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Correspondence to: Jan Hendrik Niess, MD, Department of Internal Medicine I, Ulm University, Ulm University Street, Helmholtzstr, 8/1, Ulm 89031, Germany. firstname.lastname@example.org
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The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specific intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.
The intestinal innate and adaptive immune system has evolved in response to potent stimuli derived from constituents of the commensal microflora. In most cases these local immune responses achieve tolerance to the intestinal microflora and food antigens. Defects of the tightly regulated mucosal immune responses are assumed to result in inflammatory bowel disease (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC)[1,2]. Local T cell immunity is an important compartment of the specific intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by dendritic cells (DCs) that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance[3-5]. DCs reside in mucosal tissues or recirculate in the blood and lymphoid tissues. The lamina propria of the small and large intestine are effector sites of mucosal tissues. Inductive sites are Peyer’s patches (PP), intestinal lymph follicles (iLFs), DC aggregates and mesenteric lymph nodes (MLNs) (Table (Table1).1). The local microenvironment influences the phenotype of DCs, a heterogeneous population that can be divided into conventional DCs (CD8α+CD11b-, CD4+CD11b+, CD4-CD11b+)[7,8] and plasmacytoid DCs (B220+CD11clow) (Table (Table2)2) and are characterized by a remarkable plasticity between DCs. In the lamina propria of the small and large intestine, DCs are ideally situated to survey the constituents of the commensal microflora and monitor food antigens. After antigen recognition at peripheral sites DCs migrate to regional draining lymph nodes to initiate (innate and adaptive) immune responses. This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.
The lamina propria of the small intestine is populated by CD4-CD8α- cDCs. Only 2%-5% plasmacytoid DCs reside in the small intestinal lamina propria. Mucosal DCs can be discriminated into DCs that express CX3CR1 (the receptor for fractalkine/CX3CL1) and into DCs that express the integrin αE chain CD103[13,14]. CD103+ DCs originate from Ly-6ChighCCR2high monocytes. Conversely Ly-6ClowCCR2low monocytes repopulate CX3CR1+CD11b+ mucosal DCs. CX3CR1+CD11b+ DCs directly access the intestinal lumen by extending transepithelial dendrites in a CX3CR1-dependent manner to survey the intestinal lumen, whereas CD103+ DCs induce the expression of CCR9 and α4β7 integrin on cognate CD4 and CD8 T cells to facilitate homing of T cells to small intestinal tissues[13,16] and induce the differentiation of regulatory T cells (Tregs) in the absence of exogenous cytokines.
The cLP is populated by CD4-CD8- DCs which endocytose and process antigens and induce T cell proliferation. Compared to their splenic counterparts TLR-4, -5 and -9 expression by colonic CD4-CD8-C DCs is low. Only few CD8+ and plasmacytoid DCs are found in the cLP. In human biopsies from colonic tissues, CD3-CD14-CD16-CD19-CD34- DCs with an immature state with low TLR-2 and -4 expressions were observed. In addition the presence of CD83+ and DC-SIGN+ DCs was described. Human and mouse mucosal DCs are assumed to be less responsive to microbial-derived TLR-ligands compared to spleen or blood born DCs Despite the functional subspecifications of DCs, DCs are characterized by a remarkable plasticity between DCs which is influenced by the local environment, the antigen itself or the activation state of the DC[9,20].
PP, iLF, CP and DC clusters of the small and large intestine belong to the gut associated lymphoid tissues (GALTs), secondary lymphoid structure, which lack in contrast to lymph nodes the afferent lymph and are located in close proximity to the intestinal epithelium. In PP the subepithelial dome regions beneath the follicle-associated epithelium can be discriminated from follicular and interfollicular regions, which serve as inductive sites where immune responses are primed. Specialized epithelial cells, the M cells, deliver luminal antigens to DCs located in the subepithelial dome regions beneath the follicle associated epithelium. The subepithelial dome regions are populated with CD8α-CD11b+B220- DCs and with CD8α-CD11b-B220- DCs[22,23]. By expressing high concentrations of the chemokines CCL20, CXCL16 and CCL9, the follicle-associated epithelium creates a specific micromilleu that allows DCs to selectively migrate towards the follicle associated epithelium[24,25]. Upon pathogen challenge CCR6+ DCs which are located in the interfollicular regions are recruited towards the follicle-associated epithelium to process microbial antigens, and to facilitate rapid local adaptive immune responses. In the absence of CCR6 in CCR6GFP/GFP mice CX3CR1+ DCs that lack CCR6 expression reside in the follicle-associated epithelium[23,26]. In the interfollicular regions CD11b-CD8α- and CD11b- CD8α+ DCs as well as plasmacytoid DCs are found that produce IL-12 and IL-10, and induce the differentiation of IFN-γ secreting TH1 cells, whereas the CD11b+ subsets produce low IL-12 and high IL-10 levels and prime IL-10 producing T cells[22,27]. CD8-33D1+ DCs, but not CD8α+DEC205+ DCs are specialized to present processed antigens in a MHC class II dependent manner to CD4 T cells. Reoviral antigens are sampled and processed by CD11b-CD8α- DCs to initiate TH1 adaptive immune responses likely resulting in protective host defence to viral antigens.
Intestinal lymphoid aggregates (iLAs) can be discriminated from PP, which comprises iLF and CP that are closely associated with the epithelial lining in the small and large intestine. CP were defined as tiny aggregates of c-Kit+IL-7R+ cells, whereas iLFs are constituted by solitary B follicles that are localized in the anti-mesenteric regions of the intestinal wall, and contain small numbers of mature T lymphocytes, but also c-Kit+ and IL-7R+ cells[32-34]. By analyzing large numbers of such aggregates, the classification of iLA into CP and iLF was recently challenged showing that most of them display properties intermediate between CP and iLF and were termed small intestinal lymphoid tissues (siLT). In the large intestine, subepithelial DC aggregates locate in the regions of cLP where inflammation develops. DC aggregates are formed by CD8α+, CD8α- and B220lo DCs. DCs with high MHC II expression, but low expression of the costimulatory molecules CD40, CD80 and CD86 extend transepithelial dendrites into the intestinal lumen. During colitis induced by adoptive transfer of CD45RBhi CD4 T cells into immunocompromised RAG mice, FoxP3 regulatory T cells accumulate in colonic DC aggregates producing TGF-β suggesting that DC aggregates are important structures to regulate inflammation.
Luminal antigens are sampled by lamina propria DCs and by DCs located in PP, CP, iLF and DC clusters at the base of intestinal villi. The DCs transport the sampled antigens via the lymph to MLN, where naïve T cells are primed and adaptive immune responses are induced (Figure (Figure1).1). In MLN, blood-born DCs and DCs that originate from PP or the lamina propria are present. In MLN, blood-born DCs are assumed to express CD8αhiCD11b-αLintβ7int and CD8α-CD11bhiαLloβ7lo DCs, whereas DCs derived from mucosal sites are characterized by CD8αintCD11b-αLloβ7hi and CD8α-CD11bhiαLloβ7hi expression, allowing the discrimination of DCs of distinct origins. CCR7 expression guides lamina propria DCs to MLN. Blood-born DCs enter the MLN via interactions with mucosal addressin cellular adhesion molecule (MAdCAM-1) and peripheral node adressin (PNAd) expressed by high endothelial venules (HEVs). Apoptotic cell bodies derived from intestinal epithelial cells (iECs) are phagocytosed and transported to MLN to induce tolerance against self-antigens. The depletion of MLN results in defective oral tolerance. Lamina propria DCs are continuously carrying commensal bacteria to the MLN, which can be further potentate by stimulating DCs with TLR-7/8 agonists. IgA production is induced that is supposed to limit the dissemination of commensal bacteria further than the MLN preventing effectively systemic infections.
Intestinal DCs play a key role in monitoring the intestinal lumen by continuously sampling and processing luminal antigens[46,47]. There are different pathways by which luminal antigens can gain access in the lamina propria. In all pathways, mucosal DCs are supposed to play key roles. Restricted to the ileum DCs extend transepithelial dendrites in a CX3CR1 mediated manner to survey the intestinal lumen to continuously survey the commensal microflora and to monitor food antigens[12,49]. M cells located in the follicle associated epithelium of PP are specialized epithelial cells which gained the ability to translocate luminal antigens via the intestinal barrier and deliver luminal antigens to DCs located in the subepithelial dome regions of PP. Upon pathogen challenge, CCR6+ DCs are recruited to the dome regions to process pathogens, and to trigger rapid local adaptive immune responses. As well CD11b-CD8α- CD11c+ interfollicular DCs process antigens derived from luminal reovirus. M cells within the small intestinal villous epithelium are able to translocate pathogens via the epithelial barrier to DCs located in the lamina propria. The intestinal epithelium by itself plays an important role in sensing the luminal microenvironment. The intestinal epithelium express Toll-like receptors, such as TLR2, TLR-4, TLR-5 and TLR-9 to recognize microbial derived pathogen associated molecular patterns (PAMPs) for the regulation of protective innate immune responses. As well upon LPS-stimulation iECs express the intracellular pathogen recognition pattern NOD1 and NOD2[56,57], in which mutations are associated with an increased susceptibility for CD[58,59]. IECs directly participate in intestinal antigen uptake pathways by delivering antigens or exosomes to lamina propria DCs. Secreted IgG binds to cognate luminal antigens to form IgG/antigen complexes that are recycled by neonatal FcRn receptors and delivered to lamina propria DCs[60,61]. IECs also express MHC II and may present luminal antigens to CD4 T cells. After luminal exposure with ovalbumin (OVA), OVA is taken up at apical and basolateral surfaces of the epithelial cells. Then, it enters the early endosomes and may be delivered to late endosomes where it is processed in the presence of MHC II, and presented in the context of class II to T cells. It needs to be dissected in future work whether all or specific luminal antigen acquisition routes are linked to the induction and constant renewal of tolerance and to the development of protective immune responses. DCs are assumed to play key roles in all luminal antigen acquisition routes, and are supposed to represent a major factor for the processing and presentation of orally delivered antigens and the induction of tolerance.
The gastrointestinal immune system faces the tremendous challenge to deal with potent stimuli for the innate and adaptive immune system derived from the commensal microflora and food antigens. DCs are sentinels of the mucosal immune system to survey the constituents of the luminal commensals and to trigger host responses to pathogens. It is thought that gastrointestinal diseases, such as IBDs are results of deregulated immune responses to the commensal microflora. Although germ-free (GF) mice and rats generate alloreactive T cell responses and cellular immunity to certain bacteria (after monocolonization)[65,66], the cellularity of their immune system is greatly reduced[67-69]. In this regard, the numbers of IL-17A producing TH17 cells is reduced in the lamina propria of GF animals. Because commensal flora is a major driving force of the homeostatic proliferation of naïve T cells in the periphery, the reduced cellularity in the immune system of GF mice may be the result of the deficient peripheral expansion of recent thymic T cell emigrants[71,72]. When GF mice are fed bacterial carbohydrate polysaccharide A (PSA) CD4 T cells are activated resulting in a TH1 response imprinted by DCs. After conventionalization of GF rats OX62+ DCs increased, whereas CD4+ DCs located in the follicle associated epithelium decreased indicating that CD4+ DCs phagocytose microbial derived antigens, relocate to the follicular regions, and elicit rapid immune responses to the microflora to achieve tolerance. Furthermore, it has been described that the inducible isoform of nitric oxide synthase (iNOS) expressing DCs is markedly reduced in GF or MyD88-deficient animals indicating that the commensal flora is required for the accumulation of iNOS expressing DCs at mucosal sites. In iNOS-/- animals serum IgA levels are reduced suggesting that iNOS expressing DCs play a role in IgA class switching required to prevent the uncontrolled dissemination of the commensal flora into the host.
