text:
In contrast to most dendritic-cell populations, Langerhans cells repopulate locally throughout life in the steady state, independently of any input from the blood circulation.
In contrast to quiescent skin, in major inflammatory skin injuries (such as exposure to ultraviolet B radiation) Langerhans cells are replaced by circulating monocytes.
Langerhans cells repopulate locally after a lethal dose of radiation and remain of host origin following congenic bone-marrow transplantation. By contrast, following allogeneic bone-marrow transplantation, cutaneous graft-versus-host disease occurs and leads to the elimination of recipient Langerhans cells and their replacement with donor-derived cells.
Langerhans cells are absent in mice that lack the macrophage colony-stimulating factor (M-CSF) receptor but remain unaffected in mice that lack the receptor for FMS-like-tyrosine-kinase 3 ligand (FLT3).
Langerin is not uniquely expressed by Langerhans cells in the skin, but is also expressed by dendritic cells in stratified epithelial surfaces and by a subset of dendritic cells that is present in most connective tissues, including the dermis, lung, kidney and liver. Langerin+ dendritic cells can be distinguished from Langerhans cells based on the expression of the integrin CD103 and the low expression of CD11b.
Langerhans cells (LCs) are a specialized subset of dendritic cells (DCs) that populate the epidermal layer of the skin. Langerin is a lectin that serves as a valuable marker for LCs in mice and humans. In recent years, new mouse models have led to the identification of other langerin+ DC subsets that are not present in the epidermis, including a subset of DCs that is found in most non-lymphoid tissues. In this Review we describe new developments in the understanding of the biology of LCs and other langerin+ DCs and discuss the challenges that remain in identifying the role of different DC subsets in tissue immunity.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
WFDC12-overexpressing contributes to the development of atopic dermatitis via accelerating ALOX12/15 metabolism and PAF accumulation
Cell Death & Disease Open Access 08 March 2023
Cell Communication and Signaling Open Access 19 December 2022
Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice
Nature Communications Open Access 22 July 2022
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Banchereau, J. & Steinman, R. M. Dendritic cells and the control of immunity. Nature 392, 245–252 (1998).
Valladeau, J. et al. Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12, 71–81 (2000). This paper was the first to identify langerin on the surface of human LCs and to show that langerin induces the formation of Birbeck granules.
Turville, S. G. et al. Diversity of receptors binding HIV on dendritic cell subsets. Nature Immunol. 3, 975–983 (2002).
de Witte, L. et al. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nature Med. 13, 367–371 (2007). This study reveals that langerin leads to HIV-1 degradation.
Ginhoux, F. et al. Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state. J. Exp. Med. 204, 3133–3146 (2007). Together with references 6 and 7, this paper reports the presence of langerin+ DCs in the skin that develop and function independently of LCs.
Poulin, L. F. et al. The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells. J. Exp. Med. 204, 3119–3131 (2007).
Bursch, L. S. et al. Identification of a novel population of Langerin+ dendritic cells. J. Exp. Med. 204, 3147–3156 (2007).
Wang, L. et al. Langerin expressing cells promote skin immune responses under defined conditions. J. Immunol. 180, 4722–4727 (2008).
Ginhoux, F. et al. Langerhans cells arise from monocytes in vivo. Nature Immunol. 7, 265–273 (2006). The first demonstration that LCs are absent in Mcsfr−/− mice and that monocytes repopulate LCs in inflamed skin in vivo in mice.
Langerhans, P. Uber die Nerven der menschlichen Haut. Virchows. Arch. Pathol. 44, 325–337 (1868). In this paper, entitled “On the nerves of the human skin”, Paul Langerhans reported for the first time the presence of large cells with long dendrites in the epidermis of human skin.
Stingl, G., Tamaki, K. & Katz, S. I. Origin and function of epidermal Langerhans cells. Immunol. Rev. 53, 149–174 (1980).
Schuler, G. et al. Murine epidermal Langerhans cells as a model to study tissue dendritic cells. Adv. Exp. Med. Biol. 329, 243–249 (1993).
Valladeau, J. & Saeland, S. Cutaneous dendritic cells. Semin. Immunol. 17, 273–283 (2005).
Tigelaar, R. E., Lewis, J. M. & Bergstresser, P. R. TCR γ/δ+ dendritic epidermal T cells as constituents of skin-associated lymphoid tissue. J. Invest. Dermatol. 94, 58S–63S (1990).
Birbeck, M. D., Breathnach, A. S. & Everall, J. D. An electron microscope study of basal melanocytes and high-level clear cells (langerhans cells) in vitiligo. J. Invest. Dermatol. 37, 51 (1961). This is the first description of the presence of the conspiscuous Birbeck granules in Langerhans cells.
Wolff, K. The fine structure of the Langerhans cell granule. J. Cell Biol. 35, 468–473 (1967).
Tang, A., Amagai, M., Granger, L. G., Stanley, J. R. & Udey, M. C. Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin. Nature 361, 82–85 (1993).
Cepek, K. L. et al. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the αEβ7 integrin. Nature 372, 190–193 (1994). This study reports for the first time that the integrin CD103 (also known as α E -integrin, part of the α E b 7 -integrin heterodimer) expressed on the cell surface of T cells can bind the adhesion molecule E-cadherin on epithelial cells.
Borkowski, T. A., Letterio, J. J., Farr, A. G. & Udey, M. C. A role for endogenous transforming growth factor β1 in Langerhans cell biology: the skin of transforming growth factor β1 null mice is devoid of epidermal Langerhans cells. J. Exp. Med. 184, 2417–2422 (1996). This study is the first demonstration that TGFβ1 is crucial for LC development in vivo.
Inaba, K. et al. Tissue distribution of the DEC-205 protein that is detected by the monoclonal antibody NLDC-145. I. Expression on dendritic cells and other subsets of mouse leukocytes. Cell. Immunol. 163, 148–156 (1995).
Jiang, W. et al. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature 375, 151–155 (1995).
Fithian, E. et al. Reactivity of Langerhans cells with hybridoma antibody. Proc. Natl Acad. Sci. USA 78, 2541–2544 (1981).
Hunger, R. E. et al. Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells. J. Clin. Invest. 113, 701–708 (2004).
Ronger-Savle, S. et al. TGFβ inhibits CD1d expression on dendritic cells. J. Invest. Dermatol. 124, 116–118 (2005).
Mc Dermott, R. et al. Birbeck granules are subdomains of endosomal recycling compartment in human epidermal Langerhans cells, which form where langerin accumulates. Mol. Biol. Cell 13, 317–335 (2002).
Valladeau, J. et al. Identification of mouse langerin/CD207 in Langerhans cells and some dendritic cells of lymphoid tissues. J. Immunol. 168, 782–792 (2002).
Takahara, K. et al. Identification and expression of mouse Langerin (CD207) in dendritic cells. Int. Immunol. 14, 433–444 (2002).
Kissenpfennig, A. et al. Disruption of the langerin/CD207 gene abolishes Birbeck granules without a marked loss of Langerhans cell function. Mol. Cell Biol. 25, 88–99 (2005).
Verdijk, P. et al. A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human Langerin gene. J. Invest. Dermatol. 124, 714–717 (2005).
Kelly, R. H., Balfour, B. M., Armstrong, J. A. & Griffiths, S. Functional anatomy of lymph nodes. II. Peripheral lymph-borne mononuclear cells. Anat. Rec. 190, 5–21 (1978). This is one of the first studies to show the presence of veiled (dendritic) cells in lymphatic vessels.
Drexhage, H. A., Mullink, H., de Groot, J., Clarke, J. & Balfour, B. M. A study of cells present in peripheral lymph of pigs with special reference to a type of cell resembling the Langerhans cell. Cell Tissue Res. 202, 407–430 (1979).
Hemmi, H. et al. Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-β-dependent cells. Int. Immunol. 13, 695–704 (2001).
Stoitzner, P., Tripp, C. H., Douillard, P., Saeland, S. & Romani, N. Migratory Langerhans cells in mouse lymph nodes in steady state and inflammation. J. Invest. Dermatol. 125, 116–125 (2005).
Macatonia, S. E., Knight, S. C., Edwards, A. J., Griffiths, S. & Fryer, P. Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies. J. Exp. Med. 166, 1654–1667 (1987).
Randolph, G. J., Ochando, J. & Partida-Sanchez, S. Migration of dendritic cell subsets and their precursors. Annu. Rev. Immunol. 26, 293–316 (2008).
Larsen, C. P. et al. Migration and maturation of Langerhans cells in skin transplants and explants. J. Exp. Med. 172, 1483–1493 (1990).
Pierre, P. et al. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature 388, 787–792 (1997).
Ruedl, C., Koebel, P., Bachmann, M., Hess, M. & Karjalainen, K. Anatomical origin of dendritic cells determines their life span in peripheral lymph nodes. J. Immunol. 165, 4910–4916 (2000).
Ohl, L. et al. CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 21, 279–288 (2004). This is the first paper to identify the crucial role of CCR7 in skin-DC migration to the draining lymph nodes.
Jakob, T., Ring, J. & Udey, M. C. Multistep navigation of Langerhans/dendritic cells in and out of the skin. J. Allergy Clin. Immunol. 108, 688–696 (2001).
Inaba, K. et al. High levels of a major histocompatibility complex II–self peptide complex on dendritic cells from the T cell areas of lymph nodes. J. Exp. Med. 186, 665–672 (1997).
Katz, S. I., Tamaki, K. & Sachs, D. H. Epidermal Langerhans cells are derived from cells originating in bone marrow. Nature 282, 324–326 (1979).
Frelinger, J. G., Hood, L., Hill, S. & Frelinger, J. A. Mouse epidermal Ia molecules have a bone marrow origin. Nature 282, 321–323 (1979). References 42 and 43 were the two first studies to show the haematopoietic origin of LCs.
Merad, M. et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nature Immunol. 3, 1135–1141 (2002). This is the first paper to describe how LCs replenish in situ in the steady state but are repopulated by blood precursor cells during skin injury. This paper also describes for the first time that LC repopulation in inflamed skin depends on CCR2.
Iijima, N., Linehan, M. M., Saeland, S. & Iwasaki, A. Vaginal epithelial dendritic cells renew from bone marrow precursors. Proc. Natl Acad. Sci. USA 104, 19061–19066 (2007).
Holt, P. G., Haining, S., Nelson, D. J. & Sedgwick, J. D. Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J. Immunol. 153, 256–261 (1994).
Liu, K. et al. Origin of dendritic cells in peripheral lymphoid organs of mice. Nature Immunol. 8, 578–583 (2007). This study shows that DCs cycle in situ in lymphoid organs but are maintained by circulating precursor cells.
Merad, M. et al. Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease. Nature Med. 10, 510–517 (2004).
Vishwanath, M. et al. Development of intravital intermittent confocal imaging system for studying Langerhans cell turnover. J. Invest. Dermatol. 126, 2452–2457 (2006).
