Qualification of the Second Batch Production 9-Cell Cavities Manufactured by AES and Validation of the First US Industrial Cavity Vendor for ILC

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

Research and development for electropolishing of Nb for ILC accelerator cavities

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

Kelley, Michael J.

The objectives of this project are to 1, Expand the scientific and technological understanding of the effect of post-treatment (electropolish, buffered chemical polish, low-temperature baking) on the surface of niobium; 2, Relate the knowledge to the performance of niobium superconducting radiofrequency accelerator cavities; and, 3, Thereby design and demonstrate an electropolish process that can be applied to complete cavities.

The Los Alamos Laser Acceleration of Particles Workshop and beginning of the advanced accelerator concepts field

NASA Astrophysics Data System (ADS)

Joshi, C.

2012-12-01

The first Advanced Acceleration of Particles-AAC-Workshop (actually named Laser Acceleration of Particles Workshop) was held at Los Alamos in January 1982. The workshop lasted a week and divided all the acceleration techniques into four categories: near field, far field, media, and vacuum. Basic theorems of particle acceleration were postulated (later proven) and specific experiments based on the four categories were formulated. This landmark workshop led to the formation of the advanced accelerator R&D program in the HEP office of the DOE that supports advanced accelerator research to this day. Two major new user facilities at Argonne and Brookhaven and several more directed experimental efforts were built to explore the advanced particle acceleration schemes. It is not an exaggeration to say that the intellectual breadth and excitement provided by the many groups who entered this new field provided the needed vitality to then recently formed APS Division of Beams and the new online journal Physical Review Special Topics-Accelerators and Beams. On this 30th anniversary of the AAC Workshops, it is worthwhile to look back at the legacy of the first Workshop at Los Alamos and the fine groundwork it laid for the field of advanced accelerator concepts that continues to flourish to this day.

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

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

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

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.

Cutting Edge: Notch Signaling Promotes the Plasticity of Group-2 Innate Lymphoid Cells.

PubMed

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.

Advanced Accelerator Development Strategy Report: DOE Advanced Accelerator Concepts Research Roadmap Workshop

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

None, None

Over a full two day period, February 2–3, 2016, the Office of High Energy Physics convened a workshop in Gaithersburg, MD to seek community input on development of an Advanced Accelerator Concepts (AAC) research roadmap. The workshop was in response to a recommendation by the HEPAP Accelerator R&D Subpanel [1] [2] to “convene the university and laboratory proponents of advanced acceleration concepts to develop R&D roadmaps with a series of milestones and common down selection criteria towards the goal for constructing a multi-TeV e+e– collider” (the charge to the workshop can be found in Appendix A). During the workshop, proponentsmore » of laser-driven plasma wakefield acceleration (LWFA), particle-beam-driven plasma wakefield acceleration (PWFA), and dielectric wakefield acceleration (DWFA), along with a limited number of invited university and laboratory experts, presented and critically discussed individual concept roadmaps. The roadmap workshop was preceded by several preparatory workshops. The first day of the workshop featured presentation of three initial individual roadmaps with ample time for discussion. The individual roadmaps covered a time period extending until roughly 2040, with the end date assumed to be roughly appropriate for initial operation of a multi-TeV e+e– collider. The second day of the workshop comprised talks on synergies between the roadmaps and with global efforts, potential early applications, diagnostics needs, simulation needs, and beam issues and challenges related to a collider. During the last half of the day the roadmaps were revisited but with emphasis on the next five to ten years (as specifically requested in the charge) and on common challenges. The workshop concluded with critical and unanimous endorsement of the individual roadmaps and an extended discussion on the characteristics of the common challenges. (For the agenda and list of participants see Appendix B.)« less

Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in humans and mice.

PubMed

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.

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

Low Emittance Guns for the ILC Polarized Electron Beam

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

Clendenin, J. E.; Brachmann, A.; Ioakeimidi, K.

Polarized electron beams generated by DC guns are routinely available at several accelerators including JLAB, Mainz and SLAC. These guns operate with a cathode bias on the order of -100 kV. To minimize space charge effects, relatively long bunches are generated at the gun and then compressed longitudinally external to the gun just before and during initial acceleration. For linear colliders, this compression is accomplished using a combination of rf bunchers. For the basic design of the International Linear Collider (ILC), a 120 kV DC photocathode gun is used to produce a series of nanosecond bunches that are each compressedmore » by two sub-harmonic bunchers (SHBs) followed by an L-band buncher and capture section. The longitudinal bunching process results in a significantly higher emittance than produced by the gun alone. While high-energy experiments using polarized beams are not generally sensitive to the source emittance, there are several benefits to a lower source emittance including a simpler more efficient injector system and a lower radiation load during transport especially at bends as at the damping ring. For the ILC, the SHBs could be eliminated if the voltage of the gun is raised sufficiently. Simulations using the General Particle Tracer (GPT) package indicate that a cathode bias voltage of {>=}200 kV should allow both SHBs to be operated at 433 or even 650 MHz, while {>=}500 kV would be required to eliminate the SHBs altogether. Simulations can be used to determine the minimum emittance possible if the injector is designed for a given increased voltage. A possible alternative to the DC gun is an rf gun. Emittance compensation, routinely used with rf guns, is discussed for higher-voltage DC guns.« less

Low Emittance Guns for the ILC Polarized Electron Beam

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

Clendenin, J.E.; Brachmann, A.; Ioakeimidi, K.

Polarized electron beams generated by DC guns are routinely available at several accelerators including JLAB, Mainz and SLAC. These guns operate with a cathode bias on the order of -100 kV. To minimize space charge effects, relatively long bunches are generated at the gun and then compressed longitudinally external to the gun just before and during initial acceleration. For linear colliders, this compression is accomplished using a combination of rf bunchers. For the basic design of the International Linear Collider (ILC), a 120 kV DC photocathode gun is used to produce a series of nanosecond bunches that are each compressedmore » by two sub-harmonic bunchers (SHBs) followed by an L-band buncher and capture section. The longitudinal bunching process results in a significantly higher emittance than produced by the gun alone. While high-energy experiments using polarized beams are not generally sensitive to the source emittance, there are several benefits to a lower source emittance including a simpler more efficient injector system and a lower radiation load during transport especially at bends as at the damping ring. For the ILC, the SHBs could be eliminated if the voltage of the gun is raised sufficiently. Simulations using the General Particle Tracer (GPT) package indicate that a cathode bias voltage of {ge}200 kV should allow both SHBs to be operated at 433 or even 650 MHz, while {ge}500 kV would be required to eliminate the SHBs altogether. Simulations can be used to determine the minimum emittance possible if the injector is designed for a given increased voltage. A possible alternative to the DC gun is an rf gun. Emittance compensation, routinely used with rf guns, is discussed for higher-voltage DC guns.« less

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.

Quench studies of ILC cavities

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

Eremeev, Grigory; Geng, Rongli; Palczewski, Ari

2011-07-01

Quench limits accelerating gradient in SRF cavities to a gradient lower than theoretically expected for superconducting niobium. Identification of the quenching site with thermometry and OST, optical inspection, and replica of the culprit is an ongoing effort at Jefferson Lab aimed at better understanding of this limiting phenomenon. In this contribution we present our finding with several SRF cavities that were limited by quench.

Dark current and radiation shielding studies for the ILC main linac

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

Mokhov, Nikolai V.; Rakhno, I. L.; Solyak, N. A.

2016-12-05

Electrons of dark current (DC), generated in high-gradient superconducting RF cavities (SRF) due to field emission, can be accelerated up to very high energies—19 GeV in the case of the International Linear Collider (ILC) main linac—before they are removed by focusing and steering magnets. Electromagnetic and hadron showers generated by such electrons can represent a significant radiation threat to the linac equipment and personnel. In our study, an operational scenario is analysed which is believed can be considered as the worst case scenario for the main linac regarding the DC contribution to the radiation environment in the main linac tunnel.more » A detailed modelling is performed for the DC electrons which are emitted from the surface of the SRF cavities and can be repeatedly accelerated in the high-gradient fields in many SRF cavities. Results of MARS15 Monte Carlo calculations, performed for the current main linac tunnel design, reveal that the prompt dose design level of 25 μSv/hr in the service tunnel can be provided by a 2.3-m thick concrete wall between the main and service ls.« less

Innate lymphoid cells in atherosclerosis.

PubMed

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.

Development, differentiation and diversity of innate lymphoid cells

PubMed Central

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

The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing.

PubMed

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.

Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules

PubMed Central

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

Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules.

PubMed

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.

Reduced numbers of circulating group 2 innate lymphoid cells in patients with common variable immunodeficiency.

PubMed

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.

IL-33, IL-25, and TSLP induce a distinct phenotypic and activation profile in human type 2 innate lymphoid cells.

PubMed

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.

CXCR6 Expression Is Important for Retention and Circulation of ILC Precursors.

PubMed

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.

Isolation of Human Innate Lymphoid Cells.

PubMed

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.

The Role of Innate Lymphoid Cells in Immune-Mediated Liver Diseases

PubMed Central

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

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation.

PubMed

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.

Interactive laboratory classes enhance neurophysiological knowledge in Thai medical students.

PubMed

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.

A metrology system for a high resolution cavity beam position monitor system

NASA Astrophysics Data System (ADS)

Walston, Sean; Boogert, Stewart; Chung, Carl; Fitsos, Pete; Frisch, Joe; Gronberg, Jeff; Hayano, Hitoshi; Hinton, Shantell; Honda, Yosuke; Khainovski, Oleg; Kolomensky, Yury; Loscutoff, Peter; Lyapin, Alexey; Malton, Stephen; May, Justin; McCormick, Douglas; Meller, Robert; Miller, David; Orimoto, Toyoko; Ross, Marc; Slater, Mark; Smith, Steve; Smith, Tonee; Terunuma, Nobuhiro; Thomson, Mark; Urakawa, Junji; Vogel, Vladimir; Ward, David; White, Glen

2013-11-01

International Linear Collider (ILC) interaction region beam sizes and component position stability requirements will likely be as small as a few nanometers. It is important to the ILC design effort to demonstrate that these tolerances can be achieved-ideally using a beam-based stability measurement. We developed a high resolution RF cavity Beam Position Monitor (BPM) system. A triplet of these BPMs, installed in the extraction line of the KEK Accelerator Test Facility (ATF) and tested with its ultra-low emittance beam, achieved a position measurement resolution of 15 nm. A metrology system for the three BPMs was subsequently installed. This system employed optical encoders to measure each BPM's position and orientation relative to a zero-coefficient of thermal expansion carbon fiber frame. We have demonstrated that the three BPMs behave as a rigid-body at the level of less than 5 nm.

CXCR6 Expression Is Important for Retention and Circulation of ILC Precursors

PubMed Central

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

A Major Population of Functional KLRG1- ILC2s in Female Lungs Contributes to a Sex Bias in ILC2 Numbers.

PubMed

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.

Cytokine and Lipid Mediator Regulation of Group 2 Innate Lymphoid Cells (ILC2s) in Human Allergic Airway Disease.

PubMed

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.

Identification of innate lymphoid cells in single-cell RNA-Seq data.

PubMed

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.

Ambiguous roles of innate lymphoid cells in chronic development of liver diseases.

PubMed

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.

Ambiguous roles of innate lymphoid cells in chronic development of liver diseases

PubMed Central

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

Characteristics of innate lymphoid cells (ILCs) and their role in immunological disorders (an update).

PubMed

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.

Regulation of Innate Lymphoid Cells by Aryl Hydrocarbon Receptor

PubMed Central

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

Isolation and characterization of mouse innate lymphoid cells.

PubMed

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.

Comparison of sentinel lymph node biopsy between invasive lobular carcinoma and invasive ductal carcinoma.

PubMed

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.

Innate Lymphoid Cells in Intestinal Inflammation

PubMed Central

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

The Yin and Yang of Innate Lymphoid Cells in Cancer.

PubMed

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.

Human innate lymphoid cells.

PubMed

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.

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.

Introduction to Superconducting RF Structures and the Effect of High Pressure Rinsing

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

Tajima, Tsuyoshi

2016-06-30

This presentation begins by describing RF superconductivity and SRF accelerating structures. Then the use of superconducting RF structures in a number of accelerators around the world is reviewed; for example, the International Linear Collider (ILC) will use ~16,000 SRF cavities with ~2,000 cryomodules to get 500 GeV e⁺/e⁻ colliding energy. Field emission control was (and still is) a very important practical issue for SRF cavity development. It has been found that high-pressure ultrapure water rinsing as a final cleaning step after chemical surface treatment resulted in consistent performance of single- and multicell superconducting cavities.

Group 2 innate lymphoid cells in disease

PubMed Central

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

Human intrahepatic ILC2 are IL-13positive amphiregulinpositive and their frequency correlates with model of end stage liver disease score.

PubMed

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.

Characterization of innate lymphoid cells (ILC) in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis

PubMed Central

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

Innate lymphoid cells in normal and disease: An introductory overview.

PubMed

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.

Matter, Energy, Space and Time: The International Linear Collider Physics Prospects and International Aspects

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.

Galactic Cosmic Ray Simulation at the NASA Space Radiation Laboratory

NASA Technical Reports Server (NTRS)

Norbury, John W.; Slaba, Tony C.; Rusek, Adam

2015-01-01

The external Galactic Cosmic Ray (GCR) spectrum is significantly modified when it passes through spacecraft shielding and astronauts. One approach for simulating the GCR space radiation environment at ground based accelerators would use the modified spectrum, rather than the external spectrum, in the accelerator beams impinging on biological targets. Two recent workshops have studied such GCR simulation. The first workshop was held at NASA Langley Research Center in October 2014. The second workshop was held at the NASA Space Radiation Investigators' workshop in Galveston, Texas in January 2015. The results of these workshops will be discussed in this paper.

Organization of the 17th Advanced Accelerator Concepts (AAC16) Workshop by the IEEE. Final Scientific/Technical Report On AWARD NO. DE-SC0015635

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

Sutter, David F.

The 2016 Workshop on Advanced Accelerator Concepts (AAC) was held at the Gaylord Hotel and Conference Center, National Harbor, Maryland, from July 31 through August 5, 2016. This workshop was the seventeenth in a biennial series that began at Los Alamos National Laboratory in 1982 with a workshop on laser acceleration of particles (see AIP Conf. Proc. 91). AAC16 was organized under the sponsorship of the IEEE Council on Superconductivity with financial support from the U. S. Department of Energy Office of High Energy Physics and the National Science Foundation. The scope of the AAC Workshop has grown since 1982more » to encompass a broad range of topics related to advancing accelerator science and technology beyond its current scientific and technical limits and is now an internationally acknowledged forum for interdisciplinary discussions on advanced accelerator and beam physics/technology concepts covering the widest possible range of applications. The Workshop continued the trend of growing worldwide participation, attracting world wide participation. The Workshop had a total of 256 attendees comprising (including the U.S.) representatives from 11 countries representing 65 different institutions. Each day’s schedule began with plenary sessions covering broad, cross disciplinary interests or general tutorial topics as selected by the Program Committee, followed by a break out into more narrowly focused working groups. The Workshop was organized into eight Working Groups each with a published statement of topical focus, scope of discussion and goals. A summary of the Working Group activities and conclusions is included in the American Institute of Physics’ (AIP) Conference Proceedings now available as an on line open source document. It has been a long tradition of the AAC workshops to encourage strong student participation. This is accomplished in part by subsidizing student attendance, done for this work shop by using funds from the DOE and National Science Foundation to significantly reduce student registration fees. As a result the registered student participation was 75 persons, or 29% of the total attendance of 256 persons, the highest percentage student enrollment the Workshop has ever had. This is the final report for the DOE Office of Science/Office of High Energy Physics grant NO. DE-SC0015635, entitled “Organization of the17th Advanced Accelerator Concepts Workshop by the IEEE.”« less

Innate Lymphoid Cells in Tumor Immunity.

PubMed

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.

Innate Lymphoid Cells in Tumor Immunity

PubMed Central

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

Innate Lymphoid Cells in HIV/SIV Infections.

PubMed

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.

Innate lymphoid cells in tissue homeostasis and diseases.

PubMed

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.

Innate Lymphoid Cells in HIV/SIV Infections

PubMed Central

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

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.

PubMed

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.

Seven-year survey of classical and pleomorphic invasive lobular breast carcinomas in women from southeastern Serbia: Differences in clinicopathological and immunohistochemical features.

PubMed

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.

Expansion of CD25+ Innate Lymphoid Cells Reduces Atherosclerosis

PubMed Central

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

IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function.

PubMed

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.

Innate lymphoid cells at the interface between obesity and asthma.

PubMed

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.

Type 2 innate lymphoid cells-new members of the "type 2 franchise" that mediate allergic airway inflammation.

PubMed

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.

Innate lymphoid cells in graft-versus-host disease.

PubMed

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.

Group 2 Innate Lymphoid Cells Exhibit a Dynamic Phenotype in Allergic Airway Inflammation

PubMed Central

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

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

Huang, Zhirong; Hogan, Mark

Essentially all we know today and will learn in the future about the fundamental nature of matter is derived from probing it with directed beams of particles such as electrons, protons, neutrons, heavy ions, and photons. The resulting ability to “see” the building blocks of matter has had an immense impact on society and our standard of living. Over the last century, particle accelerators have changed the way we look at nature and the universe we live in and have become an integral part of the Nation’s technical infrastructure. Today, particle accelerators are essential tools of modern science and technology.more » The cost and capabilities of accelerators would be greatly enhanced by breakthroughs in acceleration methods and technology. For the last 32 years, the Advanced Accelerator Concepts (AAC) Workshop has acted as the focal point for discussion and development of the most promising acceleration physics and technology. It is a particularly effective forum where the discussion is leveraged and promoted by the unique and demanding feature of the AAC Workshop: the working group structure, in which participants are asked to consider their contributions in terms of even larger problems to be solved. The 16th Advanced Accelerator Concepts (AAC2014) Workshop was organized by Stanford University from July 13 - 18, 2014 at the Dolce Hays Mansion in San Jose, California. The conference had a record 282 attendees including 62 students. Attendees came from 11 countries representing 66 different institutions. The workshop format consisted of plenary sessions in the morning with topical leaders from around the world presenting the latest breakthroughs to the entire workshop. In the late morning and afternoons attendees broke out into eight different working groups for more detailed presentations and discussions that were summarized on the final day of the workshop. In addition, there were student tutorial presentations on two afternoons to provide in depth education and training for the next generation of accelerator scientists. This is the final technical report on the organization and outcome of AAC2014.« less

Demountable damped cavity for HOM-damping in ILC superconducting accelerating cavities

NASA Astrophysics Data System (ADS)

Konomi, T.; Yasuda, F.; Furuta, F.; Saito, K.

2014-01-01

We have designed a new higher-order-mode (HOM) damper called a demountable damped cavity (DDC) as part of the R&D efforts for the superconducting cavity of the International Linear Collider (ILC). The DDC has two design concepts. The first is an axially symmetrical layout to obtain high damping efficiency. The DDC has a coaxial structure along the beam axis to realize strong coupling with HOMs. HOMs are damped by an RF absorber at the end of the coaxial waveguide and the accelerating mode is reflected by a choke filter mounted at the entrance of the coaxial waveguide. The second design concept is a demountable structure to facilitate cleaning, in order to suppress the Q-slope problem in a high field. A single-cell cavity with the DDC was fabricated to test four performance parameters. The first was frequency matching between the accelerating cavity and the choke filter. Since the bandwidth of the resonance frequency in a superconducting cavity is very narrow, there is a possibility that the accelerating field will leak to the RF absorber because of thermal shrinkage. The design bandwidth of the choke filter is 25 kHz. It was demonstrated that frequency matching adjusted at room temperature could be successfully maintained at 2 K. The second parameter was the performance of the demountable structure. At the joint, the magnetic field is 1/6 of the maximum field in the accelerating cavity. Ultimately, the accelerating field reached 19 MV/m and Q0 was 1.5×1010 with a knife-edge shape. The third parameter was field emission and multipacting. Although the choke structure has numerous parallel surfaces that are susceptible to the multipacting problem, it was found that neither field emission nor multipacting presented problems in both an experiment and simulation. The final parameter was the Q values of the HOM. The RF absorber adopted in the system is a Ni-Zn ferrite type. The RF absorber shape was designed based on the measurement data of permittivity and permeability at 77 K. The Q values of the HOM in the DDC are 10-100 times lower than those of a TESLA-type HOM coupler.

Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis.

PubMed

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.

Innate lymphoid cells in tissue homeostasis and diseases

PubMed Central

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

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...

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

An open-closed-loop iterative learning control approach for nonlinear switched systems with application to freeway traffic control

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.

Innate lymphoid cells in asthma: Will they take your breath away?

PubMed Central

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

Essential, dose-dependent role for the transcription factor Gata3 in the development of IL-5+ and IL-13+ type 2 innate lymphoid cells

PubMed Central

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

NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation.

PubMed

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.

Group 2 ILCs: A way of enhancing immune protection against human helminths?

PubMed

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.

Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome.

PubMed

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.

Circulating activated innate lymphoid cells and mucosal-associated invariant T cells are associated with airflow limitation in patients with asthma.

PubMed

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.

Preferential Reduction of Circulating Innate Lymphoid Cells Type 2 in Patients with Common Variable Immunodeficiency with Secondary Complications Is Part of a Broader Immune Dysregulation.

PubMed

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.

Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction.

PubMed

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.

Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells.

PubMed

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.

International Collaboration for Galactic Cosmic Ray Simulation at the NASA Space Radiation Laboratory

NASA Technical Reports Server (NTRS)

Norbury, John W.; Slaba, Tony C.; Rusek, Adam; Durante, Marco; Reitz, Guenther

2015-01-01

An international collaboration on Galactic Cosmic Ray (GCR) simulation is being formed to make recommendations on how to best simulate the GCR spectrum at ground based accelerators. The external GCR spectrum is significantly modified when it passes through spacecraft shielding and astronauts. One approach for simulating the GCR space radiation environment at ground based accelerators would use the modified spectrum, rather than the external spectrum, in the accelerator beams impinging on biological targets. Two recent workshops have studied such GCR simulation. The first workshop was held at NASA Langley Research Center in October 2014. The second workshop was held at the NASA Space Radiation Investigators' workshop in Galveston, Texas in January 2015. The anticipated outcome of these and other studies may be a report or journal article, written by an international collaboration, making accelerator beam recommendations for GCR simulation. This poster describes the status of GCR simulation at the NASA Space Radiation Laboratory and encourages others to join the collaboration.

Innate lymphoid cells in the initiation, regulation and resolution of inflammation

PubMed Central

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

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

Regulatory T cells and type 2 innate lymphoid cell-dependent asthma.

PubMed

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.

Post-accelerator issues at the IsoSpin Laboratory

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

Chattopadhyay, S.; Nitschke, J.M.

1994-05-01

The workshop on ``Post-Accelerator Issues at the Isospin Laboratory`` was held at the Lawrence Berkeley Laboratory from October 27--29, 1993. It was sponsored by the Center for Beam Physics in the Accelerator and Fusion Research Division and the ISL Studies Group in the Nuclear Science Division. About forty scientists from around the world participated vigorously in this two and a half day workshop, (c.f. Agenda, Appendix D). Following various invited review talks from leading practitioners in the field on the first day, the workshop focussed around two working groups: (1) the Ion Source and Separators working group and (2) themore » Radio Frequency Quadrupoles and Linacs working group. The workshop closed with the two working groups summarizing and outlining the tasks for the future. This report documents the proceedings of the workshop and includes the invited review talks, the two summary talks from the working groups and individual contributions from the participants. It is a complete assemblage of state-of-the-art thinking on ion sources, low-{beta}, low(q/A) accelerating structures, e.g. linacs and RFQS, isobar separators, phase-space matching, cyclotrons, etc., as relevant to radioactive beam facilities and the IsoSpin Laboratory. We regret to say that while the fascinating topic of superconducting low-velocity accelerator structure was covered by Dr. K. Shepard during the workshop, we can only reproduce the copies of the transparencies of his talk in the Appendix, since no written manuscript was available at the time of publication of this report. The individual report have been catologed separately elsewhere.« less

Isolation and analysis of group 2 innate lymphoid cells in mice.

PubMed

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.

ICOS regulates the pool of group 2 innate lymphoid cells under homeostatic and inflammatory conditions in mice.

