ii soc ctr im treg itjan ra irsd~rI-J River basins, Snot. cover distribution, Soon . water ik. \\iii s icrhr airIr i ii ’r~ ir~c rrrkrr .I
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Magnet reliability in the Fermilab Main Injector and implications for the ILC
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tartaglia, M.A.; Blowers, J.; Capista, D.
2007-08-01
The International Linear Collider reference design requires over 13000 magnets, of approximately 135 styles, which must operate with very high reliability. The Fermilab Main Injector represents a modern machine with many conventional magnet styles, each of significant quantity, that has now accumulated many hundreds of magnet-years of operation. We review here the performance of the magnets built for this machine, assess their reliability and categorize the failure modes, and discuss implications for reliability of similar magnet styles expected to be used at the ILC.
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WebAlchemist: a Web transcoding system for mobile Web access in handheld devices
NASA Astrophysics Data System (ADS)
Whang, Yonghyun; Jung, Changwoo; Kim, Jihong; Chung, Sungkwon
2001-11-01
In this paper, we describe the design and implementation of WebAlchemist, a prototype web transcoding system, which automatically converts a given HTML page into a sequence of equivalent HTML pages that can be properly displayed on a hand-held device. The Web/Alchemist system is based on a set of HTML transcoding heuristics managed by the Transcoding Manager (TM) module. In order to tackle difficult-to-transcode pages such as ones with large or complex table structures, we have developed several new transcoding heuristics that extract partial semantics from syntactic information such as the table width, font size and cascading style sheet. Subjective evaluation results using popular HTML pages (such as the CNN home page) show that WebAlchemist generates readable, structure-preserving transcoded pages, which can be properly displayed on hand-held devices.
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A hard-to-read font reduces the framing effect in a large sample.
Korn, Christoph W; Ries, Juliane; Schalk, Lennart; Oganian, Yulia; Saalbach, Henrik
2018-04-01
How can apparent decision biases, such as the framing effect, be reduced? Intriguing findings within recent years indicate that foreign language settings reduce framing effects, which has been explained in terms of deeper cognitive processing. Because hard-to-read fonts have been argued to trigger deeper cognitive processing, so-called cognitive disfluency, we tested whether hard-to-read fonts reduce framing effects. We found no reliable evidence for an effect of hard-to-read fonts on four framing scenarios in a laboratory (final N = 158) and an online study (N = 271). However, in a preregistered online study with a rather large sample (N = 732), a hard-to-read font reduced the framing effect in the classic "Asian disease" scenario (in a one-sided test). This suggests that hard-read-fonts can modulate decision biases-albeit with rather small effect sizes. Overall, our findings stress the importance of large samples for the reliability and replicability of modulations of decision biases.
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Banerjee, Jayeeta; Majumdar, Dhurjati; Majumdar, Deepti; Pal, Madhu Sudan
2010-06-01
We are experiencing a shifting of media: from the printed paper to the computer screen. This transition is modifying the process of how we read and understand a text. It is very difficult to conclude on suitability of font characters based upon subjective evaluation method only. Present study evaluates the effect of font type on human cognitive workload during perception of individual alphabets on a computer screen. Twenty six young subjects volunteered for this study. Here, subjects have been shown individual characters of different font types and their eye movements have been recorded. A binocular eye movement recorder was used for eye movement recording. The results showed that different eye movement parameters such as pupil diameter, number of fixations, fixation duration were less for font type Verdana. The present study recommends the use of font type Verdana for presentation of individual alphabets on various electronic displays in order to reduce cognitive workload.
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Thermophysical properties of undercooled liquid Co-Mo alloys
NASA Astrophysics Data System (ADS)
Han, X. J.; Wei, B.
2003-05-01
Using electromagnetic levitation in combination with the oscillating drop technique and drop calorimeter method, the surface tensions and specific heats of undercooled liquid Co-10 wt% Mo, Co-26.3 wt% Mo, and Co-37.6 wt% Mo alloys were measured. The containerless state during levitation produces substantial undercoolings up to 223 K (0.13TL), 213 K (0.13TL) and 110 K (0.07TL) respectively for these three alloys. In their respective undercooling ranges, the surface tensions were determined to be 1895 m 0.31(T m 1744), 1932 m 0.33(T m 1682), and 1989 m 0.34(T m 1607) mN mу. According to the Butler equation, the surface tensions of these three Co-Mo alloys were also calculated, and the results agree well with the experimental data. The specific heats of these three alloys are determined to be 41.85, 43.75 and 44.92 J molу Kу. Based on the determined surface tensions and specific heats, the changes in thermodynamics functions such as enthalpy, entropy and Gibbs free energy are predicted. Furthermore, the crystal nucleation, dendrite growth and Marangoni convection of undercooled Co-Mo alloys are investigated in the light of these measured thermophysical properties.
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The CNET Automated Budget System (CABS) IV.
1982-12-01
r RD-A124 173 THE CNET RUTOMATED BUDGET SYSTEM (CABS) IV(U) TRAINING 1/ ANALYSIS AND EVALUATION GROUP (NAVY) ORLANDO FL G N HODAK ET AL. DEC 82 TREG ...Ix ,A Ix A to 0 A a u H o••# •N U~~dl1 0-4 IL : IL N• €: . of, 4A "’ u j ilC x: 11-. ofl 11. 0 14 l of •joft -9 I C)l 0l 1 V) 0-0 r t 0 . Vl L-0C
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Soil CO2 flux from three ecosystems in tropical peatland of Sarawak, Malaysia
NASA Astrophysics Data System (ADS)
Melling, Lulie; Hatano, Ryusuke; Goh, Kah Joo
2005-02-01
Soil CO2 flux was measured monthly over a year from tropical peatland of Sarawak, Malaysia using a closed-chamber technique. The soil CO2 flux ranged from 100 to 533 mg C m
2 h1 for the forest ecosystem, 63 to 245 mg C m2 h1 for the sago and 46 to 335 mg C m2 h1 for the oil palm. Based on principal component analysis (PCA), the environmental variables over all sites could be classified into three components, namely, climate, soil moisture and soil bulk density, which accounted for 86% of the seasonal variability. A regression tree approach showed that CO2 flux in each ecosystem was related to different underlying environmental factors. They were relative humidity for forest, soil temperature at 5 cm for sago and water-filled pore space for oil palm. On an annual basis, the soil CO2 flux was highest in the forest ecosystem with an estimated production of 2.1 kg C m2 yr1 followed by oil palm at 1.5 kg C m2 yr1 and sago at 1.1 kg C m2 yr1. The different dominant controlling factors in CO2 flux among the studied ecosystems suggested that land use affected the exchange of CO2 between tropical peatland and the atmosphere. -
Extensibility Experiments with the Software Life-Cycle Support Environment
1991-11-01
APRICOT ) and Bit- Oriented Message Definer (BMD); and three from the Ada Software Repository (ASR) at White Sands-the NASA/Goddard Space Flight Center...Graphical Kernel System (GKS). c. AMS - The Automated Measurement System tool supports the definition, collec- tion, and reporting of quality metric...Ada Primitive Order Compilation Order Tool ( APRICOT ) 2. Bit-Oriented Message Definer (BMD) 3. LGEN: A Language Generator Tool 4. I"ilc Chc-ker 5
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Impact of calibration errors on CMB component separation using FastICA and ILC
NASA Astrophysics Data System (ADS)
Dick, Jason; Remazeilles, Mathieu; Delabrouille, Jacques
2010-01-01
The separation of emissions from different astrophysical processes is an important step towards the understanding of observational data. This topic of component separation is of particular importance in the observation of the relic cosmic microwave background (CMB) radiation, as performed by the Wilkinson Microwave Anisotropy Probe satellite and the more recent Planck mission, launched on 2009 May 14 from Kourou and currently taking data. When performing any sort of component separation, some assumptions about the components must be used. One assumption that many techniques typically use is knowledge of the frequency scaling of one or more components. This assumption may be broken in the presence of calibration errors. Here we compare, in the context of imperfect calibration, the recovery of a clean map of emission of the CMB from observational data with two methods: FastICA (which makes no assumption of the frequency scaling of the components) and an `Internal Linear Combination' (ILC), which explicitly extracts a component with a given frequency scaling. We find that even in the presence of small calibration errors (less than 1 per cent) with a Planck-style mission, the ILC method can lead to inaccurate CMB reconstruction in the high signal-to-noise ratio regime, because of partial cancellation of the CMB emission in the recovered map. While there is no indication that the failure of the ILC will translate to other foreground cleaning or component separation techniques, we propose that all methods which assume knowledge of the frequency scaling of one or more components be careful to estimate the effects of calibration errors.
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Character Sets for PLATO/NovaNET: An Expository Catalog.
ERIC Educational Resources Information Center
Gilpin, John B.
The PLATO and NovaNET computer-based instructional systems use a fixed system character set ("normal font") and an author-definable character set ("alternate font"). The alternate font lets the author construct his own symbols and bitmapped pictures. This expository catalog allows users to determine quickly (1) whether there is…
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background-color:#fff;font-size:80%;font-family:Verdana, Arial, Helvetica, sans-serif;font -weight:normal;color:#000;margin:0;padding:0;border:0;padding-bottom:25px;min-width:1000px;} /* Page Structure */ #wrapper {width:1000px;margin:0 auto;} #nrelheader {width:100%;background-color:#fff;} #topnav {width:100
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Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells
Scoville, Steven D.; Freud, Aharon G.; Caligiuri, Michael A.
2017-01-01
Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development. PMID:28396671
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Evaluation of three commercial microclimate cooling systems
NASA Astrophysics Data System (ADS)
Cadarette, Bruce S.; Decristofano, Barry S.; Speckman, Karen N.; Sawka, Michael N.
1988-11-01
Three commercially available microclimate cooling systems were evaluated for their ability to reduce heat stress in men exercising in a hot environment while wearing high insulative, low permeability clothing. The cooling systems were: (1) ILC Dover Model 19 Coolvest (ILC) (2) LSSI Coolhead(LSSI), and (3) Thermacor Cooling vest (THERM). Endurance Time (ET), Heart Rate (HR), rectal temperature (Tre), mean skin temperature (TSK), Sweating Rate (SR), Rated Perceived Exertion (RPE) and Thermal Sensation (TS) were measured. The subjects self-terminated on all LSSI tests because of headaches. Statistical analyses were performed on data collected at 60 minutes to have values on all subjects. There were no differences in HR, Tre, SR or TS values among the cooling vests. The subjects' TSK was lower (P less than 0.05) for the LSSI than THERM: and RPE values were higher (P less than 0.05) for LSSI than the other two vests. These data suggest an improved physiological response to exercise heat stress with all three commercial systems with the greatest benefit in performance time provided by the ILC cooling system.
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Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells.
Scoville, Steven D; Freud, Aharon G; Caligiuri, Michael A
2017-01-01
Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development.
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Dalmas, Elise; Lehmann, Frank M; Dror, Erez; Wueest, Stephan; Thienel, Constanze; Borsigova, Marcela; Stawiski, Marc; Traunecker, Emmanuel; Lucchini, Fabrizio C; Dapito, Dianne H; Kallert, Sandra M; Guigas, Bruno; Pattou, Francois; Kerr-Conte, Julie; Maechler, Pierre; Girard, Jean-Philippe; Konrad, Daniel; Wolfrum, Christian; Böni-Schnetzler, Marianne; Finke, Daniela; Donath, Marc Y
2017-11-21
Pancreatic-islet inflammation contributes to the failure of β cell insulin secretion during obesity and type 2 diabetes. However, little is known about the nature and function of resident immune cells in this context or in homeostasis. Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and enhanced by a diabetes milieu (glucose, IL-1β, and palmitate). IL-33 promoted β cell function through islet-resident group 2 innate lymphoid cells (ILC2s) that elicited retinoic acid (RA)-producing capacities in macrophages and dendritic cells via the secretion of IL-13 and colony-stimulating factor 2. In turn, local RA signaled to the β cells to increase insulin secretion. This IL-33-ILC2 axis was activated after acute β cell stress but was defective during chronic obesity. Accordingly, IL-33 injections rescued islet function in obese mice. Our findings provide evidence that an immunometabolic crosstalk between islet-derived IL-33, ILC2s, and myeloid cells fosters insulin secretion. Copyright © 2017 Elsevier Inc. All rights reserved.