Kamath, A. T., Henri, S., Battye, F., Tough, D. F. & Shortman, K. Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. Blood 100, 1734–1741 (2002).
Kissenpfennig, A. et al. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22, 643–654 (2005).
Bennett, C. L. et al. Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity. J. Cell Biol. 169, 569–576 (2005). References 51 and 52 were the first two papers to describe the langerin–DTR mice.
Jung, S. et al. In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity 17, 211–220 (2002). This is the first study demonstrating that elimination of DCs in vivo abrogates priming of CD8+ T cells against systemic pathogen infection.
Czernielewski, J., Vaigot, P. & Prunieras, M. Epidermal Langerhans cells — a cycling cell population. J. Invest. Dermatol. 84, 424–426 (1985). The first study to report that LCs cycle in situ.
Czernielewski, J. M. & Demarchez, M. Further evidence for the self-reproducing capacity of Langerhans cells in human skin. J. Invest. Dermatol. 88, 17–20 (1987).
Giacometti, L. & Montagna, W. Langerhans cells: uptake of tritiated thymidine. Science 157, 439–440 (1967).
Krueger, G. G., Daynes, R. A. & Emam, M. Biology of Langerhans cells: selective migration of Langerhans cells into allogeneic and xenogeneic grafts on nude mice. Proc. Natl Acad. Sci. USA 80, 1650–1654 (1983).
Kanitakis, J., Petruzzo, P. & Dubernard, J. M. Turnover of epidermal Langerhans' cells. N. Engl. J. Med. 351, 2661–2662 (2004). A study showing that in one patient that received a limb graft, LCs remained of host origin and were not replaced by blood-derived precursor cells for over 1 year after transplant.
Collin, M. P. et al. The fate of human Langerhans cells in hematopoietic stem cell transplantation. J. Exp. Med. 203, 27–33 (2006). This study shows that, in the absence of graft-versus-host disease, host LCs can remain in the skin despite complete donor-derived chimerism in the blood.
Collin, M. P., Bogunovic, M. & Merad, M. DC homeostasis in hematopoietic stem cell transplantation. Cytotherapy 9, 521–531 (2007).
Miyauchi, S. & Hashimoto, K. Epidermal Langerhans cells undergo mitosis during the early recovery phase after ultraviolet-B irradiation. J. Invest. Dermatol. 88, 703–708 (1987).
Kumamoto, T. et al. Hair follicles serve as local reservoirs of skin mast cell precursors. Blood 102, 1654–1660 (2003). This is the first demonstration that the hair follicle is also a reservoir for the mast-cell precursor.
Blanpain, C. & Fuchs, E. Epidermal stem cells of the skin. Annu. Rev. Cell Dev. Biol. 22, 339–373 (2006).
Gilliam, A. C. et al. The human hair follicle: a reservoir of CD40+ B7-deficient Langerhans cells that repopulate epidermis after UVB exposure. J. Invest. Dermatol. 110, 422–427 (1998). This study shows that after exposure to ultraviolet B radiation that depletes epidermal LCs but does not affect the hair follicle, LCs are repopulated from the hair follicle.
Bennett, C. L., Noordegraaf, M., Martina, C. A. & Clausen, B. E. Langerhans cells are required for efficient presentation of topically applied hapten to T cells. J. Immunol. 179, 6830–6835 (2007). This is one of the first demonstrations that LCs are required to initiate T-cell priming against topical antigens.
Kaplan, D. H. et al. Autocrine/paracrine TGFβ1 is required for the development of epidermal Langerhans cells. J. Exp. Med. 204, 2545–2552 (2007). This study shows that autocrine TGFβ1 is required for LC development.
Strobl, H. et al. TGF-β 1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. J. Immunol. 157, 1499–1507 (1996).
Geissmann, F. et al. Transforming growth factor β1, in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells. J. Exp. Med. 187, 961–966 (1998). This is the first demonstration that human monocytes can differentiate into LCs in vitro.
Hacker, C. et al. Transcriptional profiling identifies Id2 function in dendritic cell development. Nature Immunol. 4, 380–386 (2003). This is the first demonstration that ID2 is required for LC development.
Fainaru, O. et al. Runx3 regulates mouse TGF-β-mediated dendritic cell function and its absence results in airway inflammation. EMBO J. 23, 969–979 (2004).
Witmer-Pack, M. D. et al. Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse. J. Cell Sci. 104, 1021–1029 (1993).
Lin, H. et al. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science 320, 807–811 (2008).
Stanley, E. R. et al. Biology and action of colony-stimulating factor-1. Mol. Reprod. Dev. 46, 4–10 (1997).
Onai, N., Obata-Onai, A., Schmid, M. A. & Manz, M. G. Flt3 in regulation of type-I interferon producing and dendritic cell development. Ann. NY Acad. Sci. 1106, 253–261 (2007).
Bogunovic, M. et al. Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men. J. Exp. Med. 203, 2627–2638 (2006).
Sato, N. et al. CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, B cell outgrowth, and sustained neutrophilic inflammation. J. Exp. Med. 192, 205–218 (2000).
Cook, D. N. et al. CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity 12, 495–503 (2000).
Vanbervliet, B. et al. Sequential involvement of CCR2 and CCR6 ligands for immature dendritic cell recruitment: possible role at inflamed epithelial surfaces. Eur. J. Immunol. 32, 231–242 (2002).
Larregina, A. T. et al. Dermal-resident CD14+ cells differentiate into Langerhans cells. Nature Immunol. 2, 1151–1158 (2001).
Schaerli, P., Willimann, K., Ebert, L. M., Walz, A. & Moser, B. Cutaneous CXCL14 targets. Blood precursors to epidermal niches for Langerhans cell differentiation. Immunity 23, 331–342 (2005).
Reis e Sousa, C. Dendritic cells in a mature stage. Nature Rev. Immunol. 6, 476–483 (2006).
Jiang, A. et al. Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cellmaturation. Immunity 27, 610–624 (2007). This is the first paper to describe an alternative DC-maturation pathway that leads to the upregulation of CCR7 without inducing cytokine release and is thought to have a key role in the induction of tolerance.
Banchereau, J. et al. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767–811 (2000).
Stoitzner, P. et al. Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin/CD207. J. Invest. Dermatol. 120, 266–274 (2003).
Geissmann, F. et al. Accumulation of immature Langerhans cells in human lymph nodes draining chronically inflamed skin. J. Exp. Med. 196, 417–430 (2002).
Douillard, P. et al. Mouse lymphoid tissue contains distinct subsets of langerin/CD207 dendritic cells, only one of which represents epidermal-derived Langerhans cells. J. Invest. Dermatol. 125, 983–994 (2005).
Cheong, C. et al. Production of monoclonal antibodies that recognize the extracellular domain of mouse langerin/CD207. J. Immunol. Methods 324, 48–62 (2007).
Flacher, V. et al. Expression of langerin/CD207 reveals dendritic cell heterogeneity between inbred mouse strains. Immunology 123, 339–347 (2008).
Mayer, W. J. et al. Characterization of antigen-presenting cells in fresh and cultured human corneas using novel dendritic cell markers. Invest. Ophthalmol. Vis. Sci. 48, 4459–4467 (2007).
Santoro, A. et al. Recruitment of dendritic cells in oral lichen planus. J. Pathol. 205, 426–434 (2005).
Sung, S. S. et al. A major lung CD103 (αE)-β7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins. J. Immunol. 176, 2161–2172 (2006).
Johansson-Lindbom, B. et al. Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing. J. Exp. Med. 202, 1063–1073 (2005).
Chikwava, K. & Jaffe, R. Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders. Pediatr. Dev. Pathol. 7, 607–614 (2004). This is the first identification of langerin+CD1a+ cells in human tissue other than the skin.
Segerer, S. et al. Compartment specific expression of dendritic cell markers in human glomerulonephritis. Kidney Int. 73, 533–537 (2008). This is the first identification of langerin+CD1a+ cells in human kidneys.
Jaensson, E. et al. Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J. Exp. Med. 205, 2139–2149 (2008).
Kamath, A. T. et al. The development, maturation, and turnover rate of mouse spleen dendritic cell populations. J. Immunol. 165, 6762–6770 (2000).
Fogg, D. K. et al. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 311, 83–87 (2006).
Massberg, S. et al. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell 131, 994–1008 (2007).
Bonifaz, L. et al. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+T cell tolerance. J. Exp. Med. 196, 1627–1638 (2002). This is the first demonstration that targeting antigens to DCs in the steady state leads to tolerance.
Dudziak, D. et al. Differential antigen processing by dendritic cell subsets in vivo. Science 315, 107–111 (2007).
Schuler, G. & Steinman, R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J. Exp. Med. 161, 526–546 (1985). This study was the first to show that Langerhans cells can differentiate in vitro into DCs that can prime naive T cells.
Allan, R. S. et al. Epidermal viral immunity induced by CD8α+ dendritic cells but not by Langerhans cells. Science 301, 1925–1928 (2003). This study shows that LCs are unable to prime CD8+ T cells following epidermal HSV infection.
He, Y., Zhang, J., Donahue, C. & Falo, L. D. Jr. Skin-derived dendritic cells induce potent CD8+ T cell immunity in recombinant lentivector-mediated genetic immunization. Immunity 24, 643–656 (2006). This study shows that migratory skin DCs prime antigen-specific T cells after lentivirus-vector infection of the skin.
Jones, C. A. et al. Herpes simplex virus type 2 induces rapid cell death and functional impairment of murine dendritic cells in vitro. J. Virol. 77, 11139–11149 (2003).
Bosnjak, L. et al. Herpes simplex virus infection of human dendritic cells induces apoptosis and allows cross-presentation via uninfected dendritic cells. J. Immunol. 174, 2220–2227 (2005).
Leon, B., Lopez-Bravo, M. & Ardavin, C. Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania. Immunity 26, 519–531 (2007).
Sacks, D. L. Metacyclogenesis in Leishmania promastigotes. Exp. Parasitol. 69, 100–103 (1989).
Belkaid, Y. et al. CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major. J. Immunol. 168, 3992–4000 (2002).
Klechevsky, E. et al. Functional specializations of human epidermal langerhans cells and CD14+ dermal dendritic cells. Immunity 29, 497–510 (2008). This study shows that human LCs are efficient at cross-presenting antigens to CD8+ T cells and at inducing T H 1-cell responses, whereas dermal DCs are better at priming follicular T-helper cells and inducing B-cell antibody switching.
Ueno, H. et al. Dendritic cell subsets in health and disease. Immunol. Rev. 219, 118–142 (2007).
Stoecklinger, A. et al. Epidermal langerhans cells are dispensable for humoral and cell-mediated immunity elicited by gene gun immunization. J. Immunol. 179, 886–893 (2007).
Stoitzner, P. et al. Tumor immunotherapy by epicutaneous immunization requires langerhans cells. J. Immunol. 180, 1991–1998 (2008). This is the first demonstration that LCs are required for the induction of the antitumour immune response following epidermal vaccination with tumour antigens.