PubMed

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.

Innate lymphoid cells in secondary lymphoid organs.

PubMed

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.

MHCII-Mediated Dialog between Group 2 Innate Lymphoid Cells and CD4+ T Cells Potentiates Type 2 Immunity and Promotes Parasitic Helminth Expulsion

PubMed Central

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

Establishment and function of tissue-resident innate lymphoid cells in the skin.

PubMed

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.

Pathological and therapeutic roles of innate lymphoid cells in diverse diseases.

PubMed

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.

Migration and Tissue Tropism of Innate Lymphoid Cells

PubMed Central

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

ILC2 memory: Recollection of previous activation.

PubMed

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.

Determination of the Fate and Function of Innate Lymphoid Cells Following Adoptive Transfer of Innate Lymphoid Cell Precursors.

PubMed

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.

Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines.

PubMed

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.

Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.

PubMed

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.

Data Portfolio: instructional materials provide particle physics data in high school classrooms

NASA Astrophysics Data System (ADS)

Bardeen, Marjorie G.

2016-04-01

We discuss Data Portfolio (DP), a new suite of activities that provide experimental particle physics data to high school students and a professional development program for their teachers. DP is a website resource with a broad range of instructional materials that allows teachers to select activities of the correct level and scope for their students. Activities range from introductory to survey, investigation and exploration. DP incorporates existing elements such as masterclasses and e-Labs along with new ways of introducing students to physics concepts that underlie the data measurements and investigations. Evaluators have determined that these elements are in line with the latest standards and effective instructional models. To be successful, teachers need to be confident to use the materials, comfortable to step back so students can guide their own learning, and clever to convince administrators that they are meeting school and district requirements. Professional development workshops accompany the DP where participants experience some of these activities as their students would and plan how to use them in their classes. The first weeklong DP workshop was held in July at Fermilab. We have also held outreach workshops in conjunction with ILC workshops around the world. DP is a product of QuarkNet, a long-term professional development program embedded in the U.S. particle physics research community and funded by the National Science Foundation and the U.S. Department of Energy and supported by universities and labs across the country.

Innate lymphoid cells: a paradigm for low SSI in cleft lip repair.

PubMed

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.

Group 2 innate lymphoid cells promote beiging of adipose and limit obesity

PubMed Central

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

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

Omet, M.; Michizono, S.; Matsumoto, T.

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

Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?

PubMed

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.

T cell-derived IFN-γ downregulates protective group 2 innate lymphoid cells in murine lupus erythematosus.

PubMed

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.

Will there be energy frontier colliders after LHC?

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

Shiltsev, Vladimir

2016-09-15

High energy particle colliders have been in the forefront of particle physics for more than three decades. At present the near term US, European and international strategies of the particle physics community are centered on full exploitation of the physics potential of the Large Hadron Collider (LHC) through its high-luminosity upgrade (HL-LHC). The future of the world-wide HEP community critically depends on the feasibility of possible post-LHC colliders. The concept of the feasibility is complex and includes at least three factors: feasibility of energy, feasibility of luminosity and feasibility of cost. Here we overview all current options for post-LHC collidersmore » from such perspective (ILC, CLIC, Muon Collider, plasma colliders, CEPC, FCC, HE-LHC) and discuss major challenges and accelerator R&D required to demonstrate feasibility of an energy frontier accelerator facility following the LHC. We conclude by taking a look into ultimate energy reach accelerators based on plasmas and crystals, and discussion on the perspectives for the far future of the accelerator-based particle physics.« less

Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells

PubMed Central

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

Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells.

PubMed

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.

Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

PubMed

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.

Role of innate lymphoid cells in obesity and metabolic disease

PubMed Central

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

TSLP elicits IL-33–independent innate lymphoid cell responses to promote skin inflammation

PubMed Central

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

MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion.

PubMed

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.

β2-adrenergic receptor-mediated negative regulation of group 2 innate lymphoid cell responses.

PubMed

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.

Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.

PubMed

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.

Transcription factors controlling innate lymphoid cell fate decisions.

PubMed

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.

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

Constraints from triple gauge couplings on vectorlike leptons

DOE PAGES

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

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

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

Selective programming of CCR10+ innate lymphoid cells in skin-draining lymph nodes for cutaneous homeostatic regulation

PubMed Central

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

Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation.

PubMed

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.

BCG vaccination drives accumulation and effector function of innate lymphoid cells in murine lungs.

PubMed

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.

Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer

PubMed Central

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

Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.

PubMed

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.

Innate Lymphoid Cells Mediate Pulmonary Eosinophilic Inflammation, Airway Mucous Cell Metaplasia, and Type 2 Immunity in Mice Exposed to Ozone.

PubMed

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.

Microbiota-derived butyrate suppresses group 3 innate lymphoid cells in terminal ileal Peyer's patches.

PubMed

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.

Effectiveness of Breast MRI and (18)F-FDG PET/CT for the Preoperative Staging of Invasive Lobular Carcinoma versus Ductal Carcinoma.

PubMed

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.

Proceedings of the Fifth International Workshop on Targetry and Target Chemistry

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

Dahl, J.R.; Ferrieri, R.; Finn, R.

The goal of the International Workshop on Targetry and Target Chemistry series has always been to provide an open forum for discussion of medical radionuclide production, primarily with particle accelerators. The format is intended to encourage the participants to set the direction of the ensuing discussion, allowing the participants to focus on areas of greatest immediate interest. The preceding workshops have set this tone and this workshop was designed to continue in this spirit. The topics of each session were selected by the local organizing committee after discussion with many of the attendees of the previous workshops. The formality ofmore » the workshops has gradually increased from the first rather small, very informal gathering in Heidelburg to the larger contingent present in Villigen, but the open discussion of topics of preoccupation has been maintained. Each Workshop has had areas of particular fascination. In the Fifth workshop the major focus was on the development of new accelerators and on the production of ammonia. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.« less

Evidence of IL-17 producing innate lymphoid cells in peripheral blood from patients with enteropathic spondyloarthritis.

PubMed

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.

Group-2 innate lymphoid cells mediate ozone induced airway inflammation and hyperresponsiveness in mice

PubMed Central

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

A Proinflammatory Role of Type 2 Innate Lymphoid Cells in Murine Immune-Mediated Hepatitis.

PubMed

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.

Human innate lymphoid cells.

PubMed

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.

Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis.

PubMed

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.

Emerging concepts and future challenges in innate lymphoid cell biology

PubMed Central

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

Cutting edge: maresin-1 engages regulatory T cells to limit type 2 innate lymphoid cell activation and promote resolution of lung inflammation.

PubMed

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.

Colonization and effector functions of innate lymphoid cells in mucosal tissues

PubMed Central

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

High resolution upgrade of the ATF damping ring BPM system

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

Terunuma, N.; Urakawa, J.; /KEK, Tsukuba

2008-05-01

A beam position monitor (BPM) upgrade at the KEK Accelerator Test Facility (ATF) damping ring has been accomplished in its first stage, carried out by a KEK/FNAL/SLAC collaboration under the umbrella of the global ILC R&D effort. The upgrade consists of a high resolution, high reproducibility read-out system, based on analog and digital downconversion techniques, digital signal processing, and also tests a new automatic gain error correction schema. The technical concept and realization, as well as preliminary results of beam studies are presented.

Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy.

PubMed

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.

Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System.

PubMed

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.

Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

PubMed Central

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

Innate Lymphoid Cells: a new paradigm in immunology

PubMed Central

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

[Function and modulation of type Ⅱ innate lymphoid cells and their role in chronic upper airway inflammatory diseases].

PubMed

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.

Group 1 innate lymphoid cells in Toxoplasma gondii infection.

PubMed

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.

Aryl Hydrocarbon Receptor Promotes RORγt+ ILCs and Controls Intestinal Immunity and Inflammation

PubMed Central

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

Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion Injury.

PubMed

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.

Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

PubMed Central

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

EDITORIAL: Laser and Plasma Accelerators Workshop, Kardamyli, Greece, 2009 Laser and Plasma Accelerators Workshop, Kardamyli, Greece, 2009

NASA Astrophysics Data System (ADS)

Bingham, Bob; Muggli, Patric

2011-01-01

The Laser and Plasma Accelerators Workshop 2009 was part of a very successful series of international workshops which were conceived at the 1985 Laser Acceleration of Particles Workshop in Malibu, California. Since its inception, the workshop has been held in Asia and in Europe (Kardamyli, Kyoto, Presqu'ile de Giens, Portovenere, Taipei and the Azores). The purpose of the workshops is to bring together the most recent results in laser wakefield acceleration, plasma wakefield acceleration, laser-driven ion acceleration, and radiation generation produced by plasma-based accelerator beams. The 2009 workshop was held on 22-26 June in Kardamyli, Greece, and brought together over 80 participants. (http://cfp.ist.utl.pt/lpaw09/). The workshop involved five main themes: • Laser plasma electron acceleration (experiment/theory/simulation) • Computational methods • Plasma wakefield acceleration (experiment/theory/simulation) • Laser-driven ion acceleration • Radiation generation and application. All of these themes are covered in this special issue of Plasma Physics and Controlled Fusion. The topic and application of plasma accelerators is one of the success stories in plasma physics, with laser wakefield acceleration of mono-energetic electrons to GeV energies, of ions to hundreds of MeV, and electron-beam-driven wakefield acceleration to 85 GeV. The accelerating electric field in the wake is of the order 1 GeV cm-1, or an accelerating gradient 1000 times greater than in conventional accelerators, possibly leading to an accelerator 1000 times smaller (and much more affordable) for the same energy. At the same time, the electron beams generated by laser wakefield accelerators have very good emittance with a correspondingly good energy spread of about a few percent. They also have the unique feature in being ultra-short in the femtosecond scale. This makes them attractive for a variety of applications, ranging from material science to ultra-fast time-resolved radiobiology or chemistry. Such laser-generated beams will form the basis of the fifth generation light sources and will be compact versions of the much more expensive fourth generation XFEL, such as LCLS light sources. Laser-driven ion acceleration is also making rapid headway; one of the goals in these experiments is to produce protons and carbon ions of hundreds of MeV for oncology. These experiments are carried out using solid-target-laser interactions. There is still a number of issues to be resolved in these experiments including the origin of light ions. The paper by Willingale et al addresses this issue and demonstrates that deuteron ions originating from the front surface can gain comparable energies as those from the rear surface. Furthermore, from two-dimensional simulations they show that a proton-rich contamination layer over the surface is detrimental to deuteron ion acceleration from the rear surface but not detrimental to the front surface acceleration mechanism. Studies of different laser polarizations on ion acceleration at the rear surface were reported by Antici et al. It was shown that no real enhancement using a particular polarization was found. At higher radiation intensities, especially with the multi-petawatt lasers being planned, radiation reaction becomes important. This was reported by Chen et al who found that radiation reaction effects on ion acceleration in laser-foil interactions impeded the backward moving electrons, which enhanced the ion acceleration. An interesting new development is the use of ultra-relativistic proton beams to drive plasma wakefields. This is similar to the SLAC electron-beam-driven wakefields. However, unlike the SLAC electron beam, which is of the order of 30 fs long and matches the period of the plasma wave necessary to create the blowout or bubble regime, the ion beam is very much longer. To create shorter ion beams a magnetic compression scheme is investigated in the paper by Caldwell et al, and results for proton beam self-modulation are presented, showing encouraging results for a first experiment using a compressed 24 GeV CERN PS beam. One of the main challenges with laser wakefields is the control of electron injection. In some experiments involving the bubble regime self-injection occurs naturally. Kneip et al show that the stability of the electron beam with energies close to 1 GeV is correlated with the pointing stability of the laser focal spot and depends on the target alignment. Theory and simulations of self-injection reported by Yi et al demonstrate that there is a minimal expansion rate for efficient self-injection. In contrast to solid target ion acceleration, the electron profile in the bubble regime was shown to be manipulated by rotating the laser polarization. Simulations of self-injection into an expanding bubble are reported by Kalmykov et al with the expanding bubble effectively trapping quiescent electrons. To increase the energy of electrons in the laser wakefield scheme, guiding and injection into plasma channels is important. Andreev et al have studied supershort electron bunches in channels with the view of understanding bunch injection. Modelling of electron acceleration in centimetre long capillary tubes is also necessary for future accelerators and is the main part of the paper by Ferrari et al. One of the applications of short-pulse electron beams is in radiation generation as reported by Karagodsky et al. This is an analogue of a technique pioneered in microwave physics where inverse Compton scattering from an optical Bragg structure generates x-rays with high efficiency. The next workshop will be held on 20-24 June 2011 in Wuzhen, Zhejiang Province of China and the scientific programme will be follow the same model as in 2009.

Colonization and effector functions of innate lymphoid cells in mucosal tissues.

PubMed

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.

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.

Interactions between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System

PubMed Central

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

Interactions between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System.

PubMed

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.

Innate lymphoid cells in autoimmunity and chronic inflammatory diseases.

PubMed

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.

Control of pathogens and microbiota by innate lymphoid cells.

PubMed

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.

Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis

PubMed Central

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

The conversion of CESR to operate as the Test Accelerator, CesrTA. Part 1: overview

NASA Astrophysics Data System (ADS)

Billing, M. G.

2015-07-01

Cornell's electron/positron storage ring (CESR) was modified over a series of accelerator shutdowns beginning in May 2008, which substantially improves its capability for research and development for particle accelerators. CESR's energy span from 1.8 to 5.6 GeV with both electrons and positrons makes it ideal for the study of a wide spectrum of accelerator physics issues and instrumentation related to present light sources and future lepton damping rings. Additionally a number of these are also relevant for the beam physics of proton accelerators. This paper outlines the motivation, design and conversion of CESR to a test accelerator, CESRTA, enhanced to study such subjects as low emittance tuning methods, electron cloud (EC) effects, intra-beam scattering, fast ion instabilities as well as general improvements to beam instrumentation. While the initial studies of CESRTA focussed on questions related to the International Linear Collider (ILC) damping ring design, CESRTA is a very flexible storage ring, capable of studying a wide range of accelerator physics and instrumentation questions. This paper contains the outline and the basis for a set of papers documenting the reconfiguration of the storage ring and the associated instrumentation required for the studies described above. Further details may be found in these papers.

Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients.

PubMed

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.

The sensitivity of pre-operative axillary staging in breast cancer: comparison of invasive lobular and ductal carcinoma.

PubMed

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.

Type 2 innate lymphoid cells: at the cross-roads in allergic asthma.

PubMed

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.

Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

PubMed

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.

Aryl hydrocarbon receptor promotes RORγt⁺ group 3 ILCs and controls intestinal immunity and inflammation.

PubMed

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.

Critical role of fatty acid metabolism in ILC2 mediated barrier protection during malnutrition and helminth infection

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...

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...

AHR prevents human IL-1R1hi ILC3 differentiation to natural killer cells

PubMed Central

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

Nuclear p120-catenin regulates the anoikis resistance of mouse lobular breast cancer cells through Kaiso-dependent Wnt11 expression

PubMed Central

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

Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury

PubMed Central

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

Crosstalk between Innate Lymphoid Cells and Other Immune Cells in the Tumor Microenvironment

PubMed Central

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

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.

Damping Ring R&D at CESR-TA

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

Rubin, David L.

2015-01-23

Accelerators that collide high energy beams of matter and anti-matter are essential tools for the investigation of the fundamental constituents of matter, and the search for new forms of matter and energy. A “Linear Collider” is a machine that would bring high energy and very compact bunches of electrons and positrons (anti-electrons) into head-on collision. Such a machine would produce (among many other things) the newly discovered Higgs particle, enabling a detailed study of its properties. Among the most critical and challenging components of a linear collider are the damping rings that produce the very compact and intense beams ofmore » electrons and positrons that are to be accelerated into collision. Hot dilute particle beams are injected into the damping rings, where they are compressed and cooled. The size of the positron beam must be reduced more than a thousand fold in the damping ring, and this compression must be accomplished in a fraction of a second. The cold compact beams are then extracted from the damping ring and accelerated into collision at high energy. The proposed International Linear Collider (ILC), would require damping rings that routinely produce such cold, compact and intense beams. The goal of the Cornell study was a credible design for the damping rings for the ILC. Among the technical challenges of the damping rings; the development of instrumentation that can measure the properties of the very small beams in a very narrow window of time, and mitigation of the forces that can destabilize the beams and prevent adequate cooling, or worse lead to beam loss. One of the most pernicious destabilizing forces is due to the formation of clouds of electrons in the beam pipe. The electron cloud effect is a phenomenon in particle accelerators in which a high density of low energy electrons, build up inside the vacuum chamber. At the outset of the study, it was anticipated that electron cloud effects would limit the intensity of the positron ring, and that an instability associated with residual gas in the beam pipe would limit the intensity of the electron ring. It was also not clear whether the required very small beam size could be achieved. The results of this study are important contributions to the design of both the electron and positron damping rings in which all of those challenges are addressed and overcome. Our findings are documented in the ILC Technical Design Report, a document that represents the work of an international collaboration of scientists. Our contributions include design of the beam magnetic optics for the 3 km circumference damping rings, the vacuum system and surface treatments for electron cloud mitigation, the design of the guide field magnets, design of the superconducting damping wigglers, and new detectors for precision measurement of beam properties. Our study informed the specification of the basic design parameters for the damping rings, including alignment tolerances, magnetic field errors, and instrumentation. We developed electron cloud modelling tools and simulations to aid in the interpretation of the measurements that we carried out in the Cornell Electron-positron Storage Ring (CESR). The simulations provide a means for systematic extrapolation of our measurements at CESR to the proposed ILC damping rings, and ultimately to specify how the beam pipes should be fabricated in order to minimize the effects of the electron cloud. With the conclusion of this study, the design of the essential components of the damping rings is complete, including the development and characterization (with computer simulations) of the beam optics, specification of techniques for minimizing beam size, design of damping ring instrumentation, R&D into electron cloud suppression methods, tests of long term durability of electron cloud coatings, and design of damping ring vacuum system components.« less

Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

PubMed

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.

Max 1991: Flare Research at the Next Solar Maximum. Workshop 1: Scientific Objectives

NASA Technical Reports Server (NTRS)

Canfield, Richard C.; Dennis, Brian R.

1988-01-01

The purpose of the Max 1991 program is to gather coordinated sets of solar flare and active region data and to perform interpretive and theoretical research aimed at understanding flare energy storage and release, particle acceleration, flare energy transport, and the propagation of flare effects to Earth. The workshop was divided into four areas of concern: energy storage, energy release, particle acceleration, and energy transport.

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.

Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques

PubMed Central

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

Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma?

PubMed

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.

Project oriented klystron developments in Japan, China and India

NASA Astrophysics Data System (ADS)

Fukuda, Shigeki

2017-12-01

Modern accelerators are based on the rf technology and the klystron is the one of key components. Some special accelerator projects require their specified klystrons i.e., project-oriented klystrons. In this paper, project-oriented klystron developments for a decade in Japan are described. Related projects are ILC, cERL and SKEKB. Usually klystron is very expensive but has a finite life and needs to procure again. Trial to introduce the compatible tubes and have a competitive tender to reduce the cost is described. At the same time, since an efficiency improvement is one of the recent trend, such an attempt is also presented. International klystron collaboration among the Asian countries has been performed for a long time. In this paper, collaboration with China and India is introduced. Since topics are covered mainly author's experience, related counties described are limited.

Type 2 Innate Lymphoid Cells: Friends or Foes—Role in Airway Allergic Inflammation and Asthma

PubMed Central

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

Type 2 innate lymphoid cells: friends or foes-role in airway allergic inflammation and asthma.

PubMed

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.

Role of Type 2 Innate Lymphoid Cells in Allergic Diseases.

PubMed

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.

Beyond NK cells: the expanding universe of innate lymphoid cells.

PubMed

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.

The chemokine receptor CXCR6 controls the functional topography of interleukin-22 producing intestinal innate lymphoid cells.

PubMed

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.

Group 3 innate lymphoid cells accumulate and exhibit disease-induced activation in the meninges in EAE.

PubMed

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.

Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

PubMed

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.

Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.

PubMed

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.

Analysis of actual healthcare costs of early versus interval cholecystectomy in acute cholecystitis.

PubMed

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.

Accelerating the Development of 21st-Century Toxicology: Outcome of a Human Toxicology Project Consortium Workshop

PubMed Central

Stephens, Martin L.; Barrow, Craig; Andersen, Melvin E.; Boekelheide, Kim; Carmichael, Paul L.; Holsapple, Michael P.; Lafranconi, Mark

2012-01-01

The U.S. National Research Council (NRC) report on “Toxicity Testing in the 21st century” calls for a fundamental shift in the way that chemicals are tested for human health effects and evaluated in risk assessments. The new approach would move toward in vitro methods, typically using human cells in a high-throughput context. The in vitro methods would be designed to detect significant perturbations to “toxicity pathways,” i.e., key biological pathways that, when sufficiently perturbed, lead to adverse health outcomes. To explore progress on the report’s implementation, the Human Toxicology Project Consortium hosted a workshop on 9–10 November 2010 in Washington, DC. The Consortium is a coalition of several corporations, a research institute, and a non-governmental organization dedicated to accelerating the implementation of 21st-century Toxicology as aligned with the NRC vision. The goal of the workshop was to identify practical and scientific ways to accelerate implementation of the NRC vision. The workshop format consisted of plenary presentations, breakout group discussions, and concluding commentaries. The program faculty was drawn from industry, academia, government, and public interest organizations. Most presentations summarized ongoing efforts to modernize toxicology testing and approaches, each with some overlap with the NRC vision. In light of these efforts, the workshop identified recommendations for accelerating implementation of the NRC vision, including greater strategic coordination and planning across projects (facilitated by a steering group), the development of projects that test the proof of concept for implementation of the NRC vision, and greater outreach and communication across stakeholder communities. PMID:21948868

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.

Circulating innate lymphoid cells are unchanged in response to DAC HYP therapy.

PubMed

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.

2016 FACET-II Science Workshop Summary Report

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

Hogan, Mark J.

The second in a series of FACET-II Science Workshops was held at SLAC National Accelerator Laboratory on October 17-19, 2016 [1]. The workshop drew thirty-five participants from eighteen different institutions including CERN, DESY, Ecole Polytechnique, FNAL, JAI, LBNL, LLNL, Radiabeam, Radiasoft, SLAC, Stony Brook, Strathclyde, Tech-X, Tsinghua, UC Boulder, UCLA and UT Austin. The 2015 workshop [2, 3] helped prioritize research directions for FACET-II. The 2016 workshop was focused on understanding what improvements are needed at the facility to support the next generation of experiments. All presentations are linked to the workshop website as a permanent record.

Effects of iterative learning based signal control strategies on macroscopic fundamental diagrams of urban road networks

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.

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

PubMed Central

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

Epidermal Notch1 recruits RORγ(+) group 3 innate lymphoid cells to orchestrate normal skin repair.

PubMed

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.

SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling.

PubMed

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.

SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling

PubMed Central

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

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.

Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells

PubMed Central

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

High Power RF Testing of A 3-Cell Superconducting Traveling Wave Accelerating Structure

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

Kanareykin, Alex; Kostin, Romna; Avrakhov, Pavel

Euclid Techlabs has completed the Phase II SBIR project, entitled “High Power RF Testing of a 3-Cell Superconducting Traveling Wave Accelerating Structure” under Grant #DE-SC0006300. In this final technical report, we summarize the major achievements of Phase I of the project and review the details of Phase II of the project. The accelerating gradient in a superconducting structure is limited mainly by quenching, i.e., by the maximum surface RF magnetic field. Various techniques have been developed to increase the gradient. A traveling wave accelerating SC structure with a feedback waveguide was suggested to allow an increased transit time factor andmore » ultimately, a maximum gradient that is 22%-24% higher than in the best of the time standing wave SRF cavity solution. The proposed structure has an additional benefit in that it can be fabricated much longer than the standing wave ones that are limited by the field flatness factor. Taken together, all of these factors will result in a significant overall length and, correspondingly cost reduction of the SRF based linear collider ILC or SRF technology based FELs. In Phase I of this project, a 3-cell L-band SC traveling wave cavity was designed. Cavity shape, surface field ratios, inter-cell coupling coefficients, accelerating field flatness have been reviewed with the analysis of tuning issues. Moreover, the technological aspects of SC traveling wave accelerating structure fabrication have been studied. As the next step in the project, the Phase II experimental program included engineering design, manufacturing, surface processing and high gradient testing. Euclid Techlabs, LLC contracted AES, Inc. to manufacture two niobium cavities. Euclid Techlabs cold tested traveling wave regime in the cavity, and the results showed very good agreement with mathematical model specially developed for superconducting traveling wave cavity performance analysis. Traveling wave regime was adjusted by amplitude and phase variation of input signals due to application of developed power feeding scheme. Traveling wave excitation, adjustment and detection were successfully tested. Auxiliary equipment required for high power test such as the tuner, power and measure couplers, holding plates for VTS at Fermilab were developed and successfully tested. Both TW SRF cavities were fabricated by AES, Inc. without stiffening ribs before this company closed their production facility. Currently Roark EB welding company is finishing now welding process of the cavity for the high power testing at Fermilab VTS. Successful demonstration of high gradients in the 3-cell cavity along with studies of traveling wave excitation and tuning issues is leading to successful development of superconducting traveling wave technology for ILC applications and other future high energy SC accelerators.« less

Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates.