Although the priming of T cells mainly occurs in draining lymph nodes, antigen-rich blood from the small and large intestine is transported to the liver via the portal vein, and pressed through a network of sinusoids and scanned by antigen-presenting cells and lymphocytes in the liver[74,75] (Figure (Figure1).1). One third of liver cells are constituted by non-parenchymal cells (NPCs), which include liver sinusoidal endothelial cells (LSECs), Kupffer cells, biliary cells, stellate cells (Ito or fat-storing) cells and lymphocytes[74,75]. Resident APCs in the liver are Kupffer cells, LSEC, Ito cells and DCs. Plasmacytoid B220+CD11c+ DCs as well as B220-CD11c+ DCs are found. The latter can be further divided into major immature (CD40lo CD80lo CD86lo MHC class IIlo) CD11cint and minor mature (CD40hi CD80hi CD86hi MHC class IIhi) CD11chi DCs. Further, the presence of CD8α+CD11b- and CD8α-CD11b+ DCs has been reported. The continuous exposure of resident APCs with the bacterial cell wall derived LPS promotes the induction of CD4 regulatory T cells and may explain the dominance of IL-10 in the liver[79,80]. If Kupffer cells are depleted by gadolonium chloride treatment, liver tolerance becomes impaired raising the possibility that the liver is increasingly recognized as an innate and adaptive immune organ.
Mucosal DCs play a key role in the development of oral tolerance, a phenomenon, in which systemic immune responses to a defined peptide/protein are blunted, when the same protein has been orally fed before the rodents were systemically challenged. The triggering of oral tolerance in patients with IBD is impaired; however, the exact mechanism has not been determined. Mucosal DCs are critical for the induction of oral tolerance as shown by studies, in which flt-3 ligand was injected in mice leading to the expansion of DC subsets. After the expansion of the intestinal DC pool, enhanced oral tolerance was observed. Because oral tolerance can be transferred by adoptive transfer of T cells into recipient mice, interactions between DCs and T cells seems to be essential for the development of oral tolerance, in which CD4 CD25 FoxP3 regulatory and IL-10 and TGF-β secreting TH3 cells that suppress systemic immune responses are primed. When spleen DCs are compared to mucosal DCs, the mucosal DCs are more efficient in inducing FoxP3 expression than spleen DCs in the presence of TGF-β[86,87]. Further analyses demonstrated that CD103+ DCs are able to induce the differentiation of Treg cells via the production of the Vitamin A metabolite, retinoic acid, in presence of TGF-β, which in addition results in the recruitment of T cells and B cells to intestinal tissues[88-90]. Blocking of TGF-β abrogates the ability of CD103+ DCs to induce Treg cells[91,92]. However, parallel studies have indicated that exogenous TGF-β has not to been added to this system in order to obtain FoxP3 expressing Treg cells[86,87] raising the possibility that gut DCs activates latent TGF-β present in mucosal tissues. In this regard, the integrin αvβ8 expressed by DCs is required to activate TGF-β in vivo. Mice, in which DCs lack αvβ8, develop IBD and autoimmunity.
Oral tolerance is not impaired in PP-deficient mice demonstrating that lamina propria DCs play a key role in the development of oral tolerance by sampling the luminal content, and transporting antigens to the MLN. After depletion of the MLN, the development of oral tolerance is reduced indicating that the MLN are a major site for priming tolerance. Interestingly, it has been suggested, that intestinal self antigens can be presented by lymph node stroma cells beyond the MLNs. It also may depend on the presence of certain pathogens within the lumen, because Heligmosomoides polygyus infection correlates with DC activation and IL-10 expression. This provides evidence that the studies of intestinal microbial responses not only require the recognition of region- and compartment-specific immune responses, but the consideration of the interplay of different commensals and pathogens in modulating mucosal immune responses.
Treg cells play a key role for the development of oral tolerance, and the regulation of intestinal inflammation triggered by the intestinal microflora. CD103+ but not CD103- DCs purified from GALT-induced generation of FoxP3 cells in vitro. Treg cells can be distinguished from other T cell populations by the surface expression of the α chain of the high affinity IL-2 receptor (CD25), and the transcription factor FoxP3 that is essential for Treg development. Deadly autoimmunity is prevented by Treg cells as exemplified in X-linked immunodeficiency, polyendocrinopathy, enteropathy (IPEX) syndrome in humans. The conversion of Treg cells in the GALT can be prevented by inhibitors of retinal dehydrogenases, an enzyme that is highly expressed by CD103+ DCs, which converts retinol (vitamine A) into retinoic acid[86,87,91,99]. Retinoic acid binds to nuclear retinoic acid receptors that upon ligation can inhibit the activity of activating protein-1 (AP-1), a transcription factor, which can interfere with nuclear factor of activated T cells (NFAT)-FoxP3 complex[100,101]. However, the exact retinoic acid dependent signal transduction pathways required for the conversion of Treg cells remains to be elucidated. Retinoic acid production by CD103+ DCs also induce the up-regulation of the integrin α4β7, and the CC chemokine receptor CCR9 which binds thymus-expressed chemokine (TECK) permitting the accumulation of Treg cells intestinal tissues. The retinoic acid dependent conversation of Treg cells depends on the presence of TGF-β, a cytokine that, in the presence of IL-6 and IL-23, can also induce the generation of TH17 cells (Figure (Figure2).2). A small subset of naïve T cells in the small intestine co-express the transcription factors FoxP3 and RORγt. High expression of TGF-β represses IL-23 receptor expression and favours the generation of FoxP3 Treg cells, whereas low TGF-β expression in concert with IL-6, IL-21 and IL-23 relieves FoxP3 mediated RORγT inhibition promoting TH17 cells. TH17 cells accumulate in the lamina propria of patients with IBD indicating that TGF-β can induce regulatory and pro-inflammatory T cell subsets.
Various animal models have provided insights that mucosal DCs play a key role in IBD. However, the specific function of certain DCs are unknown and needs to be determined in future work, which will provide information on mechanisms leading to IBD and limiting intestinal inflammation to achieve protective mucosal immune responses. In agreement with animal models DCs accumulate at sites of inflammation in patients with IBD. It was found that the pathogen recognition receptors TLR-2 and -4 as well as the activation/maturation marker CD40 are upregulated by intestinal DCs derived from patients with CD. Furthermore, increased numbers of TNF-α producing MDC8+ monocytes, which may be precursors of mucosal DC populations, were found in patients with IBD and, hence, the treatment CD patients with anti-TNF-α antibodies resulted in reduced DC activation[105,106]. In inflamed tissues DCs are matured and increased in numbers. The CD83-CD80+DCSIGN+ DC subsets produce the cytokine IL-12 and IL-18, which promote TH1 development. Also, in the peripheral blood and in the lamina propria of patients with CD or UC the numbers of CD86+CD40+ DCs are increased. In addition, DCs generated ex vitro from peripheral blood monocytes of IBD patients show increased abilities to stimulate immune responses[107-109]. Mice studies indicated that DCs isolated from inflamed colonic tissues and DCs located in the terminal ileum, which continuously sample commensal bacteria produce IL-23, but little IL-12[110,111]. It was discovered that IL-10 KO mice that spontaneously develop colitis are protected from colitis when bred on IL12p19, but not on IL-12 p35-deficient mice. In similar studies, Helicobacter hepaticus infected immunocompromised RAG-/- bred on IL-12 p19 deficient mice, but not on IL-12 p35 deficient background mice were protected from colitis indicating that DC derived IL-23 plays a major role in intestinal pathology[112,113]. The formation of granulomas, histological characteristics of CD, depends on the release of IL-23 by DC-like cell types that are characterized by CD11c and F4/80 expression. Genome-wide association studies showed associations between CD and UC patients, and a gene encoding a subunit for the IL-23 receptor suggested a major role of IL-23 in the pathogenesis of IBD[115,116]. IL-23 seems to be essential for the expansion and maintenance, but not for the initial induction of IL-17 producing CD4 T cells (TH17) cells. Studies in which TH1 and TH17 cells were generated co-cultures, in which naïve T cells were cultured with fecal extracts pulsed DCs, and in the presence of TH1 or TH17 promoting cytokines indicated that TH17 cells are more pathogenic than TH1 cells. Recent published observations report that colitis induced by transfer of IFNγ-deficient T cells in RAG-/- mice is associated with elevated numbers of TH17 cells in the lamina propria. The adoptive transfer of IL-17F, but not IL-17A deficient CD4 T cells ameliorated the IBD in the transfer model[119,120]. Interesting findings implicated that the IL-1 and IL-23 dependent priming of TH17 effector cells required a NOD2 dependent pathway, and that monocyte derived DCs from CD patients with mutated NOD2 failed to efficiently activate TH17 effector cells. In this regard the TH17 cytokine IL-22 mediates mucosal defence to bacterial pathogens, and ameliorates chronic colitis in the TCRαKO model by stimulating mucus production and globlet cell restitution under inflammatory conditions. In addition IL-22, which is released by T and DCs, act together with IL-17 to clear bacterial infections at mucosal sites[123,124]. When conventional DCs are depleted in a CD11c DTR transgenic animal system by diphtheria toxin applications, the severity of colitis is suppressed in the dextran sodium sulfate (DSS) colitis model. Furthermore, in mice with an iEC specific deletion of IKKβ failed to clear Trichuris muris infection characterized by severe intestinal pathology. In these mice an increased accumulation of DCs at mucosal sites was observed that produce IL-12/23 p40 and TNF-α. In addition, an accumulation of IFN-γ producing TH1 and IL-17 producing TH17 cells in the MLN was found. Specific depletion of NEMO (IKKγ) or of both IKKα and IKKβ is essential for the activation of NF-κB activation induce IBD. Constitutive NF-κB activation in IECs by commensal flora may condition DCs to prevent tissue inflammation. Thymic stromal lymphopoietin (TSLP) produced by epithelial cells is involved in the conditioning of DCs to prime less harmful TH2 and Treg responses[126,128]. Together, these data suggest that DCs are conditioned by iECs to promote immunosuppressive T cell responses. However, DCs and their precursors are sensitive to proinflammatory activation signals, which could help to participate into the long persistence of local T cell activation patterns promoting IBD.
Mucosal DCs may have several functions in the mucosal immune system to accomplish tolerance and to maintain homeostasis. Tolerance to intestinal self antigens, oral antigens and the commensal flora is achieved by interactions of DCs with regulatory and effector T cells. DCs are also involved in triggering deleterious T cell responses to the endogenous microflora being the basis of IBD. Mucosal DCs express the integrin alpha E (CD103) or the receptor for fractalkine/CX3CR1. CX3CR1 expressing DCs are involved in luminal antigen recognition pathways, whereas CD103 DCs metabolize vitamin A to retinoic acid and are involved in the conversion of T cells to regulatory T cells. Genetically engineered mouse models, and cellular approaches will be increasingly available to study the biology of CD103 and CX3CR1 DCs in immune responses to the commensal flora, and their role in initiating and regulating intestinal inflammation. DCs maintain intestinal homeostasis allowing the peaceful coexistence with the endogenous microflora. The discovery of specific DCs associated with luminal antigen acquisition and oral tolerance will allow developing strategies for targeting defined antigen acquisition routes to design therapeutic treatments for patients with IBD.
Supported by The Deutsche Forschungsgemeinschaft, No. Ni 575/4-1
Peer reviewer: Bret Lashner, MD, Professor of Medicine, Department of Gastroenterology, Cleveland Clinic/A30, 9500 Euclid Avenue, Cleveland, OH 44195, United States
S- Editor Zhong XY E- Editor Zhang WB