Kaplan, D. H., Jenison, M. C., Saeland, S., Shlomchik, W. D. & Shlomchik, M. J. Epidermal langerhans cell-deficient mice develop enhanced contact hypersensitivity. Immunity 23, 611–620 (2005).
Steinman, R. M., Hawiger, D. & Nussenzweig, M. C. Tolerogenic dendritic cells. Annu. Rev. Immunol. 21, 685–711 (2003).
Waithman, J. et al. Skin-derived dendritic cells can mediate deletional tolerance of class I-restricted self-reactive T cells. J. Immunol. 179, 4535–4541 (2007).
Loser, K. et al. Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells. Nature Med. 12, 1372–1379 (2006).
Mehling, A. et al. Overexpression of CD40 ligand in murine epidermis results in chronic skin inflammation and systemic autoimmunity. J. Exp. Med. 194, 615–628 (2001).
GeurtsvanKessel, C. H. et al. Clearance of influenza virus from the lung depends on migratory langerin+CD11b− but not plasmacytoid dendritic cells. J. Exp. Med. 205, 1621–1634 (2008).
Belz, G. T. et al. Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-restricted antigen presentation after lung infection with virus. Proc. Natl Acad. Sci. USA 101, 8670–8675 (2004).
del Rio, M. L., Rodriguez-Barbosa, J. I., Kremmer, E. & Forster, R. CD103− and CD103+ bronchial lymph node dendritic cells are specialized in presenting and cross-presenting innocuous antigen to CD4+ and CD8+ T cells. J. Immunol. 178, 6861–6866 (2007).
Coppes-Zantinga, A. & Egeler, R. M. The Langerhans cell histiocytosis X files revealed. Br. J. Haematol. 116, 3–9 (2002).
Nezelof, C., Basset, F. & Rousseau, M. F. Histiocytosis X histogenetic arguments for a Langerhans cell origin. Biomedicine 18, 365–371 (1973).
Geissmann, F. et al. Differentiation of Langerhans cells in Langerhans cell histiocytosis. Blood 97, 1241–1248 (2001).
Emile, J. F., Fraitag, S., Leborgne, M., de Prost, Y. & Brousse, N. In situ expression of activation markers by Langerhans' cells containing GM-CSF. Adv. Exp. Med. Biol. 378, 101–103 (1995).
Nezelof, C. & Basset, F. An hypothesis Langerhans cell histiocytosis: the failure of the immune system to switch from an innate to an adaptive mode. Pediatr. Blood Cancer 42, 398–400 (2004). This is the first study showing that cells in histiocytosis X lesions contain Birbeck granules, which suggests their potential LC origin, and proposed that the term histiocytosis X should be replaced with the term Langerhans-cell histiocytosis.
Yu, R. C., Chu, C., Buluwela, L. & Chu, A. C. Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet 343, 767–768 (1994).
Willman, C. L. et al. Langerhans'-cell histiocytosis (histiocytosis X) — a clonal proliferative disease. N. Engl. J. Med. 331, 154–160 (1994).
Senechal, B. et al. Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. PLoS Med. 4, e253 (2007).
Schouten, B. et al. Expression of cell cycle-related gene products in Langerhans cell histiocytosis. J. Pediatr. Hematol. Oncol. 24, 727–732 (2002).
Savell, V. H. Jr, Sherman, T., Scheuermann, R. H., Siddiqui, A. M. & Margraf, L. R. Bcl-2 expression in Langerhans' cell histiocytosis. Pediatr. Dev. Pathol. 1, 210–215 (1998).
Bjorck, P., Banchereau, J. & Flores-Romo, L. CD40 ligation counteracts Fas-induced apoptosis of human dendritic cells. Int. Immunol. 9, 365–372 (1997).
Wong, B. R. et al. TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J. Exp. Med. 186, 2075–2080 (1997).
Bechan, G. I., Egeler, R. M. & Arceci, R. J. Biology of Langerhans cells and Langerhans cell histiocytosis. Int. Rev. Cytol. 254, 1–43 (2006).
Steiner, Q. G. et al. In vivo transformation of mouse conventional CD8α+ dendritic cells leads to progressive multisystem histiocytosis. Blood 111, 2073–2082 (2008).
Pileri, S. A. et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 41, 1–29 (2002).
Figdor, C. G., van Kooyk, Y. & Adema, G. J. C-type lectin receptors on dendritic cells and Langerhans cells. Nature Rev. Immunol. 2, 77–84 (2002).
Idoyaga, J. et al. Cutting Edge: Langerin/CD207 receptor on dendritic cells mediates efficient antigen presentation on MHC I and II products in vivo. J. Immunol. 180, 3647–3650 (2008).
Piguet, V. & Steinman, R. M. The interaction of HIV with dendritic cells: outcomes and pathways. Trends Immunol. 28, 503–510 (2007).
Hladik, F. & McElrath, M. J. Setting the stage: host invasion by HIV. Nature Rev. Immunol. 8, 447–457 (2008).
Fahrbach, K. M. et al. Activated CD34-derived Langerhans cells mediate transinfection with human immunodeficiency virus. J. Virol. 81, 6858–6868 (2007).
Riedl, E., Tada, Y. & Udey, M. C. Identification and characterization of an alternatively spliced isoform of mouse Langerin/CD207. J. Invest. Dermatol. 123, 78–86 (2004).
Ward, E. M., Stambach, N. S., Drickamer, K. & Taylor, M. E. Polymorphisms in human langerin affect stability and sugar binding activity. J. Biol. Chem. 281, 15450–15456 (2006).
Boes, M. et al. T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 418, 983–988 (2002).
Fukuzumi, T. et al. Differences in irradiation susceptibility and turnover between mucosal and connective tissue-type mast cells of mice. Exp. Hematol. 18, 843–847 (1990).
Matsumoto, Y. & Fujiwara, M. Absence of donor-type major histocompatibility complex class I antigen-bearing microglia in the rat central nervous system of radiation bone marrow chimeras. J. Neuroimmunol. 17, 71–82 (1987).
Berland, R. & Wortis, H. H. Origins and functions of B-1 cells with notes on the role of CD5. Annu. Rev. Immunol. 20, 253–300 (2002).
Merad, M. & Ginhoux, F. Dendritic cell genealogy: a new stem or just another branch? Nature Immunol. 8, 1199–1201 (2007).
Takahashi, K. et al. Heterogeneity of dendritic cells in human superficial lymph node: in vitro maturation of immature dendritic cells into mature or activated interdigitating reticulum cells. Am. J. Pathol. 153, 745–755 (1998).
Schiavoni, G. et al. ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells. Blood 103, 2221–2228 (2004).
We are grateful to R. Steinman, N. Romani, M. Udey and J. Helft for the critical review of the manuscript. We thank P. and E. Kontoyannis for their continuous support of Langerhans and Langerhans-cell histiocytosis research. We apologize to the colleagues whose work we have failed to cite owing to space limitations. M.M. is supported by the National Institutes of Health (grant numbers R01CA1121100 and R01AI0086899). F.G. is supported by the leukemia and the lymphoma research foundation.
- Langerhans cells
A type of dendritic cell that is localized in the epidermal layer of the skin.
- Single-nucleotide polymorphism
(SNP). A variation in DNA sequence in which one of the four nucleotides is substituted for another (for example, C for A). SNPs are the most frequent type of polymorphism in the genome.
The main cell type of the epidermis, which represents more than 90% of epidermal cells. Keratinocytes form an effective barrier against the entry of foreign matter and infectious agents into the body and minimize moisture loss.
- γδ T cell
A T cell that expresses the γδ T-cell receptor. γδ T cells are present in the skin, vagina and intestinal epithelium as intraepithelial lymphocytes. Although the exact function of γδ T cells is unknown, it has been suggested that mucosal γδ T cells are involved in innate immune responses.
- Birbeck granules
Granules that consist of superimposed membranes separated by repetitive zipper-like striations and contain a vesicle at one end of the membrane, which gives the granules its typical tennis-racquet shape15,16. Although the function of Birbeck granules is poorly understood, they might function in antigen presentation, as langerin was shown to route antigens from the cell surface to these structures.
- C-type lectin receptor
A receptor that binds glycosylated ligands and has many roles, such as in cell adhesion, endocytosis, natural-killer-cell target recognition and dendritic-cell activation.
- Bromodeoxyuridine labelling
(BrdU labelling). A technique in which dividing cells that have been exposed to BrdU incorporate it into their DNA. These cells can be identified by intracellular staining with antibodies that are specific for BrdU. Non-dividing cells do not incorporate BrdU.
- Congenic mice
Syngeneic mice that differ only at a single locus. Most studies in this Review have used mice that express a different isoform of the CD45 gene (Cd45.1 and Cd45.2). This CD45 protein is expressed by all haematopoietic cells, allowing to trace the donor-derived haematopoiesis in the recipient mouse.
- Graft-versus-host disease
(GVHD). Tissue damage in a recipient of allogeneic tissue (usually a bone-marrow transplant) that results from the activity of donor cytotoxic T cells recognizing the tissues of the recipient as foreign. GVHD varies markedly in its extent, but it can be life threatening in severe cases. Damage to the liver, skin and gut mucosa are common clinical manifestations.
- Pattern-recognition receptor
A host receptor (such as a Toll-like receptor) that can sense pathogen-associated molecular patterns and initiate signalling cascades (which involve the activation of nuclear factor-κB) that lead to an innate immune response.
- Peyer's patches
Collections of lymphoid tissue that are located in the mucosa of the small intestine, and have an outer epithelial-cell layer consisting of specialized epithelial cells called M cells.
The ability of certain antigen-presenting cells to load peptides that are derived from exogenous antigens onto MHC class I molecules. This property is atypical, because most cells exclusively present peptides from their endogenous proteins on MHC class I molecules. Cross-presentation is essential for the initiation of immune responses to viruses that do not infect antigen-presenting cells.
- Follicular T-helper cell
A T helper cell that is essential in determining B-cell antibody class switching.
- Contact-hypersensitivity response
A disease in which the contact allergens, which are co-applied with a suboptimal dose of haptens, are thought to activate an innate immune response that is important in the recruitment of hapten-specific T cells to the skin and the induction of the clinical symptoms.
About this article
Cite this article
Merad, M., Ginhoux, F. & Collin, M. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat Rev Immunol 8, 935–947 (2008). https://doi.org/10.1038/nri2455
This article is cited by
WFDC12-overexpressing contributes to the development of atopic dermatitis via accelerating ALOX12/15 metabolism and PAF accumulation
Cell Death & Disease (2023)
STR typing of skin swabs from individuals after an allogeneic hematopoietic stem cell transplantation
International Journal of Legal Medicine (2023)
Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors
Pediatric Drugs (2023)
Cell Communication and Signaling (2022)
Differential gene screening and bioinformatics analysis of epidermal stem cells and dermal fibroblasts during skin aging
Scientific Reports (2022)