PubMed

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.

Cytotoxic Effects of PEGylated Anti-EGFR Immunoliposomes Combined with Doxorubicin and Rhenium-188 Against Cancer Cells.

PubMed

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.

NKp46+ Innate Lymphoid Cells Dampen Vaginal CD8 T Cell Responses following Local Immunization with a Cholera Toxin-Based Vaccine

PubMed Central

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

Synergistically increased ILC2 and Th9 cells in lung tissue jointly promote the pathological process of asthma in mice.

PubMed

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.

Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in Subjects with Asthma.

PubMed

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.

Accelerating Scientific Advancement for Pediatric Rare Lung Disease Research. Report from a National Institutes of Health-NHLBI Workshop, September 3 and 4, 2015.

PubMed

Young, Lisa R; Trapnell, Bruce C; Mandl, Kenneth D; Swarr, Daniel T; Wambach, Jennifer A; Blaisdell, Carol J

2016-12-01

Pediatric rare lung disease (PRLD) is a term that refers to a heterogeneous group of rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify technologies, tools, and reagents that could be leveraged to accelerate advancement of research in this field; and (4) to develop priorities for research aimed at improving patient outcomes and quality of life. This report summarizes the workshop discussion and provides specific recommendations to guide future research in PRLD.

Considerations on Energy Frontier Colliders after LHC

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

Shiltsev, Vladimir

2016-11-15

Since 1960’s, particle colliders have been in the forefront of particle physics, 29 total have been built and operated, 7 are in operation now. At present the near term US, European and international strategies of the particle physics community are centered on full exploitation of the physics potential of the Large Hadron Collider (LHC) through its high-luminosity upgrade (HL-LHC). The future of the world-wide HEP community critically depends on the feasibility of possible post-LHC colliders. The concept of the feasibility is complex and includes at least three factors: feasibility of energy, feasibility of luminosity and feasibility of cost. Here wemore » overview all current options for post-LHC colliders from such perspective (ILC, CLIC, Muon Collider, plasma colliders, CEPC, FCC, HE-LHC) and discuss major challenges and accelerator R&D required to demonstrate feasibility of an energy frontier accelerator facility following the LHC. We conclude by taking a look into ultimate energy reach accelerators based on plasmas and crystals, and discussion on the perspectives for the far future of the accelerator-based particle physics. This paper largely follows previous study [1] and the presenta ion given at the ICHEP’2016 conference in Chicago [2].« less

The International Linear Collider Technical Design Report - Volume 3.II: Accelerator Baseline Design

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

Adolphsen, Chris

2013-06-26

The International Linear Collider Technical Design Report (TDR) describes in four volumes the physics case and the design of a 500 GeV centre-of-mass energy linear electron-positron collider based on superconducting radio-frequency technology using Niobium cavities as the accelerating structures. The accelerator can be extended to 1 TeV and also run as a Higgs factory at around 250 GeV and on the Z0 pole. A comprehensive value estimate of the accelerator is give, together with associated uncertainties. It is shown that no significant technical issues remain to be solved. Once a site is selected and the necessary site-dependent engineering is carriedmore » out, construction can begin immediately. The TDR also gives baseline documentation for two high-performance detectors that can share the ILC luminosity by being moved into and out of the beam line in a "push-pull" configuration. These detectors, ILD and SiD, are described in detail. They form the basis for a world-class experimental programme that promises to increase significantly our understanding of the fundamental processes that govern the evolution of the Universe.« less

The International Linear Collider Technical Design Report - Volume 3.I: Accelerator \\& in the Technical Design Phase

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

Adolphsen, Chris

2013-06-26

The International Linear Collider Technical Design Report (TDR) describes in four volumes the physics case and the design of a 500 GeV centre-of-mass energy linear electron-positron collider based on superconducting radio-frequency technology using Niobium cavities as the accelerating structures. The accelerator can be extended to 1 TeV and also run as a Higgs factory at around 250 GeV and on the Z0 pole. A comprehensive value estimate of the accelerator is give, together with associated uncertainties. It is shown that no significant technical issues remain to be solved. Once a site is selected and the necessary site-dependent engineering is carriedmore » out, construction can begin immediately. The TDR also gives baseline documentation for two high-performance detectors that can share the ILC luminosity by being moved into and out of the beam line in a "push-pull" configuration. These detectors, ILD and SiD, are described in detail. They form the basis for a world-class experimental programme that promises to increase significantly our understanding of the fundamental processes that govern the evolution of the Universe.« less

Immune Modules Shared by Innate Lymphoid Cells and T Cells

PubMed Central

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

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.

The pattern of invasive lobular carcinoma in the patients diagnosed with breast cancer from Balochistan.

PubMed

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.

Standard Modular Hydropower Technology Acceleration Workshop: Summary Report

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

Smith, Brennan T.; DeNeale, Scott T.; Witt, Adam M.

In support of the Department of Energy (DOE) funded Standard Modular Hydropower (SMH) Technology Acceleration project, Oak Ridge National Laboratory (ORNL) staff convened with five small hydropower technology entrepreneurs on June 14 and 15, 2017 to discuss gaps, challenges, and opportunities for small modular hydropower development. The workshop was designed to walk through SMH concepts, discuss the SMH research vision, assess how each participant’s technology aligns with SMH concepts and research, and identify future pathways for mutually beneficial collaboration that leverages ORNL expertise and entrepreneurial industry experience. The goal coming out of the workshop is to advance standardized, scalable, modularmore » hydropower technologies and development approaches with sustained and open dialogue among diverse stakeholder groups.« less

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

Dai, Jing; Quan, Sheng-Wen; Zhang, Bao-Cheng

The RF performance of a 1.3 GHz 9-cell superconducting niobium cavity was evaluated at cryogenic temperatures following surface processing by using the standard ILC-style recipe. The cavity is a TESLA-style 9-cell superconducting niobium cavity, with complete end group components including a higher order mode coupler, built in China for practical applications. An accelerating gradient of 28.6 MV/m was achieved at an unloaded quality factor of 4 x 10{sup 9}. The morphological property of mechanical features on the RF surface of this cavity was characterized through optical inspection. Correlation between the observed mechanical features and the RF performance of the cavitymore » is attempted.« less

Performance of a Nanometer Resolution BPM System

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

Vogel, V; Hayano, H; Honda, Y

2005-10-14

International Linear Collider (ILC) interaction region beam sizes and component position stability requirements will be as small as a few nanometers. it is important to the ongoing ILC design effort to demonstrate that these tolerances can be achieved--ideally using beam-based stability measurements. It has been estimated that an RF cavity BPM with modern waveform processing could provide a position measurement resolution of less than one nanometer. Such a system could form the basis of the desired beam-based stability measurement, as well as be used for other specialized purposes. They have developed a high resolution RF cavity BPM and associated electronics.more » A triplet comprised of these BPMs has been installed in the extraction line of the KEK Accelerator Test Facility (ATF) for testing with its ultra-low emittance beam. The three BPMs are rigidly mounted inside an alignment frame on six variable-length struts which can be used to move the BPMs in position and angle. they have developed novel methods for extracting the position and tilt information from the BPM signals including a robust calibration algorithm which is immune to beam jitter. To date, they have been able to demonstrate a resolution of approximately 20 nm over a dynamic range of {+-} 20 {micro}m. They report on the progress of these ongoing tests.« less

Intrinsic functional defects of type 2 innate lymphoid cells impair innate allergic inflammation in promyelocytic leukemia zinc finger (PLZF)-deficient mice.

PubMed

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.

The Role of Magnetic Resonance Imaging in the Investigation and Management of Invasive Lobular Carcinoma-A 3-Year Retrospective Study in Two District General Hospitals.

PubMed

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.

IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions.

PubMed

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.

Testing general relativity on accelerators

DOE PAGES

Kalaydzhyan, Tigran

2015-09-07

Within the general theory of relativity, the curvature of spacetime is related to the energy and momentum of the present matter and radiation. One of the more specific predictions of general relativity is the deflection of light and particle trajectories in the gravitational field of massive objects. Bending angles for electromagnetic waves and light in particular were measured with a high precision. However, the effect of gravity on relativistic massive particles was never studied experimentally. Here we propose and analyze experiments devoted to that purpose. We demonstrate a high sensitivity of the laser Compton scattering at high energy accelerators tomore » the effects of gravity. The main observable – maximal energy of the scattered photons – would experience a significant shift in the ambient gravitational field even for otherwise negligible violation of the equivalence principle. In conclusion, we confirm predictions of general relativity for ultrarelativistic electrons of energy of tens of GeV at a current level of resolution and expect our work to be a starting point of further high-precision studies on current and future accelerators, such as PETRA, European XFEL and ILC.« less

Does one need a 4.5 K screen in cryostats of superconducting accelerator devices operating in superfluid helium? lessons from the LHL

NASA Astrophysics Data System (ADS)

Lebrun, Philippe; Parma, Vittorio; Tavian, Laurent

2014-01-01

Superfluid helium is increasingly used as a coolant for superconducting devices in particle accelerators: the lower temperature enhances the performance of superconductors in high-field magnets and reduces BCS losses in RF acceleration cavities, while the excellent transport properties of superfluid helium can be put to work in efficient distributed cooling systems. The thermodynamic penalty of operating at lower temperature however requires careful management of the heat loads, achieved inter alia through proper design and construction of the cryostats. A recurrent question appears to be that of the need and practical feasibility of an additional screen cooled by normal helium at around 4.5 K surrounding the cold mass at about 2 K, in such cryostats equipped with a standard 80 K screen. We introduce the issue in terms of first principles applied to the configuration of the cryostats, discuss technical constraints and economical limitations, and illustrate the argumentation with examples taken from large projects confronted with this issue, i.e. CEBAF, SPL, ESS, LHC, TESLA, European X-FEL, ILC.

The International Linear Collider Technical Design Report - Volume 2: Physics

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

Baer, Howard; Barklow, Tim; Fujii, Keisuke

2013-06-26

The International Linear Collider Technical Design Report (TDR) describes in four volumes the physics case and the design of a 500 GeV centre-of-mass energy linear electron-positron collider based on superconducting radio-frequency technology using Niobium cavities as the accelerating structures. The accelerator can be extended to 1 TeV and also run as a Higgs factory at around 250 GeV and on the Z0 pole. A comprehensive value estimate of the accelerator is give, together with associated uncertainties. It is shown that no significant technical issues remain to be solved. Once a site is selected and the necessary site-dependent engineering is carriedmore » out, construction can begin immediately. The TDR also gives baseline documentation for two high-performance detectors that can share the ILC luminosity by being moved into and out of the beam line in a "push-pull" configuration. These detectors, ILD and SiD, are described in detail. They form the basis for a world-class experimental programme that promises to increase significantly our understanding of the fundamental processes that govern the evolution of the Universe.« less

The International Linear Collider Technical Design Report - Volume 4: Detectors

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

Behnke, Ties

2013-06-26

The International Linear Collider Technical Design Report (TDR) describes in four volumes the physics case and the design of a 500 GeV centre-of-mass energy linear electron-positron collider based on superconducting radio-frequency technology using Niobium cavities as the accelerating structures. The accelerator can be extended to 1 TeV and also run as a Higgs factory at around 250 GeV and on the Z0 pole. A comprehensive value estimate of the accelerator is give, together with associated uncertainties. It is shown that no significant technical issues remain to be solved. Once a site is selected and the necessary site-dependent engineering is carriedmore » out, construction can begin immediately. The TDR also gives baseline documentation for two high-performance detectors that can share the ILC luminosity by being moved into and out of the beam line in a "push-pull" configuration. These detectors, ILD and SiD, are described in detail. They form the basis for a world-class experimental programme that promises to increase significantly our understanding of the fundamental processes that govern the evolution of the Universe.« less

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

PubMed

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.

Guards at the gate: physiological and pathological roles of tissue-resident innate lymphoid cells in the lung.

PubMed

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.

Human innate lymphoid cells (ILCs) in filarial infections.

PubMed

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.

Innate lymphoid cells and the MHC.

PubMed

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.

Immune modules shared by innate lymphoid cells and T cells.

PubMed

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.

A Descriptive Study of the DoD-Managed Freight Forwarder Concept.

DTIC Science & Technology

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

Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses.

PubMed

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.

Accelerating Scientific Advancement for Pediatric Rare Lung Disease Research. Report from a National Institutes of Health–NHLBI Workshop, September 3 and 4, 2015

PubMed Central

Young, Lisa R.; Trapnell, Bruce C.; Mandl, Kenneth D.; Swarr, Daniel T.; Wambach, Jennifer A.

2016-01-01

Pediatric rare lung disease (PRLD) is a term that refers to a heterogeneous group of rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify technologies, tools, and reagents that could be leveraged to accelerate advancement of research in this field; and (4) to develop priorities for research aimed at improving patient outcomes and quality of life. This report summarizes the workshop discussion and provides specific recommendations to guide future research in PRLD. PMID:27925785

How to manage continuing education and retraining programs on optical physics and laser technology at a university: Moscow State experience

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.

Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.

PubMed

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.

Prevention options for positives: the effects of a health communication intervention for men who have sex with men living with HIV/AIDS.

PubMed

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.

Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis.

PubMed

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.

Epigenomic Views of Innate Lymphoid Cells.

PubMed

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.

Innate lymphoid cells, precursors and plasticity.

PubMed

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.

Epigenomic Views of Innate Lymphoid Cells

PubMed Central

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

CRADA Final Report, 2011S003, Faraday Technologies

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

Faraday Technologies

2012-12-12

This Phase I SBIR program addressed the need for an improved manufacturing process for electropolishing niobium RF superconducting cavities for the International Linear Collider (ILC). The ILC is a proposed particle accelerator that will be used to gain a deeper understanding of the forces of energy and matter by colliding beams of electrons and positrons at nearly the speed of light. The energy required for this to happen will be achieved through the use of advanced superconducting technology, specifically ~16,000 RF superconducting cavities operating at near absolute zero. The RF superconductor cavities will be fabricated from highly pure Nb, whichmore » has an extremely low surface resistance at 2 Kelvin when compared to other materials. To take full advantage of the superconducting properties of the Nb cavities, the inner surface must be a) polished to a microscale roughness < 0.1 µm with removal of at least 100 µm of material, and b) cleaned to be free of impurities that would degrade performance of the ILC. State-of-the-art polishing uses either chemical polishing or electropolishing, both of which require hydrofluoric acid to achieve breakdown of the strong passive film on the surface. In this Phase I program, Faraday worked with its collaborators at the Thomas Jefferson National Accelerator Facility (JLab) to demonstrate the feasibility of an electropolishing process for pure niobium, utilizing an environmentally benign alternative to chemical or electrochemical polishing electrolytes containing hydrofluoric acid. Faraday utilized a 31 wt% aqueous sulfuric acid solution (devoid of hydrofluoric acid) in conjunction with the FARADAYICSM Process, which uses pulse/pulse reverse fields for electropolishing, to demonstrate the ability to electropolish niobium to the desired surface finish. The anticipated benefits of the FARADAYICSM Electropolishing process will be a simpler, safer, and less expensive method capable of surface finishing high purity niobium cavities. Another potential benefit would be for the medical industry that uses hydrofluoric acid to electropolish niobium-alloy materials. The FARADAYICSM Electropolishing process will eliminate the environmental hazards posed by the use of hydrofluoric acid employed by chemical polishing and conventional electropolishing. Further, improved performance benefits may be possible. The overall objective of the Phase I program was to demonstrate that FARADAYIC Electropolishing of niobium cavities in electrolytes free of hydrofluoric acid can meet the RF superconducting performance criteria of those cavities. The FARADAYIC Electropolishing Process developed in the Phase I program was used to polish 50 mm Nb disks to a surface roughness (RA) of < 1 nm over a small area through process and post-processing optimization. An excellent level of surface cleanliness was achieved. While the desired 2K RF performance has not yet been achieved, Faraday believes that surface oxide state can be controlled through manipulation of the process parameters, to meet the 2K RF standard. Faraday is establishing apparatus and facilities infrastructure for single-cell SRF cavity electropolishing, through a synergistic effort with the Fermi National Accelerator Facility (Fermilab) to scale-up electropolishing of superconducting RF cavities. Faraday proposes to commercialize the subject technology via an IP based strategic relationship with a partner with established market channels within two primary commercialization avenues: 1) the superconducting particle accelerator community, 2) the medical device and implant market. Faraday will initially maintain Low Rate Initial Production capabilities for an application, but latterly seek a strategic partner who is solely dedicated to high rate production.« less

Detectors for Linear Colliders: Detector design for a Future Electron-Positron Collider (4/4)

ScienceCinema

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.

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.

Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.

PubMed

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.

Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

PubMed

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.

Planning for an Accelerated School. A Two Day Workshop (Stanford, California, November 17-18, 1988). Illinois Network of Accelerated Schools.

ERIC Educational Resources Information Center

Illinois State Board of Education, Springfield. Dept. of School Improvement Services.

The thesis of this conference report is that acceleration is a much more effective method than remediation for bringing at-risk children into the educational mainstream at an early age. The papers summarized in the report provide a background on the history, politics, and demography of at-risk students and suggest applications of acceleration to…

Statistical tools and control of internal lubricant content of inhalation grade HPMC capsules during manufacture.

PubMed

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.

T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation.

PubMed

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.

Proceedings of the Indo-U.S. bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival

PubMed Central

B. Kumar, Nagi; Dhurandhar, Medha; Aggarwal, Bharat; Anant, Shrikant; Daniel, Kenyon; Deng, Gary; Djeu, Julie; Dou, Jinhui; Hawk, Ernest; Jayaram, B.; Jia, Libin; Joshi, Rajendra; Kararala, Madhuri; Karunagaran, Devarajan; Kucuk, Omer; Kumar, Lalit; Malafa, Mokenge; Samathanam, G. J.; Sarkar, Fazlul; Siddiqi, Maqsood; Singh, Rana P.; Srivastava, Anil; White, Jeffrey D.

2013-01-01

With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo-U.S. collaborative Workshop focusing on “Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment” was conducted at the Moffitt Cancer Center, 29–31 May 2012. Funded by the Indo-U.S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo-U.S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop. PMID:24279005

Proceedings of the Indo-U.S. bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival.

PubMed

Kumar, Nagi B; Dhurandhar, Medha; Aggarwal, Bharat; Anant, Shrikant; Daniel, Kenyon; Deng, Gary; Djeu, Julie; Dou, Jinhui; Hawk, Ernest; Jayaram, B; Jia, Libin; Joshi, Rajendra; Kararala, Madhuri; Karunagaran, Devarajan; Kucuk, Omer; Kumar, Lalit; Malafa, Mokenge; Samathanam, G J; Sarkar, Fazlul; Siddiqi, Maqsood; Singh, Rana P; Srivastava, Anil; White, Jeffrey D

2013-02-01

With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo-U.S. collaborative Workshop focusing on “Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment” was conducted at the Moffitt Cancer Center, 29–31 May 2012. Funded by the Indo-U.S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo-U.S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop.

Proceedings of the workshop on physics at current accelerators and supercolliders

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

Hewett, J L; White, A R; Zeppenfeld, D

1993-06-02

This report contains papers from the workshop on SSC physics. The topics of these papers include: electroweak physics; electroweak symmetry breaking; heavy flavors; searches for new phenomena; strong interactions and full acceptance physics; and event simulation. These paper have been cataloged separately on the data base.

Workshop on Cosmogenic Nuclides

NASA Technical Reports Server (NTRS)

Reedy, R. C. (Editor); Englert, P. (Editor)

1986-01-01

Abstracts of papers presented at the Workshop on Cosmogenic Nuclides are compiled. The major topic areas covered include: new techniques for measuring nuclides such as tandem accelerator and resonance mass spectrometry; solar modulation of cosmic rays; pre-irradiation histories of extraterrestrial materials; terrestrial studies; simulations and cross sections; nuclide production rate calculations; and meteoritic nuclides.

(Installation of the Vinca Accelerator)

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

Zucker, A.

1991-04-22

I participated in a workshop of the physics with accelerators in Belgrade, Yugoslavia and chaired an advisory committee for the Vinca Accelerator Installation which is currently in progress. Also, I participated in meetings with the Serbian Academy of Sciences and with the Deputy Prime Minister of Serbia concerning the plans and aspirations of the nuclear research center at Vinca.

Automated optical inspection and image analysis of superconducting radio-frequency cavities

NASA Astrophysics Data System (ADS)

Wenskat, M.

2017-05-01

The inner surface of superconducting cavities plays a crucial role to achieve highest accelerating fields and low losses. For an investigation of this inner surface of more than 100 cavities within the cavity fabrication for the European XFEL and the ILC HiGrade Research Project, an optical inspection robot OBACHT was constructed. To analyze up to 2325 images per cavity, an image processing and analysis code was developed and new variables to describe the cavity surface were obtained. The accuracy of this code is up to 97 % and the positive predictive value (PPV) 99 % within the resolution of 15.63 μm. The optical obtained surface roughness is in agreement with standard profilometric methods. The image analysis algorithm identified and quantified vendor specific fabrication properties as the electron beam welding speed and the different surface roughness due to the different chemical treatments. In addition, a correlation of ρ = -0.93 with a significance of 6 σ between an obtained surface variable and the maximal accelerating field was found.

The Development of Adult Innate Lymphoid Cells

PubMed Central

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

Interstitial laser coagulation of benign prostatic hyperplasia: a minimally invasive treatment alternative

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.

HMGB1 exacerbates experimental mouse colitis by enhancing innate lymphoid cells 3 inflammatory responses via promoted IL-23 production.

PubMed

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.

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications.

PubMed

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.

High-bandwidth and flexible tracking control for precision motion with application to a piezo nanopositioner.

PubMed

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.

The orphan nuclear receptor ROR alpha and group 3 innate lymphoid cells drive fibrosis in a mouse model of Crohn's disease.

PubMed

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.

The International Linear Collider Technical Design Report - Volume 1: Executive Summary

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

Behnke, Ties; Brau, James E.; Foster, Brian

2013-06-26

The International Linear Collider Technical Design Report (TDR) describes in four volumes the physics case and the design of a 500 GeV centre-of-mass energy linear electron-positron collider based on superconducting radio-frequency technology using Niobium cavities as the accelerating structures. The accelerator can be extended to 1 TeV and also run as a Higgs factory at around 250 GeV and on the Z0 pole. A comprehensive value estimate of the accelerator is give, together with associated uncertainties. It is shown that no significant technical issues remain to be solved. Once a site is selected and the necessary site-dependent engineering is carriedmore » out, construction can begin immediately. The TDR also gives baseline documentation for two high-performance detectors that can share the ILC luminosity by being moved into and out of the beam line in a "push-pull" configuration. These detectors, ILD and SiD, are described in detail. They form the basis for a world-class experimental programme that promises to increase significantly our understanding of the fundamental processes that govern the evolution of the Universe.« less

Impact of Strain Elastography on BI-RADS classification in small invasive lobular carcinoma.

PubMed

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.

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine.

PubMed

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.

Vancomycin pre-treatment impairs tissue healing in experimental colitis: Importance of innate lymphoid cells.

PubMed

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.

Gpr109a Limits Microbiota-Induced IL-23 Production To Constrain ILC3-Mediated Colonic Inflammation.