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Fluffy, overstuffed loveseat soft cushions arent your lifestyle? This reclining loveseat from GDF has sharper, cleaner lines than your conventional reclining loveseat, which makes it a stylish addition to a mid-century contemporary, modern, modern or modern style of house. And, at only 46.46 in . in width, its easy to squeeze into a smaller space, like flats, dog dens or office spaces. Available in several colour and fabric options, such as grilling with charcoal material, navy blue fabric and standing microfiber, its easy to find the right match for your home decorations, and also the sturdiness your family needs for everyday use. The days are gone of good-looking, but uncomfortable Roloff Manual Glider Recliner you no longer need to sacrifice comfort for design. This lying loveseat functions a big, gentle, luxurious-stuffed seat cushioning with enough space for two or enough space for you to spread out and unwind.
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9.Shantell Manual Recliner By Red Barrel Studio
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If the Chesterfield is the graceful man amongst couches, the Cabriole is the grande dame. Noted for its exposed wooden and elegant legs, reminiscent of the Louis XV period, the cabriole also has a unique silhouette. It had been also a well-liked form within the work of furniture producer Jones Chippendale. Usually, the rear is 1 continuous piece without cushions and has a stylish bending line. This specific cabriole edition includes jewels in the tufts for additional allure. It is a sofa style that can be as simple or opulent as you wish. Padded with a luxurious materials like purple velvet produces a significantly different style sensation than if it were upholstered in a much more muted, textural neutral. The primary aura of elegance stems from its overall shape and lithe thighs which means it will always lend a processed air to a space.
10.Inspire Recliner By Southern Motion
Read more about Inspire Recliner By Southern Motion
This fits you if you just need a beautiful trainer. It is designed with a flared body and pillow top amrests in a cool cobblestone gray. Now, it's resilient froth soft cushions that are obsessed with inside a polyester upholstery to bring about the desired comfort. It features a sturdy part blocked frame that adds to the sturdiness. Also, feet are in a fake wood finish. It has an impressive gray color that suits with any decor. Its dimensions are 89 T by 39 D by 40 H therefore big enough to support you along with your family/friends. More importantly, it arrives completely put together. This protects you the agony of having to put together the set.