domain: literature


text:
Breast augmentation, which is also known as augmentation mammoplasty, is a plastic surgery procedure with the aim of increasing the size of a patient’s breast. The breasts are reshaped and enlarged by using breast implants. As part of preparation for breast augmentation surgery, several factors need to be considered.
The process under which breast enlargement surgery is performed is largely dependent on the goals of the patient, as there are many different options to consider. Some patients seek to have their bust line made smaller while others wish to make it larger with more volume. A diet plan must be followed before and after this procedure. It includes maintaining healthy diet rich in nutrients and vitamins and getting sufficient amount of sleep.
The aim of this article is to highlight some of these factors, as well as give advice on how a patient can get a good night’s sleep after breast augmentation surgery.
Sleeping on your back with your head raised
Sleeping on your back with your head raised is the most common way to sleep after breast augmentation. It is also recommended by most plastic surgeons who perform breast augmentation. Sleeping in this position will allow you to breathe easier while you are sleeping and will decrease the amount of pain you have during the first few days after surgery.
You do not need a pillow to sleep on your back, but if you find it more comfortable than using a pillow, then use one that is firm enough to support your head and neck but soft enough not to irritate your breasts or cause discomfort.
Sleeping on the side
Sleep on your back for the first week after surgery. This will help to minimize swelling, which can be uncomfortable. If you sleep on your stomach, there is a higher risk of developing a hematoma (a blood clot) that may require surgical removal. Also, sleeping on your stomach can cause implants to shift or move out of position. If you must sleep on your side, place two or three pillows under the arm on the side of the surgery and another pillow between your legs at night.
Sleeping on Your Back For 2 Weeks After Surgery
For two weeks after breast augmentation surgery, avoid sleeping on your back. As mentioned above, this will help minimize swelling but also helps prevent implant malpositioning (shifting or moving out of position). If you must sleep on your back during this time frame (because you are traveling), place two or three pillows under the arm on the side of the surgery and another pillow between your legs at night.
How can I prepare to sleep on my back if I am not used to it?
Sleeping on your back is the easiest position for your breast implants. It helps to make sure that your breasts are properly positioned and will not shift in any way. While sleeping on your back is the easiest, it may be uncomfortable for some people.
There are many ways to help you get used to sleeping on your back if you are not used to it:
Get a good pillow – a firm pillow that supports your head and neck in a neutral position can help keep your spine straight and prevent excessive curvature of the spine (scoliosis).
Use a body pillow – a body pillow can provide support for both sides of the body, which helps to maintain spinal alignment while sleeping on your back. You will also find that they are easier than regular pillows to adjust throughout the night as needed.
Take medication – If pain persists or becomes worse over time, talk with your doctor about taking medications such as Tylenol or ibuprofen before bedtime to help reduce swelling and irritation around the breast implants.

domain: medical


text:
Which University Has the First Masters Level Sports Administration Program?
- Does UNC have a sports management program?
- Where are sport management programs housed in universities?
- Which league has the highest credit rating?
- Which is the birthplace of modern sport and sport management?
- What is the oldest professional sports team in North America?
- What is the only sports league to ban corporate ownership?
- Which sport league uses a soft salary cap?
- What area of law has left an indelible mark on the structure and nature of labor relations in professional sports?
- Does Ohio State have a sports management program?
- Who created sports management?
- What is the difference between sports management and sports administration?
- Does UNC Charlotte have sports management?
- What is sport administration?
- Does UCLA have a sports management major?
- Does NYU have sports management?
- Does NYU have a good sports management program?
- When was the concept of fantasy sport introduced?
- When and who started the modern Olympic Games?
- Who is considered the czar of baseball?
- What is the oldest stadium in Major League Baseball?
- What state has most MLB teams?
- What is the #1 sport in America?
- Which Big Four sports league is the oldest?
- Who won the 1st world Series?
- Who was the first black person in baseball?
- Are pro sports teams corporations?
- Do any corporations own sports teams?
Similarly, Which university has the first Masters level sport administration program?
The first program in sports administration. Ohio University was the first university in the nation to develop a specialist academic sports department, and it continues to be a leader in the area of sports management Walter O’Malley, the owner of the Los Angeles Dodgers, had the idea for a postgraduate degree in sports.
Also, it is asked, What university had the first sport management academic program?
Ohio State University was the first university to offer a sport management program. Harness racing was the first professional sport in the United States Professional tennis tournaments were developed by Fred Corcoran, who made a contribution to the sport sector. The National League was formed by William Hulbert.
Secondly, What was the first organized group of professional baseball players known as?
The Cincinnati Reds were the first professional baseball team. Player associations, rather than marketing companies or broadcast media, are frequently the ones that organize tournaments nowadays. 7: In 1896, which city hosted the first modern Olympic Games?
Also, What is the term given to the amount of their own money owners have invested in the firm?
What is the phrase for the amount of money that the company’s owners have put into it with their own money? equity.
People also ask, During which year was the first sports management degree program in the world founded at Ohio University?
Related Questions and Answers
Does UNC have a sports management program?
The Undergraduate Sport Administration program at the University of North Carolina at Chapel Hill prepares students for job in high-level competitive sport environments or graduate school by providing them with course work dedicated to sport-related business.
Where are sport management programs housed in universities?
Rather of being located in the business school, institutions frequently put the program in the Kinesiology department. However, dedicated sports management departments may be found at some of the greatest colleges in the subject.
Which league has the highest credit rating?
NEW YORK (WABC) — According to Moody’s Investors Service, the NFL has the best credit among the major American professional sports, while the NHL has the worst.
Which is the birthplace of modern sport and sport management?
What is the oldest professional sports team in North America?
The Atlanta Braves are the longest-running club in North American sports.
What is the only sports league to ban corporate ownership?
Which professional sports league has outlawed corporate ownership? o The NFL is the only league in which corporate ownership of clubs is prohibited.
Which sport league uses a soft salary cap?
The NFL employs its scheduling system to promote competitive balance by assigning “easier” schedules to clubs with inferior records the previous season. A “soft” cap is something like the salary cap utilized in the NFL.
What area of law has left an indelible mark on the structure and nature of labor relations in professional sports?
For all public and private businesses, the National Labor Relations Act oversees the labor-management interaction. Except for Major League Baseball all professional sports organizations are free from antitrust regulations.
Does Ohio State have a sports management program?
For more than 40 years, Ohio State’s Sport Management department has educated students for leadership positions in the sports business.
Who created sports management?
James Mason, who helped establish one of the first sport management programs in the United States at Ohio University in 1966, was a pioneer in the field (evidence also exists of an earlier program at Florida Southern University from 1949 to 1959).
What is the difference between sports management and sports administration?
People who work in sports management are generally involved in public relations, marketing, or arranging team transactions. sports administration is mainly concerned with the day-to-day operations of a sports program.
Does UNC Charlotte have sports management?
“UNC Charlotte is in a unique position to provide real-world applications to the sports marketing and management curriculum.”
What is sport administration?
Within sports clubs and organizations, sports administrators are in charge of performing administrative responsibilities across a broad variety of activities. You may, for example, concentrate your efforts on marketing, fundraising, procurement, supply chain management, or general administration.
Does UCLA have a sports management major?
Many Bruins are perplexed as to why UCLA does not offer a sports management degree in light of its growing popularity. Sports management is an amazing opportunity for sports fans with business acumen to get into the industry.
Does NYU have sports management?
A Curriculum in Sports Management that is Cutting-Edge When you study sports management at NYU, you’ll be exposed to the industry’s dynamic potential and acquire the critical thinking skills necessary to succeed in an increasingly complicated market.
Does NYU have a good sports management program?
In the 2020 SportsBusiness Postgraduate Rankings, he is ranked #16 in the world. A complete overview of the numerous components of the sports industry is provided by this curriculum.
When was the concept of fantasy sport introduced?
Bill Winkenbach, then a part owner of the Oakland Raiders football club, convened with several pals in a New York City hotel in 1962 to form the first Fantasy Football league, which was named the GOPPPL (Greater Oakland Professional Pigskin Prognosticators League.
When and who started the modern Olympic Games?
In 1896, the first modern Olympic Games were held in Athens. Pierre de Frédy, Baron de Coubertin, was born into an aristocratic family in Paris in 1863. Boxing, fencing, horseback riding, and rowing were among his favorite activities. He was a staunch believer in the importance of sports in the development of mental energy.
Who is considered the czar of baseball?
Annotated Edition of Ban Johnson: Czar of Baseball (Contributions to the Study of Popular Culture).
What is the oldest stadium in Major League Baseball?
Fenway Park is a baseball stadium in Boston, Massachusetts.
What state has most MLB teams?
What is the #1 sport in America?
American football is a sport played in the United States
Which Big Four sports league is the oldest?
Major League Baseball (MLB) is a professional baseball league
Who won the 1st world Series?
Americans from Boston
Who was the first black person in baseball?
Despite the fact that Jackie Robinson is commonly regarded as the first African-American to play in the Major Leagues, historians at the National Baseball Hall of Fame believe Walker was the first, six decades before Robinson suited up for the Brooklyn Dodgers.
Are pro sports teams corporations?
Despite the fact that member teams are different legal entities from their leagues, they are exclusively governed by the league.
Do any corporations own sports teams?
Fifty-three professional sports teams are owned in some way by a corporation. The Atlanta Braves which are owned by Time Warner Inc.; the Anaheim Angels and Anaheim Mighty Ducks, which are controlled by Walt Disney Co.; and the Chicago Cubs which are owned by Tribune Co.
The “which company was the first modern sport business enterprise” is a question about which university has the first masters level sports administration program.
This Video Should Help:
The “money spent by sport participants, spectators, and sponsors is called” money. The first university to offer a Masters Level Sports Administration program was the University of South Carolina
- financing for sport businesses is unique because
- marketing is a unique aspect of sport management because
- which of the following is not a primary objective of general education courses?
- how are the terms sport and religion alike
- the power of sport as a social institution is seen in

domain: sports


text:
|Design||arched stone bridge|
Located some 6 km from the city centre, the bridge spans the small mountain River Besletka, and dates back to the late 12th century. Thirty-five meters in overall length (the arch itself is 13.3 m) and eight meters high, this single-arch bridge is one of the most illustrative examples of the medieval bridge design popular during the reign of Tamar of Georgia (r. 1184-1213) who is traditionally credited to have commissioned the construction of the Beslet bridge. A contemporary inscription in the early Georgian asomtavruli alphabet reads: "Christ the Lord, glorify in every possible way in both lives." An engraved cross and the Greek Τ have survived in the lower part of the left pillar of the bridge. A stone stele with Georgian inscriptions stood at the head of the bridge, but was lost during the War in Abkhazia early in the 1990s. In the vicinity of the bridge are ruins of medieval defense towers, a testimony to strategic importance of the locality.
Bridge of Besleti has been given the status of national importance monument.
|Wikimedia Commons has media related to Besleti Bridge.|

domain: history


text:
April 13 at 7pm
At LowellArts, 223 W Main St, Lowell, MI 49331
The Jukejoint Handmedowns describe themselves as a 'Big Tent' American Roots group whose eclectic set list mixes old school country & western, 70's AM pop radio hits, jazz standards, rock and roll, an extensive catalog of original material, and just about anything else that strikes their fancy.
LowellArts House Concerts feature musicians from Lowell, Greater Grand Rapids, and Lower Michigan, and are presented in the LowellArts Gallery. While listening to music, enjoy the exhibition that is on display. LowellArts is located at 223 W. Main St, Lowell, MI 49331. Tickets are $10 in advance, $12 at the door. For tickets, call LowellArts at 897-8545 or visit www.lowellartsmi.org.