PubMed

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.

Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex.

PubMed

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.

Advancing research and applications with lightning detection and mapping systems

NASA Astrophysics Data System (ADS)

MacGorman, Donald R.; Goodman, Steven J.

2011-11-01

Southern Thunder 2011 Workshop; Norman, Oklahoma, 11-14 July 2011 The Southern Thunder 2011 (ST11) Workshop was the fourth in a series intended to accelerate research and operational applications made possible by the expanding availability of ground-based and satellite systems that detect and map all types of lightning (in-cloud and cloud-to-ground). This community workshop, first held in 2004, brings together lightning data providers, algorithm developers, and operational users in government, academia, and industry.

Interleukins 12 and 15 induce cytotoxicity and early NK-cell differentiation in type 3 innate lymphoid cells.

PubMed

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.

Active flow separation control by a position-based iterative learning control algorithm with experimental validation

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.

T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation

PubMed Central

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

Why Innate Lymphoid Cells?

PubMed

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.

Back to the drawing board: Understanding the complexity of hepatic innate lymphoid cells.

PubMed

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.

A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

PubMed

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.

Engineering challenges for detectors at the ILC

DOE PAGES

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

Differentiation of Mesenchymal Stem Cells Derived from Pancreatic Islets and Bone Marrow into Islet-Like Cell Phenotype

PubMed Central

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

Experimental asthma persists in IL-33 receptor knockout mice because of the emergence of thymic stromal lymphopoietin-driven IL-9+ and IL-13+ type 2 innate lymphoid cell subpopulations.

PubMed

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.

EDITORIAL: Metrological Aspects of Accelerator Technology and High Energy Physics Experiments

NASA Astrophysics Data System (ADS)

Romaniuk, Ryszard S.; Pozniak, Krzysztof T.

2007-08-01

The subject of this special feature in Measurement Science and Technology concerns measurement methods, devices and subsystems, both hardware and software aspects, applied in large experiments of high energy physics (HEP) and superconducting RF accelerator technology (SRF). These experiments concern mainly the physics of elementary particles or the building of new machines and detectors. The papers present practical examples of applied solutions in large, contemporary, international research projects such as HERA, LHC, FLASH, XFEL, ILC and others. These machines are unique in their global scale and consist of extremely dedicated apparatus. The apparatus is characterized by very large dimensions, a considerable use of resources and a high level of overall technical complexity. They possess a large number of measurement channels (ranging from thousands to over 100 million), are characterized by fast of processing of measured data and high measurement accuracies, and work in quite adverse environments. The measurement channels cooperate with a large number of different sensors of momenta, energies, trajectories of elementary particles, electron, proton and photon beam profiles, accelerating fields in resonant cavities, and many others. The provision of high quality measurement systems requires the designers to use only the most up-to-date technical solutions, measurement technologies, components and devices. Research work in these demanding fields is a natural birthplace of new measurement methods, new data processing and acquisition algorithms, complex, networked measurement system diagnostics and monitoring. These developments are taking place in both hardware and software layers. The chief intention of this special feature is that the papers represent equally some of the most current metrology research problems in HEP and SRF. The accepted papers have been divided into four topical groups: superconducting cavities (4 papers), low level RF systems (8 papers), ionizing radiation (5 papers) and HEP experiments (8 papers). The editors would like to thank cordially all the authors who accepted our invitation to present their very recent results. A number of authors of the papers in this issue are active in the 6th European Framework Research Program CARE—Coordinated Accelerators Research in Europe and ELAN—the European Linear Accelerator Network. Some authors are active in research programs of a global extent such as the LHC, ILC and GDE—the Global Design Effort for the International Linear Collider. We also would like to thank personally, as well as on behalf of all the authors, the Editorial Board of Measurement Science and Technology for accepting this very exciting field of contemporary metrology. This field seems to be really a birthplace of a host of new metrological technologies, where the driving force is the incredibly high technical requirements that must soon be fulfilled if we dream of building new accelerators for elementary particles, new biological materials and medicine alike. Special thanks are due to Professor R S Jachowicz of Warsaw University of Technology for initiating this issue and for continuous support and advice during our work.

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.

Effects of HIV infection and ART on phenotype and function of circulating monocytes, natural killer, and innate lymphoid cells.

PubMed

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.

CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.

PubMed

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.

The orphan nuclear receptor RORα and group 3 innate lymphoid cells drive fibrosis in a mouse model of Crohn's disease.

PubMed

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.

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...

The Research Exchange, 2001.

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…

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...

Accelerated Learning and Retention: Literature Review and Workshop Review

DTIC Science & Technology

2011-03-01

effectiveness, and the committee found that neurolinguistic programming (NLP) had promise, but had not been shown to be effective. They also...Meier, 2000) have used accelerated learning in training programs . Table 3 provides concrete examples of some of the results offered by approaches...minute counts (as is the case in accelerated programs ), motivation is of critical importance. This is one reason why training interventions aimed to

The perfectly ideal accelerometer

NASA Technical Reports Server (NTRS)

Stuhlinger, Ernst

1990-01-01

Given here is a condensed version of the results and conclusions that developed during the Workshop. Upper limits of residual accelerations that can be tolerated during materials processes, presented as acceptable and as desirable limits, are shown. Designs and capabilities of various accelerometers, and their inherent problems, are compared. Results of acceleration measurements on Spacelab flights are summarized, and expected acceleration levels on the Space Station under various conditions are estimated.

LPHYS'14: 23rd International Laser Physics Workshop (Sofia, Bulgaria, 14-18 July 2014)

NASA Astrophysics Data System (ADS)

Yevseyev, Alexander V.

2014-04-01

The 23rd annual International Laser Physics Workshop (LPHYS14) will be held from 14 July to 18 July 2014 in the city of Sofia, Bulgaria, at the Ramada Sofia Hotel hosted this year by the Institute of Electronics, Bulgarian Academy of Sciences. LPHYS14 continues a series of workshops that took place in Dubna,1992; Dubna/Volga river tour, 1993; New York, 1994; Moscow/Volga river tour (jointly with NATO SILAP Workshop), 1995; Moscow, 1996; Prague, 1997; Berlin, 1998; Budapest, 1999; Bordeaux, 2000; Moscow, 2001; Bratislava, 2002; Hamburg, 2003; Trieste, 2004; Kyoto, 2005; Lausanne, 2006; Len, 2007; Trondheim, 2008; Barcelona, 2009; Foz do Iguau, 2010; Sarajevo, 2011; Calgary, 2012 and Prague, 2013. The total number of participants this year is expected to be about 400. In the past, annual participation was typically from over 30 countries. 2014 Chairpersons Sanka Gateva (Bulgaria), Pavel Pashinin (Russia) LPHYS14 will offer eight scientific section seminars and one general symposium: Seminar 1 Modern Trends in Laser Physics Seminar 2 Strong Field and Attosecond Physics Seminar 3 Biophotonics Seminar 4 Physics of Lasers Seminar 5 Nonlinear Optics and Spectroscopy Seminar 6 Physics of Cold Trapped Atoms Seminar 7 Quantum Information Science Seminar 8 Fiber Optics Symposium Extreme Light Technologies, Science and Applications Abstract of your presentation A one-page abstract should contain: title; list of all co-authors (the name of the speaker underlined); affiliations; correspondence addresses including phone numbers, fax numbers, e-mail addresses; and the text of the abstract. Abstracts should be sent to the following co-chairs of the scientific seminars and the symposium: Kirill A Prokhorov (Seminar 1) E-mail: cyrpro@gpi.ru Mikhail V Fedorov (Seminar 2) E-mail: fedorov@ran.gpi.ru Sergey A Gonchukov (Seminar 3) E-mail: gonchukov@mephi.ru Ivan A Shcherbakov (Seminar 4) E-mail: gbufetova@lsk.gpi.ru Vladimir A Makarov (Seminar 5) E-mail: makarov@msu.ilc.edu.ru Vyacheslav I Yukalov (Seminar 6) E-mail: yukalov@theor.jinr.ru Sergei P Kulik (Seminar 7) E-mail: sergei.kulik@gmail.com Sergey A Babin (Seminar 8) E-mail: babin@iae.nsk.su Nikolay B Narozhny (Symposium) E-mail: narozhny@theor.mephi.ru Deadlines Sending an entry visa support form, if needed: 15 April 2014 Receiving an abstract of your presentation: 15 April 2014 Sending a registration form: 15 April 2014 Workshop early payment fee: 15 April 2014 Workshop full payment fee: 1 July 2014 Workshop full payment fee at the conference site: on arrival Accommodation reservation (recommended): 15 May 2014 Sending a manuscript to be published in the Workshop Proceedings: 15 December 2014 Additional information for LPHYS14 can be found at www.lasphys.com

LPHYS'13: 22nd International Laser Physics Workshop (Prague, 15-19 July 2013)

NASA Astrophysics Data System (ADS)

Yevseyev, Alexander V.

2013-04-01

The 22nd annual International Laser Physics Workshop (LPHYS'13) will be held from 15-19 July 2013 in the city of Prague, Czech Republic, at the Hotel Krystal and Czech Technical University hosted this year by the Institute of Physics ASCR and Czech Technical University in Prague. LPHYS'13 continues a series of workshops that took place in Dubna, 1992; Dubna/Volga river tour, 1993; New York, 1994; Moscow/Volga river tour (jointly with NATO SILAP Workshop), 1995; Moscow, 1996; Prague, 1997; Berlin, 1998; Budapest, 1999; Bordeaux, 2000; Moscow, 2001; Bratislava, 2002; Hamburg, 2003; Trieste, 2004; Kyoto, 2005; Lausanne, 2006; León, 2007; Trondheim, 2008; Barcelona, 2009; Foz do Iguaçu, 2010; Sarajevo, 2011; and Calgary, 2012. The total number of participants this year is expected to be about 400. In the past, annual participation was typically from over 30 countries. 2013 Chairmen: Miroslav Jelinek (Czech Republic) and Pavel P Pashinin (Russia) LPHYS'13 will offer eight scientific section seminars and one general symposium: Seminar 1 Modern Trends in Laser Physics Seminar 2 Strong Field & Attosecond Physics Seminar 3 Biophotonics Seminar 4 Physics of Lasers Seminar 5 Nonlinear Optics & Spectroscopy Seminar 6 Physics of Cold Trapped Atoms Seminar 7 Quantum Information Science Seminar 8 Fiber Optics Symposium Extreme Light Technologies, Science and Applications Abstract of your presentation A one-page abstract should contain: title; list of all co-authors (the name of the speaker underlined); affiliations; correspondence addresses including phone numbers, fax numbers, e-mail addresses; and the text of the abstract. Abstracts should be sent to the following co-chairs of the scientific seminars and the symposium: Kirill A Prokhorov (Seminar 1) E-mail: cyrpro@gpi.ru Mikhail V Fedorov (Seminar 2) E-mail: fedorov@ran.gpi.ru Sergey A Gonchukov (Seminar 3) E-mail: gonchukov@mephi.ru Ivan A Shcherbakov (Seminar 4) E-mail: gbufetova@lsk.gpi.ru Vladimir A Makarov (Seminar 5) E-mail: makarov@msu.ilc.edu.ru Vyacheslav I Yukalov (Seminar 6) E-mail: yukalov@theor.jinr.ru Sergei P Kulik (Seminar 7) E-mail: sergei.kulik@gmail.com Sergey A Babin (Seminar 8) E-mail: babin@iae.nsk.su Nikolay B Narozhny (Symposium) E-mail: narozhny@theor.mephi.ru Deadlines Sending an entry visa support form, if needed: 15 April 2013 Receiving an abstract of your presentation: 15 April 2013 Sending a registration form: 15 April 2013 Workshop early payment fee: 15 April 2013 Workshop full payment fee: 1 July 2013 Workshop full payment fee at the conference site: on arrival On-campus accommodation reservation (recommended): 15 May 2013 Manuscript to be published in the Workshop proceedings: 15 December 2013 Additional information for LPHYS'13 can be found at www.lasphys.com

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.

Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination? Vaccination Strategies Based on NK Cell and ILC Memory.

PubMed

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.

Exploring and Improving Student Engagement in an Accelerated Undergraduate Nursing Program through a Mentoring Partnership: An Action Research Study.

PubMed

Bramble, Marguerite; Maxwell, Hazel; Einboden, Rochelle; Farington, Sally; Say, Richard; Beh, Chin Liang; Stankiewicz, Grace; Munro, Graham; Marembo, Esther; Rickard, Greg

2018-05-30

This Participatory Action Research (PAR) project aimed to engage students from an accelerated 'fast track' nursing program in a mentoring collaboration, using an interdisciplinary partnership intervention with a group of academics. Student participants represented the disciplines of nursing and paramedicine with a high proportion of culturally and linguistically diverse (CALD) students. Nine student mentors were recruited and paired with academics for a three-month 'mentorship partnership' intervention. Data from two pre-intervention workshops and a post-intervention workshop were coded in NVivo11 using thematic analysis. Drawing on social inclusion theory, a qualitative analysis explored an iteration of themes across each action cycle. Emergent themes were: 1) 'building relationships for active engagement', 2) 'voicing cultural and social hierarchies', and 3) 'enacting collegiate community'. The study offers insights into issues for contemporary accelerated course delivery with a diverse student population and highlights future strategies to foster effective student engagement.

On Training in Language Documentation and Capacity Building in Papua New Guinea: A Response to Bird et al.

ERIC Educational Resources Information Center

Brooks, Joseph D.

2015-01-01

In a recent article, Bird et al. (2013) discuss a workshop held at the University of Goroka in Papua New Guinea (PNG) in 2012. The workshop was intended to offer a new methodological framework for language documentation and capacity building that streamlines the documentation process and accelerates the global effort to document endangered…

The Next Linear Collider Program

Science.gov Websites

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

The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

PubMed

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.

Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.

PubMed

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.

Acceleration and Performance Modeling Workshop, Washington, DC, 14-17 May 79,

DTIC Science & Technology

1979-12-01

disturbance of the muscular systems, perhaps changes in spindle fiber output, and changes in the perceived weight of the muscle because of the acceleration...at this point either. The output models which are determining performance are essentially tied to muscular systems, through manual control (hand and...feet), and through speech, another muscular output. In normal activities the pilot, who senses changes in the visual system, the acceleration vector

Loss of thymic innate lymphoid cells leads to impaired thymopoiesis in experimental graft-versus-host disease.

PubMed

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.

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.

IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells.

PubMed

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.

Alleviation of streptozotocin-induced diabetes in nude mice by stem cells derived from human first trimester umbilical cord.

PubMed

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.

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.

Influence of semi-quantitative oestrogen receptor expression on adjuvant endocrine therapy efficacy in ductal and lobular breast cancer - a TEAM study analysis.

PubMed

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.

Distribution of Interleukin-22-secreting Immune Cells in Conjunctival Associated Lymphoid Tissue.

PubMed

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.

Advances in Large Grain/Single Crystal SC Resonators at DESY

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

W. Singer; A. Brinkmann; A. Ermakov

The main aim of the DESY large grain R&D program is to check whether this option is reasonable to apply for fabrication of ca. 1'000 XFEL cavities. Two aspects are being pursued. On one hand the basic material investigation, on the other hand the material availability, fabrication and preparation procedure. Several single cell large grain cavities of TESLA shape have been fabricated and tested. The best accelerating gradients of 41 MV/m was measured on electropolished cavity. First large grain nine-cell cavities worldwide have been produced under contract of DESY with ACCEL Instruments Co. All three cavities fulfil the XFEL specificationmore » already in first RF test after only BCP (Buffered Chemical Polishing) treatment and 800 degrees C annealing. Accelerating gradient of 27 - 29 MV/m was reached. A fabrication method of single crystal cavity of ILC like shape was proposed. A single cell single crystal cavity was build at the company ACCEL. Accelerating gradient of 37.5 MV/m reached after only 112 microns BCP and in situ baking 120 degrees C for 6 hrs with the quality factor higher as 2x1010. The developed method can be extended on fabrication of multi cell single crystal cavities.« less

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.…

Lymphoid microenvironments and innate lymphoid cells in the gut.

PubMed

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.

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

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.

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

Kalaydzhyan, Tigran

Within the general theory of relativity, the curvature of spacetime is related to the energy and momentum of the present matter and radiation. One of the more specific predictions of general relativity is the deflection of light and particle trajectories in the gravitational field of massive objects. Bending angles for electromagnetic waves and light in particular were measured with a high precision. However, the effect of gravity on relativistic massive particles was never studied experimentally. Here we propose and analyze experiments devoted to that purpose. We demonstrate a high sensitivity of the laser Compton scattering at high energy accelerators tomore » the effects of gravity. The main observable – maximal energy of the scattered photons – would experience a significant shift in the ambient gravitational field even for otherwise negligible violation of the equivalence principle. In conclusion, we confirm predictions of general relativity for ultrarelativistic electrons of energy of tens of GeV at a current level of resolution and expect our work to be a starting point of further high-precision studies on current and future accelerators, such as PETRA, European XFEL and ILC.« less

Second user workshop on high-power lasers at the Linac Coherent Light Source

DOE PAGES

Heimann, Phil; Glenzer, Siegfried

2015-05-28

The second international workshop on the physics enabled by the unique combination of high-power lasers with the world-class Linac Coherent Light Source (LCLS) free-electron X-ray laser beam was held in Stanford, CA, on October 7–8, 2014. The workshop was co-organized by UC Berkeley, Lawrence Berkeley, Lawrence Livermore, and SLAC National Accelerator Laboratories. More than 120 scientists, including 40 students and postdoctoral scientists who are working in high-intensity laser-matter interactions, fusion research, and dynamic high-pressure science came together from North America, Europe, and Asia. The focus of the second workshop was on scientific highlights and the lessons learned from 16 newmore » experiments that were performed on the Matter in Extreme Conditions (MEC) instrument since the first workshop was held one year ago.« less

Contributions of Interleukin‐33 and TSLP in a papain‐soaked contact lens‐induced mouse conjunctival inflammation model

PubMed Central

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

The Next Linear Collider Program

Science.gov Websites

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

Measurements and simulations of MAPS (Monolithic Active Pixel Sensors) response to charged particles - a study towards a vertex detector at the ILC

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.

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.

Robust design of feedback feed-forward iterative learning control based on 2D system theory for linear uncertain systems

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.

Control of Innate and Adaptive Lymphocytes by the RAR-Retinoic Acid Axis.

PubMed

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.

Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis.

PubMed

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.

Innate Lymphoid Cells: A Promising New Regulator in Fibrotic Diseases.

PubMed

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.

The Intermediate Neutrino Program

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

Adams, C.; Alonso, J. R.; Ankowski, A. M.

2017-04-03

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program (WINP) at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topicsmore » on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop.« less

Results from a workshop on research needs for modeling aquifer thermal energy storage systems

NASA Astrophysics Data System (ADS)

Drost, M. K.

1990-08-01

A workshop an aquifer thermal energy storage (ATES) system modeling was conducted by Pacific Northwest Laboratory (PNL). The goal of the workshop was to develop a list of high priority research activities that would facilitate the commercial success of ATES. During the workshop, participants reviewed currently available modeling tools for ATES systems and produced a list of significant issues related to modeling ATES systems. Participants assigned a priority to each issue on the list by voting and developed a list of research needs for each of four high-priority research areas; the need for a feasibility study model, the need for engineering design models, the need for aquifer characterization, and the need for an economic model. The workshop participants concluded that ATES commercialization can be accelerated by aggressive development of ATES modeling tools and made specific recommendations for that development.

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.

Biometric analysis of pigment dispersion syndrome using anterior segment optical coherence tomography.

PubMed

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.

Energetic particles in solar flares. Chapter 4 in the proceedings of the 2nd Skylab Workshop on Solar Flares

NASA Technical Reports Server (NTRS)

Ramaty, R.; Colgate, S. A.; Dulk, G. A.; Hoyng, P.; Knight, J. W., III; Lin, R. P.; Melrose, D. B.; Paizis, C.; Orrall, F.; Shapiro, P. R.

1978-01-01

The recent direct observational evidence for the acceleration of particles in solar flares, i.e. radio emission, bremsstrahlung X-ray emission, gamma-ray line and continuum emission, as well as direct observations of energetic electrons and ions, are discussed and intercorrelated. At least two distinct phases of acceleration of solar particles exist that can be distinguished in terms of temporal behavior, type and energy of particles accelerated and the acceleration mechanism. Bulk energization seems the likely acceleration mechanism for the first phase while Fermi mechanism is a viable candidate for the second one.

Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency.

PubMed

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.

Functional Defects in Type 3 Innate Lymphoid Cells and Classical Monocytes in a Patient with Hyper-IgE Syndrome.

PubMed

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.

Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of Ki67 assay according to histology: prognostic relevance for resected early stage 'pure' and 'mixed' lobular breast cancer.

PubMed

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.

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.

Improving Chronic Disease in the Caribbean through Evidence-based Behavioral and Social In

Cancer.gov

The Office for Behavioral and Social Sciences Research and the NCI’s Center for Global Health held a workshop entitled “Improving Chronic Disease in the Caribbean through Evidence-based Behavioral and Social Interventions”, which took place in Bridgetown, Barbados from July 21 to 24, 2015. The objectives of the workshop were to encourage the generation of research to more rapidly accelerate chronic disease prevention and management.

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.

The 1980 Goddard Space Flight Center Battery Workshop

NASA Technical Reports Server (NTRS)

Halpert, G.

1981-01-01

Several aspects of lithium primary cell technology are discussed with respect to aerospace application. Particular attention is given to the statistical analysis of battery data and accelerated testing.

The Center for Informal Learning and Schools' Informal Learning Certificate (ILC) Program: Professional Development and Community for Informal Science Educators Working with Schools. An Evaluation Report

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…

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

IL-25 Elicits Innate Lymphoid Cells and Multipotent Progenitor Type 2 Cells That Reduce Renal Ischemic/Reperfusion Injury

PubMed Central

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

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.

75 FR 53277 - Notice of Workshop on Polymers for Photovoltaic Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

... photovoltaic systems; testing, performance, and reliability of polymers in photovoltaic systems; impact of... mentioned topics; presentation of a NIST- developed accelerated aging and service life prediction...

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.

SuperB Progress Report for Accelerator

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

Biagini, M.E.; Boni, R.; Boscolo, M.

2012-02-14

This report details the progress made in by the SuperB Project in the area of the Collider since the publication of the SuperB Conceptual Design Report in 2007 and the Proceedings of SuperB Workshop VI in Valencia in 2008. With this document we propose a new electron positron colliding beam accelerator to be built in Italy to study flavor physics in the B-meson system at an energy of 10 GeV in the center-of-mass. This facility is called a high luminosity B-factory with a project name 'SuperB'. This project builds on a long history of successful e+e- colliders built around themore » world, as illustrated in Figure 1.1. The key advances in the design of this accelerator come from recent successes at the DAFNE collider at INFN in Frascati, Italy, at PEP-II at SLAC in California, USA, and at KEKB at KEK in Tsukuba Japan, and from new concepts in beam manipulation at the interaction region (IP) called 'crab waist'. This new collider comprises of two colliding beam rings, one at 4.2 GeV and one at 6.7 GeV, a common interaction region, a new injection system at full beam energies, and one of the two beams longitudinally polarized at the IP. Most of the new accelerator techniques needed for this collider have been achieved at other recently completed accelerators including the new PETRA-3 light source at DESY in Hamburg (Germany) and the upgraded DAFNE collider at the INFN laboratory at Frascati (Italy), or during design studies of CLIC or the International Linear Collider (ILC). The project is to be designed and constructed by a worldwide collaboration of accelerator and engineering staff along with ties to industry. To save significant construction costs, many components from the PEP-II collider at SLAC will be recycled and used in this new accelerator. The interaction region will be designed in collaboration with the particle physics detector to guarantee successful mutual use. The accelerator collaboration will consist of several groups at present universities and national laboratories. In Italy these may include INFN Frascati and the University of Pisa, in the United States SLAC, LBNL, BNL and several universities, in France IN2P3, LAPP, and Grenoble, in Russia BINP, in Poland Krakow University, and in the UK the Cockcroft Institute. The construction time for this collider is a total of about four years. The new tunnel can be bored in about a year. The new accelerator components can be built and installed in about 4 years. The shipping of components from PEP-II at SLAC to Italy will take about a year. A new linac and damping ring complex for the injector for the rings can be built in about three years. The commissioning of this new accelerator will take about a year including the new electron and positron sources, new linac, new damping ring, new beam transport lines, two new collider rings and the Interaction Region. The new particle physics detector can be commissioned simultaneously with the accelerator. Once beam collisions start for particle physics, the luminosity will increase with time, likely reaching full design specifications after about two to three years of operation. After construction, the operation of the collider will be the responsibility of the Italian INFN governmental agency. The intent is to run this accelerator about ten months each year with about one month for accelerator turn-on and nine months for colliding beams. The collider will need to operate for about 10 years to provide the required 50 ab{sup -1} requested by the detector collaboration. Both beams as anticipated in this collider will have properties that are excellent for use as sources for synchrotron radiation (SR). The expected photon properties are comparable to those of PETRA-3 or NSLS-II. The beam lines and user facilities needed to carry out this SR program are being investigated.« less

A Variable Energy CW Compact Accelerator for Ion Cancer Therapy

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

Johnstone, Carol J.; Taylor, J.; Edgecock, R.