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The Development of Laminated Armor
1948-09-27
U.S. Army Ramie Sea Island Mills, Inc. Ramie-Rayon Sea Island Mills, Ilc. Inconel Fabric (006R260R13) Metal Tex Co. -4- Inconel Fabric (00R21OMl6...Plies .02 U.D. Glass Mat 3111-44 4 Plies .02 IT.D. Glass Mat f 110 90 100 1 Ply Nylon Dusk(13 Oz.) I Ply 00R260R13 2-l/4# Inconel 2 Puiem Nylon Duck(13 Oz...13 Oz.) 1 Ply O07R210M16 2-1/4# Inconel 2 Pl•es Nylon Duck(13 Oz.) I Ply 007R210MI( ?-1/4# Inconel 1 Ply Nylon Duck(13 Oz.) 4 Plies .02 U.D. Mlass Mat
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Mn Impurity in Bulk GaAs Crystals
NASA Astrophysics Data System (ADS)
Pawłowski, M.; Piersa, M.; Wołoś, A.; Palczewska, M.; Strzelecka, G.; Hruban, A.; Gosk, J.; Kamińska, M.; Twardowski, A.
2006-11-01
Magnetic and electron transport properties of GaAs:Mn crystals grown by Czochralski method were studied. Electron spin resonance showed the presence of Mn acceptor A in two charge states: singly ionized A- in the form of Mn2+(d5), and neutral A0 in the form of Mn2+(d5) plus a bound hole (h). It was possible to determine the relative concentration of both types of centers from intensity of the corresponding electron spin resonance lines. Magnetization measured as a function of magnetic field (up to 6 T) in the temperature range of 2-300 K revealed overall paramagnetic behavior of the samples. Effective spin was found to be about 1.5 value, which was consistent with the presence of two types of Mn configurations. In most of the studied samples the dominance of Mn2+(d5)+h configuration was established and it increased after annealing of native donors. The total value of Mn content was obtained from fitting of magnetization curves with the use of parameters obtained from electron spin resonance. In electron transport, two mechanisms of conductivity were observed: valence band transport dominated above 70 K, and hopping conductivity within Mn impurity band at lower temperatures. From the analysis of the hopping conductivity and using the obtained values of the total Mn content, the effective radius of Mn acceptor in GaAs was estimated as a = 11 ± 3 Å.
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Transcriptional and epigenetic networks that drive helper T cell identities
Shih, Han-Yu; Sciumè, Giuseppe; Poholek, Amanda C; Vahedi, Golnaz; Hirahara, Kiyoshi; Villarino, Alejandro V; Bonelli, Michael; Bosselut, Remy; Kanno, Yuka; Muljo, Stefan A; O’Shea, John J.
2014-01-01
The discovery of the specification of CD4+ helper T cells to discrete effector “lineages” represented a watershed event in conceptualizing mechanisms of host defense and immunoregulation. However, our appreciation for the actual complexity of helper T cell subsets continues unabated. Just as the Sami language of Scandinavia has 1000 different words for reindeer, the range of fates available for a CD4+ T cell is numerous and may be underestimated. Added to the crowded scene for helper T cell subsets is the continuously growing family of innate lymphoid cells (ILCs), endowed with common effector responses and the previously defined “master regulators” for CD4+ helper T cell subsets are also shared by ILC subsets. Within the context of this extraordinary complexity are concomitant advances in the understanding of transcriptomes and epigenomes. So what do terms like “lineage commitment” and helper T cell “specification” mean in the early 21st century? How do we put all of this together in a coherent conceptual framework? It would be arrogant to assume that we have a sophisticated enough understanding to seriously answer these questions. Instead, we will review the current status of the flexibility of helper T cell responses in relation to their genetic regulatory networks and epigenetic landscapes. Recent data have provided major surprises as to what master regulators can or cannot do, how they interact with other transcription factors and impact global genome-wide changes and how all these factors come together to influence helper cell function. PMID:25123275
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Observações no infravermelho médio de objetos estelares jovens em NGC 3576
NASA Astrophysics Data System (ADS)
Barbosa, C.; Damineli, A.; Blum, R.; Conti, P.
2003-08-01
Apresentamos os resultados de observações no infravermelho médio de candidatos a objetos estelares jovens e massivos em NGC 3576. As imagens de alta resolução foram obtidas no observatório Gemini Sul com o uso dos filtros em 10,8, 7,9, 9,8, 12,5 e 18,2 mm. Nossas imagens mostram a fonte IRS 1 resolvida em 4 objetos pela primeira vez em 10 mm. Para cada objeto obtivemos a distribuição espectral de energia de 1.2 até 18 mm, bem como a temperatura de cor, a distribuição espacial e a profundidade óptica em 9,8 mm da poeira circunstelar. Apresentamos uma estimativa das massas dos objetos estudados, baseados na luminosidade emitida no infravermelho médio, bem como um modelo para explicar as diferentes características observadas de cada objeto. Finalmente discutimos a possível localização da(s) fonte(s) de ionização de NGC 3576.
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NASA Astrophysics Data System (ADS)
Fay, James A.; Sonwalkar, Nishikant
1996-05-01
This CD-ROM is designed to accompany James Fay's Introduction to Fluid Mechanics. An enhanced hypermedia version of the textbook, it offers a number of ways to explore the fluid mechanics domain. These include a complete hypertext version of the original book, physical-experiment video clips, excerpts from external references, audio annotations, colored graphics, review questions, and progressive hints for solving problems. Throughout, the authors provide expert guidance in navigating the typed links so that students do not get lost in the learning process. System requirements: Macintosh with 68030 or greater processor and with at least 16 Mb of RAM. Operating System 6.0.4 or later for 680x0 processor and System 7.1.2 or later for Power-PC. CD-ROM drive with 256- color capability. Preferred display 14 inches or above (SuperVGA with 1 megabyte of VRAM). Additional system font software: Computer Modern postscript fonts (CM/PS Screen Fonts, CMBSY10, and CMTT10) and Adobe Type Manager (ATM 3.0 or later). James A. Fay is Professor Emeritus and Senior Lecturer in the Department of Mechanical Engineering at MIT.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Barbareschi, Daniele; et al.
We describe a general purpose detector ( "Fourth Concept") at the International Linear Collider (ILC) that can measure with high precision all the fundamental fermions and bosons of the standard model, and thereby access all known physics processes. The 4th concept consists of four basic subsystems: a pixel vertex detector for high precision vertex definitions, impact parameter tagging and near-beam occupancy reduction; a Time Projection Chamber for robust pattern recognition augmented with three high-precision pad rows for precision momentum measurement; a high precision multiple-readout fiber calorimeter, complemented with an EM dual-readout crystal calorimeter, for the energy measurement of hadrons, jets,more » electrons, photons, missing momentum, and the tagging of muons; and, an iron-free dual-solenoid muon system for the inverse direction bending of muons in a gas volume to achieve high acceptance and good muon momentum resolution. The pixel vertex chamber, TPC and calorimeter are inside the solenoidal magnetic field. All four subsytems separately achieve the important scientific goal to be 2-to-10 times better than the already excellent LEP detectors, ALEPH, DELPHI, L3 and OPAL. All four basic subsystems contribute to the identification of standard model partons, some in unique ways, such that consequent physics studies are cogent. As an integrated detector concept, we achieve comprehensive physics capabilities that puts all conceivable physics at the ILC within reach.« less
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Bonamichi, Beatriz Dal Santo Francisco; Lee, Jongsoon
2017-08-01
The notion that obesity-induced inflammation mediates the development of insulin resistance in animal models and humans has been gaining strong support. It has also been shown that immune cells in local tissues, in particular in visceral adipose tissue, play a major role in the regulation of obesity-induced inflammation. Specifically, obesity increases the numbers and activation of proinflammatory immune cells, including M1 macrophages, neutrophils, Th1 CD4 T cells, and CD8 T cells, while simultaneously suppressing anti-inflammatory cells such as M2 macrophages, CD4 regulatory T cells, regulatory B cells, and eosinophils. Recently, however, new cell types have been shown to participate in the development of obesity-induced inflammation and insulin resistance. Some of these cell types also appear to regulate obesity. These cells are natural killer (NK) cells and innate lymphoid cells (ILCs), which are closely related, and invariant natural killer T (iNKT) cells. It should be noted that, although iNKT cells resemble NK cells in name, they are actually a completely different cell type in terms of their development and functions in immunity and metabolism. In this review, we will focus on the roles that these relatively new players in the metabolism field play in obesity-induced insulin resistance and the regulation of obesity. Copyright © 2017 Korean Diabetes Association.
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Dyslexie Font Does Not Benefit Reading in Children with or without Dyslexia
ERIC Educational Resources Information Center
Kuster, Sanne M.; van Weerdenburg, Marjolijn; Gompel, Marjolein; Bosman, Anna M. T.
2018-01-01
In two experiments, the claim was tested that the font "Dyslexie", specifically designed for people with dyslexia, eases reading performance of children with (and without) dyslexia. Three questions were investigated. (1) Does the Dyslexie font lead to faster and/or more accurate reading? (2) Do children have a preference for the Dyslexie…
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Metzger Filho, Otto; Giobbie-Hurder, Anita; Mallon, Elizabeth; Gusterson, Barry; Viale, Giuseppe; Winer, Eric P; Thürlimann, Beat; Gelber, Richard D; Colleoni, Marco; Ejlertsen, Bent; Debled, Marc; Price, Karen N; Regan, Meredith M; Coates, Alan S; Goldhirsch, Aron
2015-09-01
To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma. Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor-positive with high (luminal B [LB] -like) or low (luminal A [LA] -like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling. The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20). The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma. © 2015 by American Society of Clinical Oncology.
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Report of the Fermilab ILC Citizens' Task Force
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
Fermi National Accelerator Laboratory convened the ILC Citizens' Task Force to provide guidance and advice to the laboratory to ensure that community concerns and ideas are included in all public aspects of planning and design for a proposed future accelerator, the International Linear Collider. In this report, the members of the Task Force describe the process they used to gather and analyze information on all aspects of the proposed accelerator and its potential location at Fermilab in northern Illinois. They present the conclusions and recommendations they reached as a result of the learning process and their subsequent discussions and deliberations.more » While the Task Force was charged to provide guidance on the ILC, it became clear during the process that the high cost of the proposed accelerator made a near-term start for the project at Fermilab unlikely. Nevertheless, based on a year of extensive learning and dialogue, the Task Force developed a series of recommendations for Fermilab to consider as the laboratory develops all successor projects to the Tevatron. The Task Force recognizes that bringing a next-generation particle physics project to Fermilab will require both a large international effort and the support of the local community. While the Task Force developed its recommendations in response to the parameters of a future ILC, the principles they set forth apply directly to any large project that may be conceived at Fermilab, or at other laboratories, in the future. With this report, the Task Force fulfills its task of guiding Fermilab from the perspective of the local community on how to move forward with a large-scale project while building positive relationships with surrounding communities. The report summarizes the benefits, concerns and potential impacts of bringing a large-scale scientific project to northern Illinois.« less
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Metzger Filho, Otto; Giobbie-Hurder, Anita; Mallon, Elizabeth; Gusterson, Barry; Viale, Giuseppe; Winer, Eric P.; Thürlimann, Beat; Gelber, Richard D.; Colleoni, Marco; Ejlertsen, Bent; Debled, Marc; Price, Karen N.; Regan, Meredith M.; Coates, Alan S.; Goldhirsch, Aron
2015-01-01
Purpose To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma. Patients and Methods Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor–positive with high (luminal B [LB] –like) or low (luminal A [LA] –like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling. Results The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20). Conclusion The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma. PMID:26215945
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Zhang, Lei; Wang, Huaxi; Yang, Yan; Liu, Hui; Zhang, Qihao; Xiang, Qi; Ge, Renshan; Su, Zhijian; Huang, Yadong
2013-06-28
Nerve growth factor (NGF) has been reported to be involved in male reproductive physiology. However, few reports have described the activity of NGF during Leydig cell development. The objective of the present study was to examine the role of NGF during stem-Leydig-cell (SLC) regeneration. We investigated the effects of NGF on Leydig-cell (LC) regeneration by measuring mRNA levels in the adult rat testis after ethane dimethanesulfonate (EDS) treatment. Furthermore, we used the established organ culture model of rat seminiferous tubules to examine the regulation of NGF during SLC proliferation and differentiation using EdU staining, real-time PCR and western blotting. Progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs) were also used to investigate the effects of NGF on LCs at different developmental stages. NGF mRNA levels changed significantly during Leydig-cell regeneration in vivo. In vitro, NGF significantly promoted the proliferation of stem Leydig cells and also induced steroidogenic enzyme gene expression and 3β-HSD protein expression. The data from PLCs and ILCs showed that NGF could increase Cyclin D1 and Hsd 17b3 mRNA levels in PLCs and Cyclin D1 mRNA levels in ILCs. These results indicate that NGF may play an important role during LC regeneration by regulating the proliferation and differentiation of LCs at different developmental stages, from SLCs to PLCs and from PLCs to ILCs. The discovery of this effect of NGF on Leydig cells will provide useful information for developing new potential therapies for PADAM (Partial Androgen Deficiency in the Aging Male). Copyright © 2013 Elsevier Inc. All rights reserved.