domain: artistic


text:
With the USA being a major tourist destination, there are plenty of flights from London - Chicago. There are 16 major airlines flying to Chicago from London every day. Due to the competition there are ample opportunities to discover a cheap flight from London - Chicago. The main airport in Chicago is O'Hare International airport, the second busiest airport in the world. Departing from London Heathrow, a flight between London and Chicago takes about 8 hours. You can also find a flight between London and Chicago that lands at the other airport, Midway International Airport. O'Hare International lies about 15 miles outside the city of Chicago. Once you land in Chicago from London you'll want to get into the city as quickly as possible. There are taxi services, buses and car rental services there that will help you accomplish that. If you have saved money with a flight deal from London - Chicago you could splash out on a chauffeured limousine into the city.
To travel between London and Chicago at a low cost, Easyvoyage provides two major pieces of information: the calendar and the price history for London - Chicago flights. These elements will allow you to analyse the cheapest London - Chicago flights by departure date.
One of the most famous attractions in the city is the Skydeck, which is at the top of the Willis Tower, formerly known as Sears Tower. It has a glass platform called The Ledge which, at 1,353 feet off the ground, is not for the faint- hearted. Not only can you see most of the city, you can also see the four adjoining states to Illinois.2 The Chicago Bulls
If you like sports you'll know the Chicago Bulls basketball team. One of the most iconic teams in the NBA, due to the efforts of Michael Jordan during the 80's-90's. Catching a game at the United Center is a must for any sports fan.3 Cloud Gate
Cloud gate, nicknamed 'The Bean' by locals, is an art installation that can be found in Millenium Park. Designed by Anish Kapoor and officially unveiled in 2006, it is a mirrored stainless steel structure that has become a centrepiece of the public art installations found around the city.4 Chicago-style Pizza
There are many cities in the world famous for their food, but not many that can boast of their own unique variation of a classic. The deep-dish pizza is synonymous with Chicago. You can try one at Uno Chicago Grill, which is where it was first one was made in 1943 when the restaurant was known as Pizzeria Uno.5 The Museum Campus
The Museum Campus houses three of the cities greatest tourist attractions - the Shedd Aquarium, the Field Museum and the Adler Planetarium. Explore some of the finest exhibits and amazing displays of the natural world and the solar system.

domain: travel


What is Merino wool?
Itchy wool socks? No thank you! People usually picture something warm when they think of wool clothes. But they also question whether or not it is going to make them itch. That is a reasonable assessment. But Merino wool is just built different.
Merino is authentic wool. It is grown by the extremely hardy Merino sheep popularly found in New Zealand. These sheep can withstand single-digit temperatures in the winter and nearly triple-digit scorchers in the summer. And their wool helps them stay happy and comfortable. The result of these conditions is a natural fiber that is unrivalled in moisture management and body odor resistance. And it is very soft to the touch when spun into clothing. Plus, Merino sheep naturally need to be shorn or have their wool managed every year. This textile is a highly renewable resource.
We recommend Merino wool for next-to-skin pieces in the backcountry and high-output activities. Garments made from this material aim to keep you dry. Staying warm is simple when you are dry. Dry feet also blister less than wet feet.
Merino fiber works by pulling sweat away from your skin to the outside of the piece where the air can help to speed up evaporation. It does this while refusing to absorb the odor-producing bacteria created by your body.
In hot weather, you can look to pick up a lightweight layer for any part of your body, including your feet, and gain some sun protection as a bonus. Since Merino is a natural fiber that protects an animal’s skin in harsh conditions, it provides those same protective properties when woven into clothing. Sun-blocking capability varies from garment to garment. But it is still nice to have that extra assurance.
When the temperature drops, start looking for thicker layers. Smartwool’s Merino 150 baselayers are great for warm weather. The Merino 250 is excellent in winter. You can even try out a wool-insulated jacket for breathable heat containment that stays warm when wet.
Now that we’ve established how effective Merino is at wicking moisture and avoiding odor, you can see why they make great adventure socks. Just imagine taking off your socks after a long day of walking and not smelling something horrible after they have dried out.
Proper footwear is essential for life in the backcountry. Dry feet are happy feet. Fewer blisters on your soles mean less pain and agony during your trip. There are socks for all activities: running, snow sports, hiking, hunting, and everyday wear. The list goes on.
Be gentle with your precious wool. You will want these clothes to last for years to come. It is imperative to wash and dry them properly. Do not dry-clean or bleach your wool. Only cool iron them while avoiding any decoration if they need wrinkle management. To clean your Merino, wash them separately from other materials on a cool gentle cycle. Tumble dry on low or lay them out to dry. When you're on the go, you can rinse your clothes off in the sink with some gentle detergent and hang them up to dry. Some products may come with more specific instructions, but this should help you in general.
If there are any drawbacks to Merino, they are hard to think of. It is a slightly heavier material than other technical fabrics, but most Merino wool products make up for that by blending with polyester to reduce weight and boost durability. Its natural fibers are more resistant to abrasion and overuse when bound to another high-performance thread. A 100% Merino product would most likely be a very casual, lifestyle piece of clothing.
Merino wool is a must-have for the outdoor enthusiast. High-tech pieces of comfort make for a more enjoyable experience. And high-quality gear means you will not have to keep buying more and more products every year.


Sunday was cold with temperatures below seasonal average. Rained on and off for most of the day.
|From 2009 November weather|
The maximum daytime temperature today only reached 4.9°C the lowest for the month. More rain today too so we are now well in excess of the average rainfall for November. The meteorological office have warnings of severe weather for Sunday. Click here for details.
Note for Friday 27th
Our coldest day time temperature of the month.
Note for Thursday 26th
Temperatures back to average for November. Forecast is for colder weather by the weekend.
Note for Wednesday 25th
A blustery day with some sunshine and a few showers.
Note for Tuesday 24th
Cloudy and mild all day becoming windy and wet in the evening.
Note for Monday 23rd
More rain early morning then generally cloudy all day. We did have a few pleasant, but short sunny spells.


text:
More Deals & Coupons Like "DUNKIN APP: Buy a Tomato Pesto Grilled Cheese Sandwich, earn a free beverage reward (about value on large espresso drink)"
21 Jun, 1:40 amPotbelly BOGO sandwich 6/21, web & app purchases $0.01
Yesterday, 9:09 pmWendy’s Free Breakfast Sandwich Via App With Any Purchase Through June 30
Yesterday, 8:36 pmSelect SoCal Residents Only: Chick-fil-A App: Free Original Chicken Sandwich (Claim Reward by 10:30AM, Then Redeem Reward by Wed)
22 Jun, 3:34 amSelect SoCal Residents Only: Chick-fil-A App: Free Original Chicken Sandwich (Claim Reward by 10:30AM, Then Redeem Reward by Fri)
18 Jun, 2:46 amNEW Subway Coupon Codes For June~Buy One Footlong & Get One Free + More @ Subway Via App Purchase!
Yesterday, 2:18 pmTarget Circle™ Offers - 25% off Food & Beverage (YMMV)
21 Jun, 8:12 pmOrfeld Sandwich Maker $35.00 via Walmart + Free Shipping
21 Jun, 1:38 pmAeroPress Coffee and Espresso Maker: Sale $19.99
24 Jun, 11:11 pmKraft Original Flavor Macaroni and Cheese Meal (7.25 oz Box) $0.99
Today, 5:11 amSolo MacDougal Rolling Laptop Bag (Espresso) $55 $54.99

domain: food


Piano and violin students of the Clara Woolley Music Studio, Plymouth, provided a variety of sacred and secular Christmas music for holiday shoppers throughout the month of December at University Park Mall, Mishawaka. Piano solo and duet selections were played by Rebecca Shoue and Maggie Shoue, of North Liberty; Claire Marshall, of Culver; Erica Beatty, Brooklyn Beatty, Aimee Gladieux, Justin Gladieux and Jessica Gladieux, of Bourbon; Kristen Cordell, of Walkerton; Bobby Partridge and Michael Partridge, of Lake of the Woods; Rachel Badowski and Sharon Feitz, of Lakeville; and Patricia Nettrouer, Sarah Tanner, Andrea Finley, Jessica Drury, Korie Rice, Eric Johnson, Stephen Johnson, Pauline Dagaas, Britney Horvath, Elizabeth Brown, Beau Nissley, Rani Nissley and Micah Fryslie, of Plymouth. Violin solos with accompaniment and violin duets were played by Kelsey Cordell, of Walkerton; Matthew Partridge and Kristina Partridge, of Lake of the Woods; Sarah Toppe, of Rochester; and Emily Walder and Maja Howard, of Plymouth. Shirk's Piano and Organ, Mishawaka, "has been working with local malls for years, first Scottsdale and then after it closed, U.P.," said Mike Roth, vice president. Shirk's notifies some 300 music teachers in its database within a 50-mile radius, inviting them to sign up for blocks of time throughout December. "Close to 50 teachers participated," Roth said. "We cover the bases. There are little ones, junior high, high school, adults and senior adults. It's just a mix. There's a hammer dulcimer, high school choirs, a high school orchestra, piano and organ." They loan and tune a piano and organ, setting up in the center of the mall in front of what is now Macy's. It's an excellent opportunity for students to get practice playing in front of a large audience and for teachers to present their students' accomplishments for the public. That's what we like: win-win-win-win situations, for the music students, their teachers, the public and Shirk's. 'Yuletide Celebration' The Indianapolis Symphony Orchestra has been performing a very special Indiana holiday tradition since 1986 -- the Yuletide Celebration. I saw my first one in 1988. The company I was working for in Indianapolis held its Christmas party that year at the Circle Theatre, where I had served as a volunteer usher. It was one of my husband's and my first dates, so we have very fond memories of the evening. In the years since, I have been back several times. This year's was the best ever. Virtually all of the 16 singers have Broadway in their bios. If you ever have the chance to see N'Kenge, go. Of all the shining stars, she was the brightest, along with host Mike Eldred, who played the lead in Broadway's "Les Miserables." Gunn, 'Magic Flute' South Bend native Nathan Gunn sings the role of Papageno in this week's live radio broadcast of Mozart's "The Magic Flute," an abbreviated version in English, from New York's Metropolitan Opera at Lincoln Center at 1:30 p.m. Saturday on WSND, 88.9 FM. For the story background, visit www.operainfo.org. "Music Notes" appears Thursdays. If you have music news, contact Mary Jo Finley at (574) 936-7463.