2016-03-10

Cancer is the second-largest cause of death in the U.S. and approximately two-thirds of all cancer patients will receive radiation therapy with the majority of the radiation treatments performed using x-rays produced by electron linacs. Charged particle beam radiation therapy, both protons and light ions, however, offers advantageous physical-dose distributions over conventional photon radiotherapy, and, for particles heavier than protons, a significant biological advantage. Despite recognition of potential advantages, there is almost no research activity in this field in the U.S. due to the lack of clinical accelerator facilities offering light ion therapy in the States. In January, 2013, amore » joint DOE/NCI workshop was convened to address the challenges of light ion therapy [1], inviting more than 60 experts from diverse fields related to radiation therapy. This paper reports on the conclusions of the workshop, then translates the clinical requirements into accelerat or and beam-delivery technical specifications. A comparison of available or feasible accelerator technologies is compared, including a new concept for a compact, CW, and variable energy light ion accelerator currently under development. This new light ion accelerator is based on advances in nonscaling Fixed-Field Alternating gradient (FFAG) accelerator design. The new design concepts combine isochronous orbits with long (up to 4m) straight sections in a compact racetrack format allowing inner circulating orbits to be energy selected for low-loss, CW extraction, effectively eliminating the high-loss energy degrader in conventional CW cyclotron designs.« less

Understanding Collagen Organization in Breast Tumors to Predict and Prevent Metastasis

DTIC Science & Technology

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

Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells

PubMed Central

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

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.

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.

Report of the Fourth International Workshop on human X chromosome mapping 1993

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

Schlessinger, D.; Mandel, J.L.; Monaco, A.P.

1993-12-31

Vigorous interactive efforts by the X chromosome community have led to accelerated mapping in the last six months. Seventy-five participants from 12 countries around the globe contributed progress reports to the Fourth International X Chromosome Workshop, at St. Louis, MO, May 9-12, 1993. It became clear that well over half the chromosome is now covered by YAC contigs that are being extended, verified, and aligned by their content of STSs and other markers placed by cytogenetic or linkage mapping techniques. The major aim of the workshop was to assemble the consensus map that appears in this report, summarizing both consensusmore » order and YAC contig information.« less

National Synchrotron Light Source annual report 1991

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

Hulbert, S.L.; Lazarz, N.M.

1992-04-01

This report discusses the following research conducted at NSLS: atomic and molecular science; energy dispersive diffraction; lithography, microscopy and tomography; nuclear physics; UV photoemission and surface science; x-ray absorption spectroscopy; x-ray scattering and crystallography; x-ray topography; workshop on surface structure; workshop on electronic and chemical phenomena at surfaces; workshop on imaging; UV FEL machine reviews; VUV machine operations; VUV beamline operations; VUV storage ring parameters; x-ray machine operations; x-ray beamline operations; x-ray storage ring parameters; superconducting x-ray lithography source; SXLS storage ring parameters; the accelerator test facility; proposed UV-FEL user facility at the NSLS; global orbit feedback systems; and NSLSmore » computer system.« less

1995 second modulator-klystron workshop: A modulator-klystron workshop for future linear colliders

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

NONE

1996-03-01

This second workshop examined the present state of modulator design and attempted an extrapolation for future electron-positron linear colliders. These colliders are currently viewed as multikilometer-long accelerators consisting of a thousand or more RF sources with 500 to 1,000, or more, pulsed power systems. The workshop opened with two introductory talks that presented the current approaches to designing these linear colliders, the anticipated RF sources, and the design constraints for pulse power. The cost of main AC power is a major economic consideration for a future collider, consequently the workshop investigated efficient modulator designs. Techniques that effectively apply the artmore » of power conversion, from the AC mains to the RF output, and specifically, designs that generate output pulses with very fast rise times as compared to the flattop. There were six sessions that involved one or more presentations based on problems specific to the design and production of thousands of modulator-klystron stations, followed by discussion and debate on the material.« less

Workshop on Pion-Kaon Interactions (PKI2018) Mini-Proceedings

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

Amaryan, M; Pal, Bilas

This volume is a short summary of talks given at the PKI2018 Workshop organized to discuss current status and future prospects of pi -K interactions. The precise data on pi K interaction will have a strong impact on strange meson spectroscopy and form factors that are important ingredients in the Dalitz plot analysis of a decays of heavy mesons as well as precision measurement of Vus matrix element and therefore on a test of unitarity in the first raw of the CKM matrix. The workshop has combined the efforts of experimentalists, Lattice QCD, and phenomenology communities. Experimental data relevant tomore » the topic of the workshop were presented from the broad range of different collaborations like CLAS, GlueX, COMPASS, BaBar, BELLE, BESIII, VEPP-2000, and LHCb. One of the main goals of this workshop was to outline a need for a new high intensity and high precision secondary KL beam facility at JLab produced with the 12 GeV electron beam of CEBAF accelerator.« less

Electron Cloud Effects in Accelerators

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

Furman, M.A.

Abstract We present a brief summary of various aspects of the electron-cloud effect (ECE) in accelerators. For further details, the reader is encouraged to refer to the proceedings of many prior workshops, either dedicated to EC or with significant EC contents, including the entire ?ECLOUD? series [1?22]. In addition, the proceedings of the various flavors of Particle Accelerator Conferences [23] contain a large number of EC-related publications. The ICFA Beam Dynamics Newsletter series [24] contains one dedicated issue, and several occasional articles, on EC. An extensive reference database is the LHC website on EC [25].

Complement and Immunoregulation in Tissue Injury

DTIC Science & Technology

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

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.

DD-RT-PCR identifies 7-dehydrocholesterol reductase as a key marker of early Leydig cell steroidogenesis.

PubMed

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.

Scalar production in association with a Z boson at the LHC and ILC: The mixed Higgs-radion case of warped models

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.

The Development and Psychometric Properties of the Immigration Law Concerns Scale (ILCS) for HIV Testing.

PubMed

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.

Summary of the Physics Opportunities Working Group

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

Chen, Pisin; McDonald, K.T.

The Physics Opportunities Working Group was convened with the rather general mandate to explore physic opportunities that may arise as new accelerator technologies and facilities come into play. Five topics were considered during the workshop: QED at critical field strength, novel positron sources, crystal accelerators, suppression of beamstrahlung, and muon colliders. Of particular interest was the sense that a high energy muon collider might be technically feasible and certainly deserves serious study.

Summary of the Physics Opportunities Working Group

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

Chen, Pisin; McDonald, K.T.

1992-12-01

The Physics Opportunities Working Group was convened with the rather general mandate to explore physic opportunities that may arise as new accelerator technologies and facilities come into play. Five topics were considered during the workshop: QED at critical field strength, novel positron sources, crystal accelerators, suppression of beamstrahlung, and muon colliders. Of particular interest was the sense that a high energy muon collider might be technically feasible and certainly deserves serious study.

Central domain of IL-33 is cleaved by mast cell proteases for potent activation of group-2 innate lymphoid cells

PubMed Central

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

The histone deacetylase inhibitor trichostatin A suppresses murine innate allergic inflammation by blocking group 2 innate lymphoid cell (ILC2) activation

PubMed Central

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

Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

PubMed

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.

Fourth User Workshop on High-Power Lasers at the Linac Coherent Light Source

DOE PAGES

Bolme, Cindy Anne; Mackinnon, Andy; Glenzer, Siegfried

2017-05-30

The fourth international user workshop focusing on high-power lasers at the Linac Coherent Light Source (LCLS) was held in Menlo Park, CA, USA, on October 3–4, 2016. The workshop was co-organized by Los Alamos National Laboratory and SLAC National Accelerator Laboratory (SLAC), and garnered the attendance of more than 110 scientists. Participants discussed the warm dense matter and high-pressure science that is being conducted using high-power lasers at the LCLS Matter in Extreme Conditions (MEC) endstation. During the past year, there have been seven journal articles published from research at the MEC instrument. Here, the specific topics discussed at thismore » workshop were experimental highlights from the past year, current status and future commissioning of MEC capabilities, and future facility upgrades that will enable the expanded science reach of the facility.« less

Fourth User Workshop on High-Power Lasers at the Linac Coherent Light Source

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

Bolme, Cindy Anne; Mackinnon, Andy; Glenzer, Siegfried

The fourth international user workshop focusing on high-power lasers at the Linac Coherent Light Source (LCLS) was held in Menlo Park, CA, USA, on October 3–4, 2016. The workshop was co-organized by Los Alamos National Laboratory and SLAC National Accelerator Laboratory (SLAC), and garnered the attendance of more than 110 scientists. Participants discussed the warm dense matter and high-pressure science that is being conducted using high-power lasers at the LCLS Matter in Extreme Conditions (MEC) endstation. During the past year, there have been seven journal articles published from research at the MEC instrument. Here, the specific topics discussed at thismore » workshop were experimental highlights from the past year, current status and future commissioning of MEC capabilities, and future facility upgrades that will enable the expanded science reach of the facility.« less

ASA education outreach

NASA Astrophysics Data System (ADS)

Hansen, Uwe J.; Everbach, E. Carr

2003-04-01

A number of very successful Hands-on demo sessions for high school students have been a part of regular ASA meetings for some time. In addition, the Education Committee has organized a series of teacher workshops. These workshops are designed to give high school teachers relatively sophisticated tools to enhance their laboratory content. Workshops for teachers in the elementary grades prepare teachers to use music as a vehicle to introduce additional science concepts. Content and methods associated with both workshops will be discussed. Cyberspace outreach by the ASA was accelerated by the establishment of a Home Page Committee, and more recently by the On-Line Education committee, which is creating an educational website. The website provides a fun way for users to access information including acoustics information, history, demos, and links to the Technical Committee's webpages. The ASA has joined other AIP member societies in developing additional mechanisms, including road shows and nightly news spots.

Design, Project Execution, and Commissioning of the 1.8 K Superfluid Helium Refrigeration System for SRF Cryomodule Testing

DOE PAGES

Treite, P.; Nuesslein, U.; Jia, Yi; ...

2015-07-15

The Fermilab Cryomodule Test Facility (CMTF) provides a test bed to measure the performance of superconducting radiofrequency (SRF) cryomodules (CM). These SRF components form the basic building blocks of future high intensity accelerators such as the International Linear Collider (ILC) and a Muon Collider. Linde Kryotechnik AG and Linde Cryogenics have designed, constructed and commissioned the superfluid helium refrigerator needed to support SRF component testing at the CMTF Facility. The hybrid refrigerator is designed to operate in a variety of modes and under a wide range of boundary conditions down to 1.8 Kelvin set by CM design. Special features ofmore » the refrigerator include the use of warm and cold compression and high efficiency turbo expanders.This paper gives an overview on the wide range of the challenging cooling requirements, the design, fabrication and the commissioning of the installed cryogenic system.« less

What Will the Neighbors Think? Building Large-Scale Science Projects Around the World

ScienceCinema

Jones, Craig; Mrotzek, Christian; Toge, Nobu; Sarno, Doug

2017-12-22

Public participation is an essential ingredient for turning the International Linear Collider into a reality. Wherever the proposed particle accelerator is sited in the world, its neighbors -- in any country -- will have something to say about hosting a 35-kilometer-long collider in their backyards. When it comes to building large-scale physics projects, almost every laboratory has a story to tell. Three case studies from Japan, Germany and the US will be presented to examine how community relations are handled in different parts of the world. How do particle physics laboratories interact with their local communities? How do neighbors react to building large-scale projects in each region? How can the lessons learned from past experiences help in building the next big project? These and other questions will be discussed to engage the audience in an active dialogue about how a large-scale project like the ILC can be a good neighbor.

IL-9-Producing Mast Cell Precursors and Food Allergy

DTIC Science & Technology

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

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.

Role of Cathepsin C During Breast Cancer Metastasis

DTIC Science & Technology

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

Report on the fifth workshop on synchrotron x ray lithography

NASA Astrophysics Data System (ADS)

Williams, G. P.; Godel, J. B.; Brown, G. S.; Liebmann, W.

Semiconductors comprise a greater part of the United States economy than the aircraft, steel, and automobile industries combined. In future the semiconductor manufacturing industry will be forced to switch away from present optical manufacturing methods in the early to mid 1990s. X ray lithography has emerged as the leading contender for continuing production below the 0.4 micron level. Brookhaven National Laboratory began a series of workshops on x ray lithography in 1986 to examine key issues and in particular to enable United States industry to take advantage of the technical base established in this field. Since accelerators provide the brightest sources for x ray lithography, most of the research and development to date has taken place at large accelerator-based research centers such as Brookhaven, the University of Wisconsin, and Stanford. The goals of this Fifth Brookhaven Workshop were to review progress and goals since the last workshop and to establish a blueprint for the future. The meeting focused on the exposure tool, that is, a term defined as the source plus beamline and stepper. In order to assess the appropriateness of schedules for the development of this tool, other aspects of the required technology such as masks, resists and inspection and repair were also reviewed. To accomplish this, two working groups were set up, one to review the overall aspects of x ray lithography and set a time frame, the other to focus on sources.

Accelerated bridge construction and structural move : workshop.

DOT National Transportation Integrated Search

2014-03-01

The Michigan Department of Transportation (MDOT) is committed to provide the highest level of safety and : mobility during each step of a projects development and delivery. To fulfil the above commitment, MDOT : embraces technology and uses innova...

PCaPAC 2006 Proceedings

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

Pavel Chevtsov; Matthew Bickley

2007-03-30

The 6-th international PCaPAC (Personal Computers and Particle Accelerator Controls) workshop was held at Jefferson Lab, Newport News, Virginia, from October 24-27, 2006. The main objectives of the conference were to discuss the most important issues of the use of PCs and modern IT technologies for controls of accelerators and to give scientists, engineers, and technicians a forum to exchange the ideas on control problems and their solutions. The workshop consisted of plenary sessions and poster sessions. No parallel sessions were held.Totally, more than seventy oral and poster presentations as well as tutorials were made during the conference, on themore » basis of which about fifty papers were submitted by the authors and included in this publication. This printed version of the PCaPAC 2006 Proceedings is published at Jefferson Lab according to the decision of the PCaPAC International Program Committee of October 26, 2006.« less

Future Research Directions in Asthma. An NHLBI Working Group Report.

PubMed

Levy, Bruce D; Noel, Patricia J; Freemer, Michelle M; Cloutier, Michelle M; Georas, Steve N; Jarjour, Nizar N; Ober, Carole; Woodruff, Prescott G; Barnes, Kathleen C; Bender, Bruce G; Camargo, Carlos A; Chupp, Geoff L; Denlinger, Loren C; Fahy, John V; Fitzpatrick, Anne M; Fuhlbrigge, Anne; Gaston, Ben M; Hartert, Tina V; Kolls, Jay K; Lynch, Susan V; Moore, Wendy C; Morgan, Wayne J; Nadeau, Kari C; Ownby, Dennis R; Solway, Julian; Szefler, Stanley J; Wenzel, Sally E; Wright, Rosalind J; Smith, Robert A; Erzurum, Serpil C

2015-12-01

Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the NHLBI convened a group of extramural investigators for an Asthma Research Strategic Planning workshop on September 18-19, 2014, to accelerate discoveries and their translation to patients. The workshop focused on (1) in utero and early-life origins of asthma, (2) the use of phenotypes and endotypes to classify disease, (3) defining disease modification, (4) disease management, and (5) implementation research. This report summarizes the workshop and produces recommendations to guide future research in asthma.

National Synchrotron Light Source annual report 1991. Volume 1, October 1, 1990--September 30, 1991

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

Hulbert, S.L.; Lazarz, N.M.

1992-04-01

This report discusses the following research conducted at NSLS: atomic and molecular science; energy dispersive diffraction; lithography, microscopy and tomography; nuclear physics; UV photoemission and surface science; x-ray absorption spectroscopy; x-ray scattering and crystallography; x-ray topography; workshop on surface structure; workshop on electronic and chemical phenomena at surfaces; workshop on imaging; UV FEL machine reviews; VUV machine operations; VUV beamline operations; VUV storage ring parameters; x-ray machine operations; x-ray beamline operations; x-ray storage ring parameters; superconducting x-ray lithography source; SXLS storage ring parameters; the accelerator test facility; proposed UV-FEL user facility at the NSLS; global orbit feedback systems; and NSLSmore » computer system.« less

The role of inflammation in age-related disease

PubMed Central

Howcroft, T. Kevin; Campisi, Judith; Louis, Germaine Buck; Smith, Martyn T.; Wise, Bradley; Wyss-Coray, Tony; Augustine, Alison Deckhut; McElhaney, Janet E.; Kohanski, Ron; Sierra, Felipe

2013-01-01

The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation in Age-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan. Four sessions explored the intrinsic, environmental exposures and immune pathways by which chronic inflammation are generated, sustained, and lead to age-associated diseases. At the conclusion of the workshop recommendations to accelerate progress toward understanding the mechanistic bases of chronic disease were identified. PMID:23474627

Future Research Directions in Asthma. An NHLBI Working Group Report

PubMed Central

Levy, Bruce D.; Freemer, Michelle M.; Cloutier, Michelle M.; Georas, Steve N.; Jarjour, Nizar N.; Ober, Carole; Woodruff, Prescott G.; Barnes, Kathleen C.; Bender, Bruce G.; Camargo, Carlos A.; Chupp, Geoff L.; Denlinger, Loren C.; Fahy, John V.; Fitzpatrick, Anne M.; Fuhlbrigge, Anne; Gaston, Ben M.; Hartert, Tina V.; Kolls, Jay K.; Lynch, Susan V.; Moore, Wendy C.; Morgan, Wayne J.; Nadeau, Kari C.; Ownby, Dennis R.; Solway, Julian; Szefler, Stanley J.; Wenzel, Sally E.; Wright, Rosalind J.; Smith, Robert A.; Erzurum, Serpil C.

2015-01-01

Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the NHLBI convened a group of extramural investigators for an Asthma Research Strategic Planning workshop on September 18–19, 2014, to accelerate discoveries and their translation to patients. The workshop focused on (1) in utero and early-life origins of asthma, (2) the use of phenotypes and endotypes to classify disease, (3) defining disease modification, (4) disease management, and (5) implementation research. This report summarizes the workshop and produces recommendations to guide future research in asthma. PMID:26305520

Proceedings of the 2016 Workshop on the Physics and Applications of High Brightness Beams

NASA Astrophysics Data System (ADS)

Cianchi, Alessandro; Ferrario, Massimo; Musumeci, Pietro; Rosenzweig, James

2017-09-01

We are proud to present the proceedings of the latest in the series of International Committee on Future Accelerators (ICFA)-endorsed workshops on the Physics and Applications of High Brightness Beams, which has been held at the Hotel Nacional in Havana, Cuba between March 28 and April 1, 2016. In total, 135 participants coming from 14 different countries attended this historic conference. In recognition of its pioneering role in the significant blossoming of relations between Cuba and the larger scientific community, this workshop also received the endorsement of UNESCO. The workshop organization was headed by co-chairs Massimo Ferrario (INFN-LNF) and James Rosenzweig (UCLA), with the essential and energetic contributions of local organizing committee chair Fidel Antonio Castro Smirnov (InSTEC, Havana). The workshop scientific agenda was developed under the care of program committee co-chairs Pietro Musumeci (UCLA) and Luca Serafini (INFN-Milano). The publication of the proceedings we present here was led by Alessandro Cianchi (Tor Vergata). Tangible contributions to the workshop infrastructure were received from UCLA, INFN-LNF, InSTEC, EuroNNAC2, and the US National Science Foundation. The workshop web site, which contains detailed information on the scientific agenda of the meeting, is found at https://conferences.pa.ucla.edu/hbb/.

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.

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.

Probing top-Z dipole moments at the LHC and ILC

DOE PAGES

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

GATA-3 function in innate and adaptive immunity.

PubMed

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.

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.

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

The Impulsive Lifestyle Counseling Program for Antisocial Behavior in Outpatient Substance Abuse Treatment.

PubMed

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.

Summary proceedings of a workshop on Bioremediation and its Societal Implications and Concerns (BASIC)

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

Drell, D.W.; Metting, F.B. Jr.; Wuy, L.D.

1996-11-01

This document summarizes the proceedings of a workshop on Bioremediation and Its Societal Implications and Concerns (BASIC) held July 18-19, 1996 at the Airlie Center near Warrenton, Virginia. The workshop was sponsored by the Office of Health and Environmental Research (OHER), U.S. Department of Energy (DOE), as part of its fundamental research program in Natural and Accelerated Bioremediation Research (NABIR). The information summarized in these proceedings represents the general conclusions of the workshop participants, and not the opinions of workshop organizers or sponsors. Neither are they consensus opinions, as opinions differed among participants on a number of points. The generalmore » conclusions presented below were reached through a review, synthesis, and condensation of notes taken by NABIR Program Office staff and OHER program managers throughout the workshop. Specific contributions by participants during breakout sessions are recorded in bullet form in the appropriate sections, without attribution to the contributors. These contributions were transcribed as faithfully as possible from notes about the original discussions. They were edited only to make them grammatically correct, parallel in structure, and understandable to someone not familiar with the NABIR Program or BASIC element.« less

Mammary-specific inactivation of E-cadherin and p53 impairs functional gland development and leads to pleomorphic invasive lobular carcinoma in mice.

PubMed

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.

Healthy Watersheds Integrated Assessments Workshop Synthesis

EPA Science Inventory

The U.S. Environmental Protection Agency, in partnership with others, is embarking on the new Healthy Watersheds Initiative to protect our remaining healthy watersheds, prevent them from becoming impaired, and accelerate our restoration successes. In November 2010, a Healthy Wate...

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.

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.

Complement and Immunoregulation in Tissue Injury

DTIC Science & Technology

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

Bibliography on Cold Regions Science and Technology. Volume 36, Part 1, 1982.

DTIC Science & Technology

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

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.

Experimental Measurements of the Secondary Electron Yield in the Experimental Measurement of the Secondary Electron Yield in the PEP-II Particle Accelerator Beam Line

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

Pivi, M.T.F.; Collet, G.; King, F.

Beam instability caused by the electron cloud has been observed in positron and proton storage rings and it is expected to be a limiting factor in the performance of the positron Damping Ring (DR) of future Linear Colliders (LC) such as ILC and CLIC. To test a series of promising possible electron cloud mitigation techniques as surface coatings and grooves, in the Positron Low Energy Ring (LER) of the PEP-II accelerator, we have installed several test vacuum chambers including (i) a special chamber to monitor the variation of the secondary electron yield of technical surface materials and coatings under themore » effect of ion, electron and photon conditioning in situ in the beam line; (ii) chambers with grooves in a straight magnetic-free section; and (iii) coated chambers in a dedicated newly installed 4-magnet chicane to study mitigations in a magnetic field region. In this paper, we describe the ongoing R&D effort to mitigate the electron cloud effect for the LC damping ring, focusing on the first experimental area and on results of the reduction of the secondary electron yield due to in situ conditioning.« less

Trajectory measurements and correlations in the final focus beam line at the KEK Accelerator Test Facility

NASA Astrophysics Data System (ADS)

Renier, Y.; Bambade, P.; Tauchi, T.; White, G. R.; Boogert, S.