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Kovacic, Jason C; Lee, Paul; Baber, Usman; Karajgikar, Rucha; Evrard, Solene M; Moreno, Pedro; Mehran, Roxana; Fuster, Valentin; Dangas, George; Sharma, Samin K; Kini, Annapoorna S
2012-03-01
Mounting data support a 'calcification paradox', whereby reduced bone mineral density is associated with increased vascular calcification. Furthermore, reduced bone mineral density is prevalent in older persons with lower body mass index (BMI). Therefore, although BMI and coronary artery calcification (CAC) exhibit a positive relationship in younger persons, it is predicted that in older persons and/or those at risk for osteoporosis, an inverse relationship between BMI and CAC may apply. We sought to explore this hypothesis in a large group of patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). We accessed our single-center registry for 07/01/1999 to 06/30/2009, extracting data on all patients that underwent PCI. To minimize bias we excluded those at the extremes of age or BMI and non-Black/Hispanic/Caucasians, leaving 9993 study subjects (age 66.6±9.9 years). Index lesion calcification (ILC) was analyzed with respect to BMI. Comparing index lesions with no angiographic calcification to those with the most severe, mean BMI decreased by 1.11 kgm(-2); a reduction of 3.9% (P<0.0001). By multivariable modeling, BMI was an independent inverse predictor of moderate-severe ILC (m-sILC; odds ratio [OR] 0.967, 95% CI 0.953-0.980, P<0.0001). Additional fully adjusted models identified that, compared to those with normal BMI, obese patients had an OR of 0.702 for m-sILC (95% CI 0.596-0.827, P<0.0001). In a large group of PCI patients, we identified an inverse correlation between BMI and index lesion calcification. These associations are consistent with established paradigms and suggest a complex interrelationship between BMI, body size and vascular calcification. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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Abdel-Fatah, Tarek M A; Powe, Desmond G; Hodi, Zsolt; Lee, Andrew H S; Reis-Filho, Jorge S; Ellis, Ian O
2007-03-01
This study was undertaken to determine the morphologic features and frequency of putative precursor lesions involved in the development of some pure forms of special types and low grade breast carcinoma. We reviewed 147 successive tumor cases, comprising tubular carcinoma (TC); pure type (n=56) and mixed type (n=20), invasive lobular carcinoma (ILC); classic type (n=57), and tubulolobular carcinoma (TLC; n=14). The presence of preinvasive lesions including columnar cell lesions (CCLs), usual epithelial hyperplasia, ductal carcinoma in situ (DCIS), and lobular neoplasia (LN) was determined. Estrogen receptor and E-cadherin immunohistochemistry was performed. Ninety-five percent (95%) of pure TCs had associated CCLs with the majority showing flat epithelial atypia. Atypical ductal hyperplasia (ADH)/DCIS was present in 89% patients. Colocalization of CCL, ADH/DCIS, and TC was seen in 85% patients, all displaying the same cytologic-nuclear morphology in most cases. LN was seen in 16%. In ILC, 91% cases showed LN. CCL and ADH/DCIS were seen in 60% and 42% cases, respectively. E-cadherin was positive in TLC but reduced in TC and completely absent in ILC. In conclusion, our findings support the hypothesis that CCLs are associated with pure and mixed forms of TC, and that LN is involved in ILC development. Our observations suggest that these lesions represent family members of low grade precursor, in situ and invasive neoplastic lesions of the breast. Molecular studies are being performed to substantiate the hypothesis that tubular and lobular carcinomas have direct evolutionary links to CCLs and flat epithelial atypia.
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Character feature integration of Chinese calligraphy and font
NASA Astrophysics Data System (ADS)
Shi, Cao; Xiao, Jianguo; Jia, Wenhua; Xu, Canhui
2013-01-01
A framework is proposed in this paper to effectively generate a new hybrid character type by means of integrating local contour feature of Chinese calligraphy with structural feature of font in computer system. To explore traditional art manifestation of calligraphy, multi-directional spatial filter is applied for local contour feature extraction. Then the contour of character image is divided into sub-images. The sub-images in the identical position from various characters are estimated by Gaussian distribution. According to its probability distribution, the dilation operator and erosion operator are designed to adjust the boundary of font image. And then new Chinese character images are generated which possess both contour feature of artistical calligraphy and elaborate structural feature of font. Experimental results demonstrate the new characters are visually acceptable, and the proposed framework is an effective and efficient strategy to automatically generate the new hybrid character of calligraphy and font.
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Chauncey, Krysta; Holcomb, Phillip J; Grainger, Jonathan
2008-01-01
The size and font of target words were manipulated in a masked repetition priming paradigm with ERP recordings. Repetition priming effects were found in four ERP components: the N/P150, N250, P325, and N400. Neither a change in font nor a change in size across prime and target were found to affect repetition priming in the N250, P325, and N400 components. Changing font was, however, found to affect repetition priming in the N/P150 component, while the interaction between repetition priming and size was not significant in this component. These results confirm our interpretation of the N/P150 as a component sensitive to feature-level processing, and suggest that the type of prelexical and lexical processing reflected in the N250, P325, and N400 components is performed on representations that are invariant to changes in both font and size.
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NASA Astrophysics Data System (ADS)
Lan, Xin; Bai, Lu; Li, Xin; Ma, Shuang; He, Xiaozhi; Meng, Fanbao
2014-10-01
Cholesteryl-containing ionic liquid crystals (ILCs) 1-cholesteryloxycarbonylmethyl(propyl)-3-methyl(butyl)imidazolium chlorides ([Ca-Me-Im]Cl, [Ca-Bu-Im]Cl, [Cb-Me-Im]Cl and [Cb-Bu-Im]Cl) and corresponding imidazolium tetrachloroaluminates ([Ca-Me-Im]AlCl4, [Ca-Bu-Im]AlCl4, [Cb-Me-Im]AlCl4 and [Cb-Bu-Im]AlCl4) were synthesized in this work, and the chemical structure, LC behavior and ionic conductivity of all these ILCs were characterized by several technical methods. The imidazolium-based salts with Cl- ions showed chiral smectic A (SA*) phase on both heating and cooling cycles, while the tetrachloroaluminates exhibited chiral nematic (N*) phase. The mesophase was confirmed by characteristic LC textures observed by polarizing optical microscopy and typical diffractogram obtained by X-ray diffraction measurements. The samples with similar cholesteryl-linkage component showed similar phase transition temperature and entropy, indicating the cholesteryl component influence predominately on the phase transition rather than alkyl substituents on the imidazole ring. The imidazolium tetrachloroaluminates display relatively low phase transition temperature compared with the precursor chlorides. The functional difference in LC behavior and ionic conductivity were discussed by investigated the structural difference between the Cl--containing and AlCl4-containing materials. The imidazolium chlorides exhibited layer structure both in crystal and mesophase states, and should be organized with a ‘head-to-tail’ organization to form interdigitated monolayer structures due to the tight ion pairs. But the imidazolium tetrachloroaluminates displayed layer structure only in crystal phase, and should be organized in ‘head-to-head’ arrangements form bilayer structures due to loose combination of ion pairs despite of hydrogen-bond and electrostatic attraction interaction.
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The Role of Memory Activation in Creating False Memories of Encoding Context
ERIC Educational Resources Information Center
Arndt, Jason
2010-01-01
Using 3 experiments, I examined false memory for encoding context by presenting Deese-Roediger-McDermott themes (Deese, 1959; Roediger & McDermott, 1995) in usual-looking fonts and by testing related, but unstudied, lure items in a font that was shown during encoding. In 2 of the experiments, testing lure items in the font used to study their…
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-03-02
... all text in charts, tables, figures, and graphs. Use a font that is either 12 point or larger. Use one of the following fonts: Times New Roman, Courier, Courier New, or Arial. An amended application submitted in any other font (including Times Roman and Arial Narrow) will not be accepted. The page limits...
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ERIC Educational Resources Information Center
Haugen, Theresa Tetrick
2010-01-01
This study examined font and layout alternatives for mild special education children in third through sixth grade. Of this group, twelve were boys and two were girls, seven were suburban students and seven were urban students. During the first phase, the students were observed reading four different fonts, then the participant named the easiest…
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The Effect of a Specialized Dyslexia Font, Opendyslexic, on Reading Rate and Accuracy
ERIC Educational Resources Information Center
Wery, Jessica J.; Diliberto, Jennifer A.
2017-01-01
A single-subject alternating treatment design was used to investigate the extent to which a specialized dyslexia font, OpenDyslexic, impacted reading rate or accuracy compared to two commonly used fonts when used with elementary students identified as having dyslexia. OpenDyslexic was compared to Arial and Times New Roman in three reading tasks:…
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Multi-font printed Mongolian document recognition system
NASA Astrophysics Data System (ADS)
Peng, Liangrui; Liu, Changsong; Ding, Xiaoqing; Wang, Hua; Jin, Jianming
2009-01-01
Mongolian is one of the major ethnic languages in China. Large amount of Mongolian printed documents need to be digitized in digital library and various applications. Traditional Mongolian script has unique writing style and multi-font-type variations, which bring challenges to Mongolian OCR research. As traditional Mongolian script has some characteristics, for example, one character may be part of another character, we define the character set for recognition according to the segmented components, and the components are combined into characters by rule-based post-processing module. For character recognition, a method based on visual directional feature and multi-level classifiers is presented. For character segmentation, a scheme is used to find the segmentation point by analyzing the properties of projection and connected components. As Mongolian has different font-types which are categorized into two major groups, the parameter of segmentation is adjusted for each group. A font-type classification method for the two font-type group is introduced. For recognition of Mongolian text mixed with Chinese and English, language identification and relevant character recognition kernels are integrated. Experiments show that the presented methods are effective. The text recognition rate is 96.9% on the test samples from practical documents with multi-font-types and mixed scripts.
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Left-handed and right-handed U(1) gauge symmetry
NASA Astrophysics Data System (ADS)
Nomura, Takaaki; Okada, Hiroshi
2018-01-01
We propose a model with the left-handed and right-handed continuous Abelian gauge symmetry; U(1) L × U(1) R . Then three right-handed neutrinos are naturally required to achieve U(1) R anomaly cancellations, while several mirror fermions are also needed to do U(1) L anomaly cancellations. Then we formulate the model, and discuss its testability of the new gauge interactions at collider physics such as the large hadron collider (LHC) and the international linear collider (ILC). In particular, we can investigate chiral structure of the interactions by the analysis of forward-backward asymmetry based on polarized beam at the ILC.
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ID’ing Innate and Innate-like Lymphoid Cells
Verykokakis, Mihalis; Zook, Erin C.; Kee, Barbara L.
2014-01-01
Summary The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. PMID:25123285
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ID'ing innate and innate-like lymphoid cells.
Verykokakis, Mihalis; Zook, Erin C; Kee, Barbara L
2014-09-01
The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B- and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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IL-33: biological properties, functions, and roles in airway disease.