This cop has obviously lost his mind. Jayar Jackson breaks it down on The Watchlist. Watch LIVE on weekdays at noon ET.
Host Jayar Jackson reacts to a must-watch list of videos of the day, which will cover news, politics, society, culture, current events, and more.
Help support our mission and get perks. Membership protects TYT’s independence from corporate ownership and allows us to provide free live shows that speak truth to power for people around the world. See Perks:
#TYT #TheWatchlist #JayarJackson
You know and people have a right to be Safe in their homes they have a right For their property to be safe even when Part of their home may be torn away and These looters that's unacceptable Absolutely unacceptable I would highly Suggest that if a looter breaks into Your home comes into your home or you're There to steal stuff that you take your Gun and you shoot him you shoot him so That he looks like grated cheese because You know what that's one looter that Won't break into anyone else's home and Take advantage of them when they're the Most vulnerable and the most weak This Chef Grady Judd talking about Looters coming to people's homes after Hurricane Ian make them look like grated Cheese keep that in mind shoot them on Site if you think they're looters shoot Them who cares when you give people a Broad Authority like this you have no Idea in what under what circumstances Their mindset is in especially after Disaster and also who they think are Looters which has also of course been Influenced by Society too but I just Want to make a a small Point here Because I get Petty with these things Um if you shoot someone up they probably Look like grated cheese that's more If You shred them their girls would look Like swiss cheese if you shoot them get It right first Grady anyways uh there's
The another ironic part about this whole Thing though as you see he's talking About if you see someone approach your Door get to shooting them because it's Your door it's your domain See if you recognize this guy uh saying This Sheriff Grady Judd tells us this was Quite the close call for the victim After the Father and Son fired seven Shots into her car she drove to this Circle K and called 9-1-1 now what I'm About to tell you you just absolutely Cannot believe Sheriff Judd says it all Started with a package delivered to the Wrong door on Saturday morning when a Neighbor realized that package of Medication was for 73 year old Gino Colin Costa he drops it off at the Correct address Sheriff Judd says Colin Cost and his 15 year old son received Alerts from The Ring camera of an Unknown person at the door So what do they do They think they're being broken into Are you kidding me The dude Is being a good neighbor and he simply Goes there and Returns the package to The appropriate address The dude is the same dude that said Shoot people on site when they approach Your house because they they're looters And they're running through your stuff
Either it goes up more about the story Because we did just do this a little While ago in case you guys uh remember That Um those the father and son in that Situation then came out started shooting At someone else that they thought was an Intruder looter whatever the hell it is Watch more All right I've got it I can call it Eastbound 62nd uh just passing 18. [Applause] These high rates Maddie's still black now passing 12th Street uh I know well Bravo see if we Can get some of these oh and he's going To lose it right here he crashed he's Crashing uh 62nd and it's gonna be just Shy of 10th Street on the south side of The road Eagle no one's got out of the car should Be three of them let's get FB rolling Pretty bad crash [Music] Looks like a normal maybe police chase Chase that ended badly but there's Layers to this that make it even worse Uh that crash had three teenagers in it 15 16 years old all three of them Uh before that car flipped and landed Badly Um Pinellas County Sheriff officers Happened to be in this area just Patrolling an unrelated theft of a car
Maybe something else in a building and They noticed an aerial shot of these Three teenagers walking up in the middle Of the night and they said let's see What they're doing and they found this Let's watch how this whole thing started Flight deputies witnessed three Juveniles later identified as Mario Bonilla keandra clang and Malachi Daniels steal an unlocked Maserati Patrol deputies intercepted and Attempted to stop the vehicle however it Accelerated to over 100 miles per hour [Music] [Applause] [Music] Probably surprised to see those cops on The net quickly when they thought no one Was there uh and also as they mentioned He said he's blacked out so the Headlights were not on at all uh really Quick let's show the aftermath because The NBC News reported how that car Crashed and then also again as they said One of those teenagers happened to not Make it after that crash but um the Aftermath is and look at this car was Crazy let's watch this The Sheriff's Office says the teens kept Walking until arriving at 28th Street Where a 2016 Maserati was parked outside A home Sheriff Gutierrez says a 15 year Old teen was seen walking up to the Vehicle to check if it was open
And he used a shirt to open the door Handle of the car the team discovered The Maserati was unlocked with the keys Inside that's when the sheriff says the Team decided to take it for a drive Along with a 15 year old and 16 year old Passenger the teen driver pulled out of The driveway with no lights on and took Off onto 62nd Avenue North the car Starts fishtailing over the road he had No control over the car at that point The car runs up over the curb runs Across the sign of the business behind Me the car flips the teens were all Pinellas County Schools students Sheriff Terry says they snuck out of their home But it wasn't their first time nearly a Month ago they got in trouble by the Kenneth City Police Department for Walking in a residential area at four in The morning wearing all black clothes With their faces covered Sad story uh the they said the 15 year Old sit in the front uh pastors he died For the driver who I think was 16 is Getting charged with murder because it Was middle of a a crime being conducted


text:
Flashcards in Dentistry Final Deck (94):
General sequence for complete Prophy
Oral cavity evaluated, large pieces of calculus removed, periodontal area probed for pocket depth & presence of subgingival calculus.
Subgingival calculus removed, teeth evaluated, degree of disease evaluated, further diagnostic tests performed.
Medium. Most common head type. Labradors and DSH, ex.
Short wide heads. Commonly results in crowded and rotated premolars.
Boxers, Persians ex.
Long narrow heads.
Collies, seal point Siamese ex.
Incisal and maxillary bones hold the teeth.
Portion of the roof of the mouth that consists of hard bone. Covered with mucous membrane w/irregular ridges called "Rugae palatinae"
Posterior portion of roof of the mouth, no underlying bone. Separates the oral cavity from the pharynx.
Lateral palatine fold or fauca
The area in which the two jaws join in the back of the oral cavity
Lower jaw. Covered by muscle and skin ventrally, mucous membrane becomes the gingiva at the mucogingival line
Hinge joint that joins mandible to maxilla
Vestibule of oral cavity
Part of oral mucosa between the cheeks or lips and the alveolar ridge (teeth/gingiva)
Part of the tooth above the gumline covered in enamel
Hardest substance in the body. Covers the crown of the tooth, above the gumline. Produced by ameloblasts.
Indentation close to the gumline where the enamel thins.
Also called cementoenamel junction or cervical line
Underneath the gumline, sits in the socket (alveolus)
Deepest part of the root.
Prophylaxis or Prophy
Prevention or protective treatment for disease
Where blood vessels and nerves enter the tooth
Apical delta (small channels)
Apical foramen (larger canals)
Tip or pointed prominence on the occlusal surface of the crown
Make up the bulk of the tooth, produced by odontoblasts
Innermost portion of the tooth. Lined by odontoblasts and contains nerves, blood vessels, different cells and fibrous tissue
Portion of the pulp chamber below the gumline
Hardening and tighter attachment of the epithelial tissue of the attached gingiva that makes it able to withstand chewing
The portion of gingiva that is not directly attached to the tooth or supporting structure
Free gingival groove
Slight groove between free and attached gingiva
Area between free gingiva and tooth when healthy and without a space
Space between free gingiva and tooth. Considered diseased tissue when periodontal disease is present
Less densely keratinized gingival tissue covering the bones
Structures that support the tooth: periodontal ligament, cementum, sharpey's fibers, alveolar bone
Fibrous structure that holds tooth In place in the socket
Material that can repair itself if damaged and attaches periodontal ligament ti the tooth
Bone of the jaw in which the tooth rests
Dental formula for puppy
2x(3/3 i, 1/1 c, 3/3p)=28
Time line for puppy teeth
Primary incisors erupt at 3-4 weeks, canines at 3 weeks; premolars from 4-12 weeks.
Fall out (exfoliate) about 1-2 weeks before adult teeth eruption
Adult dog dental formula
2x(3/3 I, 1/1 C, 4/4 P, 2/3 M)=42
Used for gnawing and grooming
Used for holding and tearing
Used for cutting and breaking up
Used for grinding
Dog adult teeth timeline
Incisors erupt at 3-5 months, canine & premolar at 4-6 months, molars at 5-7 months
Kitten dental formula
2x(3/3 i, 1/1 c, 3/2 p)=26
Kitten teeth timeline
Incisors erupt at 2-3 weeks, canines at 3-4 weeks, premolars at 3-6 weeks
Cat dental formula
2x(3/3 I, 1/1 C, 3/2 P, 1/1 M)=30
Cat adult teeth timeline
Incisors erupt at 3-4 months, canines at 4-5, premolars at 4-6 months, molars at 4-5 months
Dog teeth with one root
Incisors, canines, first premolar, mandibular third molar
(101-105, 201-205, 301-305, 311, 401-405, 411)
Dog teeth with 2 roots
Maxillary second and third premolars; mandibular second, third, and fourth premolars; mandibular first and second molars
(106, 107, 206, 207, 306-310, 496-410)
Dog teeth with three roots
Maxillary fourth premolar, and first and second molars
Cat teeth with one root
Incisors, canines, maxillary second premolar
101-104, 106, 201-204, 206, 301-304, 401-404)
Cat teeth with two roots
Maxillary third premolar, mandibular third and fourth premolars, mandibular first molar
(107, 207, 307-309, 407-409)
Cat teeth with three roots
Maxillary fourth premolar
Tooth in the cat with a varying number of roots
Maxillary first molar (feline)
The area in which the roots join the crown. In two-rooted it is bi-, in three-rooted it is Tri-
The direction toward the outside of the teeth
Toward the cheeks
Toward the middle of the mouth
Palatal for the maxillary
Lingual for the mandible
Side of the tooth closest to the center line of the dental arch
Side of the tooth farthest from the center line of the dental arch
Direction towards the crown
Toward the root of the tooth
Area between two teeth
The way teeth fit together. Cats and dogs have a "sectorial" one with chewing occurring on the sides of the teeth.
Anatomic numbering order
Right/left, maxillary/mandibular, ordinal number, type of tooth
Teeth missing in a cat
Maxillary First premolar, mandibular first and second premolars (105, 205, 305, 306, 405, 406)
Rule of four and nine
The canine tooth is always 04 and the first molar is always 09 regardless of how many teeth are actually in the mouth
Matrix of connective tissue consisting of bundles of strong collagenous fibers connecting periosteum to bone
The tissue that lines most of the oral cavity outside the mucogingival line, ends at the lips.
Normal sulcus depths
0-3 mm in dogs
0-1 mm in cats
A defect in enamel production
Junction between the gingiva attached to the underlying bone (attached gingiva) and the flap overlying the tooth (free gingiva)
Free gingival margin recedes towards the tooth root and the neck/root structure becomes exposed
Bacterial layer that forms on the teeth
Dead bacteria on the tooth that has calcified
Inspects for plaque and calculus that was missed during the prophy
Fracture class 1
Enamel fx. Chip fracture, enamel loss. Most do not require tx
Fracture class 2
Uncomplicated crown fx. Enamel and sentinel, but no pulp exposure.
Fracture class 2b
Complicated crown fx. Enamel, dentine, and pulp exposure
Fracture class 3
Uncomplicated crown-root fx. Fracture of the crown and root that does not expose pulp
Fracture class 3b
Complicated crown-root fx. Fracture of the crown and root that exposes pulp - aka slab fracture
Fracture class 4
Root fracture, non salvageable
Mandibular teeth in contact with palatal side of maxillary teeth
Absence of teeth
Space between two adjacent teeth not in contact with each other
Extracting primary teeth, prevent malocclusion, removes possible obstruction
Partial displacement of the tooth
Complete displacement of the tooth
Oral nasal fistula
Abnormal opening into the nasal cavity
Benign, caused by periodontal disease
Iatrogenic orthodontic disease
Attempts to correct orthodontic problems
Inflammation of the gingiva
Infection of the structures surrounding the tooth (periodontium)
Root canal therapy
Friction on teeth due to external objects (bars, toys, etc)
Friction of teeth rubbing against each other due to occlusion