2013-06-01

The Accelerator Test Facility 2 (ATF2) commissioning group aims to demonstrate the feasibility of the beam delivery system of the next linear colliders (ILC and CLIC) as well as to define and to test the tuning methods. As the design vertical beam sizes of the linear colliders are about few nanometers, the stability of the trajectory as well as the control of the aberrations are very critical. ATF2 commissioning started in December 2008, and thanks to submicron resolution beam position monitors (BPMs), it has been possible to measure the beam position fluctuation along the final focus of ATF2 during the 2009 runs. The optics was not the nominal one yet, with a lower focusing to make the tuning easier. In this paper, a method to measure the noise of each BPM every pulse, in a model-independent way, will be presented. A method to reconstruct the trajectory’s fluctuations is developed which uses the previously determined BPM resolution. As this reconstruction provides a measurement of the beam energy fluctuations, it was also possible to measure the horizontal and vertical dispersion function at each BPMs parasitically. The spatial and angular dispersions can be fitted from these measurements with uncertainties comparable with usual measurements.

Third user workshop on high-power lasers at the Linac Coherent Light Source

DOE PAGES

Bolme, Cynthia Anne; Glenzer, Sigfried; Fry, Alan

2016-03-24

On October 5–6, 2015, the third international user workshop focusing on high-power lasers at the Linac Coherent Light Source (LCLS) was held in Menlo Park, CA, USA [1 R. Falcone, S. Glenzer, and S. Hau-Riege, Synchrotron Radiation News 27(2), 56–58 (2014)., 2 P. Heimann and S. Glenzer, Synchrotron Radiation News 28(3), 54–56 (2015).]. Here, the workshop was co-organized by Los Alamos National Laboratory and SLAC National Accelerator Laboratory. More than 110 scientists attended from North America, Europe, and Asia to discuss high-energy-density (HED) science that is enabled by the unique combination of high-power lasers with the LCLS X-rays at themore » LCLS-Matter in Extreme Conditions (MEC) endstation.« less

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.

Measurement and Characterization of the Acceleration Environment on Board the Space Station

NASA Technical Reports Server (NTRS)

Baugher, Charles R. (Editor)

1990-01-01

This workshop provides a comprehensive overview of the work and status of each of these areas to provide a basis for establishing a systematic approach to the challenge of avoiding these difficulties during the Space Station era of materials experimentation. The discussions were arranged in the order of: the scientific understanding of the requirements for a micro-gravity environment, a history of acceleration measurements on spacecraft, the state of accelerometer technology, and the current understanding of the predicted Space Station environment.

Systems analysis of a low-acceleration research facility

NASA Technical Reports Server (NTRS)

Martin, Gary L.; Ferebee, Melvin J., Jr.; Wright, Robert L.

1988-01-01

The Low-Acceleration Research Facility (LARF), an unmanned free-flier that is boosted from low-earth orbit to a desired altitude using an orbital transfer vehicle is discussed. Design techniques used to minimize acceleration-causing disturbances and to create an ultra-quiet workshop are discussed, focusing on residual acceleration induced by the environment, the spacecraft and experiments. The selection and integration of critical subsystems, such as electrical power and thermal control, that enable the LARf to accomodate sub-microgravity levels for extended periods of time are presented, including a discussion of the Low-Acceleration Module, which will supply the payload with 25.0 kW of power, and up to 11.8 kW in the low-power mode. Also, the data management, communications, guidance, navigation and control, and structural features of supporting subsystems are examined.

Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells

PubMed Central

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

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.

Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells.

PubMed

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.

Dynamic balance between master transcription factors determines the fates and functions of CD4 T cell and innate lymphoid cell subsets

PubMed Central

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

Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion through Myeloid Cell Retinoic Acid Production.

PubMed

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.

Contributions to the mini-workshop on beam-beam compensation in the Tevatron

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

Shiltsev, V.

1998-02-01

The purpose of the Workshop was to assay the current understanding of compensation of the beam-beam effects in the Tevatron with use of low-energy high-current electron beam, relevant accelerator technology, along with other novel techniques of the compensation and previous attempts. About 30 scientists representing seven institutions from four countries--FNAL, SLAC, BNL, Novosibirsk, CERN, and Dubna were in attendance. Twenty one talks were presented. The event gave firm ground for wider collaboration on experimental test of the compensation at the Tevatron collider. This report consists of vugraphs of talks given at the meeting.

Catastrophic disruption of asteriods and satellites; Proceedings of the International Workshop, Pisa, Italy, July 30-August 2, 1985

NASA Astrophysics Data System (ADS)

Davis, D. R.; Farinella, P.; Paolicchi, P.; Zappala, V.

Theoretical, numerical, and experimental investigations of the violent disruption of asteroids or planetary satellites are discussed in reviews and reports. Topics examined include acceleration techniques and results of experiments simulating catastrophic fragmentation events; laboratory simulations of catastrophic impact; scaling laws for the catastrophic collisions of asteroids; asteroid collisional history, the origin of the Hirayama families, and disruption of small satellites; and the implications of the inferred compositions of a steroids for their collisional evolution. Diagrams, graphs, tables, and a summary of the discussion at the workshop are provided.

Catastrophic disruption of asteriods and satellites; Proceedings of the International Workshop, Pisa, Italy, July 30-August 2, 1985

NASA Technical Reports Server (NTRS)

Davis, D. R. (Editor); Farinella, P. (Editor); Paolicchi, P. (Editor); Zappala, V. (Editor)

1986-01-01

Theoretical, numerical, and experimental investigations of the violent disruption of asteroids or planetary satellites are discussed in reviews and reports. Topics examined include acceleration techniques and results of experiments simulating catastrophic fragmentation events; laboratory simulations of catastrophic impact; scaling laws for the catastrophic collisions of asteroids; asteroid collisional history, the origin of the Hirayama families, and disruption of small satellites; and the implications of the inferred compositions of a steroids for their collisional evolution. Diagrams, graphs, tables, and a summary of the discussion at the workshop are provided.

Reduced withdrawal and failure rates of accelerated nursing students enrolled in pharmacology is associated with a supportive intervention.

PubMed

Doggrell, Sheila Anne; Schaffer, Sally

2016-02-01

To reduce nursing shortages, accelerated nursing programs are available for domestic and international students. However, the withdrawal and failure rates from these programs may be different than for the traditional programs. The main aim of our study was to improve the retention and experience of accelerated nursing students. The academic background, age, withdrawal and failure rates of the accelerated and traditional students were determined. Data from 2009 and 2010 were collected prior to intervention. In an attempt to reduce the withdrawal of accelerated students, we set up an intervention, which was available to all students. The assessment of the intervention was a pre-post-test design with non-equivalent groups (the traditional and the accelerated students). The elements of the intervention were a) a formative website activity of some basic concepts in anatomy, physiology and pharmacology, b) a workshop addressing study skills and online resources, and c) resource lectures in anatomy/physiology and microbiology. The formative website and workshop was evaluated using questionnaires. The accelerated nursing students were five years older than the traditional students (p < 0.0001). The withdrawal rates from a pharmacology course are higher for accelerated nursing students, than for traditional students who have undertaken first year courses in anatomy and physiology (p = 0.04 in 2010). The withdrawing students were predominantly the domestic students with non-university qualifications or equivalent experience. The failure rates were also higher for this group, compared to the traditional students (p = 0.05 in 2009 and 0.03 in 2010). In contrast, the withdrawal rates for the international and domestic graduate accelerated students were very low. After the intervention, the withdrawal and failure rates in pharmacology for domestic accelerated students with non-university qualifications were not significantly different than those of traditional students. The accelerated international and domestic graduate nursing students have low withdrawal rates and high success rates in a pharmacology course. However, domestic students with non-university qualifications have higher withdrawal and failure rates than other nursing students and may be underprepared for university study in pharmacology in nursing programs. The introduction of an intervention was associated with reduced withdrawal and failure rates for these students in the pharmacology course.

PREFACE: Joint IPPP Durham/Cockcroft Institute/ICFA Workshop on Advanced QED methods for Future Accelerators

NASA Astrophysics Data System (ADS)

Bailey, I. R.; Barber, D. P.; Chattopadhyay, S.; Hartin, A.; Heinzl, T.; Hesselbach, S.; Moortgat-Pick, G. A.

2009-11-01

The joint IPPP Durham/Cockcroft Institute/ICFA workshop on advanced QED methods for future accelerators took place at the Cockcroft Institute in early March 2009. The motivation for the workshop was the need for a detailed consideration of the physics processes associated with beam-beam effects at the interaction points of future high-energy electron-positron colliders. There is a broad consensus within the particle physics community that the next international facility for experimental high-energy physics research beyond the Large Hadron Collider at CERN should be a high-luminosity electron-positron collider working at the TeV energy scale. One important feature of such a collider will be its ability to deliver polarised beams to the interaction point and to provide accurate measurements of the polarisation state during physics collisions. The physics collisions take place in very dense charge bunches in the presence of extremely strong electromagnetic fields of field strength of order of the Schwinger critical field strength of 4.4×1013 Gauss. These intense fields lead to depolarisation processes which need to be thoroughly understood in order to reduce uncertainty in the polarisation state at collision. To that end, this workshop reviewed the formalisms for describing radiative processes and the methods of calculation in the future strong-field environments. These calculations are based on the Furry picture of organising the interaction term of the Lagrangian. The means of deriving the transition probability of the most important of the beam-beam processes - Beamsstrahlung - was reviewed. The workshop was honoured by the presentations of one of the founders, V N Baier, of the 'Operator method' - one means for performing these calculations. Other theoretical methods of performing calculations in the Furry picture, namely those due to A I Nikishov, V I Ritus et al, were reviewed and intense field quantum processes in fields of different form - namely those present in intense lasers - were also presented. Within the Furry picture the lowest order physics processes are represented by one vertex Feynman diagrams. Additionally, higher order processes in the Furry picture are thought to be important and are still not fully studied. The Advanced QED methods workshop also benefited greatly from reports on ongoing and planned experimental work on quantum processes in intense external fields. Some of the experiments reviewed were the NA43 and NA63 experiments using the inter atomic fields in aligned crystals at CERN. In the past, evidence has been obtained from successful experiments using an intense laser at the SLAC experiment E144. The possibility now exists for new experiments with intense laser light with the planned XFEL at DESY and the European Extreme Light Infrastructure. For upcoming accelerator projects, computer simulations of the first order processes in the Furry Picture during the bunch-bunch collision are being performed using the programs CAIN and Guinea-Pig++. The implementation of spin dynamics in these simulation programs was reported on at the workshop. This relatively small workshop generated a very productive intermix of theoretical, experimental and computational developments covering this important field of physics. Fruitful discussions took place covering improvements to the models, estimations of the remaining theoretical uncertainties and future updates to the existing simulations. It was felt that ongoing workshops in the same field would be of benefit to all those involved. The organisers would like to express their sincere thanks to all of the attendees for their contributions, to the staff of the Cockcroft Institute for hosting the workshop, to the IPPP at Durham for providing substantial funding and administrative support, and to ICFA for their sponsorship. We would also like to thank IOP Publishing for their assistance in publishing our proceedings in the Journal of Physics: Conference Series.

High-Power Testing of 11.424-GHz Dielectric-Loaded Accelerating Structures

NASA Astrophysics Data System (ADS)

Gold, Steven; Gai, Wei

2001-10-01

Argonne National Laboratory has previously described the design, construction, and bench testing of an X-band traveling-wave accelerating structure loaded with a permittivity=20 dielectric (P. Zou et al., Rev. Sci. Instrum. 71, 2301, 2000.). We describe a new program to build a test accelerator using this structure. The accelerator will be powered by the high-power 11.424-GHz radiation from the magnicon facility at the Naval Research Laboratory ( O.A. Nezhevenko et al., Proc. PAC 2001, in press). The magnicon is expected to provide up to 30 MW from each of two WR-90 output waveguide arms in pulses of up to 1 microsecond duration, permitting tests up to a gradient of 40 MV/m. Still higher power pulses (100-500 MW) may be available at the output of an active pulse compressor driven by the magnicon ( A.L. Vikharev et al., Proc. 9th Workshop on Advanced Accelerator Concepts.).

Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial.

PubMed

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.

Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial

PubMed Central

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

NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration.

PubMed

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.

Inverse relationship between body mass index and coronary artery calcification in patients with clinically significant coronary lesions.

PubMed

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.

High frequency of coexistence of columnar cell lesions, lobular neoplasia, and low grade ductal carcinoma in situ with invasive tubular carcinoma and invasive lobular carcinoma.

PubMed

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.

CARE activities on superconducting RF cavities at INFN Milano

NASA Astrophysics Data System (ADS)

Bosotti, A.; Pierini, P.; Michelato, P.; Pagani, C.; Paparella, R.; Panzeri, N.; Monaco, L.; Paulon, R.; Novati, M.

2005-09-01

The SC RF group at INFN Milano-LASA is involved both in the TESLA/TTF collaboration and in the research and design activity on superconducting cavities for proton accelerators. Among these activities, some are supported by the European community within the CARE project. In the framework of the JRASRF collaboration we are developing a coaxial blade tuner for ILC (International Linear Collider) cavities, integrated with piezoelectric actuators for the compensation of the Lorenz force detuning and microphonics perturbation. Another activity, regarding the improved component design on SC technology, based on the information retrieving about the status of art on ancillaries and experience of various laboratories involved in SCRF, has started in our laboratory. Finally, in the framework of the HIPPI collaboration, we are testing two low beta superconducting cavities, built for the Italian TRASCO project, to verify the possibility to use them for pulsed operation. All these activities will be described here, together with the main results and the future perspectives.

Cavity Processing and Preparation of 650 MHz Elliptical Cell Cavities for PIP-II

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

Rowe, Allan; Chandrasekaran, Saravan Kumar; Grassellino, Anna

The PIP-II project at Fermilab requires fifteen 650 MHz SRF cryomodules as part of the 800 MeV LINAC that will provide a high intensity proton beam to the Fermilab neutrino program. A total of fifty-seven high-performance SRF cavities will populate the cryomodules and will operate in both pulsed and continuous wave modes. These cavities will be processed and prepared for performance testing utilizing adapted cavity processing infrastructure already in place at Fermilab and Argonne. The processing recipes implemented for these structures will incorporate state-of-the art processing and cleaning techniques developed for 1.3 GHz SRF cavities for the ILC, XFEL, andmore » LCLS-II projects. This paper describes the details of the processing recipes and associated chemistry, heat treatment, and cleanroom processes at the Fermilab and Argonne cavity processing facilities. This paper also presents single and multi-cell cavity test results with quality factors above 5·10¹⁰ and accelerating gradients above 30 MV/m.« less

Characterization of the International Linear Collider damping ring optics

NASA Astrophysics Data System (ADS)

Shanks, J.; Rubin, D. L.; Sagan, D.

2014-10-01

A method is presented for characterizing the emittance dilution and dynamic aperture for an arbitrary closed lattice that includes guide field magnet errors, multipole errors and misalignments. This method, developed and tested at the Cornell Electron Storage Ring Test Accelerator (CesrTA), has been applied to the damping ring lattice for the International Linear Collider (ILC). The effectiveness of beam based emittance tuning is limited by beam position monitor (BPM) measurement errors, number of corrector magnets and their placement, and correction algorithm. The specifications for damping ring magnet alignment, multipole errors, number of BPMs, and precision in BPM measurements are shown to be consistent with the required emittances and dynamic aperture. The methodology is then used to determine the minimum number of position monitors that is required to achieve the emittance targets, and how that minimum depends on the location of the BPMs. Similarly, the maximum tolerable multipole errors are evaluated. Finally, the robustness of each BPM configuration with respect to random failures is explored.

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.

Latest R&D news and beam test performance of the highly granular SiW-ECAL technological prototype for the ILC

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.

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.

ID’ing Innate and Innate-like Lymphoid Cells

PubMed Central

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

ID'ing innate and innate-like lymphoid cells.

PubMed

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.

IL-33: biological properties, functions, and roles in airway disease.

PubMed

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.

Quality of Life as reported by school children and their parents: a cross-sectional survey

PubMed Central

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

A Summary of the NASA Fusion Propulsion Workshop 2000

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Turchi, Peter J.; Santarius, John F.; Schafer, Charles (Technical Monitor)

2001-01-01

A NASA Fusion Propulsion Workshop was held on Nov. 8 and 9, 2000 at Marshall Space Flight Center (MSFC) in Huntsville, Alabama. A total of 43 papers were presented at the Workshop orally or by posters, covering a broad spectrum of issues related to applying fusion to propulsion. The status of fusion research was reported at the Workshop showing the outstanding scientific research that has been accomplished worldwide in the fusion energy research program. The international fusion research community has demonstrated the scientific principles of fusion creating plasmas with conditions for fusion burn with a gain of order unity: 0.25 in Princeton TFTR, 0.65 in the Joint European Torus, and a Q-equivalent of 1.25 in Japan's JT-60. This research has developed an impressive range of physics and technological capabilities that may be applied effectively to the research of possibly new propulsion-oriented fusion schemes. The pertinent physics capabilities include the plasma computational tools, the experimental plasma facilities, the diagnostics techniques, and the theoretical understanding. The enabling technologies include the various plasma heating, acceleration, and the pulsed power technologies.

Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells.

PubMed

Jovanovic, Ivan P; Pejnovic, Nada N; Radosavljevic, Gordana D; Pantic, Jelena M; Milovanovic, Marija Z; Arsenijevic, Nebojsa N; Lukic, Miodrag L

2014-04-01

The role of IL-33/ST2 pathway in antitumor immunity is unclear. Using 4T1 breast cancer model we demonstrate time-dependent increase of endogenous IL-33 at both the mRNA and protein levels in primary tumors and metastatic lungs during cancer progression. Administration of IL-33 accelerated tumor growth and development of lung and liver metastases, which was associated with increased intratumoral accumulation of CD11b(+) Gr-1(+) TGF-β1(+) myeloid-derived suppressor cells (MDSCs) that expressed IL-13α1R, IL-13-producing Lin(-) Sca-1(+) ST2(+) innate lymphoid cells (ILCs) and CD4(+) Foxp3(+) ST2(+) IL-10(+) Tregs compared to untreated mice. Higher incidence of monocytic vs. granulocytic MDSCs and plasmocytoid vs. conventional dendritic cells (DCs) was present in mammary tumors of IL-33-treated mice. Intratumoral NKp46(+) NKG2D(+) and NKp46(+) FasL(+) cells were markedly reduced after IL-33 treatment, while phosphate-buffered saline-treated ST2-deficient mice had increased frequencies of these tumoricidal natural killer (NK) cells compared to untreated wild-type mice. IL-33 promoted intratumoral cell proliferation and neovascularization, which was attenuated in the absence of ST2. Tumor-bearing mice given IL-33 had increased percentages of splenic MDSCs, Lin(-) Sca-1(+) ILCs, IL-10-expressing CD11c(+) DCs and alternatively activated M2 macrophages and higher circulating levels of IL-10 and IL-13. A significantly reduced NK cell, but not CD8(+) T-cell cytotoxicity in IL-33-treated mice was observed and the mammary tumor progression was not affected when CD8(+) T cells were in vivo depleted. We show a previously unrecognized role for IL-33 in promoting breast cancer progression through increased intratumoral accumulation of immunosuppressive cells and by diminishing innate antitumor immunity. Therefore, IL-33 may be considered as an important mediator in the regulation of breast cancer progression. © 2013 UICC.

Assessing the response of the Gulf Coast to global change

NASA Astrophysics Data System (ADS)

Anderson, John B.; Törnqvist, Torbjörn E.; Day, John

2012-11-01

Gulf Coastal Science Consortium Workshop;Houston, Texas, 28-29 June 2012 The newly formed Gulf Coastal Science Consortium held its first workshop at Rice University. The creation of the consortium was prompted by two recent incidents. One incident involved censorship of a book chapter on Galveston Bay by the Texas Commission on Environmental Quality that omitted all references to climate change and accelerated sea-level rise. The other incident was the adoption of legislation in North Carolina that requires planners and developers to assume a linear sea-level rise projection, despite compelling scientific evidence for a multifold increase in sea-level rise in historical time.

Remediation of Groundwater Contaminated by Nuclear Waste

NASA Astrophysics Data System (ADS)

Parker, Jack; Palumbo, Anthony

2008-07-01

A Workshop on Accelerating Development of Practical Field-Scale Bioremediation Models; An Online Meeting, 23 January to 20 February 2008; A Web-based workshop sponsored by the U.S. Department of Energy Environmental Remediation Sciences Program (DOE/ERSP) was organized in early 2008 to assess the state of the science and knowledge gaps associated with the use of computer models to facilitate remediation of groundwater contaminated by wastes from Cold War era nuclear weapons development and production. Microbially mediated biological reactions offer a potentially efficient means to treat these sites, but considerable uncertainty exists in the coupled biological, chemical, and physical processes and their mathematical representation.

Summary of the 2014 Beam-Halo Monitoring Workshop

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

Fisher, Alan

2015-09-25

Understanding and controlling beam halo is important for high-intensity hadron accelerators, for high-brightness electron linacs, and for low-emittance light sources. This can only be achieved by developing suitable diagnostics. The main challenge faced by such instrumentation is the high dynamic range needed to observe the halo in the presence of an intense core. In addition, measurements must often be made non-invasively. This talk summarizes the one-day workshop on Beam-Halo Monitoring that was held at SLAC on September 19 last year, immediately following IBIC 2014 in Monterey. Workshop presentations described invasive techniques using wires, screens, or crystal collimators, and non-invasive measurementsmore » with gas or scattered electrons. Talks on optical methods showed the close links between observing halo and astronomical problems like observing the solar corona or directly observing a planet orbiting another star.« less

Burkitt lymphoma research in East Africa: highlights from the 9th African organization for research and training in cancer conference held in Durban, South Africa in 2013

PubMed Central

2014-01-01

A one-day workshop on Burkitt lymphoma (BL) was held at the 9th African Organization for Research and Training in Cancer (AORTIC) conference in 2013 in Durban, South Africa. The workshop featured 15 plenary talks by delegates representing 13 institutions that either fund or implement research on BL targeting AORTIC delegates primarily interested in pediatric oncology. The main outcomes of the meeting were improved sharing of knowledge and experience about ongoing epidemiologic BL research, BL treatment in different settings, the role of cancer registries in cancer research, and opportunities for African scientists to publish in scientific journals. The idea of forming a consortium of BL to improve coordination, information sharing, accelerate discovery, dissemination, and translation of knowledge and to build capacity, while reducing redundant efforts was discussed. Here, we summarize the presentations and discussions from the workshop. PMID:25686906

It may be possible to use Microscopic Black Holes as a Propulsion Beam

NASA Astrophysics Data System (ADS)

Kriske, Richard

2017-04-01

Several years ago during the commissioning of the LHC, the question as to whether a miniature Black Hole would be formed, and what to do with it if it was, came up as a legitimate topic of discussion. It was calculated at that time that although it was possible, the possibility was extremely small, and it would evaporate quickly, and would be safely ejected into space, as its mass would be so great as to simply continue along its inertial path, out the end of the circular LHC accelerator. New improvements to the LHC are the increase in energy to about 15 TEV. Linear accelerators, such as the ILC, claim to be able to produce much higher TEV, as they collide electrons and positrons, as opposed to Protons, as does the LHC. This author has heard incredible numbers, such as 250 TEV, with a beam current of 1 Amp. With this incredible increase in Energy and Current, one could turn the Black Hole investigation around, and try to determine how one could produce a steady stream of Microscopic Black Holes. A Black Hole machine. When the Black Holes evaporate do they expand, space in space time. Would the old theory of expanding space behind a craft warp space, and enable the craft to exceed the speed of light. The warp theory was proposed before Star Trek, is it now feasible to prove?

Beam dynamic simulations of the CLIC crab cavity and implications on the BDS

NASA Astrophysics Data System (ADS)

Shinton, I. R. R.; Burt, G.; Glasman, C. J.; Jones, R. M.; Wolski, A.