domain: design


text:
Combination anabolic and antiresorptive therapy for osteoporosis: Opening the anabolic window
- John P. Bilezikian
- … show all 1 hide
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Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently increased our options. By stimulating bone formation, anabolic agents reduce fracture incidence by improving bone qualities in addition to increasing bone mass. The only anabolic agent currently approved for osteoporosis by the US Food and Drug Administration, teriparatide (recombinant human parathyroid hormone [1–34]), has emerged as a major approach to selected patients with osteoporosis. Recombinant human parathyroid hormone (1–84) is also available in Europe. Teriparatide increases bone density and bone turnover, improves microarchitecture, and changes bone size. The incidence of vertebral and nonvertebral fractures is reduced. A current concept in the mechanism of teriparatide action is related to its effect to stimulate processes associated with bone formation before it stimulates processes associated with bone resorption. This sequence of events has led to the concept of the anabolic window, the period of time when teriparatide is maximally anabolic. Newer approaches to the use of teriparatide alone and in combination with antiresorptive agents have led to ways in which the anabolic window can be expanded.
- Hodsman AB, Bauer DC, Dempster D, et al.: Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev 2005, 26:688–703. CrossRef
- Canalis E, Giustina A, Bilezikian JP: Mechanisms of anabolic therapies for osteoporosis. N Engl J Med 2007, 357:905–916. CrossRef
- Dempster DW, Parisien M, Silverberg SJ, et al.: On the mechanism of cancellous bone preservation in postmenopausal women with mild primary hyperparathyroidism. J Clin Endocrinol Metab 1999, 84:1562–1566. CrossRef
- Girotra M, Rubin M, Bilezikian J: The use of parathyroid hormone in the treatment of osteoporosis. Rev Endocr Metab Disord 2006, 7:113–121. CrossRef
- Jiang Y, Zhao JJ, Mitlak BH, et al.: Recombinant human parathyroid hormone (1–34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res 2003, 18:1932–1941. CrossRef
- Sellmeyer DE, Black DM, Palermo L, et al.: Heterogeneity in skeletal response to full-length parathyroid hormone (PTH) in the treatment of osteoporosis. Osteoporos Int 2007, 18:973–979. CrossRef
- Burr DB, Hirano T, Turner CH, et al.: Intermittently administered human parathyroid hormone(1–34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys. J Bone Miner Res 2001, 16:157–165. CrossRef
- Keaveny TM, Hoffman PE, Kepperdahl, et al.: Comparison of the effects of teriparatide and alendronate on parameters of total hip strength as assessed by finite element analysis [abstract]. J Bone Miner Res 2007, 22(Suppl 1):S26.
- Borggrefe J, Graeff C, Nickelsen TN, et al.: Effects of 2 year teriparatide treatment on 3-D femoral neck bone distribution, geometry, and bone strength: results from the EUROFORS study [abstract]. J Bone Miner Res 2007, 22(Suppl 1):S75.
- Parfitt AM: Parathyroid hormone and periosteal bone expansion. J Bone Miner Res 2002, 17:1741–1743. CrossRef
- Zanchetta JR, Bogado CE, Ferretti JL, et al.: Effects of teriparatide [recombinant human parathyroid hormone (1–34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res 2003, 18:539–543. CrossRef
- Lindsay R, Silverman SL, Cooper C, et al.: Risk of new vertebral fracture in the year following a fracture. JAMA 2001, 285:320–323. CrossRef
- Neer RM, Arnaud CD, Zanchetta JR, et al.: Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001, 344:1434–1441. CrossRef
- Gallagher JC, Genant HK, Crans GG, et al.: Teriparatide reduces the fracture risk associated with increasing number and severity of osteoporotic fractures. J Clin Endocrinol Metab 2005, 90:1583–1587. CrossRef
- Marcus R, Wang O, Satterwhite J, Mitlak B: The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis. J Bone Miner Res 2003, 18:18–23. CrossRef
- Prince R, Sipos A, Hossain A, et al.: Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res 2005, 20:1507–1513. CrossRef
- Hodsman AB, Hanley DA, Ettinger MP, et al.: Efficacy and safety of human parathyroid hormone-(1–84) in increasing bone mineral density in postmenopausal osteoporosis. J Clin Endocrinol Metab 2003, 88:5212–5220. CrossRef
- Fox J, Miller MA, Recker RR, et al.: Treatment of postmenopausal osteoporotic women with parathyroid hormone 1–84 for 18 months increases cancellous bone formation and improves cancellous architecture: a study of iliac crest biopsies using histomorphometry and micro computed tomography. J Musculoskelet Neuronal Interact 2005, 5:356–357.
- Greenspan SL, Bone HG, Ettinger MP, et al.: Effect of recombinant human parathyroid hormone (1–84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann Intern Med 2007, 146:326–339.
- Antoniucci DM, Sellmeyer DE, Bilezikian JP, et al.: Elevations in serum and urinary calcium with parathyroid hormone (1–84) with and without alendronate for osteoporosis. J Clin Endocrinol Metab 2007, 92:942–947. CrossRef
- Kurland ES, Cosman F, McMahon DJ, et al.: Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 2000, 85:3069–3076. CrossRef
- Orwoll ES, Scheele WH, Paul S, et al.: The effect of teriparatide [human parathyroid hormone (1–34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 2003, 18:9–17. CrossRef
- Kaufman JM, Orwoll E, Goemaere S, et al.: Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int 2004, 16:510–516. CrossRef
- Cosman F, Nieves J, Woelfert L, et al.: Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal. J Bone Miner Res 2001, 16:925–931. CrossRef
- Ettinger B, San Martin J, Crans G, Pavo I: Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res 2004, 19:745–751. CrossRef
- Cosman F, Nieves J, Zion M, et al.: Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med 2005, 353:566–575. CrossRef
- Miller P, Lindsay R, Watts N, et al.: Patients previously treated with risedronate demonstrate greater responsiveness to teriparatide than those previously treated with alendronate: the Optamise trial. J Bone Miner Res 2007, 22(Suppl 1):S26.
- Delmas P, Watts N, Miller P, et al.: Bone turnover markers demonstrate greater earlier responsiveness to teriparatide following treatment with risedronate compared with alendronate: the Optamise study. J Bone Miner Res 2007, 22(Suppl 1):S27.
- Black DM, Greenspan SL, Ensrud KE, et al.: The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 2003, 349:1207–1215. CrossRef
- Finkelstein JS, Hayes A, Hunzelman JL, et al.: The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 2003, 349:1216–1226. CrossRef
- Deal C, Omizo M, Schwartz EN, et al.: Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebocontrolled trial. J Bone Miner Res 2005, 20:1905–1911. CrossRef
- Misof BM, Roschger P, Cosman F, et al.: Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 2003, 88:1150–1156. CrossRef
- Lindsay R, Scheele WH, Neer R, et al.: Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch Intern Med 2004, 164:2024–2030. CrossRef
- Kurland ES, Heller SL, Diamond B, et al.: The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone (1–34)]. Osteoporos Int 2004, 15:992–997. CrossRef
- Lindsay R, Nieves J, Formica C, et al.: Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 1997, 350:550–555. CrossRef
- Lane NE, Sanchez S, Modin GW, et al.: Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial. J Bone Miner Res 2000, 15:944–951. CrossRef
- Black DM, Bilezikian JP, Ensrud KE, et al.: One year of alendronate after one year of parathyroid hormone (1–84) for osteoporosis. N Engl J Med 2005, 353:555–565. CrossRef
- Harper KD, Krege JH, Marcus R, Mitlak BH: Comments on initial experience with teriparatide in the United States. Curr Med Res Opin 2006, 22:1927. CrossRef
- Vahle JL, Long GG, Sandusky G, et al.: Bone neoplasms in F344 rats given teriparatide [rhPTH(1–34)] are dependent on duration of treatment and dose. Toxicol Pathol 2004, 32:426–438. CrossRef
- Jimenez C, Kim W, Al Sagier F, et al.: Primary hyperparathyroidism and osteosarcoma: examination of a large osteosarcoma cohort identifies unique characteristics. J Bone Miner Res 2003, 18(Suppl 2):LB6.
- Tashjian AH Jr, Gagel RF: Teriparatide [human PTH(1–34)]: 2.5 years of experience on the use and safety of the drug for the treatment of osteoporosis. J Bone Miner Res 2006, 21:354–365. CrossRef
- Harper KD, Krege JH, Marcus R, Mitlak BH: Osteosarcoma and teriparatide? J Bone Miner Res 2007, 22:334. CrossRef
- Levin G, Mazouz C: Transdermally-delivered PTH(1–34), a new treatment for osteoporotic patients: results of phase I studies. J Bone Miner Res 2007, 22(Suppl 1):S324.
- Horwitz MJ, Tedesco MB, Gundberg C, et al.: Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 2003, 88:569–575. CrossRef
- Black DM, Rosen CJ: Parsimony with PTH: is a single weekly injection of PTH superior to a larger cumulative dose given daily? J Bone Miner Res 2002, 17(Suppl 1):SA367.
- Ponnapakkam T, Matsushita O, Sakon J, Gensure RC: Weekly administration of a novel parathyroid hormone—collagen binding domain fusion protein increases bone mineral density by more than 15 percent in normal mice. J Bone Miner Res 2007, 22(Suppl 1):S64.
- Cosman F, Nieves JW, Zion M, et al.: Effects of PTH rechallenge 1 year after the first PTH course in patients on long-term alendronate. J Bone Miner Res 2005, 20(Suppl 1):1079.
- Gowen M, Stroup GB, Dodds RA, et al.: Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J Clin Invest 2000, 105:1595–1604. CrossRef
- Ethgen D, Danoff T, Schultz M, et al.: Antagonism of calcium sensing receptor stimulates dose-related release of endogenous parathyroid hormone in normal volunteers: a proof of concept study. J Bone Miner Res 2007, 22(Suppl 1):S128.
- Rubin MR, Bilezikian JP: New anabolic therapies in osteoporosis. Endocrinol Metab Clin North Am 2003, 32:285–307. CrossRef
- Combination anabolic and antiresorptive therapy for osteoporosis: Opening the anabolic window
Current Osteoporosis Reports
Volume 6, Issue 1 , pp 24-30
- Cover Date
- Print ISSN
- Online ISSN
- Current Science Inc.
- Additional Links
- Author Affiliations
- 1. Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA

domain: literature


text:
Markets tended a little firmer.
- Chicago wheat December up US4.75c/bu to 588.75c/bu;
- Kansas wheat December down 2c/bu to 729c/bu;
- Minneapolis wheat December up 3.75c/bu to 783.5c/bu;
- MATIF wheat December up €1.25/t to €238.50/t;
- Black Sea wheat has not quoted since 11 August;
- Corn December up 6c/bu to 482.25c/bu;
- Soybeans May 2024 up 4.5c/bu to 1353.5c/bu;
- Winnipeg November canola up C$1.80/t to $736.10/t;
- Winnipeg May 2024 canola up C$0.20/t to $757.50/t;
- MATIF rapeseed November 2023 up €8.75/t to €449/t;
- MATIF rapeseed May 2024 up €3 to €470.25/t;
- ASX January 2024 wheat down A$0.50/t to $427/t;
- ASX January 2024 barley unchanged at A$370/t;
- AUD dollar eased 6 points to US$0.6448.
Black Sea market analyst SovEcon revised down the 2023-24 Russian wheat crop forecast by 0.5Mt to 91.6Mt amid worsening prospects for Siberia and the south. The outlook in Siberia deteriorated due to heavy rain and yield results in the south fell as harvest progressed. Despite a slight reduction in the Russian wheat crop estimate, wheat supply will remain high, continuing to exert pressure on global prices.
Ukraine’s Agriculture Ministry will introduce a licencing system for maize, rapeseed, sunflowerseed and wheat exports to Romania, Poland, Bulgaria, Slovakia and Hungary as part of an action plan to satisfy concerns expressed by the EU states. Ukraine will coordinate with the European Commission and the five member states.
Egypt’s GASC bought 120,000t Romanian wheat in a tender that closed yesterday. GASC was seeking wheat for 1-15 Nov shipment and paid $272/t.
It is being reported that Egypt will switch to sourcing almost half a million tonnes of wheat from Russia to France and Bulgaria after Moscow objected to the pricing. The deal was booked at $270/t including freight, lower than the unofficial price floor Russian officials were trying to implement at the time.
China has reportedly booked at least 20 cargoes of soybeans from Brazil and Argentina over the past two weeks for delivery during October, November and into December.
Algeria’s state grains agency OAIC is believed to be continuing negotiations on its wheat tender which closed on Tuesday. There was no clear consensus among traders about the volume purchased but there are rumours it could be up to 700kt priced at $272/t c&f. It also purchased 30,000t feed barley from optional origins at $223.00-$225.00 c&f, Oct shipment.
Wednesday was a slower day across local markets. Grower bids were mostly softer due to offshore weakness and all that did was dry up liquidity. The local market continues to focus on the dry and hot weather, with very little on the forecast to get excited about.
Current crop feed barley in Kwinana reached $385/t FIS Kwinana via Clear Grain Exchange yesterday, and new crop WA values held around the $390/t FIS level best grower bid. Some ASW Kwinana old crop wheat traded $400/t, and new crop bids for APW1 MG in WA were lower yesterday. It was bid around $428/t FIS Kwinana and there was very little interest on the sell side.
Some early barley is being harvested around the Queensland Western Darling Downs towns of Condamine and Dulacca this week, with yields around 2.5t/ha and quality reportedly good on the early crops.
Line ups are currently showing 2.72Mt of total grain on the shipping stem for September, including 1.56Mt wheat, 682kt barley, 279kt canola and 194kt sorghum. We have seen a slight increase in average vessel wait time, with Adelaide, Brisbane, Geraldton and Kwinana all increasing, while wait time in Albany decreased. Overall, the maximum wait time is less than 8 days; there are 10 vessels anchored and 11 loading at Australian ports.

domain: agronomy


text:
Batman v Superman: Dawn of Justice may only be 27 percent “Fresh” on Rotten Tomatoes, but I’d bet the percentage of people impressed by the visual effects is much higher.
No matter what you think of the film overall, there’s little denying the effects work is impressive. Sure, some of it (like Doomsday) is distracting, but this new video will amaze you by the sheer amount of effects in the film. Here you’ll see a lot of detail work and set extension, as well some full action scenes too. If you’re like me, it’ll give you a new appreciation of the craft that went into the troubled blockbuster.
That’s just the work of one effects house, too. (Scanline VFX, if you missed it). There were certainly lots of others who added their hard work to the film’s visuals. Now, if only the same amount of hard work was applied to the... nope. Just going to leave it there. It’s the holidays, after all.

domain: entertainment


text:
By Jack Tarrant
TOKYO (Reuters) – Japanese football has been built around defensive solidity and organisation in recent years but with new coach Hajime Moriyasu removing the shackles and adopting a more attacking style of play the Samurai Blue hope to light up the Asian Cup with goals.
Japan will be among the favourites at the Jan. 5 to Feb. 1 tournament in the United Arab Emirates, where they begin their campaign for a record-extending fifth continental title in Group F alongside Oman, Turkmenistan and Uzbekistan.
In five friendly games under former international midfielder Moriyasu so far, Japan have compiled four wins and a draw, scoring 15 goals along the way.
The highlight of his short time in charge was a 4-3 win over Uruguay in October, where Japan’s more expansive style of play was there for all to see.
Moriyasu has stuck with the same formation as his predecessor Akira Nishino, who replaced Vahid Halilhodzic in April before exiting after the World Cup, with three attacking midfielders deployed behind a central striker.
Moriyasu, however, has changed personnel and asked the trio to attack with more commitment and threat.
Behind experienced Werder Bremen forward Yuya Osako, Moriyasu’s preferred three of Ritsu Doan, Shoya Nakajima and Takumi Minamino have just 18 caps between them.
Salzburg’s Minamino has four goals to his name since Moriyasu took over but it is diminutive 24-year-old Nakajima who has caught the eye, with his pace and vision sure to excite in the UAE.
A 4-0 rout of Kyrgyzstan in their final tune-up marked a third clean sheet in five games for Japan’s defence, which is led by captain Maya Yoshida.
Yoshida was the only man in Moriyasu’s most recent squad with over 50 caps and, along with midfielder Gaku Shibasaki, is one of only two players to have featured at an Asian Cup.
Moriyasu may also look to bring in some additional experience to the squad, with Borussia Dortmund’s Shinji Kagawa and defender Yuto Nagatomo, who is currently out injured, likely candidates for call-ups.
(Editing by Peter Rutherford)