Drake, Li Yin; Kita, Hirohito
2017-07-01
Interleukin (IL)-33 is a key cytokine involved in type 2 immunity and allergic airway diseases. Abundantly expressed in lung epithelial cells, IL-33 plays critical roles in both innate and adaptive immune responses in mucosal organs. In innate immunity, IL-33 and group 2 innate lymphoid cells (ILC2s) provide an essential axis for rapid immune responses and tissue homeostasis. In adaptive immunity, IL-33 interacts with dendritic cells, Th2 cells, follicular T cells, and regulatory T cells, where IL-33 influences the development of chronic airway inflammation and tissue remodeling. The clinical findings that both the IL-33 and ILC2 levels are elevated in patients with allergic airway diseases suggest that IL-33 plays an important role in the pathogenesis of these diseases. IL-33 and ILC2 may also serve as biomarkers for disease classification and to monitor the progression of diseases. In this article, we reviewed the current knowledge of the biology of IL-33 and discussed the roles of the IL-33 in regulating airway immune responses and allergic airway diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Quality of Life as reported by school children and their parents: a cross-sectional survey
Jozefiak, Thomas; Larsson, Bo; Wichstrøm, Lars; Mattejat, Fritz; Ravens-Sieberer, Ulrike
2008-01-01
Background Comprehensive evidence exists regarding the discrepancy between children's reports and parents' by proxy reports on emotional and behavioural problems. However, little is yet known about factors influencing the extent to which child self- and parent by proxy reports differ in respect of child Quality of Life (QoL). The aim of the study was to investigate the degree of discrepancy between child and parent by proxy reports as measured by two different QoL instruments. Methods A representative Norwegian sample of 1997 school children aged 8–16 years, and their parents were studied using the Inventory of Life Quality (ILC) and the 'Kinder Lebensqualität Fragebogen' (KINDL). Child and parent reports were compared by t-test, and correlations were calculated by Pearson product moment coefficient. Psychometric aspects were examined in regard to both translated QoL instruments (internal consistency by Cronbach's alpha and test-retest reliability by intraclass correlation coefficients). Results Parents evaluated the QoL of their children significantly more positively than did the children. Correlations between mother-child and father-child reports were significant (p < 0.01) and similar but low to moderate (r = 0.32; and r = 0.30, respectively, for the KINDL, and r = 0.30 and r = 0.26, respectively, for the ILC). Mother and father reports correlated moderately highly (r = 0.54 and r = 0.61 for the KINDL and ILC, respectively). No significant differences between correlations of mother-daughter/son and father-daughter/son pairs in regard to reported child QoL were observed on either of the two instruments. Conclusion In the present general population sample, parents reported higher child QoL than did their children. Concordance between child and parent by proxy report was low to moderate. The level of agreement between mothers and fathers in regard to their child's QoL was moderate. No significant impact of parent and child gender in regard to agreement in ratings of child QoL was found. Both the child and parent versions of the Norwegian translations of the KINDL and ILC can be used in surveys of community populations, but in regard to the self-report of 9–10 years old children, only the KINDL total QoL scale or the ILC are recommended. PMID:18489777
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El-Mezayen, Nesrine S; El-Hadidy, Wessam F; El-Refaie, Wessam M; Shalaby, Th I; Khattab, Mahmoud M; El-Khatib, Aiman S
2017-11-28
Liver fibrosis is a global health problem without approved treatment. Imatinib inhibits two key profibrotic pathways; platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) and thus can be used to treat liver fibrosis. However, conventional imatinib therapy is hampered by low concentration at target tissue and increased toxicity to other tissues especially heart, lung and liver. Since hepatic stellate cells (HSCs) are the main contributors to liver fibrosis pathogenesis and sole hepatic vitamin A (V A ) storage cells, they can be actively targeted by coupling liposomes to V A . In this study, novel V A -coupled imatinib-loaded liposomes (ILC) were prepared and optimized regarding V A -coupling efficiency, imatinib entrapment efficiency, and particle size. Preferential accumulation of the selected formula in liver was proved by tracing intraperitoneally (i.p.)-injected V A -coupled liposomes loaded with Nile Red (LCNR) to rats with CCl 4 -induced liver fibrosis using live animal imaging. Co-localization of LCNR with immunofluorescently-labeled PDGFR-β in frozen liver tissue sections confirmed HSCs targeting. ILC bio-distribution, following single i.p. injection, revealed 13.5 folds higher hepatic accumulation than conventional imatinib in addition to limited bio-distribution to other organs including heart and lung reflecting diminished adverse effects. ILC therapy resulted in a potent inhibition of phosphorylated PDGFR-β expression when compared to conventional imatinib. Subsequently, there was a statistically significant improvement in liver function tests and reversal of hepatotoxicity along with liver fibrosis. Anti-fibrotic effect was evident from histopathologic Ishak score reduction as well as normalization of the level of profibrotic mediators (hydroxyproline, TGF-B and matrix metalloproteinase-2). Thus, HSC-targeted imatinib therapy shows outstanding anti-fibrotic effects with reduced cytotoxicity compared to conventional imatinib. It can represent a promising novel approach for liver fibrosis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.
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Slattery, Timothy J; Yates, Mark; Angele, Bernhard
2016-12-01
Despite the large number of eye movement studies conducted over the past 30+ years, relatively few have examined the influence that font characteristics have on reading. However, there has been renewed interest in 1 particular font characteristic, letter spacing, which has both theoretical (visual word recognition) and applied (font design) importance. Recently published results that letter spacing has a bigger impact on the reading performance of dyslexic children have perhaps garnered the most attention (Zorzi et al., 2012). Unfortunately, the effects of increased interletter spacing have been mixed with some authors reporting facilitation and others reporting inhibition (van den Boer & Hakvoort, 2015). The authors present findings from 3 experiments designed to resolve the seemingly inconsistent letter-spacing effects and provide clarity to researchers and font designers and researchers. The results indicate that the direction of spacing effects depend on the size of the default spacing chosen by font developers. Experiment 3 found that interletter spacing interacts with interword spacing, as the required space between words depends on the amount of space used between letters. Interword spacing also interacted with word type as the inhibition seen with smaller interword spacing was evident with nouns and verbs but not with function words. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
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The dependence of crowding on flanker complexity and target-flanker similarity
Bernard, Jean-Baptiste; Chung, Susana T.L.
2013-01-01
We examined the effects of the spatial complexity of flankers and target-flanker similarity on the performance of identifying crowded letters. On each trial, observers identified the middle character of random strings of three characters (“trigrams”) briefly presented at 10° below fixation. We tested the 26 lowercase letters of the Times-Roman and Courier fonts, a set of 79 characters (letters and non-letters) of the Times-Roman font, and the uppercase letters of two highly complex ornamental fonts, Edwardian and Aristocrat. Spatial complexity of characters was quantified by the length of the morphological skeleton of each character, and target-flanker similarity was defined based on a psychometric similarity matrix. Our results showed that (1) letter identification error rate increases with flanker complexity up to a certain value, beyond which error rate becomes independent of flanker complexity; (2) the increase of error rate is slower for high-complexity target letters; (3) error rate increases with target-flanker similarity; and (4) mislocation error rate increases with target-flanker similarity. These findings, combined with the current understanding of the faulty feature integration account of crowding, provide some constraints of how the feature integration process could cause perceptual errors. PMID:21730225
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Iconographic dental typography. A dental character font for computer graphics.
McCormack, J
1991-06-08
The recent massive increase in available memory for microcomputers now allows multiple font faces to be stored in computer RAM memory for instant access to the screen and for printed output. Fonts can be constructed in which the characters are not just letters or numbers, but are miniature graphic icons--in this instance pictures of teeth. When printed on an appropriate laser printer, this produces printed graphics of publishing quality.
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Trichoscopy of Steroid-Induced Atrophy.
Pirmez, Rodrigo; Abraham, Leonardo S; Duque-Estrada, Bruna; Damasco, Patrícia; Farias, Débora Cadore; Kelly, Yanna; Doche, Isabella
2017-10-01
Intralesional corticosteroid (IL-CS) injections have been used to treat a variety of dermatological and nondermatological diseases. Although an important therapeutic tool in dermatology, a number of local side effects, including skin atrophy, have been reported following IL-CS injections. We recently noticed that a subset of patients with steroid-induced atrophy presented with ivory-colored areas under trichoscopy. We performed a retrospective analysis of trichoscopic images and medical records from patients presenting ivory-colored areas associated with atrophic scalp lesions. In this paper, we associate this feature with the presence of steroid deposits in the dermis and report additional trichoscopic features of steroid-induced atrophy on the scalp, such as prominent blood vessels and visualization of hair bulbs.
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Neural Measures Reveal Implicit Learning during Language Processing.
Batterink, Laura J; Cheng, Larry Y; Paller, Ken A
2016-10-01
Language input is highly variable; phonological, lexical, and syntactic features vary systematically across different speakers, geographic regions, and social contexts. Previous evidence shows that language users are sensitive to these contextual changes and that they can rapidly adapt to local regularities. For example, listeners quickly adjust to accented speech, facilitating comprehension. It has been proposed that this type of adaptation is a form of implicit learning. This study examined a similar type of adaptation, syntactic adaptation, to address two issues: (1) whether language comprehenders are sensitive to a subtle probabilistic contingency between an extraneous feature (font color) and syntactic structure and (2) whether this sensitivity should be attributed to implicit learning. Participants read a large set of sentences, 40% of which were garden-path sentences containing temporary syntactic ambiguities. Critically, but unbeknownst to participants, font color probabilistically predicted the presence of a garden-path structure, with 75% of garden-path sentences (and 25% of normative sentences) appearing in a given font color. ERPs were recorded during sentence processing. Almost all participants indicated no conscious awareness of the relationship between font color and sentence structure. Nonetheless, after sufficient time to learn this relationship, ERPs time-locked to the point of syntactic ambiguity resolution in garden-path sentences differed significantly as a function of font color. End-of-sentence grammaticality judgments were also influenced by font color, suggesting that a match between font color and sentence structure increased processing fluency. Overall, these findings indicate that participants can implicitly detect subtle co-occurrences between physical features of sentences and abstract, syntactic properties, supporting the notion that implicit learning mechanisms are generally operative during online language processing.
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Ho, Jacqueline; Bailey, Michelle; Zaunders, John; Mrad, Nadine; Sacks, Raymond; Sewell, William; Harvey, Richard J
2015-01-01
Nasal polyposis is a common development in chronic rhinosinusitis (CRS), and sinus mucosa and polyp tissue have been used interchangeably in studies investigating CRS. However, potential differences may exist between these 2 tissue types, which have not been entirely characterized. A cross-sectional study of CRS with nasal polyposis (CRSwNP) patients undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies and corresponding polyp tissue were obtained from the same sinus cavity via flow cytometry, single-cell suspensions identified type 2 innate lymphoid cells (ILC2s), CD4 and CD8 T cells, activated CD4 and CD8 T cells, plasma cells, plasmacytoid dendritic cells (pDCs), regulatory T cells, T follicular helper cells, B cells, and immunoglobulin A (IgA)(+) and IgG(+) B cells. Cells were measured as a percentage of CD45(+) cells. Paired nonparametric comparisons between sinus and polyp tissue were performed. Ten patients (50% female; age 48 ± 16 years) were recruited. Significantly elevated ILC2 levels were found in polyp tissue compared to sinus mucosa (0.12 [0.07 to 0.23] vs 0.07 [0.04 to 0.16], p = 0.02), as well as plasma cells (2.25 [0.84 to 3.68] vs 1.18 [0.74 to 2.41], p = 0.01); pDCs (0.15 [0.12 to 0.50[ vs 0.04 [0.02 to 0.17], p = 0.03); activated CD8 T cells (29.22 [17.60 to 41.43] vs 16.32 [10.07 to 36.16], p = 0.04) and IgG(+) B cells (6.96 [0.06 to 11.82] vs 1.51 [0.38 to 5.13], p = 0.04). Other cell populations showed no significant differences. Polyps have a similar cellular composition to that of mucosa. Higher levels of ILC2s, plasma cells, pDCs, activated CD8 T cells, and IgG(+) B cells in polyp tissue may be reflective of cell populations driving nasal polyp development. The cellular machinery of CRS is present in polyps and representative of the disease process. This pilot study strongly suggests that a larger study would provide significant insights into the relationship of sinus mucosa to pathogenesis of nasal polyps. © 2014 ARS-AAOA, LLC.