2011-11-01

The Compact Linear Collider (CLIC) is a proposed electron positron linear collider design aiming to achieve a centre of mass energy of up to 3 TeV. The main accelerating structures in CLIC operate at an X-band frequency of 11.994 GHz with an accelerating gradient of 100 MV/m. The present design requires the beams to collide at a small crossing angle of 10 mrad per line giving a resultant overall crossing angle of 20 mrad. Transverse deflecting cavities, referred to as "Crab cavities", are installed in the beam delivery system (BDS) of linear collider designs in order to ensure the final luminosity at the interaction point (IP) is comparable to that in a head on collision. We utilise the beam tracking code PLACET combined with the beam-beam code GUINEA-PIG to calculate the resulting luminosity at the IP. We follow a similar tuning procedure to that used for the design of the ILC crab cavities and anitcrab cavities. However an unexpected loss in luminosity of 10% was observed for the 20 mrad design was observed. It was discovered that the action of the crab cavities can affect the geometric aberrations resulting from the sextupoles used to correct chromatic effects in the beam delivery system. This has direct consequences regarding the design of the present CLIC BDS.

PREFACE: XIII International Workshop on Neutrino Factories, Super beams and Beta beams (NUFACT11)

NASA Astrophysics Data System (ADS)

Blondel, Alain; Efthymiopoulos, Ilias; Prior, Gersende

2013-02-01

These proceedings present the written contributions from participants of the International Workshop on Neutrino Factories, Superbeams and Betabeams (NuFact11), which was held in Geneva, Switzerland, on 1-6 August 2011. This was the 13th of the series of NuFact annual meetings, which started in 1999. The six-day scientific programme of NuFact11 consisted of 42 plenary and 111 parallel talks and various poster sessions, with the participation of 191 researchers from 19 countries. In addition the International Neutrino Summer School 2011 was held in the two weeks preceding the workshop. It was intended for young scientists starting their research in neutrino physics in such a way that they would be able to participate and contribute to the workshop. The objective of the NuFact workshops is to build up, time after time, the scientific knowledge on accelerator facilities aimed at the study of neutrino oscillation. The organization of the workshop is tailored to ensure continuity and growth of knowledge: working group conveners have a mandate of three consecutive meetings and maintain an updated list of questions. In order to emphasize further the 'work' (by opposition to 'shop') part of the meeting, we organized a 'round table discussion' at the beginning of the workshop, in which the invitees were asked not only to provide their answers to a preset list of questions, but to propose their own questions to the participants. This was quite successful and we have compiled the answers in this book. Topics addressed at NuFact included neutrino oscillation physics, neutrino cross-sections and detectors, accelerator physics, muon physics and high-intensity applications of muons beams. This variety of subjects is reflected in these proceedings. The editors hope to provide more than enjoyable and fruitful reading for those interested in neutrino physics, a stepping stone along the path to always more insightful research on these mysterious neutrinos, which certainly contain the solution to several essential questions. It is a pleasure to thank CERN, University of Geneva, the Swiss Institute for Particle Physics (CHIPP) and the European FP7 mandate EuCARD that sponsored the meeting and the Summer School. The Editors wish to thank the Scientific Program Committee and the Working group conveners for their engagement in making NUFACT11 a success, and all participants for the high quality of their contributions. The Local organizing committee members worked beyond the call of duty to ensure a great and lively working atmosphere during the meeting. The Editors: Alain Blondel, Ilias Efthymiopoulos and Gersende Prior

Workshop on Probing Frontiers in Matter with Neutron Scattering, Wrap-up Session Chaired by John C. Browne on December 14, 1997, at Fuller Lodge, Los Alamos, New Mexico

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

Mezei, F.; Thompson, J.

1998-12-01

The Workshop on Probing Frontiers in Matter with Neutron Scattering consisted of a series of lectures and discussions about recent highlights in neutron scattering. In this report, we present the transcript of the concluding discussion session (wrap-up session) chaired by John C. Browne, Director of Los Alamos National Laboratory. The workshop had covered a spectrum of topics ranging from high T{sub c} superconductivity to polymer science, from glasses to molecular biology, a broad review aimed at identifying trends and future needs in condensed matter research. The focus of the wrap-up session was to summarize the workshop participants' views on developmentsmore » to come. Most of the highlights presented during the workshop were the result of experiments performed at the leading reactor-based neutron scattering facilities. However, recent advances with very high power accelerators open up opportunities to develop new approaches to spallation technique that could decisively advance neutron scattering research in areas for which reactor sources are today by far the best choice. The powerful combination of neutron scattering and increasingly accurate computer modeling emerged as another area of opportunity for research in the coming decades.« less

Trichoscopy of Steroid-Induced Atrophy.

PubMed

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.

Corrosion on Fatigue and Fatigue Crack Growth in Aircraft Structural Materials

DTIC Science & Technology

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

Proceedings of RIKEN BNL Research Center workwhop on RHIC spin

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

SOFFER,J.

1999-10-06

This RHIC Spin Workshop is the 1999 annual meeting of the RHIC Spin Collaboration, and the second to be hosted at Brookhaven and sponsored by the RIKEN BNL Research Center. The previous meetings were at Brookhaven (1998), Marseille (1996), MIT in 1995, Argonne 1994, Tucson in 1991, and the Polarized Collider Workshop at Penn State in 1990. As noted last year, the Center provides a home for combined work on spin by theorists, experimenters, and accelerator physicists. This proceedings, as last year, is a compilation of 1 page summaries and 5 selected transparencies for each speaker. It is designed tomore » be available soon after the workshop is completed. Speakers are welcome to include web or other references for additional material. The RHIC spin program and RHIC are rapidly becoming reality. RHIC has completed its first commissioning run, as described here by Steve Peggs. The first Siberian Snake for spin has been completed and is being installed in RHIC. A new polarized source from KEK and Triumf with over 1 milliampere of polarized H{sup minus} is being installed, described by Anatoli Zelenski. They have had a successful test of a new polarimeter for RHIC, described by Kazu Kurita and Haixin Huang. Spin commissioning is expected next spring (2000), and the first physics run for spin is anticipated for spring 2001. The purpose of the workshop is to get everyone together about once per year and discuss goals of the spin program, progress, problems, and new ideas. They also have many separate regular forums on spin. There are spin discussion sessions every Tuesday, now organized by Naohito Saito and Werner Vogelsang. The spin discussion schedule and copies of presentations are posted on http://riksg01.rhic.bnl.gov/rsc. Speakers and other spinners are encouraged to come to BNL and to lead a discussion on your favorite idea. They also have regular polarimeter and snake meetings on alternate Thursdays, led by Bill McGahern, the lead engineer for the accelerator spin effort (Thomas Roser is the spokesperson). Waldo Mackay, the Project Manager for spin, leads a weekly accelerator meeting on spin issues on Wednesdays. Finally, Phenix, STAR, and the pp2pp Collaboration have regular collaboration meetings including spin, and spin working groups.« less

PREFACE: Acceleration and radiation generation in space and laboratory plasmas

NASA Astrophysics Data System (ADS)

Bingham, R.; Katsouleas, T.; Dawson, J. M.; Stenflo, L.

1994-01-01

Sixty-six leading researchers from ten nations gathered in the Homeric village of Kardamyli, on the southern coast of mainland Greece, from August 29-September 4, 1993 for the International Workshop on Acceleration and Radiation Generation in Space and Laboratory Plasmas. This Special Issue represents a cross-section of the presentations made at and the research stimulated by that meeting. According to the Iliad, King Agamemnon used Kardamyli as a dowry offering in order to draw a sulking Achilles into the Trojan War. 3000 years later, Kardamyli is no less seductive. Its remoteness and tranquility made it an ideal venue for promoting the free exchange of ideas between various disciplines that do not normally interact. Through invited presen tations, informal poster discussions and working group sessions, the Workshop brought together leaders from the laboratory and space/astrophysics communities working on common problems of acceleration and radiation generation in plasmas. It was clear from the presentation and discussion sessions that there is a great deal of common ground between these disciplines which is not at first obvious due to the differing terminologies and types of observations available to each community. All of the papers in this Special Issue highlight the role collective plasma processes play in accelerating particles or generating radiation. Some are state-of-the-art presentations of the latest research in a single discipline, while others investi gate the applicability of known laboratory mechanisms to explain observations in natural plasmas. Notable among the latter are the papers by Marshall et al. on kHz radiation in the magnetosphere ; Barletta et al. on collective acceleration in solar flares; and by Dendy et al. on ion cyclotron emission. The papers in this Issue are organized as follows: In Section 1 are four general papers by Dawson, Galeev, Bingham et al. and Mon which serves as an introduction to the physical mechanisms of acceleration and radiation generation in plasmas. The next section includes state-of-the-art papers on laboratory accelerators driven by lasers (Nakajima et al., Shukla, Johnson et al.), microwaves (Nishida et al., Bogomolov et al.) and by particle beams (Ogata et al.). Also in this section are theoretical papers presenting new work on synchrotron like oscillations in plasma waves (Fedele) and two types of laboratory radiation sources, FEL's (Marshall et al.) and ionization fronts (Lai et al.), and Frantzeskakis et al. described the Hamiltonian analysis of a slow-wave autonomous cyclotron buncher. Section 3 contains papers on astrophysical plasmas, with the general presentations of Colgate and Krishnan. Kazanas and Krishnan address active galactic nuclei (AGNs). Thielheim discusses general acceleration mech anisms in rotating magnetized systems. Asseo discussed Langmuir solitons in pulsars and Blackman et al. treat magnetic reconnection relativistically. Su et al. analyze the possibility of plasma wave excitation and particle acceleration by neu trinos from supernovae. Dogiel et al. on cosmic ray scattering by MHD fluctuations. The papers in Section 4 treat fusion plasmas (Dendy et al. and Lashmore-Davies et al.). Section 5, space plasmas, includes papers on acceleration processes in the magnetosphere (Anagnostopoulos and Marshall et al.) and the sun (Barletta et al.). It is evident from the Workshop and the papers collected here that this is indeed a rich field of investigations and that both the natural and laboratory plasma communities can benefit from the cross-fertilization of ideas between them. We wish to thank the authors and attendees for their contributions to the success of this workshop, Dr Philip Debenham and Dr David Sutter of the U.S. D.o.E. and Dr Charles Roberson of the U.S. O.N.R. for their financial support (Grants DE-FGO3-93ER40776 and N00014-93-1-0814), and the ECC Twinning Grant SC1*-CT92-0773. We appreciate the considerable local support from Mr Glegles and his staff at the Agricultural Bank of Greece. We thank Mr V. Tataronis, mayor of Kardamyli, and members of the Kardamyli organizing committee and the community for their incredible hospitality. The excellent work of the Conference Secretaries, Ms Shirin Mistry and Mrs Sheila Shield is gratefully acknowledged. Finally, a special thank you goes to Mr S. C. Katsouleas who is so much more than our local organizing chairman.

HPV16-E7 Expression in skin induces TSLP secretion, type 2 ILC infiltration and atopic dermatitis-like lesions

PubMed Central

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

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.

Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells.

PubMed

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.

Construction and performance of a silicon photomultiplier/extruded scintillator tail-catcher and muon-tracker

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.

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.

Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity.

PubMed

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.

T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production

PubMed Central

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

IL-33-mediated protection against experimental cerebral malaria is linked to induction of type 2 innate lymphoid cells, M2 macrophages and regulatory T cells.

PubMed

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.

IL-33-Mediated Protection against Experimental Cerebral Malaria Is Linked to Induction of Type 2 Innate Lymphoid Cells, M2 Macrophages and Regulatory T Cells

PubMed Central

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

Bronchopulmonary Dysplasia: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

PubMed Central

McEvoy, Cindy T.; Jain, Lucky; Schmidt, Barbara; Abman, Steven; Bancalari, Eduardo

2014-01-01

Bronchopulmonary dysplasia (BPD) is the most common complication of extreme preterm birth. Infants who develop BPD manifest aberrant or arrested pulmonary development and can experience lifelong alterations in cardiopulmonary function. Despite decades of promising research, primary prevention of BPD has proven elusive. This workshop report identifies current barriers to the conduct of primary prevention studies for BPD and causal pathways implicated in BPD pathogenesis. Throughout, we highlight promising areas for research to improve understanding of normal and aberrant lung development, distinguish BPD endotypes, and ascertain biomarkers for more targeted therapeutic approaches to prevention. We conclude with research recommendations and priorities to accelerate discovery and promote lung health in infants born preterm. PMID:24754823

Preface to the Focus Issue: chaos detection methods and predictability.

PubMed

Gottwald, Georg A; Skokos, Charalampos

2014-06-01

This Focus Issue presents a collection of papers originating from the workshop Methods of Chaos Detection and Predictability: Theory and Applications held at the Max Planck Institute for the Physics of Complex Systems in Dresden, June 17-21, 2013. The main aim of this interdisciplinary workshop was to review comprehensively the theory and numerical implementation of the existing methods of chaos detection and predictability, as well as to report recent applications of these techniques to different scientific fields. The collection of twelve papers in this Focus Issue represents the wide range of applications, spanning mathematics, physics, astronomy, particle accelerator physics, meteorology and medical research. This Preface surveys the papers of this Issue.

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

Bolme, Cynthia Anne; Glenzer, Sigfried; Fry, Alan

On October 5–6, 2015, the third international user workshop focusing on high-power lasers at the Linac Coherent Light Source (LCLS) was held in Menlo Park, CA, USA [1 R. Falcone, S. Glenzer, and S. Hau-Riege, Synchrotron Radiation News 27(2), 56–58 (2014)., 2 P. Heimann and S. Glenzer, Synchrotron Radiation News 28(3), 54–56 (2015).]. Here, the workshop was co-organized by Los Alamos National Laboratory and SLAC National Accelerator Laboratory. More than 110 scientists attended from North America, Europe, and Asia to discuss high-energy-density (HED) science that is enabled by the unique combination of high-power lasers with the LCLS X-rays at themore » LCLS-Matter in Extreme Conditions (MEC) endstation.« less

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

Interlaboratory comparison for the measurement of particle size and zeta potential of silica nanoparticles in an aqueous suspension

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.

Selective magnetic resonance imaging (MRI) in invasive lobular breast cancer based on mammographic density: does it lead to an appropriate change in surgical treatment?

PubMed

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.

Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis.

PubMed

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.

A Preliminary Evaluation of a Short Online Training Workshop for TPACK Development

ERIC Educational Resources Information Center

Alsofyani, Mohammed Modeef; bin Aris, Baharuddin; Eynon, Rebecca

2013-01-01

National plans in higher education institutions are being developed in various aspects of the academic world for technology integration. Short online training has the potential for accelerating and facilitating the implementation of those plans. So far, a little is known about the suitability of this mode of training for faculty members'…

Fermilab Today

Science.gov Websites

Workshop at LPC 2014 - One West 2 p.m. Particle Astrophysics Seminar (NOTE LOCATION) - WH6NW Speaker: Chris at LPC 2014 - One West 3:30 p.m. Director's Coffee Break - WH2XO 4 p.m. Accelerator Physics and . Magnetrons don't normally allow this kind of control. One solution, Chase realized, is to apply a well-known

Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report

PubMed Central

Blackwell, Timothy S.; Tager, Andrew M.; Borok, Zea; Moore, Bethany B.; Schwartz, David A.; Anstrom, Kevin J.; Bar-Joseph, Ziv; Bitterman, Peter; Blackburn, Michael R.; Bradford, William; Brown, Kevin K.; Chapman, Harold A.; Collard, Harold R.; Cosgrove, Gregory P.; Deterding, Robin; Doyle, Ramona; Flaherty, Kevin R.; Garcia, Christine Kim; Hagood, James S.; Henke, Craig A.; Herzog, Erica; Hogaboam, Cory M.; Horowitz, Jeffrey C.; King, Talmadge E.; Loyd, James E.; Lawson, William E.; Marsh, Clay B.; Noble, Paul W.; Noth, Imre; Sheppard, Dean; Olsson, Julie; Ortiz, Luis A.; O’Riordan, Thomas G.; Oury, Tim D.; Raghu, Ganesh; Roman, Jesse; Sime, Patricia J.; Sisson, Thomas H.; Tschumperlin, Daniel; Violette, Shelia M.; Weaver, Timothy E.; Wells, Rebecca G.; White, Eric S.; Kaminski, Naftali; Martinez, Fernando J.; Wynn, Thomas A.; Thannickal, Victor J.

2014-01-01

The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U.S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI. PMID:24160862

Research and Teaching About the Deep Earth

NASA Astrophysics Data System (ADS)

Williams, Michael L.; Mogk, David W.; McDaris, John

2010-08-01

Understanding the Deep Earth: Slabs, Drips, Plumes and More; Virtual Workshop, 17-19 February and 24-26 February 2010; Images and models of active faults, subducting plates, mantle drips, and rising plumes are spurring new excitement about deep-Earth processes and connections between Earth's internal systems and plate tectonics. The new results and the steady progress of Earthscope's USArray across the country are also providing a special opportunity to reach students and the general public. The pace of discoveries about the deep Earth is accelerating due to advances in experimental, modeling, and sensing technologies; new data processing capabilities; and installation of new networks, especially the EarthScope facility. EarthScope is an interdisciplinary program that combines geology and geophysics to study the structure and evolution of the North American continent. To explore the current state of deep-Earth science and ways in which it can be brought into the undergraduate classroom, 40 professors attended a virtual workshop given by On the Cutting Edge, a program that strives to improve undergraduate geoscience education through an integrated cooperative series of workshops and Web-based resources. The 6-day two-part workshop consisted of plenary talks, large and small group discussions, and development and review of new classroom and laboratory activities.

Future directions in idiopathic pulmonary fibrosis research. An NHLBI workshop report.

PubMed

Blackwell, Timothy S; Tager, Andrew M; Borok, Zea; Moore, Bethany B; Schwartz, David A; Anstrom, Kevin J; Bar-Joseph, Ziv; Bitterman, Peter; Blackburn, Michael R; Bradford, William; Brown, Kevin K; Chapman, Harold A; Collard, Harold R; Cosgrove, Gregory P; Deterding, Robin; Doyle, Ramona; Flaherty, Kevin R; Garcia, Christine Kim; Hagood, James S; Henke, Craig A; Herzog, Erica; Hogaboam, Cory M; Horowitz, Jeffrey C; King, Talmadge E; Loyd, James E; Lawson, William E; Marsh, Clay B; Noble, Paul W; Noth, Imre; Sheppard, Dean; Olsson, Julie; Ortiz, Luis A; O'Riordan, Thomas G; Oury, Tim D; Raghu, Ganesh; Roman, Jesse; Sime, Patricia J; Sisson, Thomas H; Tschumperlin, Daniel; Violette, Shelia M; Weaver, Timothy E; Wells, Rebecca G; White, Eric S; Kaminski, Naftali; Martinez, Fernando J; Wynn, Thomas A; Thannickal, Victor J; Eu, Jerry P

2014-01-15

The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U.S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI.

Proceedings of the Oak Ridge Electron Linear Accelerator (ORELA) Workshop

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

Dunn, M.E.

2006-02-27

The Oak Ridge National Laboratory (ORNL) organized a workshop at ORNL July 14-15, 2005, to highlight the unique measurement capabilities of the Oak Ridge Electron Linear Accelerator (ORELA) facility and to emphasize the important role of ORELA for performing differential cross-section measurements in the low-energy resonance region that is important for nuclear applications such as nuclear criticality safety, nuclear reactor and fuel cycle analysis, stockpile stewardship, weapons research, medical diagnosis, and nuclear astrophysics. The ORELA workshop (hereafter referred to as the Workshop) provided the opportunity to exchange ideas and information pertaining to nuclear cross-section measurements and their importance for nuclearmore » applications from a variety of perspectives throughout the U.S. Department of Energy (DOE). Approximately 50 people, representing DOE, universities, and seven U.S. national laboratories, attended the Workshop. The objective of the Workshop was to emphasize the technical community endorsement for ORELA in meeting nuclear data challenges in the years to come. The Workshop further emphasized the need for a better understanding of the gaps in basic differential nuclear measurements and identified the efforts needed to return ORELA to a reliable functional measurement facility. To accomplish the Workshop objective, nuclear data experts from national laboratories and universities were invited to provide talks emphasizing the unique and vital role of the ORELA facility for addressing nuclear data needs. ORELA is operated on a full cost-recovery basis with no single sponsor providing complete base funding for the facility. Consequently, different programmatic sponsors benefit by receiving accurate cross-section data measurements at a reduced cost to their respective programs; however, leveraging support for a complex facility such as ORELA has a distinct disadvantage in that the programmatic funds are only used to support program-specific measurements. As a result, ORELA has not received base funding to support major upgrades and significant maintenance operations that are essential to keep the facility in a state of readiness over the long term. As a result, ORELA has operated on a ''sub-bare-minimum'' budget for the past 10 to 15 years, and the facility has not been maintained at a level for continued reliable operation for the long term. During the Workshop, Jerry McKamy (NNSA/NA-117) used a hospital patient metaphor that accurately depicts the facility status. ORELA is currently in the intensive care unit (ICU) on life support, and refurbishment efforts are needed to get the ''patient'' off life support and out to an ordinary hospital room. McKamy further noted that the DOE NCSP is planning to fund immediate refurbishment tasks ($1.5 M over three years) to help reestablish reliable ORELA operation (i.e., move ORELA from ICU to an ordinary hospital room). Furthermore, the NCSP will work to identify and carry out the actions needed to discharge ORELA from the ''hospital'' over the next five to seven years. In accordance with the Workshop objectives, the technical community publicly endorsed the need for a reliable ORELA facility that can meet current and future nuclear data needs. These Workshop proceedings provide the formal documentation of the technical community endorsement for ORELA. Furthermore, the proceedings highlight the past and current contributions that ORELA has made to the nuclear industry. The Workshop further emphasized the operational and funding problems that currently plague the facility, thereby limiting ORELA's operational reliability. Despite the recent operational problems, ORELA is a uniquely capable measurement facility that must be part of the overall U.S. nuclear data measurement portfolio in order to support current and emerging nuclear applications. The Workshop proceedings further emphasize that ORNL, the technical community, and programmatic sponsors are eager to see ORELA reestablish reliable measurement operation and be readily available to address nuclear data challenges in the United States.« less

Macrophage and Innate Lymphoid Cell Interplay in the Genesis of Fibrosis

PubMed Central

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

Cooperative Security in Northeast Asia. A China-Japan-South Korea Coalition Approach

DTIC Science & Technology

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

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.

Xeroderma pigmentosum and other diseases of human premature aging and DNA repair: Molecules to patients

PubMed Central

Niedernhofer, Laura J.; Bohr, Vilhelm A.; Sander, Miriam; Kraemer, Kenneth H.

2012-01-01

A workshop1 to share, consider and discuss the latest developments in understanding xeroderma pigmentosum and other human diseases caused by defects in nucleotide excision repair (NER) of DNA damage was held on September 21–24, 2010 in Virginia. It was attended by approximately 100 researchers and clinicians, as well as several patients and representatives of patient support groups. This was the third in a series of workshops with similar design and goals: to emphasize discussion and interaction among participants as well as open exchange of information and ideas. The participation of patients, their parents and physicians was an important feature of this and the preceding two workshops. Topics discussed included the natural history and clinical features of the diseases, clinical and laboratory diagnosis of these rare diseases, therapeutic strategies, mouse models of neurodegeneration, molecular analysis of accelerated aging, impact of transcriptional defects and mitochondrial dysfunction on neurodegeneration, and biochemical insights into mechanisms of NER and base excision repair. PMID:21708183

PROCEEDINGS OF RIKEN BNL RESEARCH CENTER WORKSHOP ON RHIC SPIN PHYSICS III AND IV, POLARIZED PARTONS AT HIGH Q2 REGION, AUGUST 3, 2000 AT BNL, OCTOBER 14, 2000 AT KYOTO UNIVERSITY.

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

BUNCE, G.; VIGDOR, S.