domain: biology


The Buffalo Bills did not acquire running back LeSean McCoy in a trade to have him splitting the rushing duties. According to McCoy’s teammate and longtime Bills’ running back Fred Jackson, the team has some pretty hefty plans for McCoy this season.
“I don’t know exactly what my role is going to be,” Jackson told WGR-AM. “They say that they want Shady to get 300-plus carries next year. So that’s a guy you’re feeding the ball all the time. So I’ll be ready when my number is called.”
As for Jackson, he was the lead ball carrier in 2014 with 141 carries resulting in 525 rushing yards and two touchdowns. He is sure to see a dip in production this season. Bills running backs coach Anthony Lynn reportedly claimed that they are going to cut Jackson’s carries in half “to produce a fresher Fred Jackson and a more explosive Fred Jackson.” (via the Buffalo News).
The question is now whether Jackson, 34, will even make the Bills’ final roster once training camp concludes. The team is stacked at the position with Bryce Brown, Anthony Dixon and fifth-round draft pick Karlos Williams.
Earlier in the year when McCoy joined the Bills, Jackson said Shady would have to fight to steal the starting job from him. It now appears that Jackson will have to fight just to remain on the team.
Photo: USA Today Sports


text:
You can play ROMs on your computer system by grabbing them. These types of files are categorized matching to gaming systems. You can choose which ones you need to play and save all of them on your harddisk. If you have a conveyable version of the game, it might not work on your pc. If not, then you can down load it on the web. Alternatively, you can get a copy of your game. The choice is usually entirely your own.
After transfering the game titles, you can set up them by using the range of motion folder that you have mounted on your pc. You can pick the games that you want to install. The rom file is located in your hard disk. The games are organized in categories. If you see a video game that you want to put in, go to that folder and choose one. This pokemon emerald game rom is definitely an easy method and will require much time. But it’s important to recognize that you can’t down load any online games online.
To download a, first get the rom folder on your own hard drive. The folder might contain all the video gaming that are attached with your computer. Afterward, choose which usually types you want to set up. Once you’ve mounted the games, you can start playing them. Once you have installed all of them, you’ll need to install the range of motion. Kids of action folder might contain all of the different rom files that are available in your hard drive.

domain: game


text:
Adding more LS
would be fine but do not put it in all at once. You would do better to add only ˝" or so at a day to allow the "critters" in the sandbed to migrate to the surface.
I find using a small plastic cup best. Allow it to sit just a hair below the surface of the water in the tank until it fills slowly with water. The gentley ease it down to the bottom and ease it out. Don't dump, just let it slide out easy. It would be a good idea to turn off the powerheads in the area you work on. The few minutes it will take won't do any harm but will lessen the murkiness.
No need to worry about the fish. I swapped out my CC
for sand with a "full" tank (rock, corals and fish) and did not move a thing (or lose any either

domain: design


text:
Heavy Snowfall in West Lothian, Wednesday, 4th April 2018Add to Lightbox Download
Heavy Snowfall in West Lothian, Wednesday, 4th April 2018
More heavy snow fell in West Lothian this afternoon causing traffic problems for drivers.
An accident on the A899 in Livingston caused long tailbacks heading north
Alex Todd | EEm
- Alex Todd/ Edinburgh Elite media
- Image Size
- 3793x3018 / 1.1MB

domain: news


text:
The morning private afterparty
Small birthday party
Full analog process, Pentacon Six TL CZ Jena 80mm , Ilford HP5 Plus
& my sweetie
all photos taken with a cheap 18-70 mm Nikkor DX lens
Jiri Havrda and me 😁
Full analog process, Canon EOS 500N
One of the memories of Sicily. It’s been a few years since I started paragliding. This image is from Montagna Grande near the city of Trapani. At night we had to explain to the police that we came to Sicily to dive :). I will not forget their strict view and words: No volare… no parapendio !

domain: geography


After the confirmation that Jim Ross and Jerry Lawler both will be appearing at the upcoming Raw 25th-anniversary episode, WWE has confirmed several more names for the upcoming show.
Below is an updated list of stars confirmed to be a part of the January 22nd episode of Raw, including none other than the Texas Rattle Snake, Stone Cold Steve Austin:
Free agent John Cena
WWE Universal Champion Brock Lesnar
WWE Hall of Famers Jim Ross and Jerry Lawler
WWE Hall of Famers Kevin Nash and Scott Hall
WWE Hall of Famer Ric Flair
The Bella Twins
JBL and Ron Simmons
The Dudley Boyz
WWE Hall of Famer Steve Austin
DX: WWE Hall of Famer Shawn Michaels, Triple H, and The New Age Outlaws
It’s worth mentioning here that apart from these legends, superstars from both Raw and SmackDown Live will also be appearing at the event.


They Tried to Shut Me Down But I'm Going to Keep Telling the Truth
Get the most useful specifications data and other technical specs for the Nissan Murano 4-Door S AWD V6. See body style, engine info and more specs. Maybe if I were younger I would have gotten the SE but the SL seemed to fit me better.:cool: Nissan Murano SL AWD Midnight Blue / Cafe Latte Leather. Nissan Murano SE, centered wide dash shot. Nissan Murano SE, speedometer/tachometer. Nissan.
Used Nissan Murano SE - Specs & Features ; hp @ 5, rpm · lb-ft @ 4, rpm · 24 · Double overhead cam (DOHC). The Murano is powered by Nissan's beefy liter V6, the same engine found in the Z sports car, putting out horsepower. It comes with a continuously. Accelerations, 1/4 mile time and top speed for Nissan Murano SE AWD (cont. variable) ( kW / PS / hp). Performance review with mph.


text:
AUCASSIN & NICOLETE, by Vojtech Preissig & Andrew Lang - 1931 [Signed Ltd Ed]
Aucassin et Nicolete
illustrations by Vojtěch Preissig
translation by Andrew Lang
SIGNED by V. Preissig, Limited Edition, published by: Limited Editions Club, 1931.
Hardback is overall in VERY GOOD- condition.
- Vintage illustrated cloth covers with geometric patterns.
- Boards exhibit some dirt and edgewear with gently bumped corners, and some board at corners, near spine, and 3" from spine at back head edge.
- Spine features bright gilt title and design.
- Spine ends are broken and chipped, moreso at foot where 1/2" of cloth is missing. Some cracking along edge, and across head.
- Binding remains secure.
- Original pastedowns are free of writing with decoration near the hinges.
- Close examination reveals cracked gutter at first decorated page.
- Handmade paper displays typical uneven edges fore and foot, some of which are lightly bumped.
- Head of text block was inked in yellow. Foot edge of pages shows a little age warping in most of book.
- Illustrations and designs remain clear and crisp throughout.
- Interior is gently age-toned.
- Inside pages are free of writing and intentional marks.
- Book may exhibit additional minor signs of age or wear.
77 pages. 8 x 11.75 inches.
Hand-numbered as #1364 of 1500 printed.
Back flyleaf reads "This edition of Aucassin and Nicolete consists of fifteen hundred copies published for the members of the Limited Editions Club. It was designed and illustrated by Vojtech Preisseg; printed in the Preisseg type and decorative material, on J. W. Zanders hand-made paper, by the Statni Tiskarna in Praha; and bound by A. Tvrdy of the same locality, in Czekoslovakia. This copy is number 1364" -- followed by Vojtěch Preisseg's signature.
A retelling of the classic medieval--12th or 13th century--French chantefable (ie., story-song). Most likely intended as a performance, it is a parody play, mostly of the Arthurian romance. The prose and poetry are written in a style reminiscent of old English verbiage (ex., thou hast).
A visually rich presentation of this story, it is lavishly illustrated throughout in 4-colors, with some pictures inline, to offer at least one image per opening. Each page includes design elements, with titles for full-page illustrations.
Vojtěch Preissig (31 July 1873 – 11 June 1944) was a Czech typographer, printmaker, designer, illustrator, painter and teacher. [Wikipedia]
AS IS! Please see photos. More photos available upon request.
International first class shipping includes a handling charge to cover insurance.
Domestic orders over $250 include a handling charge to cover signature confirmation.