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Bergot, Anne-Sophie; Monnet, Nastasia; Tran, Le Son; Mittal, Deepak; Al-Kouba, Jane; Steptoe, Raymond J.; Grimbaldeston, Michele A.; Frazer, Ian H.; Wells, James W.
2014-01-01
Atopic dermatitis is a common pruritic and inflammatory skin disorder with unknown etiology. Most commonly occurring during early childhood, atopic dermatitis is associated with eczematous lesions and lichenification, in which the epidermis becomes hypertrophied resulting in thickening of the skin. In this study, we report an atopic dermatitis-like pathophysiology results in a murine model following the expression of the high-risk Human Papillomavirus (HPV) 16 oncoprotein E7 in keratinocytes under the Keratin 14 promoter. We show that HPV 16 E7 expression in the skin is associated with skin thickening, acanthosis and light spongiosis. Locally, HPV 16 E7 expressing skin secreted high levels of TSLP and contained increased numbers of ILCs. High levels of circulating IgE were associated with increased susceptibility to skin allergy in a model of cutaneous challenge, and to airway bronchiolar inflammation, enhanced airway goblet cell metaplasia and mucus production in a model of atopic march. Surprisingly, skin pathology occurred independently of T-cells and mast cells. Thus, our findings suggest that the expression of a single HPV oncogene in the skin can drive the onset of atopic dermatitis-like pathology through the induction of TSLP and type 2 ILC infiltration. PMID:25601274
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bane, K.L.F.; Adolphsen, C.; Li, Z.
In a future linear collider, such as the International Linear Collider (ILC), trains of high current, low emittance bunches will be accelerated in a linac before colliding at the interaction point. Asymmetries in the accelerating cavities of the linac will generate fields that will kick the beam transversely and degrade the beam emittance and thus the collider performance. In the main linac of the ILC, which is filled with TESLA-type superconducting cavities, it is the fundamental (FM) and higher mode (HM) couplers that are asymmetric and thus the source of such kicks. The kicks are of two types: one, duemore » to (the asymmetry in) the fundamental RF fields and the other, due to transverse wakefields that are generated by the beam even when it is on axis. In this report we calculate the strength of these kicks and estimate their effect on the ILC beam. The TESLA cavity comprises nine cells, one HM coupler in the upstream end, and one (identical, though rotated) HM coupler and one FM coupler in the downstream end (for their shapes and location see Figs. 1, 2) [1]. The cavity is 1.1 m long, the iris radius 35 mm, and the coupler beam pipe radius 39 mm. Note that the couplers reach closer to the axis than the irises, down to a distance of 30 mm.« less
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Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity
NASA Astrophysics Data System (ADS)
van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique
2014-04-01
The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.
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Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity.
van de Pavert, Serge A; Ferreira, Manuela; Domingues, Rita G; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R; Habani, Yasmin; Haak, Esther; Santori, Fabio R; Littman, Dan R; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J Pedro; Mebius, Reina E; Veiga-Fernandes, Henrique
2014-04-03
The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.
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Principal Component 2-D Long Short-Term Memory for Font Recognition on Single Chinese Characters.
Tao, Dapeng; Lin, Xu; Jin, Lianwen; Li, Xuelong
2016-03-01
Chinese character font recognition (CCFR) has received increasing attention as the intelligent applications based on optical character recognition becomes popular. However, traditional CCFR systems do not handle noisy data effectively. By analyzing in detail the basic strokes of Chinese characters, we propose that font recognition on a single Chinese character is a sequence classification problem, which can be effectively solved by recurrent neural networks. For robust CCFR, we integrate a principal component convolution layer with the 2-D long short-term memory (2DLSTM) and develop principal component 2DLSTM (PC-2DLSTM) algorithm. PC-2DLSTM considers two aspects: 1) the principal component layer convolution operation helps remove the noise and get a rational and complete font information and 2) simultaneously, 2DLSTM deals with the long-range contextual processing along scan directions that can contribute to capture the contrast between character trajectory and background. Experiments using the frequently used CCFR dataset suggest the effectiveness of PC-2DLSTM compared with other state-of-the-art font recognition methods.
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Emotional and persuasive perception of fonts.
Juni, Samuel; Gross, Julie S
2008-02-01
The aim of this study was to explore the latent affective and persuasive meaning attributed to text when appearing in two commonly used fonts. Two satirical readings were selected from the New York Times. These readings (one addressing government issues, the other education policy) were each printed in Times New Roman and Arial fonts of the same size and presented in randomized order to 102 university students, who ranked the readings on a number of adjective descriptors. Analysis showed that satirical readings in Times New Roman were perceived as more funny and angry than those in Arial, the combination of emotional perception which is congruent with the definition of satire. This apparent interaction of font type with emotional qualities of text has implications for marketing, advertising, and the persuasive literature.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Lei; Wang, Huaxi; Yang, Yan
Highlights: •Nerve growth factor has shown significant changes on mRNA levels during Adult Leydig cells regeneration. •We established the organ culture model of rat seminiferous tubules with ethane dimethyl sulphonate (EDS) treatment. •Nerve growth factor has shown proliferation and differentiation-promoting effects on Adult stem Leydig cells. •Nerve growth factor induces progenitor Leydig cells to proliferate and differentiate and immature Leydig cells to proliferate. -- Abstract: Nerve growth factor (NGF) has been reported to be involved in male reproductive physiology. However, few reports have described the activity of NGF during Leydig cell development. The objective of the present study was tomore » examine the role of NGF during stem-Leydig-cell (SLC) regeneration. We investigated the effects of NGF on Leydig-cell (LC) regeneration by measuring mRNA levels in the adult rat testis after ethane dimethanesulfonate (EDS) treatment. Furthermore, we used the established organ culture model of rat seminiferous tubules to examine the regulation of NGF during SLC proliferation and differentiation using EdU staining, real-time PCR and western blotting. Progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs) were also used to investigate the effects of NGF on LCs at different developmental stages. NGF mRNA levels changed significantly during Leydig-cell regeneration in vivo. In vitro, NGF significantly promoted the proliferation of stem Leydig cells and also induced steroidogenic enzyme gene expression and 3β-HSD protein expression. The data from PLCs and ILCs showed that NGF could increase Cyclin D1 and Hsd 17b3 mRNA levels in PLCs and Cyclin D1 mRNA levels in ILCs. These results indicate that NGF may play an important role during LC regeneration by regulating the proliferation and differentiation of LCs at different developmental stages, from SLCs to PLCs and from PLCs to ILCs. The discovery of this effect of NGF on Leydig cells will provide useful information for developing new potential therapies for PADAM (Partial Androgen Deficiency in the Aging Male)« less
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NASA Astrophysics Data System (ADS)
Lamberty, Andrée; Franks, Katrin; Braun, Adelina; Kestens, Vikram; Roebben, Gert; Linsinger, Thomas P. J.
2011-12-01
The Institute for Reference Materials and Measurements has organised an interlaboratory comparison (ILC) to allow the participating laboratories to demonstrate their proficiency in particle size and zeta potential measurements on monomodal aqueous suspensions of silica nanoparticles in the 10-100 nm size range. The main goal of this ILC was to identify competent collaborators for the production of certified nanoparticle reference materials. 38 laboratories from four different continents participated in the ILC with different methods for particle sizing and determination of zeta potential. Most of the laboratories submitted particle size results obtained with centrifugal liquid sedimentation (CLS), dynamic light scattering (DLS) or electron microscopy (EM), or zeta potential values obtained via electrophoretic light scattering (ELS). The results of the laboratories were evaluated using method-specific z scores, calculated on the basis of consensus values from the ILC. For CLS (13 results) and EM (13 results), all reported values were within the ±2 | z| interval. For DLS, 25 of the 27 results reported were within the ±2 | z| interval, the two other results were within the ±3 | z| interval. The standard deviations of the corresponding laboratory mean values varied between 3.7 and 6.5%, which demonstrates satisfactory interlaboratory comparability of CLS, DLS and EM particle size values. From the received test reports, a large discrepancy was observed in terms of the laboratory's quality assurance systems, which are equally important for the selection of collaborators in reference material certification projects. Only a minority of the participating laboratories is aware of all the items that are mandatory in test reports compliant to ISO/IEC 17025 (ISO General requirements for the competence of testing and calibration laboratories. International Organisation for Standardization, Geneva, 2005b). The absence of measurement uncertainty values in the reports, for example, hindered the calculation of zeta scores.
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Bansal, Gaurav J; Santosh, Divya; Davies, Eleri L
2016-01-01
The purpose of this study was to evaluate whether high mammographic density can be used as one of the selection criteria for MRI in invasive lobular breast cancer (ILC). In our institute, high breast density has been used as one of the indications for performing MRI scan in patients with ILC. We divided the patients in two groups, one with MRI performed pre-operatively and other without MRI. We compared their surgical procedures and analyzed whether surgical plan was altered after MRI. In case of alteration of plan, we analyzed whether the change was adequate by comparing post-operative histological findings. Between 2011 and 2015, there were a total of 1601 breast cancers with 97 lobular cancers, out of which 36 had pre-operative MRI and 61 had no MRI scan. 12 (33.3%) had mastectomy following MRI, out of which 9 (25%) had change in surgical plan from conservation to mastectomy following MRI. There were no unnecessary mastectomies in the MRI group. However, utilization of MRI in this cohort of patients did not reduce reoperation rate (19.3%). Lobular carcinoma in situ (LCIS) was identified in 60% of reoperations on post-surgical histology. Patients in the "No MRI" group had higher mastectomy rate 26 (42.6%), which was again appropriate. High mammographic density is a useful risk stratification criterion for selective MRI in ILC within a multidisciplinary team meeting setting. Provided additional lesions identified on MRI are confirmed with biopsy, pre-operative MRI does not cause unnecessary mastectomies. Used in this selective manner, reoperation rates were not eliminated, albeit reduced when compared to literature. High mammographic breast density can be used as one of the selection criteria for pre-operative MRI in ILC without an increase in inappropriate mastectomies with potential time and cost savings. In this cohort, re-excisions were not reduced markedly with pre-operative MRI.
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1985-09-12
Views of STS-33/51L crew personnel Prime McAuliffe and Backup Morgan at the ILC Facility during clothing selection and Building #37 during food sampling, and with the rest of the STS-33/51L crew. 40074: "Teacher-in-Space" Participant Barbara Morgan (right) is briefed on her suit and on personal hygiene equipment to be used on the STS-51L Mission. 1. JSC - Education Program (Teacher in Space) 2. Barbara Morgan 3. Christa McAuliffe 4. STS-33/51L - Crew Training (Uniforms/Food/Crew)
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Font size and viewing distance of handheld smart phones.
Bababekova, Yuliya; Rosenfield, Mark; Hue, Jennifer E; Huang, Rae R
2011-07-01
The use of handheld smart phones for written communication is becoming ubiquitous in modern society. The relatively small screens found in these devices may necessitate close working distances and small text sizes, which can increase the demands placed on accommodation and vergence. Font size and viewing distance were measured while subjects used handheld electronic devices in two separate trials. In the first study (n=129), subjects were asked to show a typical text message on their own personal phone and to hold the device "as if they were about to read a text message." A second trial was conducted in a similar manner except subjects (n=100) were asked to view a specific web page from the internet. For text messages and internet viewing, the mean font size was 1.1 M (range, 0.7 to 2.1 M) and 0.8 M (range, 0.3 to 1.4 M), respectively. The mean working distance for text messages and internet viewing was 36.2 cm (range, 17.5 to 58.0 cm) and 32.2 cm (range, 19 to 60 cm), respectively. The mean font size for both conditions was comparable with newspaper print, although some subjects viewed text that was considerably smaller. However, the mean working distances were closer than the typical near working distance of 40 cm for adults when viewing hardcopy text. These close distances place increased demands on both accommodation and vergence, which could exacerbate symptoms. Practitioners need to consider the closer distances adopted while viewing material on smart phones when examining patients and prescribing refractive corrections for use at near, as well as when treating patients presenting with asthenopia associated with nearwork. Copyright © 2011 American Academy of Optometry
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IL-9-producing cells in the development of IgE-mediated food allergy.