2001-03-15

International workshop on II Polarized Partons at High Q2 region 11 was held at the Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto, Japan on October 13-14, 2000, as a satellite of the international conference ''SPIN 2000'' (Osaka, Japan, October 16-21,2000). This workshop was supported by RIKEN (The Institute of Physical and Chemical Research) and by Yukawa Institute. The scientific program was focused on the upcoming polarized collider RHIC. The workshop was also an annual meeting of RHIC Spin Collaboration (RSC). The number of participants was 55, including 28 foreign visitors and 8 foreign-resident Japanese participants, reflecting the international naturemore » of the RHIC spin program. At the workshop there were 25 oral presentations in four sessions, (1) RHIC Spin Commissioning, (2) Polarized Partons, Present and Future, (3) New Ideas on Polarization Phenomena, (4) Strategy for the Coming Spin Running. In (1) the successful polarized proton commissioning and the readiness of the accelerator for the physics program impressed us. In (2) and (3) active discussions were made on the new structure function to be firstly measured at RHIC, and several new theoretical ideas were presented. In session (4) we have established a plan for the beam time requirement toward the first collision of polarized protons. These proceedings include the transparencies presented at the workshop. The discussion on ''Strategy for the Coming Spin Running'' was summarized by the chairman of the session, S. Vigdor and G. Bunce.« less

STREAM2016: Streaming Requirements, Experience, Applications and Middleware Workshop

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

Fox, Geoffrey; Jha, Shantenu; Ramakrishnan, Lavanya

The Department of Energy (DOE) Office of Science (SC) facilities including accelerators, light sources and neutron sources and sensors that study, the environment, and the atmosphere, are producing streaming data that needs to be analyzed for next-generation scientific discoveries. There has been an explosion of new research and technologies for stream analytics arising from the academic and private sectors. However, there has been no corresponding effort in either documenting the critical research opportunities or building a community that can create and foster productive collaborations. The two-part workshop series, STREAM: Streaming Requirements, Experience, Applications and Middleware Workshop (STREAM2015 and STREAM2016), weremore » conducted to bring the community together and identify gaps and future efforts needed by both NSF and DOE. This report describes the discussions, outcomes and conclusions from STREAM2016: Streaming Requirements, Experience, Applications and Middleware Workshop, the second of these workshops held on March 22-23, 2016 in Tysons, VA. STREAM2016 focused on the Department of Energy (DOE) applications, computational and experimental facilities, as well software systems. Thus, the role of “streaming and steering” as a critical mode of connecting the experimental and computing facilities was pervasive through the workshop. Given the overlap in interests and challenges with industry, the workshop had significant presence from several innovative companies and major contributors. The requirements that drive the proposed research directions, identified in this report, show an important opportunity for building competitive research and development program around streaming data. These findings and recommendations are consistent with vision outlined in NRC Frontiers of Data and National Strategic Computing Initiative (NCSI) [1, 2]. The discussions from the workshop are captured as topic areas covered in this report's sections. The report discusses four research directions driven by current and future application requirements reflecting the areas identified as important by STREAM2016. These include (i) Algorithms, (ii) Programming Models, Languages and Runtime Systems (iii) Human-in-the-loop and Steering in Scientific Workflow and (iv) Facilities.« less

Quantum Sensing for High Energy Physics

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

van Bibber, Karl; Boshier, Malcolm; Demarteau, Marcel

The Coordinating Panel for Advanced Detectors (CPAD) of the APS Division of Particles and Fields organized a first workshop on Quantum Sensing for High Energy Physics (HEP) in early December 2017 at Argonne National Laboratory. Participants from universities and national labs were drawn from the intersecting fields of Quantum Information Science (QIS), high energy physics, atomic, molecular and optical physics, condensed matter physics, nuclear physics and materials science. Quantum-enabled science and technology has seen rapid technical advances and growing national interest and investments over the last few years. The goal of the workshop was to bring the various communities togethermore » to investigate pathways to integrate the expertise of these two disciplines to accelerate the mutual advancement of scientific progress.« less

The Standard Model from LHC to future colliders.

PubMed

Forte, S; Nisati, A; Passarino, G; Tenchini, R; Calame, C M Carloni; Chiesa, M; Cobal, M; Corcella, G; Degrassi, G; Ferrera, G; Magnea, L; Maltoni, F; Montagna, G; Nason, P; Nicrosini, O; Oleari, C; Piccinini, F; Riva, F; Vicini, A

This review summarizes the results of the activities which have taken place in 2014 within the Standard Model Working Group of the "What Next" Workshop organized by INFN, Italy. We present a framework, general questions, and some indications of possible answers on the main issue for Standard Model physics in the LHC era and in view of possible future accelerators.

Where are we now? And where are we going? A report from the Accelerate Brain Cancer Cure (ABC2) Low-grade Glioma Research Workshop

PubMed Central

Huse, Jason T.; Wallace, Max; Aldape, Kenneth D.; Berger, Mitchel S.; Bettegowda, Chetan; Brat, Daniel J.; Cahill, Daniel P.; Cloughesy, Timothy; Haas-Kogan, Daphne A.; Marra, Marco; Miller, C. Ryan; Nelson, Sarah J.; Salama, Sofie R.; Soffietti, Riccardo; Wen, Patrick Y.; Yip, Stephen; Yen, Katharine; Costello, Joseph F.; Chang, Susan

2014-01-01

Diffuse gliomas consist of both low- and high-grade varieties, each with distinct morphological and biological features. The often extended periods of relative indolence exhibited by low-grade gliomas (LGG; WHO grade II) differ sharply from the aggressive, rapidly fatal clinical course of primary glioblastoma (GBM; WHO grade IV). Nevertheless, until recently, the molecular foundations underlying this stark biological contrast between glioma variants remained largely unknown. The discoveries of distinctive and highly recurrent genomic and epigenomic abnormalities in LGG have both informed a more accurate classification scheme and pointed to viable avenues for therapeutic development. As such, the field of neuro-oncology now seems poised to capitalize on these gains to achieve significant benefit for LGG patients. This report will briefly recount the proceedings of a workshop held in January 2013 and hosted by Accelerate Brain Cancer Cure (ABC2) on the subject of LGG. While much of the meeting covered recent insights into LGG biology, its focus remained on how best to advance the clinical management, whether by improved preclinical modeling, more effective targeted therapeutics and clinical trial design, or innovative imaging technology. PMID:24305708

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

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

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

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.

PREFACE: 1st Tensor Polarized Solid Target Workshop

NASA Astrophysics Data System (ADS)

2014-10-01

These are the proceedings of the first Tensor Spin Observables Workshop that was held in March 2014 at the Thomas Jefferson National Accelerator Facility in Newport News, Virginia. The conference was convened to study the physics that can be done with the recently approved E12-13-011 polarized target. A tensor polarized target holds the potential of initiating a new generation of tensor spin physics at Jefferson Lab. Experiments which utilize tensor polarized targets can help clarify how nuclear properties arise from partonic degrees of freedom, provide unique insight into short-range correlations and quark angular momentum, and also help pin down the polarization of the quark sea with a future Electron Ion Collider. This three day workshop was focused on tensor spin observables and the associated tensor target development. The workshop goals were to stimulate progress in the theoretical treatment of polarized spin-1 systems, foster the development of new proposals, and to reach a consensus on the optimal polarized target configuration for the tensor spin program. The workshop was sponsored by the University of New Hampshire, the Jefferson Science Associates, Florida International University, and Jefferson Lab. It was organized by Karl Slifer (chair), Patricia Solvignon, and Elena Long of the University of New Hampshire, Douglas Higinbotham and Christopher Keith of Jefferson Lab, and Misak Sargsian of the Florida International University. These proceedings represent the effort put forth by the community to begin exploring the possibilities that a high-luminosity, high-tensor polarized solid target can offer.

MR-2016 US-Japan Workshop on Magentic Reconnection Travel Support

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

Forest, Cary

The US-Japan workshop on Magnetic Reconnection (MR2016), was held in Napa California from March 7th through 11th, 2016. Details about the program, including invited speakers can be found here: (http://www.magneticreconnection.org/mr2016). Background: The MR Workshop is an international meeting that began in 2000 with its original focus on magnetic reconnection serving as a link between the research groups in US and Japan. Since then, the meeting has grown and is now recognized as one of the primary international workshops on magnetic reconnection. In its format, researchers from both the laboratory community and from the space research community have held 12 workshopsmore » bringing together the diverse researchers from the space and laboratory experimental fields. Plasma physics is the common language that ties together all scientists who study the waves, particle acceleration and heating, magnetic reconnection, dynamos, global and micro-stability of plasmas, magnetic turbulence and plasma’s transport problems. The meeting received $9,575 from the U.S. Dept. of Energy funding. This support was used to cover the registration fees ($575 per person) and accommodations for ten junior colleagues (graduate students and postdocs). Applications were solicited and then reviewed by the program committee based on recommendations from the applicants’ advisers.« less

Proceedings of the workshop on B physics at hadron accelerators

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

McBride, P.; Mishra, C.S.

1993-12-31

This report contains papers on the following topics: Measurement of Angle {alpha}; Measurement of Angle {beta}; Measurement of Angle {gamma}; Other B Physics; Theory of Heavy Flavors; Charged Particle Tracking and Vertexing; e and {gamma} Detection; Muon Detection; Hadron ID; Electronics, DAQ, and Computing; and Machine Detector Interface. Selected papers have been indexed separately for inclusion the in Energy Science and Technology Database.

Accelerated Insertion of Materials - Composites

DTIC Science & Technology

2001-08-28

Details • Damage Tolerance • Repair • Validation of Analysis Methodology • Fatigue • Static • Acoustic • Configuration Details • Damage Tolerance...Sensitivity – Fatigue – Adhesion – Damage Tolerance – All critical modes and environments Products: Material Specifications, B-Basis Design Allowables...Demonstrate damage tolerance AIM-C DARPA DARPA Workshop, Annapolis, August 27-28, 2001 Requalification of Polymer / Composite Parts • Material Changes – Raw

Perspectives of Patients, Caregivers and Researchers on Research Priorities in Donation and Transplantation in Canada: A Pilot Workshop.

PubMed

Allard, Julie; Durand, Céline; Anthony, Samantha J; Dumez, Vincent; Hartell, David; Hébert, Marie-Josée; West, Lori J; Wright, Linda; Fortin, Marie-Chantal

2017-02-01

It is vitally important to seek input from key stakeholders to increase the quality and relevance of health-related research and accelerate its adoption into practice. Patients and caregivers have rarely been involved in setting research priorities in the transplantation and donation field. The objectives of this explorative study are: (i) to discuss research priorities within the Canadian National Transplant Research Program during a priority-setting exercise with patients, caregivers, organ donors and researchers and (ii) to compare the identified priorities with research published in 2 prestigious transplantation journals. A pilot workshop attended by 10 patients and caregivers and 5 researchers was held in Montréal (Quebec, Canada) in August 2014 to identify research priorities. Priorities were identified using a thematic analysis of the workshop transcription conducted by multiple coders. These priorities were compared with the topics of research articles published in 2 major transplantation journals between 2012 and 2014. The themes of the 10 research priorities identified by study participants were related to different research domains: social, cultural, and environmental health factors (4); biomedical or clinical (4); and research about health systems and services (2). 26.7% of the research articles published were related to the identified priorities. Thirteen percent looked at ways to improve graft survival and 8.5% looked at the development of tolerance, 2 priorities identified by participants. Fewer than 5% examined the other 8 research priorities identified as important by workshop participants. This is the first study reporting patients' and researchers' priorities in the field of transplantation and donation in Canada. There is a discrepancy between topics that key stakeholders find important and research published in 2 major transplantation journals. The research priorities identified during our initial workshop will be validated through a national survey and workshop.

Kitty for the kitty

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.

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

Garrett, J.D.

These proceedings report the deliberations of a 3 1/2 day workshop on the Production and Use of Intense Radioactive Ion Beams at the Isospin Laboratory, which was held at the Joint Institute for Heavy Ion Research in Oak Ridge, Tennessee, October 1992. The purpose of this workshop was not to duplicate the programs of other recent radioactive ion beam workshops or international conferences that have focused on the scientific concepts which radioactive beams can, and in fact already are, addressing. Instead, the intent was to address the technical problems associated with the construction of the next generation ISOL facility andmore » to initiate a discussion of the type of experimental equipment that should be developed for such a facility. We have tried to bring together in Oak Ridge the world`s experts in radioactive targets/ion sources, light and heavy-ion accelerators, and detection systems. After 1 1/2 days of overview presentations, the participants divided into three discussion groups (Experiments with Radioactive Beams, Target Ion Sources and Mass Separation, and Accelerators-Primary and Secondary) for 1 1/2 days of detailed discussions of the most pertinent issues. The final session was devoted to reports from each of the discussion groups and a general discussion of where to go from here. An outgrowth of these discussions was the establishment of working groups to coordinate future technical developments associated with the pertinent issues. The proceedings include the text of all the overview presentations, reports from each discussion group, as well as contributions from those participants who chose to provide the text of their presentations in the discussion groups and the Concluding Remarks. Selected papers have been indexed separately for inclusion in the Energy Science and Technology Database.« less

IAA Space Exploration Conference

NASA Technical Reports Server (NTRS)

Davis, Jeffrey R.; Richard Elizabeth E.

2014-01-01

The NASA Human Health and Performance Center (NHHPC) was established in October 2010 to facilitate development of partnerships and collaborative projects in human health and performance with a focus on Earthspace benefits. The membership, which now stands at over 135 members from around the world, was developed to span the government, academic, industry and non-profit sectors, making the NHHPC a global convener in human health and performance. International members include organizations from Germany, the United Kingdom, Spain, Japan, South Africa, and India. The virtual center facilitates sharing of best practices and development of collaborative opportunities through a variety of vehicles, including annual in-person workshops, Innovation Lecture Series and Member to Member Connect webcasts, quarterly electronic newsletters, web postings, and electronic member announcements. The NHHPC has conducted four workshops leading to several collaborative projects between members, with the most recent workshop held focusing on new organizational business models for accelerating innovation. This short paper will discuss how the NHHPC facilitates partnerships and the collaborative research and technology developments projects with applications to both the NASA mission and life on Earth.

Tobacco and the Movies

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

The determination of ethyl glucuronide in hair: Experiences from nine consecutive interlaboratory comparison rounds.

PubMed

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.

AhR modulates the IL-22-producing cell proliferation/recruitment in imiquimod-induced psoriasis mouse model.

PubMed

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.

IL-17 producing innate lymphoid cells 3 (ILC3) but not Th17 cells might be the potential danger factor for preeclampsia and other pregnancy associated diseases.

PubMed

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.

Mapping of NKp46+ Cells in Healthy Human Lymphoid and Non-Lymphoid Tissues

PubMed Central

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

Model-Free Primitive-Based Iterative Learning Control Approach to Trajectory Tracking of MIMO Systems With Experimental Validation.

PubMed

Radac, Mircea-Bogdan; Precup, Radu-Emil; Petriu, Emil M

2015-11-01

This paper proposes a novel model-free trajectory tracking of multiple-input multiple-output (MIMO) systems by the combination of iterative learning control (ILC) and primitives. The optimal trajectory tracking solution is obtained in terms of previously learned solutions to simple tasks called primitives. The library of primitives that are stored in memory consists of pairs of reference input/controlled output signals. The reference input primitives are optimized in a model-free ILC framework without using knowledge of the controlled process. The guaranteed convergence of the learning scheme is built upon a model-free virtual reference feedback tuning design of the feedback decoupling controller. Each new complex trajectory to be tracked is decomposed into the output primitives regarded as basis functions. The optimal reference input for the control system to track the desired trajectory is next recomposed from the reference input primitives. This is advantageous because the optimal reference input is computed straightforward without the need to learn from repeated executions of the tracking task. In addition, the optimization problem specific to trajectory tracking of square MIMO systems is decomposed in a set of optimization problems assigned to each separate single-input single-output control channel that ensures a convenient model-free decoupling. The new model-free primitive-based ILC approach is capable of planning, reasoning, and learning. A case study dealing with the model-free control tuning for a nonlinear aerodynamic system is included to validate the new approach. The experimental results are given.

Nuclear Methods for Transmutation of Nuclear Waste: Problems, Perspextives, Cooperative Research - Proceedings of the International Workshop

NASA Astrophysics Data System (ADS)

Khankhasayev, Zhanat B.; Kurmanov, Hans; Plendl, Mikhail Kh.

1996-12-01

The Table of Contents for the full book PDF is as follows: * Preface * I. Review of Current Status of Nuclear Transmutation Projects * Accelerator-Driven Systems — Survey of the Research Programs in the World * The Los Alamos Accelerator-Driven Transmutation of Nuclear Waste Concept * Nuclear Waste Transmutation Program in the Czech Republic * Tentative Results of the ISTC Supported Study of the ADTT Plutonium Disposition * Recent Neutron Physics Investigations for the Back End of the Nuclear Fuel Cycle * Optimisation of Accelerator Systems for Transmutation of Nuclear Waste * Proton Linac of the Moscow Meson Factory for the ADTT Experiments * II. Computer Modeling of Nuclear Waste Transmutation Methods and Systems * Transmutation of Minor Actinides in Different Nuclear Facilities * Monte Carlo Modeling of Electro-nuclear Processes with Nonlinear Effects * Simulation of Hybrid Systems with a GEANT Based Program * Computer Study of 90Sr and 137Cs Transmutation by Proton Beam * Methods and Computer Codes for Burn-Up and Fast Transients Calculations in Subcritical Systems with External Sources * New Model of Calculation of Fission Product Yields for the ADTT Problem * Monte Carlo Simulation of Accelerator-Reactor Systems * III. Data Basis for Transmutation of Actinides and Fission Products * Nuclear Data in the Accelerator Driven Transmutation Problem * Nuclear Data to Study Radiation Damage, Activation, and Transmutation of Materials Irradiated by Particles of Intermediate and High Energies * Radium Institute Investigations on the Intermediate Energy Nuclear Data on Hybrid Nuclear Technologies * Nuclear Data Requirements in Intermediate Energy Range for Improvement of Calculations of ADTT Target Processes * IV. Experimental Studies and Projects * ADTT Experiments at the Los Alamos Neutron Science Center * Neutron Multiplicity Distributions for GeV Proton Induced Spallation Reactions on Thin and Thick Targets of Pb and U * Solid State Nuclear Track Detector and Radiochemical Studies on the Transmutation of Nuclei Using Relativistic Heavy Ions * Experimental and Theoretical Study of Radionuclide Production on the Electronuclear Plant Target and Construction Materials Irradiated by 1.5 GeV and 130 MeV Protons * Neutronics and Power Deposition Parameters of the Targets Proposed in the ISTC Project 17 * Multicycle Irradiation of Plutonium in Solid Fuel Heavy-Water Blanket of ADS * Compound Neutron Valve of Accelerator-Driven System Sectioned Blanket * Subcritical Channel-Type Reactor for Weapon Plutonium Utilization * Accelerator Driven Molten-Fluoride Reactor with Modular Heat Exchangers on PB-BI Eutectic * A New Conception of High Power Ion Linac for ADTT * Pions and Accelerator-Driven Transmutation of Nuclear Waste? * V. Problems and Perspectives * Accelerator-Driven Transmutation Technologies for Resolution of Long-Term Nuclear Waste Concerns * Closing the Nuclear Fuel-Cycle and Moving Toward a Sustainable Energy Development * Workshop Summary * List of Participants

Summary report of working group 5: Beam sources, monitoring and control

NASA Astrophysics Data System (ADS)

Conde, Manoel; Zgadzaj, Rafal

2017-03-01

This paper summarizes the topics presented in Working Group 5 at the 17th Advanced Accelerator Concepts Workshop, which was held from 31 July to 5 August 2016 at the Gaylord Hotel and Conference Center, National Harbor, MD, USA. The presentations included a variety of topics covering cathode and RF gun design, new user facilities, beam phase space manipulation, and a range of novel diagnostic techniques.

Accelerating cancer therapy development: the importance of combination strategies and collaboration. Summary of an Institute of Medicine workshop.

PubMed

LoRusso, Patricia M; Canetta, Renzo; Wagner, John A; Balogh, Erin P; Nass, Sharyl J; Boerner, Scott A; Hohneker, John

2012-11-15

Cancer cells contain multiple genetic changes in cell signaling pathways that drive abnormal cell survival, proliferation, invasion, and metastasis. Unfortunately, patients treated with single agents inhibiting only one of these pathways--even if showing an initial response--often develop resistance with subsequent relapse or progression of their cancer, typically via the activation of an alternative uninhibited pathway. Combination therapies offer the potential for inhibiting multiple targets and pathways simultaneously to more effectively kill cancer cells and prevent or delay the emergence of drug resistance. However, there are many unique challenges to developing combination therapies, including devising and applying appropriate preclinical tests and clinical trial designs, prioritizing which combination therapies to test, avoiding overlapping toxicity of multiple agents, and overcoming legal, cultural, and regulatory barriers that impede collaboration among multiple companies, organizations, and/or institutions. More effective strategies to efficiently develop combination cancer therapies are urgently needed. Thus, the Institute of Medicine's National Cancer Policy Forum recently convened a workshop with the goal of identifying barriers that may be impeding the development of combination investigational cancer therapies, as well as potential solutions to overcome those barriers, improve collaboration, and ultimately accelerate the development of promising combinations of investigational cancer therapies. ©2012 AACR.

Enhancement of Electron Acceleration in Laser Wakefields by Random Fields

NASA Astrophysics Data System (ADS)

Tataronis, J. A.; Petržílka, V.

1999-11-01

There is increasing evidence that intense laser pulses can accelerate electrons to high energies. The energy appears to increase with the distance over which the electrons are accelerated. This is difficult to explain by electron trapping in a single wakefield wave.^1 We demonstrate that enhanced electron acceleration can arise in inhomogeneous laser wakefields through the effects of spontaneously excited random fields. This acceleration mechanism is analogous to fast electron production by random fields near rf antennae in fusion devices and helicon plasma sources.^2 Electron acceleration in a transverse laser wave due to random field effects was recently found.^3 In the present study we solve numerically the governing equations of an ensemble of test electrons in a longitudinal electric wakefield perturbed by random fields. [1pt] Supported by the Czech grant IGA A1043701 and the U.S. DOE under grant No. DE-FG02-97ER54398. [1pt] 1. A. Pukhov and J. Meyer-ter-Vehn, in Superstrong Fields in Plasmas, AIP Conf. Proc. 426, p. 93 (1997). 2. V. Petržílka, J. A. Tataronis, et al., in Proc. Varenna - Lausanne Fusion Theory Workshop, p. 95 (1998). 3. J. Meyer-ter-Vehn and Z. M. Sheng, Phys. Plasmas 6, 641 (1999).

Genomic features of lobular breast carcinoma

Cancer.gov

Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified molecular characteristics of a type of breast cancer, invasive lobular carcinoma (ILC), that distinguishes it from invasive ductal carcinoma (IDC), the most common invasive breast cancer subtype.

Genomic features of lobular breast carcinoma - TCGA

Cancer.gov

Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified molecular characteristics of a type of breast cancer, invasive lobular carcinoma (ILC), that distinguishes it from invasive ductal carcinoma (IDC), the most common invasive breast cancer subtype.

Distribution and Dynamic Properties of Xenon Dissolved in the Ionic Smectic Phase of [C16mim][NO3]: MD Simulation and Theoretical Model.

PubMed

Frezzato, Diego; Saielli, Giacomo

2016-03-10

We have investigated the structural and dynamic properties of Xe dissolved in the ionic liquid crystal (ILC) phase of 1-hexadecyl-3-methylimidazolium nitrate using classical molecular dynamics (MD) simulations. Xe is found to be preferentially dissolved within the hydrophobic environment of the alkyl chains rather than in the ionic layers of the smectic phase. The structural parameters and the estimated local diffusion coefficients concerning the short-time motion of Xe are used to parametrize a theoretical model based on the Smoluchowski equation for the macroscopic dynamics across the smectic layers, a feature which cannot be directly obtained from the relatively short MD simulations. This protocol represents an efficient combination of computational and theoretical tools to obtain information on slow processes concerning the permeability and diffusivity of the xenon in smectic ILCs.

Isolation and Flow Cytometry Analysis of Innate Lymphoid Cells from the Intestinal Lamina Propria.

PubMed

Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas

2017-01-01

The intestinal mucosa constitutes the biggest surface area of the body. It is constantly challenged by bacteria, commensal and pathogenic, protozoa, and food-derived irritants. In order to maintain homeostasis, a complex network of signaling circuits has evolved that includes contributions of immune cells. In recent years a subset of lymphocytes, which belong to the innate immune system, has caught particular attention. These so-called innate lymphoid cells (ILC) reside within the lamina propria of the small and large intestines and rapidly respond to environmental challenges. They provide immunity to various types of infections but may also contribute to organ homeostasis as they produce factors acting on epithelial cells thereby enhancing barrier integrity. Here, we describe how these cells can be isolated from their environment and provide an in-depth protocol how to visualize the various ILC subsets by flow cytometry.