domain: news


text:
Personas sometimes get a bit of bad press. If they are done right they can be an invaluable design aid, but if they are done badly they can be nothing more than ugly stereotypes. We’re looking to make personas a core part of the way we design services so we’ve been doing some thinking around how we can ensure that we avoid the bad persona pitfalls.
When we talk about personas we talk in terms of archetypes rather than stereotypes. That's important because there are some key distinctions to make between the two.
Just as a smell or flavour can trigger a memory of our childhood, personas should remind us of real people we have met. Good personas foster empathy, bring research to life and allow us to engage with customers at every stage of the design process, whether they are in the room with us or not.
There is lots of evidence out there to support the use of good quality personas in design and innovation. Organisations like The Well Told Story Group are using archetypes to great effect in order to improve social outcomes in Africa and have provided part of our inspiration to reinvigorate the use of personas here at Bromford.
In order to ensure that our personas are good archetypes we have developed a set of overarching principles to guide us:
By focusing our work around our guiding principles we are able to create personas which tell a story and bring our research to life.
We use personas as a way to communicate qualitative research about people who we have shadowed, interviewed or observed in some way. Personas help us to understand people in a wider context than our services alone. A picture paints a thousand words so we are trying to get better at using photographs of people and their things in order to compliment our research and inform the stories we are curating.
In order to draw together a consolidated summary of the people we have met we depict a persona as an individual person. However, in fact personas are not a representation of a single individual but rather a synthesised set of observations representing many real people. Personas help us to understand people in greater depth than data might do on its own, helping us understand why people behave in certain ways, and helping us uncover their goals, motivations and concerns.
We are really protective of our persona principles, especially #3 - Personas must be based on qualitative data (gathered by us). The difference between a stereotype and an archetype is research. Personas are bad when professionals create them from the comfort of their office with little or no evidence to back them up.
Personas are just one way we take ourselves from a position of thinking to a position of knowing.
Thinking something is true without the evidence to back it up leads to bad personas and bad personas lead to bad design decisions, so it’s important to build personas based on facts and evidence. I remember seeing a tweet from Carrie Bishop which summarised this point and inspired this image.
Good personas are built on rich insights not conjecture. We believe that good personas have several key characteristics:
Good personas reflect patterns observed in research
Good personas focus on what is currently happening
Good personas are realistic, not idealised and assume the attributes of several real people
Good personas help us understand:
Good personas provide value in a variety of ways:
Good personas can help validate or disprove a design decision
Good personas can help us decide which direction to take
Good personas provide agile learning not statistical viability
Good personas provide inspiration during idea generation
Good personas give voice to the end user and foster empathy
In order to gather the fact based evidence we need to design a set of personas we use observation and conversation based around a topic guide, rather than a rigid set of questions, such as a questionnaire. Often the most insightful conversation happens after the questions have been answered and our conversations are as much about picking up on the stuff that isn't said as they are about the stuff that is.

domain: psychology


text:
Jun 9, 2014 10:11 AM by Associated Press
ALTADENA, Calif. (AP) - Authorities say an Arroyo Pacific Academy high school teacher is in jail for allegedly abducting three students.
Los Angeles County sheriff's deputies say 34-year-old John Edward Maust was arrested Sunday for investigation of kidnapping, false imprisonment, and criminal threats. He is being held on $100,000 bail.
Deputies say three 17-year-olds were driving in Altadena Saturday night when they the teacher standing on a corner. When they stopped, investigators say Maust asked for a ride.
Something Maust said caused the driver to pull over and the students to jump out, but deputies say Maust ordered them back, pulled a knife and told them to go to a fast food restaurant.
One student called 911. When he saw a helicopter, Maust left. Early Sunday, Maust walked into the sheriff's substation and surrendered.
(Copyright 2014 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.)
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The ideal solution for all those cases in which high energy load resistance, small dimensions and low cost are required.
The strong points of CFP resistors are a very simple construction, high quality ceramic and a proper selection of the wire.
- low cost
- high power
- high overload resistance
- ROHS compliant


text:
Bill Goldstein talks about New From Heaven:
Tune in at 7 pm EST for an on-air discussion of News From Heaven.
Jennifer Haigh's story "Paramour" has been selected to appear in this year's Best American Short Stories anthology.
"Like all my stories, it is a mash-up of several things that interest me intensely—in this case, other people's marriages, sex and innocence, the theater, fathers and daughters, and Ukrainians."
Read more or buy the anthology here.


text:
Commonly used in small business that want the flexibility of Traditional (Pre-Tax) and Roth (Post-Tax) contributions. These plans are easy to manage and provide the investor with a wider range of investment options than a 401k or 403b does.
Another commonly used business plan for small businesses. The business has to have less than 100 employees, but the contributions can only be made on a Traditional (Pre-Tax) basis.
A type of employer plan for businesses/organizations in the public and nonprofit sectors. These plans do have some interesting differences when it comes to withdrawing funds as you are not required to wait until you are 59 1/2 to withdraw without a penalty. For more information please see a tax professional.
How to Bake a Pie-R-A
Bull and Bear Go To Market
Preparation is the Key to Retirement

domain: finance


text:
COVID has done an interesting thing to the population. All of the sudden, people are out en masse in nature! The public health side of me is so excited to see people exercising more, and outside nonetheless! The tree hugger side of me wants to tell everybody to go home and leave the beautifu…
Want your thoughts, ideas or opinions published? Submit a letter to the editor.

domain: sociology


text:
Looking for the full Houzz experience?
88,948 floating shelf Home Design Photos
did the floating console cabinet come from? Thank you for your response.
where can I buy this floating cabinet?
What wood species is the floating console? Thanks!
idea of a floating shelf in the dining room
Add a shelf to your dining room! A floating shelf in a warm finish, with barely noticeable drawers able to hide table linens, can be functional and feel rich. For shelves like this one, work with a carpenter or woodworker to secure it properly and be sure the wall can hold the weight.
Woodvalley House - Interiors
I need 2 or 3 of the long, thick floating shelf in a stained black.
purchase the floating shelf?
nice shelf and pictures for entrance
Floating shelf with lit art above
Change DP doors to glass shelf built in?
floating shelf, love it
SHELF AND PICTURES VERY BALANCED
Floating shelf at front door
shelf in the entry-way
install a floating shelf.
Floating Shelf...Like floating shelf...floating wall table...Entry shelf...buffet shelf...Floating console...floating shelf?...Shelf for foyer...Entrance hall shelf...the shelf...floating shelves
"calming" shelf decor against TV! Where could I find the painting? or artist?
Where did you get the floating shelve from? What are the dimensions?
like versatility of moveable cabinet underneath TV and floating shelf above.
shelf over tv at lease minimizes impact
Shelf close to tv. Serves as mantle
Shelf over TV to minimize it
I like floating shelf and mounted TV Easy to do?
low console + shelf above (but no space for components and cords are visible)
with a shelf. If your TV setup is looking a little lonely, try installing a floating shelf on the wall above it. Keep the shelf close to the top of the screen (6 to 12 inches away) and fill it with a collection of favorite art, books and objects.
Northern VA Landscape Architect & Designer
Best of Houzz 2013 & 2014
Best of Houzz 2013 & 2014
Since 1999, we have worked with homeowners to develop truly unique and distinctive outdoor living spaces. We specialize in upscale poolscapes, hardscapes and landscapes.
Capitol Hill Row House
the artwork is on a floating shelf, it would be uneven if you tried to hang it on the brick wall
floating shelf for prints vs hanging them
A small floating shelf on the exposed brick displays art work neatly and practically.
displayed on floating shelf dining room
Invisible shelf with pictures on wall
chapeau 29 resolute lighting floating shelf for wood block prints
floating shelf on the exposed brick wall so pictures hang evenly
small floating shelf on the exposed brick
Instead of hanging a row of prints (impossible to keep straight)lean them on a narrow shelf (molding?)
small floating shelf. The framed art pieces are Japanese woodblock prints by Hiroshige from the "Hundred Famous Views of Edo."White bowls: Verona, CB2
Giulietti Schouten Architects
Entry with tile floors, board formed concrete and red door
love the floating rack with storage
The floating box shelving units were custom made and installed by the cabinet maker for the project. There are well documneted installation diagreams and instructions. I would suggest that you search "floating box shelving installation" It would be easier to review waht is avaialble than for me to try
Hello: I absolutely love that shelf. Could you please let me know who designed/makes it? Thanks so much.
find the floating shelf and drawer at Niedermaier.
love the floating shelf.. was this custom made or could you tell me where it can be acquired please... thanks
Depending on the size, the shelf with a drawer runs between $5k - $7k.
What is the price on that shelf?
shelf as entry table with bench under
layout, floating stainless steel shelf,mirror, lamps
for foyer--like idea of floating table
Love the idea of the floating shelf and the stool under it.
J. Kramer Corp.
Modern home with pool
How did you hang the floating cabinet?
Simplistic but works with the floating shelf.
The floating shell from IKEA.Ideas for the family room upstairs
floating shelf under TV
open concept, floating, interesting.
found our floating wall shelf!
floating media shelf
Floating wall mounted console
Floating entertainment center
media shelf, floating
Floating cabinet under tv
the floating cabinent
Floating shelf with tv over
TV en floating shelf
floating media center
Hanging shelf under tv
vertical shelf turned horizontal.
Floating cabinet...hanging tv shelf...Family shelf...Shelf on wall....Floating shelf...floating storage...Cool shelf under TV...Floating console...TV floating shelve...like wall shelf...floating shelf
Floating shelves holding family photos & art and swing arm wall sconces are part of the essentials for late night reads in the Master Bedroom. Photo credit ~ Anni Lissee
I really want to do something similiar but I keep thinking the shelf will fall on my face when I'm sleeping!
Where did you get this shelf? I have been looking for wide one for a long time.
Floating Shelf - Try IKEA, Home Depot, Lowes.....they come in different lengths. Not pricey.
I have had my floating shelves installed over 10 yrs ago....still as sturdy as the day they were installed. Make sure you follow the instructions with the floating shelves and use proper wall anchors
My floating shelves are anchored to the studs. Seems safe to me.