Shik, Dana; Tomar, Sunil; Lee, Jee-Boong; Chen, Chun-Yu; Smith, Andrew; Wang, Yui-Hsi
2017-01-01
Food allergy is a harmful immune reaction driven by uncontrolled type 2 immune responses. Considerable evidence demonstrates the key roles of mast cells, IgE, and TH2 cytokines in mediating food allergy. However, this evidence provides limited insight into why only some, rather than all, food allergic individuals are prone to develop life-threatening anaphylaxis. Clinical observations suggest that patients sensitized to food through the skin early in life may later develop severe food allergies. Aberrant epidermal thymic stromal lymphopoietin and interleukin (IL) 33 production and genetic predisposition can initiate an allergic immune response mediated by dendritic cells and CD4 + TH2 cells in inflamed skin. After allergic sensitization, intestinal IL-25 and food ingestion enhance concerted interactions between type 2 innate lymphoid cells (ILC2s) and CD4 + TH2 cells, which perpetuate allergic reactions from the skin to the gut. IL-4 and cross-linking of antigen/IgE/FcεR complexes induce emigrated mast cell progenitors to develop into the multi-functional IL-9-producing mucosal mast cells, which produce prodigious amounts of IL-9 and mast cell mediators to drive intestinal mastocytosis in an autocrine loop. ILC2s and TH9 cells may also serve as alternative cellular sources of IL-9 to augment the amplification of intestinal mastocytosis, which is the key cellular checkpoint in developing systemic anaphylaxis. These findings provide a plausible view of how food allergy develops and progresses in a stepwise manner and that atopic signals, dietary allergen ingestion, and inflammatory cues are fundamental in promoting life-threatening anaphylaxis. This information will aid in improving diagnosis and developing more effective therapies for food allergy-triggered anaphylaxis.
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IL-9–producing cells in the development of IgE-mediated food allergy
Shik, Dana; Tomar, Sunil; Lee, Jee-Boong; Chen, Chun-Yu; Smith, Andrew; Wang, Yui-Hsi
2016-01-01
Food allergy is a harmful immune reaction driven by uncontrolled type-2 immune responses. Considerable evidence demonstrates the key roles of mast cells, IgE, and TH2 cytokines in mediating food allergy. However, this evidence provides limited insight into why only some, rather than all, food allergic individuals are prone to develop life-threatening anaphylaxis. Clinical observations suggest that patients sensitized to food through the skin early in life may later develop severe food allergies. Aberrant epidermal thymic stromal lymphopoietin and interleukin (IL) 33 production and genetic predisposition can initiate an allergic immune response mediated by dendritic cells and CD4+TH2 cells in inflamed skin. After allergic sensitization, intestinal IL-25 and food ingestion enhance concerted interactions between type-2 innate lymphoid cells (ILC2s) and CD4+TH2 cells, which perpetuate allergic reactions from skin to the gut. IL-4 and crosslinking of antigen/IgE/FcεR complexes induce emigrated mast cell progenitors to develop into the multi-functional IL-9–producing mucosal mast cells, which produce prodigious amounts of IL-9 and mast cell mediators to drive intestinal mastocytosis in an autocrine loop. ILC2s and TH9 cells may also serve as alternative cellular sources of IL-9 to augment the amplification of intestinal mastocytosis, which is the key cellular checkpoint in developing systemic anaphylaxis. These findings provide a plausible view of how food allergy develops and progresses in a stepwise manner and that atopic signals, dietary allergen ingestion, and inflammatory cues are fundamental in promoting life-threatening anaphylaxis. This information will aid in improving diagnosis and developing more effective therapies for food allergy–triggered anaphylaxis. PMID:27909880
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Macrophage and Innate Lymphoid Cell Interplay in the Genesis of Fibrosis
Hams, Emily; Bermingham, Rachel; Fallon, Padraic G.
2015-01-01
Fibrosis is a characteristic pathological feature of an array of chronic diseases, where development of fibrosis in tissue can lead to marked alterations in the architecture of the affected organs. As a result of this process of sustained attrition to organs, many diseases that involve fibrosis are often progressive conditions and have a poor long-term prognosis. Inflammation is often a prelude to fibrosis, with innate and adaptive immunity involved in both the initiation and regulation of the fibrotic process. In this review, we will focus on the emerging roles of the newly described innate lymphoid cells (ILCs) in the generation of fibrotic disease with an examination of the potential interplay between ILC and macrophages and the adaptive immune system. PMID:26635811
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NASA Astrophysics Data System (ADS)
Coronel-Beltrán, Ángel; Álvarez-Borrego, Josué
2010-01-01
We present, in this paper, a comparative analysis of the letters in Times New Roman (TNR), Courier New (CN) and Arial (Ar) font types in plain and italic style and the effects of five foreground/background color combinations using an invariant digital correlation system with a nonlinear filter with k = 0.3. The evaluation of the output plane with this filter is given by the peak-to-correlation energy (PCE) metric. The results show that the letters in TNR font have a better mean PCE value when compared with the CN and Ar fonts. This result is in agreement with some studies on text legibility and for readability where the reaction time (RT) of some participant individuals reading a text is measured. We conclude that the PCE metric is proportional to 1/RT.
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Multipartite Entanglement classes via Negativity Fonts
NASA Astrophysics Data System (ADS)
Sharma, Santosh Shelly; Sharma, Naresh Kumar
2012-02-01
The number and types of K-way negativity fonts in canonical form of an N-qubit state depends on the nature and amount of quantum coherences in the state. Non zero determinants of negativity fonts, characterizing a given state, are easily written down and reflect the entanglement microstructure of the superposition. A classification criterion for multipartite entangled states, based on negativity fonts in canonical state and decomposition of global partial transpose in terms of K-way partially transposed operators, is proposed. Inequivalent sub-classes are labelled by N-qubit local unitary invariants. A complete classification of four qubit states is obtained. The number of major families for N>3 is found to be 2^N-2N. Classification of four qubit states indicates that a small number of relevant polynomial invariants is enough to classify N-qubit states.
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[Explicit memory for type font of words in source monitoring and recognition tasks].
Hatanaka, Yoshiko; Fujita, Tetsuya
2004-02-01
We investigated whether people can consciously remember type fonts of words by methods of examining explicit memory; source-monitoring and old/new-recognition. We set matched, non-matched, and non-studied conditions between the study and the test words using two kinds of type fonts; Gothic and MARU. After studying words in one way of encoding, semantic or physical, subjects in a source-monitoring task made a three way discrimination between new words, Gothic words, and MARU words (Exp. 1). Subjects in an old/new-recognition task indicated whether test words were previously presented or not (Exp. 2). We compared the source judgments with old/new recognition data. As a result, these data showed conscious recollection for type font of words on the source monitoring task and dissociation between source monitoring and old/new recognition performance.
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Halin, Niklas
2016-01-01
The purpose of this study was to investigate the distractive effects of background speech, aircraft noise and road traffic noise on text memory and particularly to examine if displaying the texts in a hard-to-read font can shield against the detrimental effects of these types of background sounds. This issue was addressed in an experiment where 56 students read shorter texts about different classes of fictitious creatures (i.e., animals, fishes, birds, and dinosaurs) against a background of the aforementioned background sounds respectively and silence. For half of the participants the texts were displayed in an easy-to-read font (i.e., Times New Roman) and for the other half in a hard-to-read font (i.e., Haettenschweiler). The dependent measure was the proportion correct answers on the multiple-choice tests that followed each sound condition. Participants’ performance in the easy-to-read font condition was significantly impaired by all three background sound conditions compared to silence. In contrast, there were no effects of the three background sound conditions compared to silence in the hard-to-read font condition. These results suggest that an increase in task demand—by displaying the text in a hard-to-read font—shields against various types of distracting background sounds by promoting a more steadfast locus-of-attention and by reducing the processing of background sound. PMID:27555834
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Effect of font size, italics, and colour count on web usability.
Bhatia, Sanjiv K; Samal, Ashok; Rajan, Nithin; Kiviniemi, Marc T
2011-04-01
Web usability measures the ease of use of a website. This study attempts to find the effect of three factors - font size, italics, and colour count - on web usability. The study was performed using a set of tasks and developing a survey questionnaire. We performed the study using a set of human subjects, selected from the undergraduate students taking courses in psychology. The data computed from the tasks and survey questionnaire were statistically analysed to find if there was any effect of font size, italics, and colour count on the three web usability dimensions. We found that for the student population considered, there was no significant effect of font size on usability. However, the manipulation of italics and colour count did influence some aspects of usability. The subjects performed better for pages with no italics and high italics compared to moderate italics. The subjects rated the pages that contained only one colour higher than the web pages with four or six colours. This research will help web developers better understand the effect of font size, italics, and colour count on web usability in general, and for young adults, in particular.
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Effect of font size, italics, and colour count on web usability
Samal, Ashok; Rajan, Nithin; Kiviniemi, Marc T.
2013-01-01
Web usability measures the ease of use of a website. This study attempts to find the effect of three factors – font size, italics, and colour count – on web usability. The study was performed using a set of tasks and developing a survey questionnaire. We performed the study using a set of human subjects, selected from the undergraduate students taking courses in psychology. The data computed from the tasks and survey questionnaire were statistically analysed to find if there was any effect of font size, italics, and colour count on the three web usability dimensions. We found that for the student population considered, there was no significant effect of font size on usability. However, the manipulation of italics and colour count did influence some aspects of usability. The subjects performed better for pages with no italics and high italics compared to moderate italics. The subjects rated the pages that contained only one colour higher than the web pages with four or six colours. This research will help web developers better understand the effect of font size, italics, and colour count on web usability in general, and for young adults, in particular. PMID:24358055
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Carretero, Gustavo P B; Saraiva, Greice K V; Cauz, Ana C G; Rodrigues, Magali A; Kiyota, Sumika; Riske, Karin A; Dos Santos, Alcindo A; Pinatto-Botelho, Marcos F; Bemquerer, Marcelo P; Gueiros-Filho, Frederico J; Chaimovich, Hernan; Schreier, Shirley; Cuccovia, Iolanda M
2018-05-09
Antimicrobial peptides (AMPs) work as a primary defense against pathogenic microorganisms. BP100, (KKLFKKILKYL-NH 2 ), a rationally designed short, highly cationic AMP, acts against many bacteria, displaying low toxicity to eukaryotic cells. Previously we found that its mechanism of action depends on membrane surface charge and on peptide-to-lipid ratio. Here we present the synthesis of two BP100 analogs: BP100‑alanyl‑hexadecyl‑1‑amine (BP100-Ala-NH-C 16 H 33 ) and cyclo(1‑4)‑d‑Cys 1 , Ile 2 , Leu 3 , Cys 4 -BP100 (Cyclo(1‑4)‑cILC-BP100). We examined their binding to large unilamellar vesicles (LUV), conformational and functional properties, and compared with those of BP100. The analogs bound to membranes with higher affinity and a lesser dependence on electrostatic forces than BP100. In the presence of LUV, BP100 and BP100-Ala-NH-C 16 H 33 acquired α-helical conformation, while Cyclo(1‑4)‑cILC-BP100) was partly α-helical and partly β-turn. Taking in conjunction: 1. particle sizes and zeta potential, 2. effects on lipid flip-flop, 3. leakage of LUVs internal contents, and 4. optical microscopy of giant unilamellar vesicles, we concluded that at high concentrations, all three peptides acted by a carpet mechanism, while at low concentrations the peptides acted by disorganizing the lipid bilayer, probably causing membrane thinning. The higher activity and lesser membrane surface charge dependence of the analogs was probably due to their greater hydrophobicity. The MIC values of both analogs towards Gram-positive and Gram-negative bacteria were similar to those of BP100 but both analogues were more hemolytic. Confocal microscopy showed Gram-positive B. subtilis killing with concomitant extensive membrane damage suggestive of lipid clustering, or peptide-lipid aggregation. These results were in agreement with those found in model membranes. Copyright © 2018. Published by Elsevier B.V.