domain: library


text:
Budget 2014: American corporate houses ready to pump money into India
Anticipating major economic reforms in the maiden budget to be presented by the new Indian government, Corporate America has said it is ready to invest in IndiaJuly 09, 2014 | comments ( 0 ) |
Anticipating major economic reforms in the maiden budget to be presented by the new Indian government, Corporate America has said it is ready to invest billions of dollars in India but the budget must match "pragmatism with unbridled enthusiasm".
Through this budget, the Obama Administration, policy makers, corporate sector and economists in the US are hoping to see a strong sign of a the major economic reforms which were promised by Prime Minister Narendra Modi during his election campaign.
At the same time, they are also expecting some tough unpopular measures to be announced, which India watchers in the US believe are necessary to bring the economy back on track and revive the annual growth rate of more than eight per cent.
Corporate America is hoping that Finance Minister Arun Jaitley, who will present the budget tomorrow, would bring in an era of clarity, predictability and transparency in the system that would help in creating an investment-friendly environment.
US India Business Council (USIBC) sees this budget as an extremely important opportunity for India's administration to begin to meet the high expectations of both Indian and international industry, said USIBC acting president Diane Farrell. "The global community is ready, with billions of dollars in long-term capital, to increase investment in India," Farrell said.
"Critical policy reforms, including reversing the harmful retrospective tax amendment and passing insurance FDI liberalisation with full voting rights to 49 per cent, will help boost the economy and get the investment climate back on track," Farrell said. Ron Somers of the India First Group said, "The world will be watching Prime Minister Modi's first budget. To attract a herd of investors rushing to India, this budget, more than others in the past, must match pragmatism with unbridle .. enthusiasm. This is India's moment." "In a word, boldness is the need of the hour. The earlier government had shied away from using India's budget to announce 'big bang' reforms, but just such a shock is needed more than ever," Somers said.
"In a word, boldness is the need of the hour. The earlier government had shied away from using India's budget to announce 'big bang' reforms, but just such a shock is needed more than ever," Somers said.
Richard M Rossow, Wadhwani Chair in US India Policy Studies at the Center for Strategic and International Studies, noted that the impact of the actual budget itself is perhaps a bit oversold these days as compared to a decade ago when customs duties were high and there were major differences in the tax treatment of different industries and products. "Now that rates are down and tax treatment is more common across industries, the budget's impact on the economy is less important than the other changes that take place throughout the year, reducing the timeline for projects to break ground, lifting FDI caps, sector regulation, etc.
"The Budget Speech, of course, is expected to highlight many of these reforms the government intends to adopt," Rossow said. Noting that market sentiments and business mood are positive under the central government led by Prime Minister Modi, President of USA-India Chamber of Commerce Karun Rishi said this is the time to take tough decisions to jumpstart the economic growth and curb inflation. "There is no magic bullet. Some key growth oriented budget announcements on taxation .. FDI, disinvestment, infrastructure and controlling deficit can help shape the fiscal policy direction. Investors like clarity and transparency. The Finance Minister must come out with pragmatic measures to give boost to the economic growth instead of announcing populist measures," Rishi said. "Substantial allocations should be made towards health. Healthy citizens are the backbone of an economic power. 2014 budget must increase outlay on medical research & development, biotechnology . access to innovative medicines, education and hygiene. Budget must send clear message to boost pharma R&D and make India an innovation hub with global partnerships," he said.
- Reliance Retail & Jio to jointly launch new e-commerce platform
- CCI gives nod to Samara Capital-Amazon's joint bid to buy More
- SoftBank eyes 40% stake in FirstCry for $400 million
- Vivo India launches 'Vivo Xchange' program in partnership with Cashify.in
- Milkbasket expands operations to Bengaluru
- Manyavar launches another store in Punjab
- Ola raises Rs 150 crore from Flipkart's Co-Founder Sachin Bansal
- Ananth Narayanan steps down as Myntra Jabong CEO
- DailyNinja celebrates 15 million orders fulfilled
- John Jacobs looks to garner Rs 500 crore revenue by March 2021

domain: politics


text:
Positive effects of breastfeeding on the health of infants include:
Breastfeeding reduces the risk of acute infections such as diarrhoea, pneumonia, ear infection, haemophilus influenza, meningitis and urinary tract infection (WHO 2007).
Lower risk of developing necrotising enterocolitis in preterm and low birth weight infants (King 2005; Boyd et al 2007).
Breastfeeding has a preventative effect on the early development of asthma, allergic rhinitis, atopic dermatitis and food allergy symptoms (Schanler & Atkinson 2005).
Breastfeeding improves cognitive development (Kramer et al 2008).
It promotes the maternal-infant relationship (Kramer et al 2008).
It also protects against chronic conditions in the future such as type 1 diabetes, ulcerative colitis and Crohn's disease (WHO 2007).
Breastfeeding during infancy is associated with lower mean blood pressure and total serum cholesterol, and with lower prevalence of type 2 diabetes, overweight and obesity during adolescence and adult life (WHO 2007).
It is always available, at the right temperature and free!
The World Health Organisation (2007) recommends exclusive breastfeeding for the first six months of life.
It is recognised that the health of preterm babies benefits greatly from the ingestion of their mothers breastmilk due to a number of factors including the presence of active enzymes that enhance the maturation of the underdeveloped gut, anti-infective properties which protect the newborn from infection and earlier tolerance of full enteral feeding (Boyd et al 2007).
Despite the benefits of breast milk, the nutrient levels in breast milk may not fully meet the increased nutritional needs of the preterm infant, particularly energy, protein, sodium, calcium, phosphorus and some vitamins (King 2005; Edmond and Bahl 2007; McCormick et al 2009).
Preterm infants who have accumulated deficits in calcium and phosphate by the time of hospital discharge have a higher risk of low bone mineralisation, metabolic bone disease and slow skeletal growth compared to infants born at term.
Fortification of expressed breast milk (EBM) can minimise these deficiencies in preterm infants <32 weeks gestation and infants with a birth weight <1500g (Edmond and Bahl 2007)(Rationale 2).
Other babies may benefit from having their EBM fortified but their requirements will be different to those of the preterm infant (Rationale 3):
Infants who are fluid restricted, eg those with cardiac or renal anomalies.
Infants who are failing to thrive due to increased requirements or losses, eg in malaborptive states.
When fortification is required, an aseptic technique must be used when handling the EBM (Shaw & Rathwell 2010)(Rationale 4).
Methods of increasing the nutritional intake of the preterm infant
The first step to improve nutritional intake should be to slowly increase the volume of EBM given (Rationale 5). Well preterm infants >1500g can tolerate up to 220ml/kg (King 2005) although an iron supplement will be needed.
If the maximum volume of EBM tolerated provides inadequate nutrition for growth, then fortification should be considered. A commercial breast milk fortifier (BMF) has the advantage over suplementing with a liquid preterm formula (Rationale 6).
Supplementation with a source of energy alone is not advised (King 2005)(Rationale 7). A multi-nutrient BMF is recommended.
How to add breast milk fortifier to EBM on the ward
This procedure should be carried out as an aseptic non-touch technique in a clean area of the ward. (Shaw & Rathwell 2010)(Rationale 8). Use the ward milk kitchen when available (Rationale 9). It should be done as close to the feed time as possible (Rationale 10).
The decision to fortify EBM for a preterm baby must be made by the medical consultant (Rationale 11).
The breast milk fortifier must be prescribed by the medical staff on the infant's prescription chart (Rationale 12). Urea and electrolyte levels must be carefully monitored (Rationale 13). Serum copper and zinc levels should be checked when starting BMF (Rationale 14).
Repeat serum levels of copper and zinc after two weeks and then monthly thereafter (Rationale 15).
Fortification of EBM should be performed by a trained member of staff. In certain circumstances, this may also be done by the mother under supervision (Rationale 16).
Check the following:
Add the prescribed fortification ie NUTRIPREM BMF to the correct amount of feed (Rationale 20):
- To make ½ strength feed - add one sachet to 100ml EBM.
- To make full strength feed - add one sachet to 50ml EBM.
Shake the bottle vigorously for 30-60 seconds (Rationale 21)
Label and date the bottle and fed the fortified EBM immediately (Rationale 17).
Ideally the feed should be given within 10 minutes of fortification (Rationale 22).
If the fortified feed cannot be given immediately, seal and place in the milk feed refrigerator on the ward. Use within 24 hours (Rationale 23).
Any excess defrosted EBM that has not been fortified must be discarded if not used within 24 hours (Shaw & Rathwell 2010)(Rationale 24)
Any fresh EBM should be refrigerated or frozen for later use (Shaw & Rathwell 2010) (Rationale 25).
Rationale 1: It is species specific.
Rationale 2: Breast feeding is not usually possible in infants < 34 weeks gestation therefore breast milk must be expressed (Schauler & Atkinson 2005).
Rationale 3: Preterm and term infants have different nutritional requirements.
Rationale 4: To prevent contamination of the EBM.
Rationale 5: Nutritional adequacy can be achieved if sufficient feed volumes are given (King 2005).
Rationale 6: It will allow more of the mother's milk to be used (King 2005).
Rationale 7: It will reduce the protein-energy ratio to an unacceptable level (King 2005).
Rationale 8: To prevent contamination of the feed.
Rationale 9: To avoid loss of immunological factors.
Rationale 10: To prevent a rise in osmolality of the feed which can begin within 10 minutes of fortification (King 2005).
Rationale 11: To ensure that addition of BMF is clinically indicated and safe.
Rationale 12: To ensure the correct dose is given.
Rationale 13: Infants receiving BMF have shown raised urea, calcium and phosphate levels.
Rationale 14: To obtain baseline levels of these nutrients.
Rationale 15: To monitor any decline in copper and zinc status.
Rationale 16: To ensure that the prescription is accurately implemented.
Rationale 17: To ensure that this is a safe procedure.
Rationale 18: To prevent wastage of EBM.
Rationale 19: To prevent contamination of EBM.
Rationale 20: To ensure that the nutrient value of the feed is increased as prescribed.
Rationale 21: To ensure an even distribution of fortifier in the breast milk (manufacturer recommendation).
Rationale 22: To minimise bacterial growth and a rise in osmolality.
Rationale 23: To ensure that the feed is safely stored at the correct temperature.
Rationale 24: To minimise bacterial growth and prevent contamination.
Rationale 25: To ensure safe storage of the EBM.
Boyd CA, Quigley MA, Brocklehurst P (2007) Formula versus donor breast milk for feeding preterm or low birth weight infants. Archives of Disease in Childhood 92: 169-175.
Edmond K, Bahl R (2007) Optimal Feeding of Low-birth Weight Infants: Technical Review. Geneva, WHO.
King C (2005) Feeding and Nutrition in the Preterm Infant. Oxford, Churchill Livingstone
Kramer MS (2008) Breastfeeding and Child Cognitive Development. Archives of General Psychiatry 65: 578-585.
Meyer R (2009) Feeding practices in the first six months of life. Journal of Family Health Care 19(1): 13-16.
Schanler RJ, Atkinson SA (2005) Nutrition in Paediatrics. Ohio, Digital Education Publishing Inc
Shaw V, Rathwell A (2010) Clinical Guideline: Expressing and handling breast milk. London, Great Ormond Street Hospital for Children NHS Trust
World Health Organisation (2007) Evidence on the Long-Term Effects of Breastfeeding: Systematic Reviews and Meta-analyses. Geneva, WHO
Document control information
Annette Rathwell, Neonatal Nurse Advisor, NICU
Vanessa Shaw, Head of Dietetics, Dietetics
Annette Rathwell, Neonatal Nurse Advisor, NICU
Clinical Practice Committee
First introduced: 16 September 2004
Date approved: 3 October 2011
Review schedule: Two years
Next review: 2 October 2013
Document version: 4.0
Replaces version: 3.0