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At GolfPutting, we're committed to delivering accurate, trustworthy information. Our expert-authored content is rigorously fact-checked and sourced from credible authorities. Discover how we uphold the highest standards in providing you with reliable knowledge.
Frisbee golf, also known as "disc golf" is a sport that can be played either competitively or for recreational purposes. To play this game, a player will aim a type of disc similar to a Frisbee® at various targets with baskets attached. Similar to traditional golf, the player will keep track of how many attempts it takes to get the disc into the target basket; the player who takes the fewest throws will be the winner.
The game was first invented in the 1960s in the United States, by a California man named George Sappenfield. In his original version, sort of obstruction, such as fire hydrants and light posts, could be used as a target for the disc. The first real Frisbee golf course, in which standard targets were established, was created by "Steady Ed" Headrick, a player in La Canada Flintridge, California.
Headrick also formed the Disc Golf Association and several other professional organizations for players, in an attempt to standardize the rules of the game and to establish tournaments between players throughout the world. Headrick was so passionate about Frisbee golf that when he died, he ordered to have his cremated ashes made into discs for the game, which were given to his friends and family.
Today, there are more than 2,000 courses for Frisbee golf, most of which are located in the United States. As in regular golf, the courses generally have 18 holes, though some smaller courses only have 9 holes. The courses are generally located in public parks, and are free to play on.
There are many different kinds of discs that are used in Frisbee golf. The three main categories that all fall into are putters, mid-range discs, and drivers. Depending on where the player is on the course and his strategy for reaching the target, he will want to determine which of the three types to use to achieve the best throw. It is possible to purchase discs made out of several different types of plastic, from a fairly flimsy type to a premium brand. In general, the discs are made of thicker and firmer plastic than a traditional recreational Frisbee®.
The sport is very popular among both men and women, and many colleges have their own Frisbee golf teams or clubs. Though the game has the most recognition in the United States, it is rising in popularity in other countries.

domain: hobby


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140 Burbank Drive, Tazewell, Virginia, 24651
This 3 bedroom, 2 and a half bath brick ranch is located Gratton,Virginia is perfect for a first time home buyer or someone looking to down size to have everything on one level. The home boasts a car port, a little over 9 acres and even has a small barn in the back. This home is located in a quiet neighborhood and with the property, this home is a must see. Call to schedule your viewing today.

domain: geography


text:
Super Kamagra GГјnstig
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domain: medical


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Buttery shortbread is baked until crisp, then half-dipped in dark chocolate and toasted coconut for a delicious treat!
12tbspunsalted butterat room temperature
7.5ozby weight all purpose flour(1.5 cups measured)
1cupsweetened shredded coconut
2cupssemisweet or bittersweet chocolate chipsmelted
Either in a stand mixer fitted with the paddle attachment or in a bowl with a hand mixer, whip the butter on medium speed for about 30 seconds to spread it around the bowl.
With the mixer still on medium, add the sugar. Cream the butter and sugar together for 30-60 seconds on medium, until the two have been combined.
Briefly mix in the sea salt and almond extract.
Add the flour all at once and take care to only mix the flour with the wet ingredients until just combined. Be careful not to overmix. The dough will be crumbly and that’s fine.
Dump the crumbly shortbread out onto a big piece of plastic wrap and shape it into a rectangle. It should clump together smoothly.
Refrigerate the dough for at least one hour, but two is better if you have the time.
After the dough has chilled, preheat the oven to 350 degrees F.
Once preheated, place the coconut on a sheet pan and place it in the oven, giving the coconut a stir every 5 minutes or so. The coconut can take between 5 and 15 minutes to take on color, and it’s ready to be removed from the oven when it’s a golden brown color.
Lightly flour your countertop and roll the chilled shortbread out to about 1/4 inch thickness. Use a cookie cutter to cut out shapes and place the cutouts on a baking sheet.
Bake the cookies for 13-17 minutes, depending on how brown you like your shortbread. My husband likes soft shortbread with no color (13 minutes), and I like the shortbread golden brown and crisp (17 minutes).
Let the cookies cool completely, then dip half the cookie in the chocolate and sprinkle it with the toasted coconut. Let the chocolate harden and enjoy!

domain: food


text:
More than a hundred persons are said to have been injured in Western Sahara's capital, observing the UN Human Rights day and frustrated over EU's new illegal fisheries agreement with Morocco in their waters. Videos keep coming in. See series.
The demonstrators called for right to self-determination. On 10 December, they were met by Moroccan forces. Several injured, including a group of foreign activists from the Canary Islands, who were later set free.
The local hospital received more than 90 injured following the demonstrations on 10 December, according to Associated Press. A journalist from AP, Paul Shamme, was present at some of the demonstrations, but he was removed by Moroccan security personnel.
Se videos below:
Here is from a large demonstration in the Tantan street in El Aaiún, 11 December.
Some activists from the Canary Islands also took part in the demonstrations. They are wearing orange tshirts. From 04:21, the Spaniards are detained:
Here is another video of the same demonstration.
Here, demonstrators are attacked by Moroccan security personnel, and beaten:
This is apparently a video of the US journalist Paul Shamme, stopped by Moroccans, prevented from reporting.
Demo from 8 December:
The UN Working Group on Arbitrary Detention has ruled in favour of the two Saharawi sisters Sultana and Luara Khaya.
The torture and detention of 10 Saharawi students by Moroccan authorities must be investigated and denounced. This is the demand in a complaint submitted today to the UN Special Procedures.
A 16 day-long campaign will shed light on violence committed against women in occupied Western Sahara.
One film festival in the world is different from all others. Read Asria Taleb's encounter with a festival audience in the Saharawi refugee camps in Algeria - including her connection with a complete stranger.