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-user-select: none; -moz-user-select: none; -ms-user-select: none; user-select: none; } #text-abb { font -size: 14px; } #text-abb text { font-family: Arial, Helvetica, sans-serif; } #map_base svg { max-height
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Katzir, Tami; Hershko, Shirley; Halamish, Vered
2013-01-01
Research on reading development has focused on the linguistic, cognitive, and recently, metacognitive skills children must master in order to learn to read. Less focus has been devoted to how the text itself, namely the perceptual features of the words, affects children’s learning and comprehension. In this study, we manipulated perceptual properties of text by presenting reading passages in different font sizes, line lengths, and line spacing to 100 children in the second and fifth grades. For second graders (Experiment 1), decreasing font size, as well as increasing line length, yielded significantly lower comprehension scores. Line spacing had no effect on performance. For fifth graders (Experiment 2), decreasing font size yielded higher comprehension scores, yet there were no effects for line length and line spacing. Results are discussed within a "desirable difficulty" approach to reading development. PMID:24069266
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Latest Results of ILC High-Gradient R&D 9-cell Cavities at JLAB
DOE Office of Scientific and Technical Information (OSTI.GOV)
Geng, Rongli
2008-02-11
It has been over a year since JLAB started processing and testing ILC 9-cell cavities in the frame work of ILC high-gradient cavity R&D, aiming at the goal of a 35 MV/m gradient at a Q of 1E10 with a yield of 90%. The necessary cavity processing steps include field flatness tuning, electropolishing (EP), hydrogen out-gassing under vacuum, high-pressure water rinsing, clean room assembly, and low temperature bake. These are followed by RF test at 2 Kelvin. Ultrasonic cleaning with Micro-90, an effective post-EP rinsing recipe discovered at JLAB, is routinely used. Seven industry manufactured 9-cell TESLAshape cavities are processedmore » and tested repeatedly. So far, 33 EP cycles are accumulated, corresponding to more than 65 hours of active EP time. An emphasis put on RF testing is to discern cavity quench characteristics, including its nature and its location. Often times, the cavity performance is limited by thermal-magnetic quench instead of field emission. The quench field in some cavities is lower than 20 MV/m and remains unchanged despite repeated EP, implying material and/or fabrication defects. The quench field in some other cavities is high but changes unpredictably after repeated EP, suggesting processing induced defects. Based on our experience and results, several areas are identified where improvement is needed to improve cavity performance as well as yield.« less
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NASA Astrophysics Data System (ADS)
Wagner, Albrecht
2006-04-01
Over the past century, physicists have sought to explain the character of the matter and energy in our universe, to show how the basic forces of nature and the building blocks of matter come about, and to explore the fabric of space and time. In the past three decades, experiments at laboratories around the world have given us a precise confirmation of the underlying theory called the standard model. These particle physics advances have a direct impact for our understanding of the structure of the universe, both at its inception in the Big Bang, and in its evolution to the present and future. The final synthesis is not yet fully clear, but we know with confidence that major discoveries expanding the standard model framework will occur at the next generation of accelerators. The Large Hadron Collider (LHC) being built at CERN will take us into the discovery realm. The proposed International Linear Collider (ILC) will extend the discoveries and provide a wealth of precision measurements that are essential for giving deeper understanding of their meaning, and pointing the way to further evolution of particle physics in the future. A world-wide consensus has formed for a baseline ILC project at energies of 500 GeV and beyond. The choice of the superconducting technology as basis for the ILC has paved the way for a global design effort which has now taken full speed.
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Technical Order Managers Reference Data.
1981-05-01
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16 CFR 1633.4 - Prototype testing requirements.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Prototype testing requirements. 1633.4... STANDARD FOR THE FLAMMABILITY (OPEN FLAME) OF MATTRESS SETS The Standard § 1633.4 Prototype testing... three specimens of each prototype to be tested according to § 1633.7 and obtain passing test results...
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Motion Sickness Prevention by Stroboscopic Environment during Simulated Military Transport
2009-07-20
4 Data collection instruments ...Physician’s Desk Reference, 2001). Alternative remedies such as acupuncture, acupressure, acustimulation, and hypnosis are becoming increasingly popular...questions regarding the material. The passage was presented on 8.5 x 11 paper with 20 point Times New Roman font. Data collection instruments Motion
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Net Survey: "Top Ten Mistakes" in Academic Web Design.
ERIC Educational Resources Information Center
Petrik, Paula
2000-01-01
Highlights the top ten mistakes in academic Web design: (1) bloated graphics; (2) scaling images; (3) dense text; (4) lack of contrast; (5) font size; (6) looping animations; (7) courseware authoring software; (8) scrolling/long pages; (9) excessive download; and (10) the nothing site. Includes resources. (CMK)
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Dynamic Visual Acuity While Walking in Normals and Labyrinthine-Deficient Patients
NASA Technical Reports Server (NTRS)
Hillman, Edward J.; Bloomberg, Jacob J.; McDonald, P. Vernon; Cohen, Helen S.
1996-01-01
We describe a new, objective, easily administered test of dynamic visual acuity (DVA) while walking. Ten normal subjects and five patients with histories of severe bilateral vestibular dysfunctions participated in this study. Subjects viewed a visual display of numerals of different font sizes presented on a laptop computer while they stood still and while they walked on a motorized treadmill. Treadmill speed was adapted for 4 of 5 patients. Subjects were asked to identify the numerals as they appeared on the computer screen. Test results were reasonably repeatable in normals. The percent correct responses at each font size dropped slightly while walking in normals and dropped significantly more in patients. Patients performed significantly worse than normals while standing still and while walking. This task may be useful for evaluating post-flight astronauts and vestibularly impaired patients.
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Experimental Investigation of Oblique Wing Aerodynamics at Low Speed
2007-03-01
0\\circ’); grid on; title(’\\it C_L vs \\alpha no winglets (50 mph)’,’FontWeight’,’bold’,’FontSize’,11); xlabel(’Angle of Attack (\\alpha)’); ylabel
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WATERSHED AND OTHER PLACE-BASED RISK ASSESSMENTS
Place-based assessments include regional, watershed and other geographically focused assessments.
Watershed Assessments and Methods
The watershed ... -
Progress of ILC High Gradient SRF Cavity R&D at Jefferson Lab
DOE Office of Scientific and Technical Information (OSTI.GOV)
R.L. Geng, J. Dai, G.V. Eremeev, A.D. Palczewski
2011-09-01
Latest progress of ILC high gradient SRF cavity R&D at Jefferson Lab will be presented. 9 out of 10 real 9-cell cavities reached an accelerating gradient of more than 38 MV/m at a unloaded quality factor of more than 8 {center_dot} 109. New understandings of quench limitation in 9-cell cavities are obtained through instrumented studies of cavities at cryogenic temperatures. Our data have shown that present limit reached in 9-cell cavities is predominantly due to localized defects, suggesting that the fundamental material limit of niobium is not yet reached in 9-cell cavities and further gradient improvement is still possible. Somemore » examples of quench-causing defects will be given. Possible solutions to pushing toward the fundamental limit will be described.« less
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Design of An 18 MW Beam Dump for 500 GeV Electron/Positron Beams at An ILC
DOE Office of Scientific and Technical Information (OSTI.GOV)
Amann, John; /SLAC; Arnold, Ray
This article presents a report on the progress made in designing 18 MW water based Beam Dumps for electrons or positrons for an International Linear Collider (ILC). Multi-dimensional technology issues have to be addressed for the successful design of the Beam Dump. They include calculations of power deposition by the high energy electron/positron beam bunch trains, computational fluid dynamic analysis of turbulent water flow, mechanical design, process flow analysis, hydrogen/oxygen recombiners, handling of radioactive 7Be and 3H, design of auxiliary equipment, provisions for accident scenarios, remote window exchanger, radiation shielding, etc. The progress made to date is summarized, the currentmore » status, and also the issues still to be addressed.« less
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FPGA-based Klystron linearization implementations in scope of ILC
Omet, M.; Michizono, S.; Matsumoto, T.; ...
2015-01-23
We report the development and implementation of four FPGA-based predistortion-type klystron linearization algorithms. Klystron linearization is essential for the realization of ILC, since it is required to operate the klystrons 7% in power below their saturation. The work presented was performed in international collaborations at the Fermi National Accelerator Laboratory (FNAL), USA and the Deutsches Elektronen Synchrotron (DESY), Germany. With the newly developed algorithms, the generation of correction factors on the FPGA was improved compared to past algorithms, avoiding quantization and decreasing memory requirements. At FNAL, three algorithms were tested at the Advanced Superconducting Test Accelerator (ASTA), demonstrating a successfulmore » implementation for one algorithm and a proof of principle for two algorithms. Furthermore, the functionality of the algorithm implemented at DESY was demonstrated successfully in a simulation.« less
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Development of an S-band cavity Beam Position Monitor for ATF2
NASA Astrophysics Data System (ADS)
Heo, A.; Kim, E.-S.; Kim, H.; Son, D.; Honda, Y.; Tauchi, T.
2013-04-01
We have developed an S-band cavity Beam Position Monitor (BPM) in order to measure the position of an electron beam in the final focus area at ATF2, which is the test facility for the final focus design for the International Linear Collider (ILC). The lattice of the ILC Beam Delivery System (BDS) has been modified, requiring a larger physical aperture of 40 mm in the final focus area. The beam orbit measurement in this area is now covered with high resolution S-Band cavity BPMs. In this paper we summarize the design of the cavity BPM and the first experimental results. The calibration slopes were measured as 0.87 counts/μm in the x-coordinate direction and 1.16 counts/μm in the y-coordinate direction.
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Dollar Summary of Federal Supply Classification and Service Category by Company. Part 1 (AA11-AZ16)
1990-01-01
4 -4 4 I ~ z I % - . - 4 : -4 )1 4 : 41 -I I I I Z NI 0m m - 4 a _4 it m 4 cc -D 0 m m 4- _4 LU LU 0 24 tm x. 0. IL4 ..4 x. ’x x. . ILC C-) 0) 414- C1...Ql I CKI < 2 0 (4) I cm m 0 c. w 00wcom 0 --4 r- co w l c, W 0000 0000 ( tm ’ N -o "- -4 o’ V.L t v w L - w - o -40( cl m LA m44 -4 Cl) 1, en -4 L...l ) C 4 ) 0 ) ) tdC ) 0 t a C) a) C ) cl 0 I C)1 I I I I I = - -4 I I I n -4 Im -0 LU w 4L 4 4 - 4o 0 01 I 4 L. I oA CO 0 41 1 0 IV C) (13 ml Cl IV
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Arditi, Aries; Cho, Jianna
2015-01-01
Using lower-case fonts varying only in serif size (0%, 5%, and 10% cap height), we assessed legibility using size thresholds and reading speed. Five percentage serif fonts were slightly more legible than sans serif, but the average inter-letter spacing increase that serifs themselves impose, predicts greater enhancement than we observed. RSVP and continuous reading speeds showed no effect of serifs. When text is small or distant, serifs may, then, produce a tiny legibility increase due to the concomitant increase in spacing. However, our data exhibited no difference in legibility between typefaces that differ only in the presence or absence of serifs. PMID:16099015
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Sanocki, Thomas; Dyson, Mary C
2012-01-01
Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading.