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My coworker Tisa's Japanese pen pal, Hiroko, is visiting her from Japan this week. Tisa brought her and her husband in yesterday to introduce her to her coworkers. Hiroko is such a sweet woman, and she brought all of the women in our office these packages of bubble bath. I wish I could read Japanese so I could know what the packages say. Maybe Chie could help me out. :))) The photo I took with my digital camera is not very good and I'm not sure why. Usually the pictures I take with it are really clear, but maybe it was the way the light reflected on the packages or something similar that made it look a little blurred.
I started crocheting a doily to give to Hiroko, but for some reason I was having problems with it, and the yarn I was using wasn't looking right, so I decided to start another one in a lilac color. I know I won't be able to finish it in time to give it to Hiroko before she leaves to go home, but I'll just mail it to her in Japan. I don't have any idea how much that will be in postage, but it's not something I'm worried about. I just wanted her to have a nice handmade gift.
On Sunday Eddie and I went to his mom's for Easter dinner and I had to take some pictures of the flowers in her yard. They were absolutely gorgeous. She has such a green thumb. I think she could put a stick in the ground and something would sprout out of it. I wish I had such a green thumb. About the only thing I've managed to have flourish are some African Violets I have in my office. I used to have trouble with them until I discovered self-watering pots. Of course, the pots on this page are pretty expensive, and I found one of mine at Tuesday Morning for around $5.00, and the other two at Home Depot for around $5 to $6. I also saw some pretty ones recently at Walmart. I bought one of those to give as a gift to a friend of mine. I'm trying right now to find her a pretty African Violet, but they seem to be scarce here now for some reason. Maybe they are out of season.
Here are the pictures of my mother-in-law's flowers. One is an azalea and the others are roses.

domain: artistic


associationwebsiteA notebook computer specification page named IdeaPad S530-131WL, the processor column readsCore i7-9550U, i5-9250U and i3-9130U are all new features.。
At the same time,According to Lenovo, there seems to be little difference in performance between i7-9550U and i7-8565U, i5-9250U and i3-9130U. The latter three are eight generations of new Core Rui products released by Intel in August, which belong to Whiskey Lake family.
Earlier news said that the 9-generation low-voltage Core CPU for notebook platform is expected to be released in Q2 in 2019, with thermal design power consumption of 15W and 2MB three-slow per core.
Whether the Core 9000U processors are 10nm Ice Lake or newly exposed Comet Lake is unknown. Due to the delay of 10 nm, the process of 14 nm is optimized and re-optimized, and the lineup is in some confusion.


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Manufacturing Companies for FTXL Power Distribution Box to Benin Manufacturer
Exterior and dimensions
We will make every effort to be outstanding and perfect, and accelerate our steps for standing in the rank of international top-grade and high-tech enterprises for Manufacturing Companies for FTXL Power Distribution Box to Benin Manufacturer, We welcome customers, business associations and friends from all parts of the world to contact us and seek cooperation for mutual benefits.
FTXL power distribution box is suitable for all types of wet and dust places and it is applicable to low-voltage distribution system of the textile, metallurgy, chemical industry, mining, machinery, with three-phase three-pole of rated current less than 630A, four-pole or five-pole, for power supply and lighting distribution with features of flexible, mobile, reliable, safe . The incoming line assemble QSA switch, partition door operated which could reduce the arc damage to the operator. Shunt switch can be flexibly configured and it is feasible to add control equipment, such as time relay, AC contactors, etc according to user requirements.
For years experience . We specialized in Motor Control , breakers, contactors ,PLC,HIM . We major deal with brand of Schneider , Siemens ,Mitsubishi, Allen-Bradley, ABB, GE ,Moeller, Omron, SMC,SICK, LS.
A Voyage to Arcturus is a novel by Scottish writer David Lindsay, first published in 1920. It combines fantasy, philosophy, and science fiction in an exploration of the nature of good and evil and their relationship with existence. It has been described by critic and philosopher Colin Wilson as the “greatest novel of the twentieth century” and was a central influence on C. S. Lewis’ Space Trilogy.
Chapter 1. The Seance – 00:00
Chapter 2. In the Street – 29:50
Chapter 3. Starkness – 42:02
Chapter 4. The Voice – 52:17
Chapter 5. The Night of Departure – 1:04:27
Chapter 6. Joiwind – 1:19:25
Chapter 7. Panawe – 1:57:22
Chapter 8. The Lusion Plain – 2:32:03
Chapter 9. Oceaxe – 2:53:12
Chapter 10. Tydomin – 3:40:52
Chapter 11. On Disscourn – 4:31:04
Chapter 12. Spadevil – 4:52:07
Chapter 13. The Wombflash Forest – 5:29:14
Chapter 14. Polecrab – 5:42:50
Chapter 15. Swaylone’s Island – 6:18:05
Chapter 16. Leehallfae – 7:02:18
Chapter 17. Corpang – 7:52:16
Chapter 18. Haunte – 8:39:26
Chapter 19. Sullenbode – 9:25:50
Chapter 20. Barey – 10:05:09
Chapter 21. Muspel – 10:44:48


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A hundred years ago, and for many centuries before, Midsummer’s Eve was celebrated throughout Ireland on the 23 June, that is, on Saint John’s Eve.
The bonfire was central to the activities of Midsummer’s Eve, and those who witnessed the flames more than a lifetime ago noted that the landscape was filled with hundreds of bonfires, creating a beautiful aspect by illuminating the country as far as the eye could see. These fires were lit on elevated sites including mountain tops and hills, but also in fields, at crossroads and on the streets and in squares of towns and villages throughout the country. In Dublin bonfires were outlawed by the Lord Mayor in the 1700’s, and as a substitute, the towns’ people attached candles to trees and bushes to maintain the tradition in some form. Gradually, during the nineteenth century, coercion bills were brought in an attempt to eliminate bonfires from many towns and villages across Ireland, but these bills, while having limited in their success, failed to end the popular tradition of lighting bonfires on Saint John’s Eve. While the tradition of lighting bonfires on Saint John’s Eve has declined substantially over the past century the tradition is still observed in certain parts of the country up to the present day.
Bonfires in previous centuries were fed on materials that were readily available and easily obtained; in some areas straw, reeds and wood were collected throughout the whole six months leading up to Midsummer’s Eve, while in other areas the bonfire was principally made of turf, with every inhabitant of the village donating their own share to feed the bonfire. Well into the last century the ancient Irish tradition of burning animal bones continued, some believe in imitation of ancient sacrifices, in certain parts of Munster and Connaught, the addition of which created crackling noises, bright stray sparks, while, at the same time, providing the origin of their very name “bone-fire”, now generally spelled and often pronounced as bonfire.
The Midsummer’s bonfire are traditionally thought to increase fertility and produce luck, while passing through the flames of the fire was also thought to provide protection from both the fairies and the evil eye. Many accounts relate how cattle were driven through the flames between two persons who each held lighted sheaf of straw or reeds, known as a “cleer”. Members of the household also jumped through the fire, as did lovers who held hands in the hope of encouraging their own fertility. In County Cavan, a century ago, it was still believed that if you ate your supper by the fire on Midsummer’s Eve you would be protected from hunger throughout the coming year, while farmers often spread a sod of turf, coal, ashes, or even holy water on their crops as a method of protection from diseases including blight on Midsummer Eve.
Games and amusements were performed by many who attended, caps were often grabbed from unsuspecting heads and thrown or, at least, pretended to be thrown in the flames by the more boisterous members of the community. Spectators at the bonfires also fashioned bundles of reeds or straw which, when lit, were waved through the air, and in some places including Belmullet in County Mayo sods of lighted turf were thrown to the sky in the belief that the air would be purified through the motion of these smouldering sods. Additionally, a lighted piece of turf or a coal was often taken from the bonfire and carried home to relight the hearth in the household, which according to many accounts, was annually quenched on Midsummer’s Eve.*
*It is worth mentioning that quenching the fire on Midsummer’s Eve was only observed in some localities, as there was a strong tradition in many parts of Ireland of keeping the hearth fire burning continuously for years, or even decades, on end.
Mac Lir, Mananaan. ‘The Folklore of Months’. Journal of the Cork Historical and Archaeological Society, Second series II (1896), 157, 316, 365.
Mahon, Rev. Michael P. Ireland’s Fairy Lore, Boston, 1919.
Mason, William Shaw. A Statistical Account or Parochial Survey of Ireland. Dublin, London and Edinburg, 1814-19.
O’Hanlon, Rev. John (Lageniensis). Irish Folk Lore: Traditions and Superstitions of the Country; with Humorous Tales. London, 1870.
Ó Súilleabháin, Amhlaoibh. The Diary of an Irish Countryman 1827 – 1835. Translated from the Irish by Tomás de Bhaldraithe. Cork/Dublin 1970/1979.
Piers, Sir Henry, A Chorographical Description of the County of West-Meath, A.D. 1682
Synge, J. M. In Connemara. Dublin, 1979.
Warburton, John & others. History of the City of Dublin. Dublin, 1818.
Various articles from the Folklore Journal 1881 – 1916

domain: history


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London is swinging again! After being considered a "conservative" destination for many years, London is now one of the hottest, busiest cities in the world. In this completely revised and updated edition, visitors to historic London will find restaurants, shops, and museums fit for a Queen (including the newly renovated food courts at Harrods), plus trips to Greenwich (where the largest ongoing millennium celebration will take place all year), Cambridge, Oxford, Bath, and much more.
- Publication Date:
- 01 / 08 / 2000