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Liu, Tianyin; Yeh, Su-Ling
2018-01-01
The left-side bias (LSB) effect observed in face and expert Chinese character perception is suggested to be an expertise marker for visual object recognition. However, in character perception this effect is limited to characters printed in a familiar font (font-sensitive LSB effect). Here we investigated whether the LSB and font-sensitive LSB effects depend on participants’ familiarity with global structure or local component information of the stimuli through examining their transfer effects across simplified and traditional Chinese scripts: the two Chinese scripts share similar overall structures but differ in the visual complexity of local components in general. We found that LSB in expert Chinese character processing could be transferred to the Chinese script that the readers are unfamiliar with. In contrast, the font-sensitive LSB effect did not transfer, and was limited to characters with the visual complexity the readers were most familiar with. These effects suggest that the LSB effect may be generalized to another visual category with similar overall structures; in contrast, effects of within-category variations such as fonts may depend on familiarity with local component information of the stimuli, and thus may be limited to the exemplars of the category that experts are typically exposed to. PMID:29608570
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Brown, Melissa A; Weinberg, Rebecca B
2018-01-01
Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis, are autoimmune CNS inflammatory diseases. As a result of a breakdown in the relatively impermeable blood-brain barrier (BBB) in affected individuals, myelin-specific CD4 + and CD8 + T cells gain entry into the immune privileged CNS and initiate myelin, oligodendrocyte, and nerve axon destruction. However, despite the absolute requirement for T cells, there is increasing evidence that innate immune cells also play critical amplifying roles in disease pathogenesis. By modulating the character and magnitude of the myelin-reactive T cell response and regulating BBB integrity, innate cells affect both disease initiation and progression. Two classes of innate cells, mast cells and innate lymphoid cells (ILCs), have been best studied in models of allergic and gastrointestinal inflammatory diseases. Yet, there is emerging evidence that these cell types also exert a profound influence in CNS inflammatory disease. Both cell types are residents within the meninges and can be activated early in disease to express a wide variety of disease-modifying cytokines and chemokines. In this review, we discuss how mast cells and ILCs can have either disease-promoting or -protecting effects on MS and other CNS inflammatory diseases and how sex hormones may influence this outcome. These observations suggest that targeting these cells and their unique mediators can be exploited therapeutically.
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Potential and challenges of the physics measurements with very forward detectors at linear colliders
NASA Astrophysics Data System (ADS)
Božović Jelisavčić, Ivanka; Kačarević, G.; Lukić, S.; Poss, S.; Sailer, A.; Smiljanić, I.; FCAL Collaboration
2016-04-01
The instrumentation of the very forward region of a detector at a future linear collider (ILC, CLIC) is briefly reviewed. The status of the FCAL R&D activity is given with emphasis on physics and technological challenges. The current status of studies on absolute luminosity measurement, luminosity spectrum reconstruction and high-energy electron identification with the forward calorimeters is given. The impact of FCAL measurements on physics studies is illustrated with an example of the σHWW ṡBR (H →μ+μ-) measurement at 1.4 TeV CLIC.
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Spectroscopic Studies of Lasing Transitions in the Diatomic Mercury Halides.
1983-08-01
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Acton, Rachel B; Vanderlee, Lana; White, Christine; Hammond, David
2016-10-20
Several countries have proposed changes to calorie labelling on nutrition facts tables (NFTs) on pre-packaged foods. As most research to date has examined general use of NFTs, there is a lack of evidence to guide specific design changes to calorie information on labels. This study examined the efficacy of various calorie labelling formats on recall, comprehension, and consumer preferences for calorie information. Experiments were conducted as part of an online survey with a national sample of 2,008 Canadians aged 16-24. In Task 1, participants were shown one of six labelling formats (e.g., %DV, Traffic Light) with calories in either small or large font, and asked to recall the amount of calories. Task 2 examined comprehension of calories in the context of recommended daily intake (RDI), using the same NFT as in Task 1. Task 3 identified participants' preferences for labelling formats. NFTs with calories in large font enhanced calorie recall (p < 0.001). When small font was displayed, the Traffic Light format performed best at improving recall (p < 0.01). With large font, the highest recall was in the Current, RDI and Traffic Light formats (all p < 0.05). Comprehension of servings per RDI was highest in the Infographic format, with no difference by font size (p < 0.001). Respondents preferred the large font calorie condition and the Infographic format (p < 0.001). Enhancements in visibility and design can improve the efficacy of calorie labelling on pre-packaged foods. The findings have direct implication for proposed changes to calorie labelling on NFTs in Canada and the United States.
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17 CFR 240.14c-4 - Presentation of information in information statement.
Code of Federal Regulations, 2010 CFR
2010-04-01
... documents, such as type size and font, by presenting all required information in a format readily... printed information statements shall be in roman type at least as large and as legible as 10-point modern type except that to the extent necessary for convenient presentation, financial statements and other...
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NASA Astrophysics Data System (ADS)
2016-11-01
Officials at the International Linear Collider (ILC) - a proposed successor to the Large Hadron Collider at CERN - have turned to Hello Kitty to help promote the project, which is set to be built in Japan.
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Ko, Ya-Hsien
2017-11-01
This study explored and identified the effects of luminance contrast, colour combinations, font, and search time on brand icon legibility. A total of 108 participants took part in the experiment. As designed, legibility was measured as a function of the following independent variables: four levels of luminance contrast, sixteen target/background colour combinations, two fonts, and three search times. The results showed that a luminance contrast of 18:1 provided readers with the best legibility. Yellow on black, yellow on blue, and white on blue were the three most legible colour combinations. One of this study's unique findings was that colour combinations may play an even more important role than luminance contrast in the overall legibility of brand icon design. The 12-s search time corresponded with the highest legibility. Arial font was more legible than Times New Roman. These results provide some guidance for brand icon and product advertisement design. Copyright © 2017 Elsevier Ltd. All rights reserved.
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A Study of the Radio Continuum Far Infrared Correlation at Small Scales in the Galaxy
NASA Astrophysics Data System (ADS)
Rodriguez-Martinez, Monica I.; Allen, R. J.; Wiklind, T.; Loinard, L.
2006-12-01
We present a study of the behavior of the Radio Continuum (RC) Far Infrared (FIR) correlation on scales corresponding to the size of small molecular clouds. This was done by comparing the spatial distribution of RC emission and FIR emission from a sample of several regions, distributed within the range 79∘ ≤ l ≤ 174∘ in the Galaxy. We have examined the 408 and 1420 MHz mosaic images of the sample, from the Canadian Galactic Plane Survey (CGPS), which later were compared with images at 60 and 100 μm. Preliminary results suggest that the RC -FIR correlation still holds at small scales, since a good qualitative correlation between RC and FIR emission is found. The physical process involved that may cause such correlation will be discussed as well as the nature of the RC emission. This research makes use of data from the Canadian Galactic Plane Survey.
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A New Pixels Flipping Method for Huge Watermarking Capacity of the Invoice Font Image
Li, Li; Hou, Qingzheng; Lu, Jianfeng; Dai, Junping; Mao, Xiaoyang; Chang, Chin-Chen
2014-01-01
Invoice printing just has two-color printing, so invoice font image can be seen as binary image. To embed watermarks into invoice image, the pixels need to be flipped. The more huge the watermark is, the more the pixels need to be flipped. We proposed a new pixels flipping method in invoice image for huge watermarking capacity. The pixels flipping method includes one novel interpolation method for binary image, one flippable pixels evaluation mechanism, and one denoising method based on gravity center and chaos degree. The proposed interpolation method ensures that the invoice image keeps features well after scaling. The flippable pixels evaluation mechanism ensures that the pixels keep better connectivity and smoothness and the pattern has highest structural similarity after flipping. The proposed denoising method makes invoice font image smoother and fiter for human vision. Experiments show that the proposed flipping method not only keeps the invoice font structure well but also improves watermarking capacity. PMID:25489606
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Glantz, Stanton
The principal aim of this roadmap is to place the US and Fermilab in the best position to host the International Linear Collider (ILC). The strategy must be resilient against the many vicissitudes that will attend the development of such a large project. Pier Oddone will explore the tension between the needed concentration of effort to move a project as large as the ILC forward and the need to maintain the breadth of our field. America's leading health organizations agree. Smoking on screen is the #1 recruiter of new adolescent smokers in the United States - 390,000 kids a year,more » of whom 120,000 will die from tobacco-caused diseases. That's more Americans than die from drunk driving, criminal violence, illicit drugs, and HIV/AIDS combined. Why does Hollywood still promote smoking? Is it corrupt? Or stupid?« less
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Becker, R; Lô, I; Sporkert, F; Baumgartner, M
2018-07-01
The increasing request for hair ethyl glucuronide (HEtG) in alcohol consumption monitoring according to cut-off levels set by the Society of Hair Testing (SoHT) has triggered a proficiency testing program based on interlaboratory comparisons (ILC). Here, the outcome of nine consecutive ILC rounds organised by the SoHT on the determination of HEtG between 2011 and 2017 is summarised regarding interlaboratory reproducibility and the influence of procedural variants. Test samples prepared from cut hair (1mm) with authentic (in-vivo incorporated) and soaked (in-vitro incorporated) HEtG concentrations up to 80pg/mg were provided for 27-35 participating laboratories. Laboratory results were evaluated according to ISO 5725-5 and provided robust averages and relative reproducibility standard deviations typically between 20 and 35% in reasonable accordance with the prediction of the Horwitz model. Evaluation of results regarding the analytical techniques revealed no significant differences between gas and liquid chromatographic methods In contrast, a detailed evaluation of different sample preparations revealed significantly higher average values in case when pulverised hair is tested compared to cut hair. This observation was reinforced over the different ILC rounds and can be attributed to the increased acceptance and routine of hair pulverisation among laboratories. Further, the reproducibility standard deviations among laboratories performing pulverisation were on average in very good agreement with the prediction of the Horwitz model. Use of sonication showed no effect on the HEtG extraction yield. Copyright © 2018 Elsevier B.V. All rights reserved.
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Barnie, Prince A; Lin, Xin; Liu, Yueqin; Xu, Huaxi; Su, Zhaoliang
2015-01-01
In pregnancy, the immunologic system plays an important role that ensures normal pregnancy development and can as well promote the development of complications. Pregnancy success appears to rely on a discrete balance between the Th cytokines, which are involved in fetal growth and development. Preeclampsia and gestational diabetes are known complications associated with pregnancy. However, the source of the increased IL-17 cytokine in preeclampsia and other pregnancy associated diseases still remains unclear amidst numerous inconsistencies. The recent identification of innate lymphoid cells (ILC) has raised more doubts about the sources of most of the Th associated cytokines. We investigated the source of peripheral IL-17 levels in preeclamptic, gestational diabetics and chronic diabetics compared to healthy pregnancy subjects. To evaluate the source of the increased IL-17 cytokine among preeclampsia, chronic diabetic and gestational diabetic patients we investigated the proportion of Th17 cell populations in peripheral blood mononuclear cells using flow cytometry as well as analyzing levels of IFN-γ, IL-17, IL-1β and HMGB1. This study found that the Th17 cell populations in peripheral blood of preeclamptic, gestational nor chronic diabetes during pregnancy did not correlate with the increased IL-17. We report that the increased IL-17 levels observed in patients with preeclampsia, gestational diabetes and chronic diabetes are associated with innate lymphoid cells 3 (ILC3) and may pose threats to the fetus if disregulated.
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Mapping of NKp46+ Cells in Healthy Human Lymphoid and Non-Lymphoid Tissues
Tomasello, Elena; Yessaad, Nadia; Gregoire, Emilie; Hudspeth, Kelly; Luci, Carmelo; Mavilio, Domenico; Hardwigsen, Jean; Vivier, Eric
2012-01-01
Understanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor γt (RORγt) transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs, and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORγt+ ILCs with a lineage−CD94−CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases. PMID:23181063
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Modeling radiation loads in the ILC main linac and a novel approach to treat dark current
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mokhov, Nilolai V.; Rakhno, Igor L.; Tropin, Igor S.
Electromagnetic and hadron showers generated by electrons of dark current (DC) can represent a significant radiation threat to the ILC linac equipment and personnel. In this study, a commissioning scenario is analysed which is considered as the worst-case scenario for the main linac regarding the DC contribution to the radiation environment in the tunnel. A normal operation scenario is analysed as well. An emphasis is made on radiation load to sensitive electronic equipment—cryogenic thermometers inside the cryomodules. Prompt and residual dose rates in the ILC main linac tunnels were also calculated in these new high-statistics runs. A novel approach wasmore » developed—as a part of general purpose Monte Carlo code MARS15—to model generation, acceleration and transport of DC electrons in electromagnetic fields inside SRF cavities. Comparisons were made with a standard approach when a set of pre-calculated DC electron trajectories is used, with a proper normalization, as a source for Monte Carlo modelling. Results of MARS15 Monte Carlo calculations, performed for the current main linac tunnel design, reveal that the peak absorbed dose in the cryogenic thermometers in the main tunnel for 20 years of operation is about 0.8 MGy. The calculated contact residual dose on cryomodules and tunnel walls in the main tunnel for typical irradiation and cooling conditions is 0.1 and 0.01 mSv/hr, respectively.« less